http://www.vitaminpost.ca Wed, 08 Sep 2010 11:26:43 +0000 http://www.vitaminpost.ca/news/165/Saw-Palmetto-Doesn%27t-Work.html Sun, 12 Jul 2009 05:04:00 +0000 http://www.vitaminpost.ca/news/165/Saw-Palmetto-Doesn%27t-Work.html Holistic International
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PS & Ginkgo in one pill
Well, all right: the headline is an
exaggeration -- but it’s not that as far from
the truth as you might think. Saw
palmetto is the most common herbal for
benign prostatic hyperplasia (BPH), the
noncancerous swelling of the prostate
gland which affects nearly all men to some
degree beginning in late middle age, leading
to discomfort, nocturia (the need to get
up in the middle of the night for a trip to
the bathroom), frequent and sudden
urges to urinate even when the bladder is
not full, intermittency (dribbling at the
end of the urinary stream), and
incomplete emptying of the bladder
when urinating. Saw palmetto, along with a
few other herbals, is reached for in health
food stores across North America almost
by reflex. And there is evidence that this
botanical is helpful for improving the
symptoms of BPH1. This can also be said of
β-sitosterol5, and to a lesser extent of such
herbals as 2 and stinging
nettle3,4, as well as the amino acid
combination Paraprost (glycine, alanine,
and glutamic acid)7, which is widely used for
prostate concerns in Japan. But (and this is a
big “but”) when it comes to the underlying
disease process itself, there is absolutely
no evidence that any of these natural
therapies actually reduces the of the
prostate -- that is, they fail to actually
address the underlying problem, as opposed
to its symptoms. Indeed, controlled trials
which have investigated this point have
specifically reported that there is no effect
on prostate volume from taking saw
palmetto1 or β-sitosterol6, the most
evidence-backed of the standard prostate
health botanicals.
By contrast, there is plenty of evidence that
finasteride (Proscar®), the most famous drug
therapy for BPH, can reduce prostate
Holistic International™
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Volume 1 Issue 2 August 2000
Preventative
Alternative
Ayurvedic
Holistic
Naturopathic
Orthomolecular
Cover Story
Throw your Saw
Palmetto out!
Defined Pollen Extract
for Prostate Health.
Pg.1
Breaking Health News
Is Beta-
Carotene toxic?
There is a difference!
Pg. 9
New Supplement
Review
A quick look at a
few new products that
shine! Pg. 12
A cut above the
rest
Holistic International
and Jarrow
Formulations’ hottest
new products. Pg. 17
I want to know!
We take your most difficult
questions. Pg. 18
pg.1
Image credit to Focus on Grain by Alan Blackwood 1986 from Focus on Resources series by Wayland Publishers Ltd.
volume. Unfortunately, finasteride is slow
(one year minimum) to take effect, does not
work with several classes of patients, is very
expensive, and has significant side effects,
including erectile dysfunction and loss
of libido. So men are left with a poor
choice: herbs which provide symptomatic
improvement with no halt to the loss of
prostate health, or a drug treatment which
addresses the core problem, but causes
problems of its own. But there is a way out
of this dilemma. A herbal remedy long
available in Europe is just now becoming
available in North America. It’s all-natural,
inexpensive, and free of significant side
effects; it improves symptoms; it works
faster than most other therapies, including
saw palmetto; it shows promise for more
prostate health concerns than just BPH;
and it has been proven to reduce prostate
volume in controlled clinical trials. It is a
defined pollen extract, sold under such
trade names as Cernitin, Cernilton, and
Prostaphil®, and it stands poised to
revolutionize the way many men approach
prostate health.
This substance should not be confused
with bee pollen. Bee pollen is a mixture of
whatever pollens with which the insects
happen to have come into contact. The
pollen extract, by contrast, is a mixture of
several specific pollen sources (primarily rye,
but also including timothy grass, corn,
hazel, sallow, aspen, oxye, and pine pollens).
Also, bee pollen in its raw form is covered
with a microscopic husk which prevents its
full assimilation by humans; by contrast, the
pollen extract discussed here is a
standardized extract, which incorporates a
specific 20:1 ratio of lipid- and
water-soluble components extracted under
low-temperature conditions to bypass the
pollen’s protective sheath.
Proven in Controlled Trials
Many people find it strange that something
as simple as flower pollen could have
powerful effects on prostate health. And
yet the clinical evidence is plain:
standardized pollen extract quickly
improves prostate symptoms and
reduces prostate volume. In one
double-blind, controlled study8, sixty men
with symptomatic BPH received either the
pollen extract or placebo for six months.
Sixty-nine percent of men receiving the
pollen extract showed improved overall
symptoms, compared to less than a third
of the placebo group; the differences were
statistically significant for such measures as
fewer incidences of nocturia, decreased
leftover urine in the bladder after
urination (“residual urine volume”), and
reductions in the volume of the prostate
as measured by ultrasound (see Figure 2).
Compared to the placebo group, there were
also more improvements reported by men
receiving the pollen extract in hesitancy
(inability to release urinary flow) and
intermittency, but these results were not
strong enough, in this small a group over
this short a period, to be statistically
meaningful.
Another double-blind, placebo-controlled
trial of the pollen extract was reported by
Becker and Ebeling9. Ninety-six men with
BPH completed the twelve-week trial,
during which the men were on either the
pollen extract or the placebo for one six
week period, and then “crossed over” to
the other pill. Statistically significant
results were experienced while the men
were taking the pollen extract in
nocturia and residual urine volume,
Volume 1, number 2
August 2000
Dr. Traj P.S. Nibber
Michael Rae
Danika Challand
Shebodo@Hotmail.com
Cindi Armstrong
Holistic International, manufacturers
and distributors of the most exciting
lines of envelope-pushing nutritional
supplements in Canada, welcomes you to
this issue of The Holistic Lifestyle,
published eight times a year. The Holistic
Lifestyle is designed to provide our
customers with essential information
and news of breakthrough research to
help you make the best decisions to meet
your health goals through supplements
and lifestyle choices.
The Holistic Lifestyle also provides news
about Holistic International and its
products, along with trade shows,
retailer information, and government
regulations and their impact on your
health freedom.
Comments? Questions?
We want to hear from you!
The Holistic Lifestyle
4404 - 12 Street North East Box #92
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T2E 6K9
The content of this newsletter is provided for
informational purposes only, and is not intended as
medical advice for individuals, which can only be
provided by a healthcare professional.
Contents © Holistic International™ 2000; Design ©
Danika Challand 2000.
pg.2
00
100
90
80
70
0
0 14 42 days
β−sitosterol
N = 20
R
Cornilton
N = 19
Figure 1: Significant reduction (p < 0.01) of the
serum PSA after 6 weeks' Defined Pollen
Extract. Redrawn from (17).
To date, no trial has directly compared the
therapeutic effect of the pollen extract to
saw palmetto. However, based on the
available evidence, it is clear that the pollen
extract is superior to saw palmetto on
several points. Most important is the fact,
noted above, that while it may improve
symptoms such as nocturia and peak flow
rate, saw palmetto has never been
shown to reduce prostate -- whereas
several trials, as we have seen, have
reported just this for the pollen extract.
This means that saw palmetto can only
address symptoms, while the defined
pollen extract can
actually help the
underlying disease. The
difference is crucial,
especially from the perspective of the
long-term prostate health of the men
taking these herbals, who may delay surgery
because of symptomatic relief. Also, it is
clear that saw palmetto does not work as
quickly, or for as many men, as does the
pollen extract: from the published
evidence1,18, it would appear that four to six
months are required to report significant
improvements in symptoms using saw
palmetto, whereas Becker and Ebeling10
could report improvement after only six
weeks! And, indeed, there is now some
question18, 19 as to whether saw palmetto
actually of any help at all in BPH; the
arguments are complex, and space is
limited, so we will not enter into this
debate.
Several other open trials of the efficacy of
standardized pollen extract against BPH
have been performed13, 14, 15, and these have
also been successful, but because of their
small size and uncontrolled design, we will
move on.
Other Prostate Concerns
BPH, of course, is not the only prostate
disorder that men may face. Another is
chronic prostatitis (CP), an ongoing
inflammation of the prostate gland,
reflected in the presence of markers of
inflammation in the prostate fluid. Chronic
along with borderline significant decreases
in daytime urinary frequency. The
investigating physicians reported “very
good” or “good” improvement during
the pollen phase of in 55.2% of the men,
whereas only 13% of the placebo-phase
men were so reported; and while “poor”
results were reported on placebo for
41.9% of the men, only 3.4% of the pollen
extract males’ progress was so rated. These
results were also significant from a
statistical perspective -- amazing results
over the course of a mere six weeks, with so
few men enrolled in the trial. When these
men were followed up for just twelve
additional weeks in an open-label study10,
the pollen extract also significantly
improved daytime urinary frequency,
while residual urine was decreased by
47%. Results which did not meet the
criteria for statistical significance included
reduced painful urination, urgency, and
discomfort, while 40.4% of men showed
reductions in prostatic volume (as
compared to 12.1% of the placebo group).
In a massive open-label observational
study11 on men with several prostate
disorders, including 1,116 with BPH, those
men with BPH and chronic prostatitis (see
below) experienced a 55.9% reduction in
prostate volume while on the pollen
extract, along with decreases in residual
urine, increases in urine flow rate, and
greater total urine volume with
decreased time taken to empty the
bladder. Both patients and physicians rated
the average improvement “good to very
good.”
Better than Other Botanicals
How do these results stack up to prostate
herbals the more common in North
America? Fortunately, controlled trials have
been performed to answer this question,
and the answer is “very well, thank you.” In
a head-to-head trial against Tadenan (the
best-studied and most famous brand of
in Europe), Dutkiewicz12
reported that 78% of the men in the
pollen extract group reported subjective
improvements, versus “only” 55% of
the group. Another trial16
compared it with Paraprost: significant
improvement in residual urinary
volume, flow rate, and (again, most
importantly) was seen in
the pollen extract group; the lenth of
time required to urinate was also better as
compared to the Paraprost group.
The most impressive comparison is that
with β-sitosterol -- both because
β-sitosterol is perhaps the most rigorously
studied of all the common prostate health
herbals, and because of
the unique insight the
trial yielded about the
power of the pollen
extract. The trial17 found that while there
were improvements in both groups for
subjective symptoms, painful urination,
and frequent urination, greater progress
was made in the pollen extract group,
while the groups equally demonstrated
improvements in straining, urinary
volume, residual volume, and
intermittency. This trial also measured
the levels of prostate-specific antigen
(PSA), a marker used to detect prostate
cancer, along with prostatic acid
phosphatase (PAP), a measure normally
elevated in many prostatic dysfunctions.
Measuring these markers was a first for
both botanicals. Both PAP and PSA were
significantly reduced in the defined
pollen extract group, whereas no
significant change was reported in
the β-sitosterol group (See figure 1).
Reductions in the volume
of the prostate as measpg.
3
suggested that the active ingredient in the
pollen extract might be a cyclic hydroxamic
acid called 2,4-dihydroxy-2H-1,4-benzox
azin-3(4H)-one (DIBOA).
Yet other investigators have disputed this
conclusion32: they found that DIBOA
could inhibit a breast cancer line,
and found compounds in the pollen extract
which were more more potent inhibitors
of the prostate cancer cell line. All of
these compounds appear to work by
inducing cell death in the cancer cells32.
Meanwhile, yet another group of
researchers has reported a whole new
category of tumor-inhibitory substances in
rye pollen: the secalosides43.
Thus, while DIBOA must play some role in
the anti-prostate cancer effect of the
defined pollen extract, it is not the only
active ingredient with anti-cancer power in
the test tube, and other compounds may be
responsible for the specific effect on prostate
cancer cells. Whatever the true active
ingredient, however, one thing is clear:
defined pollen extract may prove to be
potent nutritional support against
prostate -- and perhaps other -- cancers.
In this context, the lowering of PSA
levels experienced by men receiving the
pollen extract17 is very tantalizing. But we
cannot be certain that this means a
prostatitis is sometimes caused by
recurrent bacterial infection, but is often
present in the absence of such “nasties;” at
least some prostatitis may actually be caused
by unusual muscle tensions at the base of
the pelvis20, and a trial is being launched at
Stanford University to see if behavioral
therapy can help ease the symptoms where
this is the root problem. There is also
prostatodynia, which is distinct from CP
in that the chemical markers of
inflammation are not seen in the prostatic
fluid. It is very important to note that there
is no evidence that saw palmetto or the
other common herbals for BPH are
helpful for these conditions, with the
possible exception of Paraprost25. Because
the symptoms of these disorders sound
similar, many men with CP or prostatodynia
mistakenly self-medicate with saw palmetto,
with the result that their symptoms remain
and their health problem goes untreated.
Even when physicians are consulted (which
is always the best course of action), the
relative ignorance of many mainstream
MDs about the herbal pharmacy
leads them to give the
go-ahead for this useless
course of action. By
contrast, several open trials
have found the pollen
extract to be helpful for CP and
prostatodynia11, 21, 22, 23, 24. Rugendorff et al
ran one such trial21, in which 72 men with
CP or prostatodynia uncomplicated by
prostate stones or non-prostatic
complications like blockages of the bladder
“neck” were administered the defined
pollen extract. Examination by digital
rectal exam, urine flow, and white blood
cell count along with other immune
markers found that 78% of these men
were helped by defined pollen extract. A
second group of men whose CP was
complicated by the factors mentioned
above were not found to benefit, however.
Hope for Prostate Cancer
An even graver prostate health concern for
many men is prostate cancer. In men,
excluding skin cancer, prostate cancer is the
single most commonly-contracted cancer
form, with a new diagnosis every two
minutes in the United States and a new
death every fifteen minutes. The American
Cancer Society estimates that 180 400 men
will be diagnosed with prostate cancer in
the United States in this year alone -- and
diagnosed prostate cancer represents a
mere fraction of the total incidence of this
disease. Autopsy studies36, 37 show that 15
to 30% of men over 50, and 60 to 70
percent of men over the age of 80, have
latent, undiagnosed prostate cancer.
There has been exciting progress made in
the last few years in the discovery of
natural ways of reducing the risk of
prostate cancer, including successful
double-blind, placebo-controlled trials with
selenium26, alpha-tocopherol27, and the
carotenoid lycopene28. Preliminary
evidence now suggests that it is possible
that the defined pollen extract may yet
prove to be a safe, natural herb to help the
fight against the second greatest cause of
cancer death in men.
In the course of
attempts to discover
the components of the
extract which inhibit
prostate cell growth, a
fraction of the lipid-soluble extract in the
defined pollen extract (labelled FV-7) has
been discovered which appears to have the
power to halt the growth of prostate cancer
cells. In 1990, Habib at coworkers29 tested
defined pollen extract to see what its effects
would be on the growth (in test-tube
conditions) of nine cancerous and
noncancerous cell lines derived from
humans. They found that, of the cell lines
tested, the pollen extract would
inhibit the growth of prostate cell lines.
Further, it was noted that the growth
inhibition applied only to the epithelial cells
of the prostate (the gland itself), not the
stroma (the surrounding smooth muscle
cells). Later studies30, 31 on FV-7 found that
this subfraction of the defined pollen
extract inhibited the growth of a human
prostate cancer line. These investigators
Statistically significant results
were experienced while the men
were taking the pollen extract in
nocturia and residual urine volume.
pg.4
oxioreductase (HSORred) enzymes, which
convert DHT to the less-stimulating 3-α-
and 3-β-diol. In other words, the pollen
extract directly decreases both the synthesis
and the clearance of DHT. What the end
result of this would be is unclear, but the
net effect on DHT activity
levels in the prostate could
very well be zero. Clearly,
more studies are needed, but
direct inhibition of DHT may
not be a key mechanism of the pollen’s
activity.
Another possible mechanism of prostate
shrinkage by the pollen extract was
identified by Japanese researchers39. These
investigators subjected rats to high levels of
testosterone so that they would develop
BPH, and then administered the defined
pollen extract. While significantly reducing
the weight of the prostate, the pollen
extract elevated zinc levels in the gland
-- this, despite the fact that there is very
little zinc in the extract itself. When present
in the prostate, zinc has anti-5AR activity40,
and also reduces the binding of male
hormones41 and prolactin42 to the
prostate cell receptor, all of which would
be expected to reduce the growthtriggering
eggects of these hormones.
Since zinc levels are depressed in BPH and
prostate cancer44, simply taking zinc orally
may not increase zinc levels specifically in the
prostate, and may thus not be effective at
safe dosages.
Furthermore, the pollen extract inhibits
absorption of the toxic heavy metal
cadmium45, which is linked with prostate
cancer in many studies46 and which can
directly cause prostatic growth and cancer
in animal models47. Levels of cadmium are
increased in both BPH and prostate
cancer44. But while these effects on
mineral metabolism might help explain a
slowing of growth in the prostate, and enhance
any anti-cancer effect the pollen extract
may prove to have, they probably do not
explain the reported reductions in prostate
volume. Thus, while the fact of reduced
reduction in risk of prostate cancer:
Proscar®, for instance, also lowers PSA, but
does not appear to have any effect on this
terrible disease. Thus, it is possible that this
lowering of PSA may reduce the
usefulness of the PSA test as a marker for
prostate cancer (as is known to happen with
Proscar®); as with Proscar®, then, it seems
prudent to suggest that men should have
their PSA checked before starting on the
pollen extract, to establish a baseline from
which future tests can be evaluated. Though
the test-tube results will clearly have to be
confirmed in living humans, the forty-year
safety record of defined pollen extract and
its ability to lower PSA certainly make it
worth a second look by those concerned
with this deadliest and most intimate of
killers.
How Does it Work?
By now, many readers will be wondering how
exactly the defined pollen extract can exert
such profound effects on prostate health.
There are some hints in the literature, but
final answers still escape us. Partly, what we
are seeing is an anti-inflammatory effect:
in test tube studies, the pollen extract
inhibits the conversion of arachidonic
acid to series 2 eicosanoids, which are
local, cellular “hormones” which promote
inflammation. Because inflammation is the
key marker of chronic prostatitis, it is
obvious how this would be helpful in cases
of CP, but it may also enhance any
anticancer effects of the extract. This is
because cancer cells use series 2 eicosanoids
-- most notably prostaglandin E2 (PGE2)
-- to defend themselves from the body’s
immune system34, because PGE2 inhibits
natural killer cell activity. Thus, substances
which inhibit series-2 eicosanoid formation
may have anti-cancer effects as well as
anti-inflammatory ones.
Another mechanism at work in the
symptomatic improvement generated by
the pollen extract is its effects on smooth
muscle tone in the urinary tract. In
isolated urinary tract muscle cells57, 58, 59, and
one trial in humans35, it has been found that
the pollen extract balances the muscle tone
of the urethra and bladder, resulting in less
pinching off of the urine stream. This
would help explain the extract’s
improvement in such symptoms as
incomplete bladder emptying, hesitancy, or
intermittency. It may also
explain some of the results in
chronic prostatitis, since (as
noted above) unusual
muscular tensions may play a
role in much CP.
But the exact method by which the defined
pollen extract exerts its most exciting
influence on the prostate -- namely, its
ability to reduce the actual volume of the
prostate -- remains unknown. As noted
above, test-tube studies have shown29 that
the pollen extract does directly inhibit the
growth of prostate cells, but how exactly it
does this remains an enigma. One logical
assumption would be that the pollen extract
is exerting effects on the hormones which
drive BPH. Proscar®, the most successful
drug therapy for BPH, also reduces prostate
volume. It does so by inhibiting 5-α-
reductase (5AR), the enzyme which
converts testosterone into the much more
prostate-stimulating dihydrotestosterone
(DHT). Defined pollen extracts, likewise,
inhibit 5AR38; however, they also
inhibit the less-known hydroxysteroid
Both PAP and PSA were
significantly reduced in the
defined pollen extract
group.
pg.5
29
27
25
23
0
Figure 2: Prostate volume. Redrawn from (8).
31
mm
pre post
S.E.
S.E.
S.E.
S.E.
-4,6% Placebo (n=24) -18, 2% Cernilton (n=29)
prostate volume remains on solid ground,
the mechanisms of this revolutionary effect
remain elusive.
Not Just for the Prostate... And Not Just
for Men!
Most people taking the pollen extract are
using it for the health of their prostate,
which is by far the best-backed usage for
this botanical. Yet there are hints in the
literature of a broad range of other
applications which get much less attention.
One such property is detoxification and
liver protection. In addition to the
reduction in cadmium absorption
mentioned above45, investigators in Poland
have found that the defined pollen extract
provides protection against such toxins
as ammonium fluoride48, 49, paracetamol
(an anti-inflammatory and pain killer which
is among the drugs most commonly
consumed in toxic overdose)50, organic
solvents51, allyl alcohol52, 54, the deadly
carbon tetrachloride52, and
galctosamine52, 53 in lab animals. Some of
this protection may be due to the
antioxidant properties of the extract55,
along with its ability to increase levels of
liver detoxification enzymes56.
Another possible benefit from the pollen
extract may be protection from
atherosclerosis. In one study, animals fed
a high-fat diet along with defined pollen
extracts had lower cholesterol and
triglycerides compared to animals not
receiving the pollen extracts55. Another
study56 reported that such animals had
reduced total cholesterol and elevated
HDL (“good”) cholesterol, along with
reductions in atherosclerotic plaques:
the group receiving the high-fat diet alone
had a plaque intensity of 85.5%, while the
group which also received the defined
pollen extract had only a 33.7% plaque
intensity.
Finally, although we emphasize that the
evidence is purely anecdotal, in some parts of
the world more women buy defined pollen
extracts than men, because they have found
that the pollen extract helps with
urinary incontinence -- a result very
consistent with the improved bladder and
urethral smooth muscle tone balance35, 57-59
which the pollen extract is known to yield.
Funding is presently being sought to run a
controlled trial on this application.
The Future of Prostate Care
Proscar® and other drugs for BPH are
effective, but come with side effects and a
cost which make drug therapy unattractive
to many men. The natural alternatives most
common on Canadian health food store
shelves may help relieve symptoms, but do
not ultimately address the underlying
disease. But defined pollen extract has been
effectively helping European men with
many prostate health problems for decades
now, and is proven to do what no other
herbal can: shrink swollen prostates. As the
pollen itself is golden, so defined pollen
extract may open up a golden age for safe,
natural therapy for the most personal of
male health concerns.
pg.6
To the people of South America, it’s Chanca
Piedra, the “stone breaker.” In Ayurvedic
tradition, it’s Bahupatra . Botanists classify it as
Phyllanthus niruri. Hurricane Weed, Seed On
The Leaf, Feuilles de la Fievre, Child’s
Pick-a-back, Tamalaka, Turi Hutan ... whatever
you call it, this short tropical shrub is famed for
its healing powers.
Western science is beginning to confirm Chanca
Piedra’s ability to support the health of the
detoxification organs. From increasing the
flushing-out of the kidneys, to relaxing the
smooth muscles of the bladder, urethra, and
biliary tract, to guarding the liver against toxins
and the replication of some viruses, Chanca
Piedra may support the function of the body’s
detoxification systems in many ways ... and by
many names.
Traditional herbal medicine for:
-Kidney stones
-Gallstones
-Liver protection & detoxification
-Immune support and more!
A stone by any
other name ...
(42) Leake et al, “Interaction between prolactin and zinc in the human
prostate gland.” J Endocrinol. 1984 Jul; 102(1): 73-6.
(43) Jaton et al, “The secalosides, novel tumor cell growth inhibitory
glycosides from a pollen extract.” J Nat Prod. 1997 Apr; 60(4): 356-
60.
(44) Habib et al, "Metal-androgen interralationships in carcinoma and
hyperplasia of the human prostate." J Endocrinol 1976 Oct; 71(1):
133-41.
(45) Howaniec et al, “The role of cernitin in cadmium effect on the
absorption processes in rat small intestine.” Acta Physiol Pol. 1988
May-Jun; 39(3): 188-94.
(46) Waalkes & Rehm, “Cadmium and prostate cancer.” J Toxicol
Environ Health. 1994 Nov; 43(3): 251-69.
(47) Hoffmann et al, “Carcinogenic effects of cadmium on the prostate
of the rat.” J Cancer Res Clin Oncol. 1985; 109(3): 193-9.
(48) Humiczewska et al, “The effect of the pollen extracts quercitin and
cernitin on the liver, lungs, and stomach of rats intoxicated with
ammonium fluoride.” Folia Biol (Krakow). 1994; 42(3-4): 157-66.
(49) Mysliwiec , “Effect of pollen extracts (cernitin preparation) on
selected biochemical parameters of liver in the course of chronic
ammonium fluoride poisoning in rats.” Ann Acad Med Stetin. 1993;
39: 71-85.
(50) Juzwiak et al, “Experimental evaluation of the effect of pollen
extract on the course of paracetamol poisoning.” Ann Acad Med Stetin.
1993; 39: 57-69.
(51) Ceglecka, “Effect of pollen extract (cernitin) on the course of poisoning
with organic solvents.” Ann Acad Med Stetin 1992; 38: 79-95.
(52) Samochowiec & Wojcicki, “The effect of pollen on the changes in
the liver of laboratory rats evoked by ethionine, carbon tetrachloride, allyl
alcohol and galactosamine.” Arch Exp Veterinarmed 1989; 43(4):
521-32.
(53) Wojcicki et al, “The effect of Cernitins on galactosamine-induced
hepatic injury in rat.” Arch Immunol Ther Exp (Warsz). 1985; 33(2):
361-70.
(54) Wojcicki et al, “The protective effect of pollen extracts against allyl
alcohol damage of the liver.” Arch Immunol Ther Exp (Warsz). 1985;
33(6): 841-9.
(55) Wojcicki et al, “Study on the antioxidant properties of pollen
extracts.” Arch Immunol Ther Exp (Warsz) 1987; 35(5): 725-9.
(56) Wojcicki et al, “Effect of pollen extract on the development of
experimental atherosclerosis in rabbits.” Atherosclerosis 1986 Oct;
62(1): 39-45.
(57) Onodera et al, “Effects of cernitin pollen extract (CN-009) on the
isolated bladder smooth muscles and the intravesical pressure.” Nippon
Yakurigaku Zasshi 1991 May; 97(5): 267-76.
(58) Kimura et al, “Micturition activity of pollen extract: contractile
effects on bladder and inhibitory effects onurethral smooth muscle of
mouse and pig.” Planta Med.1986 Apr; 2: 148-151.
(59) Nakase et al, “Inhibitory effect and synergism of cernitin pollen
extract on the urethral smooth muscle and diaphragm of the rat.”
Nippon Yakurigaku Zasshi /Folia Pharmacol Japan. 1988 Jun; 91(6):
385-392.
(1) Wilt et al, “Saw palmetto extracts for treatment of benign prostatic
hyperplasia: a systematic review.” JAMA. 1998 Nov 11;280 (18):
1604-9.
(2) Breza et al, “Efficacy and acceptability of tadenan (Pygeum
africanum extract) in the treatment of benign prostatic hyperplasia
(BPH): a multicentre trial in central Europe.” Curr Med Res Opin.
1998;14(3):127-39.
(3) Romics, “Observations with Bazoton in the management of prostatic
hyperplasia.” Int Urol Nephrol. 1987; 19(3): 293-7.
(4) Vontobel et al, “Results of a double-blind study on the effectiveness of
ERU (extractum radicis Urticae) capsules in conservative treatment of
benign prostatic hyperplasia.” Urologe A. 1985 Jan; 24(1): 49-51.
(5) Wilt et al, “b-sitosterol for the treatment of benign prostatic hyperplasia:
a systematic review.” BJU Int. 1999 Jun; 83(9): 976-83.
(6) Berges et al, “Randomised, placebo-controlled, double-blind clinical
trial of beta-sitosterol in patients with benign prostatic hyperplasia. Betasitosterol
study group.” Lancet. 1995 Jun 17; 345(8964): 1529-32.
(7) Feinblatt & Gant, "Value of glycine, alanine and glutamic acid
combination." J Maine Med Assoc. 1958 Mar; 49(3).
(8) Buck et al, “Treatment of outflow tract obstruction due to benign
prostatic hyperplasia with the pollen extract, cernilton. A double-blind,
placebo-controlled study.” Br J Urol. 1990 Oct; 66(4): 398-404.
(9) Becker and Ebeling, “Conservative treatment of benign prostatic
hyperplasia (BPH) with cernilton N -- results of a placebo-controlled
double-blind study.” Urologe (B). 1988; 28: 301-6.
(10) Becker & Ebeling, “Phytotherapy of BPH with cernilton
N––results of a controlled prospective study.” Urologe (B). 1991; 31:
113-6.
(11) Ebeling, “Therapeutic results of defined pollen-extract in patients
with chronic prostatitis or BPH accompanied by chronic prostatitis.” in
Schmiedt et al (eds), Therapy of Prostatitis, (Munich: Zuckerschwerdt
Verlag, 1986): 154-160.
(12) Dutkiewicz, “Usefulness of cernilton in the treatment of benign
prostatic hyperplasia.” Int Urol Nephrol. 1996 96; 28(1): 49-53.
(13) Yasumoto et al, “Clinical evaluation of long-term treatment using
cernitin pollen extract in patients with benign prostatic hyperplasia.”
Clin Ther. 1995 Jan-Feb; 17(1): 82-7.
(14) Hayashi et al, “Clinical evaluation of cernilton in benign prostatic
hypertrophy&91;.” Hinyokika Kiyo. 1986 Jan; 32(1): 135-41.
(15) Ueda et al, “Clinical evaluation of cernilton on benign prostatic
hyperplasia.” Hinyokika Kiyo. 1985 Jan; 31(1): 187-91.
(16) Maekawa et al, “Clinical evaluation of rnilton on benign prostatic
hypertrophy--a multiple center double-blind study with Paraprost.”
Hinyokika Kiyo. 1990 Apr; 36(4): 495-516.
(17) Bräuer, “The treatment of benign prostate hyperplasia with
phytopharmaca. A comparative study of cernitin vs. beta-sitosterol.”
Therapiewoche. 1986; 36: 1686-96.
(18) Lowe & Ku, “Phytotherapy in treatment of benign prostatic
hyperplasia: a critical review.” Urology. 1996 Jul; 48(1): 12-20.
(19) Dreikorn & Schonhofer, “Status of phytotherapeutic drugs in treatment
of benign prostatic hyperplasia.” Urologe A. 1995 Mar;
34(2): 119-29.
(20) Zermann et al, “Chronic prostatitis: a myofascial pain syndrome?”
Infect Urol. 1999; 12(3):84-88.(21) Rugendorff et al, “Results of
treatment with pollen extract (cernilton N) in chronic prostatitis and
prostatodynia.”Br J Urol. 1993 Apr; 71(4): 433-8.
(22) Suzuki et al, “Clinical effect of cernilton in chronic prostatitis.”
Hinyokika Kiyo. 1992 Apr; 38(4): 489-94.
(23) Buck et al, “Treatment of chronic prostatitis and prostatodynia
with pollen extract.” Br J Urol. 1989 Nov; 64(5): 496-9.
(24) Jodai et al, “A long-term therapeutic experience with Cernilton in
chronic prostatitis.” Hinyokika Kiyo. 1988 Mar; 34(3): 561-8.
(25) Okada et al, “Clinical application of PPC for nonspecific chronic
prostatitis.” Hinyokika Kiyo. 1985 Jan; 31(1): 179-85.
(26) Clarket al, “Decreased incidence of prostate cancer with selenium
supplementation: results of adouble-blind cancer prevention trial.” Br J
Urol. 1998 May; 81(5): 730-4.
(27) Heinonen, “Prostate cancer and supplementation with alpha-tocopherol
and beta-carotene: incidence and mortality in a controlled trial.” J
Natl Cancer Inst. 1998 Mar 18; 90(6): 440-6.
(28) Kucuck et al , “Lycopene supplementation in men with localized
prostate cancer (PCa) reduces grade and volume of preneoplasia (PIN)
and tumor, decreases serum PSA, and modulates biomarkers of growth
and differentiation.” Meeting of the Am Assoc Cancer Res. 1999
April.
(29) Habib et al, “In vitro evaluation of the pollen extract, cernitin T-
60, in the regulation of prostate cell growth.” Br J Urol. 1990 Oct;
66(4): 393-7.
(30) Habib et al, “Identification of a prostate inhibitory substance in a
pollen extract.” Prostate. 1995 Mar; 26(3): 133-9.
(31) Zhang et al, “Isolation and characterization of a cyclic
hydroxamic acid from a pollen extract, which inhibits cancerous cell
growth in vitro.” J Med Chem. 1995 Feb 17; 38(4): 735-8.
(32) Roberts et al, “Cyclic hydroxamic acid inhibitors of prostate
cancer cell growth: selectivity andstructure activity relationships.”
Prostate. ce1998 Feb 1; 34(2): 92-9.
(33) Loschen & Ebeling, “Inhibition of arachidonic acid cascade by
extract of rye pollen.” Arzneimittelforschung. 1991 Feb; 41(2): 162-7.
(34) Uotila, “Inhibition of prostaglandin E2 formation and histamine
action in cancer immunotherapy.” Cancer Immunol Immunother. 1993
Sep; 37(4): 251-4.
(35) Takeuchi et al, “Quantitative evaluation of the effectiveness of
cernilton on benign prostatic hypertrophy.”Hinyokika Kiyo/Acta Urol
Jpn. 1981; 27: 317-326.
(36) Lundberg & Berge, “Prostate carcinoma: an autopsy study.” Scand
J Urol NephroI. 1970; 4(2): 93-7.
(37) Harvei, “Epidemiology of prostatic cancer.” Tidsskr Nor
Laegeforen. 1999 Oct 10; 119(24): 3589-94.
(38) Tunn & Krieg, ”Alterations in the intraprostatic hormonal
metabolism by the pollen extract cernilton N.” in Vahlensieck &
Rutishauser (eds), Benign Prostate Diseases. (New York: Thieme
Medical Publishers, 1992): 109-114.
(39) Ito et al, “Antiprostatic hypertrophic action of cernitin pollenextract
(cernilton).” Oyo Yakuri / Pharmacometrics 1986; 31(1): 1-
11.
(40) Leake et al, “The effect of zinc on the 5 alpha-reduction of
testosterone by the hyperplastic human prostate gland.” J Steroid
Biochem. 1984 Feb; 20(2): 651-5.
(41) Leake et al, “Subcellular distribution of zinc in the benign and
malignant human prostate: evidence for a direct zinc androgen
interaction.” Acta Endocrinol (Copenh). 1984 Feb; 105(2):281-8.
pg.7
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Beta-carotene, the main pigment which
gives the orange color to sweet potatoes
and carrots, is well-known and wellrepresented
in the daily supplement
regimen of nearly all health-conscious
North Americans. For many years, this
nutrient was thought to be simply a source
of provitamin A -- that is, a substance
from which the body could make vitamin A
itself (retinol). But all this began to change
in the early 1980s, when a powerful, largescale
epidemiologic study1 revealed an
astonishing connection between intake of
this carotenoid and lung cancer: men who
took in the greatest amount of
carotenes were seven to eight times less
likely to develop lung cancer than those
who took in the least -- a result
unaffected by their varying intake of retinol
or other nutrients. This result represented a
risk reduction so great as to indicate that
smokers with the highest carotene
intakes had the same relative risk for
lung cancer as non-smokers in
lower-intake groups. Since 1977, 53 of 135
epidemiological studies have found
significant reduction of risk for cancer
from β-carotene, measured as dietary
intake or plasma levels; fully half of the
remainder also found risk reductions, but
the results were not strong enough to be
considered statistically significant.
This result was in line with evidence
accumulated before and since on the role of
β-carotene as a potent antioxidant
(especially as a quencher of singlet
oxygen (1O2)) with anticarcinogenic
powers. Extensive experimental work in lab
animals5 and isolated cells6 indicated that
β-carotene can prevent the
development of cancer, and even stop
the growth of existing cancerous cells.
Cellular studies found that β-carotene
could decrease transformation of
benign tumors to malignant cancers,
increase the cell-to-cell communication
normally lost by cancer cells, prevent UV
damage, reduce chromosome
biochemistry is upset by the massive doses
of free radicals to which smoking exposes
smokers’ lungs and bodies. When a free
radical is quenched by an antioxidant, the
“lonely electron” is given a mate by the
antioxidant molecule. In the process,
however, the antioxidant itself becomes a free
radical. Progress is only possible because the
new free radical is less toxic than the old
one. The body’s antioxidant defenses are
designed to work as a team, with one
antioxidant quenching a free radical, and
then being itself quenched by another
antioxidant in turn, leading to progressively
less toxic byproducts, until vitamin C -- the
final acceptor -- is finally flushed out
through the kidneys. It’s like a game of
“hot potato,” with the potato cooling off
with each pass.
In smokers, however, this process is
interrupted, because smoking rapidly
depletes other antioxidants. As a result,
giving β-carotene alone to smokers may
have resulted in a high level of toxic
β-carotene “radicals” accumulating in the
lungs from contact with cigarette smoke,
with no vitamins C and E available to
detoxify them11. Interestingly, later analysis
of the ATBC and CARET
data suggested no risk, or
even a protective effect, for
β-carotene in light smokers
even as heavy smokers seemed
to show increased risk2,3. A more recent
trial using a combination of antioxidants4
found that β-carotene in combination
with selenium and vitamin E
significantly cut cancer risk; better
results might have been expected had
vitamin C been included. In fact, a new
Physicians’ Health Study13 is now under way
which will use a combination of E, C,
β-carotene, and a multivitamin against
cancer and cardiovascular disease; we await
the results with great optimism. In food, of
course -- the source of b-carotene in the
original epidemiological studies --
β-carotene always comes along with
vitamins C and E; supplement programs
should follow this pattern.
The ATBC subjects’ high intake of alcohol
may also have been a factor, because
high-dose alcohol interacts dangerously
with β-carotene because of their use of
common liver detoxification
instability induced by viruses, kill tumor
cells in some cancer lines, and even induce
differentiation, turning some cancer cells
into normal, healthy ones again6.
Excitement built, and double-blind,
randomized, placebo-controlled trials in
men at very high risk for lung cancer were
initiated: the Alpha-Tocopherol and
Beta-Carotene (ATBC) Cancer
Prevention Study, and the Carotene and
Retinol Efficacy Trial (CARET).
Unbelievable Results
The results came as a complete surprise.
The trials7,8 were called off early in 1995
and 1996, because preliminary analysis not
only failed to find any improvement in lung
cancer rates in the active groups, there was
a non-significant suggestion of an
in lung cancer rates! And while an
analysis published as a press release in the
New England Journal of Medicine declared
that another large β-carotene trial -- the
Physicians’ Health Study -- had found no
such risks, it found no benefit either.
On the one hand, the excess cancer
incidence was not statistically
significant, so there is the temptation to
ignore the results until better
data are available; but when
two seperate, large-trials seem
to show the same increased
risk, caution is in order. So
what might be going on here?
Flawed Trials
Actually, probably several things at once.
For one thing, there is the high-risk
populations used: ATBC and CARET
deliberately chose to study men who were
long-term smokers (and, in ATBC’s case,
also asbestos workers!) in order to get a
clear therapeutic result. But it now appears
from new human trials that, while
β-carotene can prevent the cells from
becoming cancerous (initiation)9, it may not
be able to halt the spread of existing
cancers (progression)10. Subjects at very
high risk may thus have already have
early-stage cancer when the trial began,
and β-carotene may not affected them.
Worse, it would appear that smoking may
make β-carotene a health hazard when
it is given . This is because the
teamwork involved in antioxidant
β-c i l
-
IS YOUR BETA
CAROTENE TOXIC?
The version in your multivitamin may be hazardous to
your health!
pg.9
marker of lipid peroxidation (free radical
damage to cell membranes, LDL, etc) were
measured. Not only did the all-trans
β-carotene fail to provide any measurable
antioxidant protection compared to the
dummy pill, but the group receiving
synthetic β-carotene actually had 13%
markers of free radical damage
than the placebo group! Although this
result was not statistically significant, it
contrasts sharply with the group receiving
the natural-source supplement, which
delivered a 76% reduction in
peroxidation markers. Similar results
were reported in a test-tube study by Levin
and Mokady26.
This lack of antioxidant ability is bad
enough in itself -- suggesting, as it does,
that the synthetic β-carotene administered
to the ATBC and CARET smokers could
not have helped them -- but further
investigation suggests a more chilling
conclusion. First is the possibility that
synthetic β-carotene supplements may
actually deplete the body of the natural
isomer. This is because both forms of
β-carotene use the same absorption
pathway, which only allows a limited
transport of this carotenoid at a given
time15, so that large-dose synthetic
β-carotene supplements may actually
inhibit absorption of the natural
- form of β-carotene. Ironically, in fact,
the liver appears to transport the trans form
more efficiently than the cis isomer18, so that
taking in one unit of synthetic β-carotene
might prevent more than one unit of the
pathways12.Nearly all of the apparent
excess lung cancer in the CARET
group was in a subpopulation with high
alcohol intake2; and, similarly, the risk of
cancer appeared to be higher in regular
drinkers than non-drinkers in ATBC3,
although this finding has recently been
disputed16.
The Wrong Molecule
But perhaps the most disastrous failure in
the design of the controlled trials is that
they used the wrong β-carotene. For
most supplements, whether they are
derived from cellular “factories” or
pharmaceutical ones makes no difference
to their chemical structure or biological
activity; natural versus synthetic vitamin E
is one of a very few exceptions to the rule.
Crucially, β-carotene is another.
The β-carotene used in CARET and ATBC
was synthetic β-carotene, which is
from the β-carotene
found in food. Synthetic β-carotene is
entirely in the “ ” form; by contrast,
natural β-carotene is a mixture of
and isomers. Many health-conscious
people are by now aware of the great
difference between the trans fatty acids in
partially hydrogenated vegetable oils and
the cis fats in natural EFA sources. In trans
bonds, the hydrogens attached to two
adjoining double-bonded carbons are on
opposite sides of the molecule, giving it a
flat molecular shape. Cis isomers, by
contrast, have one double bond in which
the two carbons’ hydrogens are on the same
side of the molecule’s backbone; and since
the two hydrogens repel one another
(because they both cary a positive charge --
an effect rather like two magnets aligned at
their “north” end), the molecule is bent at
this point (see Figure 3).
Synthetic β-carotene:
Not an Antioxidant
We do not want to bore you with detailed
chemistry, so let us get to the point: while
trans β-carotene can still be used to make
vitamin A, only the form is directly
useful as an antioxidant in the body! In
one trial14 , subjects were given either
natural β-carotene supplements from the
algae Dunaliella bardawil, synthetic
β-carotene, or a placebo, and levels of a
active antioxidant isomer from being
absorbed. To understand the problem,
think of a group of prank callers tying up
telephone lines of an organization,
preventing legitimate callers from making
contact. Now imagine that there are more
pranksters than callers with real reasons for
trying to get through. Now imagine that the
lines being tied up are used by 9-1-1
emergency operators ...
Some have speculated that the absorption
inhibition issue could be even more serious,
since an overload of synthetic β-carotene
might be expected to also reduce uptake of
other carotenoids such as lycopene,
lutein, and α-carotene. One preliminary
report on the ATBC subjects paradoxically
reported that lutein was, indeed, depressed
in those receiving synthetic β-carotene, but
that some other carotenoids were actually
increased in serum19. Several other reports,
however, have shown no association
between intake of the artificial supplement
and levels of any carotenoid other than
β-carotene itself 23, 24, 25.
Artificial β-carotene Damages Genes
An even greater reason to stay away from
the use of synthetic β-carotene
supplements was given by a recent study
which found that, while both natural and
synthetic β-carotene protected immune
cells from damage by gamma radiation,
synthetic β-carotene caused
chromosome damage in these cells,
with the number of damaged cells
increasing with the dosage17! By contrast,
natural β-carotene caused no such
spontaneous damage. In the same study,
natural β-carotene protected cells from
DNA cross-linking induced by the
antibiotic mitomycin C, which the
synthetic form was not reported to do.
A small trial reported just before the ATBC
alarm sounded shows that these are not just
theoretical concerns. The trial was
conducted patients with precancerous cells
in their stomachs. It assigned the patients to
receive one of three supplements: natural
β-carotene, synthetic β-carotene, or a
placebo. When the researchers looked at
the results, they found that only the
natural supplement had reduced the
abnormal cellular development21.
IS YOUR BETA CAROTENE TOXIC?
pg.10
Thus, the synthetic β-carotene used in
ATBC, CARET, and most β-carotene
supplements available on the market appear
to simultaneously inhibit the absorption of
beneficial cis β-carotene, and to be
themselves possible carcinogens. In sum,
synthetic β-carotene supplements may
be worse than useless: they may
actually be harmful, especially to
high-risk populations like those in the large
trials. The only reason we can see for the
use of the artificial supplement in CARET
and ATBC is its low cost; in retrospect, as a
letter to the New England Journal of
Medicine put it, the use of this supplement
“is neither hard to understand nor easy to
forgive.”22
Choosing the Right β-Carotene
To recap: there are many reasons to believe
that the results of the large-scale trials of
β-carotene were the results of flawed
design, and that we should trust the
extensive epidemiological, animal, and
cellular evidence that β-carotene can
prevent the development of cancer. The
evidence strongly suggests that a central
flaw in the ATBC and CARET trials may
have been the use of synthetic (all-trans)
supplements. Fortunately, the problem of
synthetic β-carotene is not inescapable:
while most multivitamins, ACES
combinations, and stand-alone β-carotene
supplements still use the artificial molecule,
supplements are available which
contain natural β-carotene exclusively,
usually derived from marine algae. These
supplements deliver β-carotene in the
natural form, with the vital cis isomers
present. But we have to learn from the
trials’ other mistakes as well. It is important
to ensure that you are also taking a
spectrum of antioxidants with your
β-carotene, especially vitamins C and E. It
may also be important to avoid excessive
consumption of alcohol -- a wise policy
in any case. And, most important of all --
for your own sake, quit smoking.
Your body can only absorb fat-soluble
vitamins (like CoQ10, betacarotene,
tocotrienols, and
lycopene) when they’re dissolved in
fat. To get
maximum benefits make sure there’s
a little fat in the meal when you
swallow the pill-- and never take
them on an empty stomach!
References
(1) Shekelle et al (1981), “ Dietary vitamin A and risk of cancer in the
Western Electric study.” Lancet 2(8257): 1185-90.
(2) Omenn et al (1996), “Risk factors for lung cancer and for
intervention effects in CARET.” J Natl Cancer Inst 88: 1550-9
[revised conclusions&91;.
(3) Albanes et al (1996), “Alpha tocopherol and beta carotene
supplements in the Alpha Tocopherol and Beta Carotene trial: effects of
baseline characteristics and study compliance.” J Natl Cancer Inst 88:
1560-70 [revised conclusions&91;.
(4) Blot et al (1993), “Nutrition intervention trials in Linxian, China:
supplementation with specific vitamin/mineral combinations, cancer
incidence, and disease-specific mortality in the general population.” J
Natl Cancer Inst 85(18): 1483-92.
(5) Toma et al (1995), “Effectiveness of beta-carotene in cancer
hemoprevention.” Eur J Cancer Prev 4(3): 213-24.
(6) Krinksy (1996), “Cellular aspects of carotenoid actions.” In
Cadenas & Packer (eds), Handbook of Antioxidants (Antioxidants in
Health & Disease): 315-36. INSERT CITY: Marcel Dekker.
(7) Albanes et al (1995), “Effects of alpha-tocopherol and beta-carotene
supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene
Cancer Prevention Study.” Am J Clin Nutr 62(6 Suppl): 1427S-
1430S.
(8) Omenn et al (1996), “Effects of a combination of beta carotene and
vitamin A on lung cancer and cardiovascular disease.” N Engl J Med
334(18):1150-5.
(9) van Poppel et al (1992), “Beta-carotene supplementation in smokers
reduces the frequency of micronuclei in sputum.” Br J Cancer 66(6):
1164-8.
(10) van Poppel et al (1992), “No influence of beta-carotene on
smoking-induced DNA damage as reflected by sister chromatid
exchanges.” Int J Cancer 51(3): 355-8.
(11) Wang & Russell (1999), “Procarcinogenic and anticarcinogenic
effects of beta-carotene.” Nutr Rev 57(9 Pt 1): 263-72.
(12) Leo & Lieber (1999), “Alcohol, vitamin A, and beta-carotene:
adverse interactions, including hepatotoxicity and carcinogenicity. Am J
Clin Nutr 69(6): 1071-85.
(13) Christen et al (2000), “Design of Physicians' Health Study II--a
randomized trial of beta-carotene, vitamins E and C, and multivitamins,
in prevention of cancer, cardiovascular disease, and eye disease, and review
of results of completed trials.” Ann Epidemiol 10(2): 125-34.
(14) Ben-Amotz & Levy (1996), “Bioavailability of a natural isomer
mixture compared with synthetic all-trans beta-carotene in human
serum.” Am J Clin Nutr 63(5): 729-34.
(15) Erdman et al (1993), “Absorption and transport of carotenoids.”
Ann N Y Acad Sci 691: 76-85.
(16) Woodson et al (1999), “Association between alcohol and lung cancer
in the alpha-tocopherol, beta-carotene cancer prevention study in
Finland.” Cancer Causes Control 10(3): 219-26.
(17) Xue et al (1998), “Comparative studies on genotoxicity and
antigenotoxicity of natural and synthetic beta-carotene stereoisomers.”
Mutat Res 418(2-3): 73-8.
(18) Erdman et al (1998), “All-trans beta-carotene is absorbed
preferentially to 9-cis beta-carotene, but the latter accumulates in the
tissues of domestic ferrets (Mustela putorius puro).” J Nutr 128(11):
2009-13.
(19) Albanes et al (1997), “Effects of supplemental beta-carotene, cigarette
smoking, and alcohol consumption on serum carotenoids in the
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.” Am J
Clin Nutr 66(2): 366-72.
(20) Neuman et al (1999), “Prevention of exercise-induced asthma by
a natural isomer mixture of beta-carotene.” Ann Allergy Asthma
Immunol 82(6): 549-53.
(21) Yeum et al (1995), “B-carotene intervention trial in premalignant
gastric lesions.” J Am Coll Nutr 14(5): 536.
(22) von Eggers-Doering (1996), “Antioxidant vitamins, cancer, and
cardiovascular disease.” N Engl J Med 335(14): 1065.
(23) Pappalardo (1997), “Plasma (carotenoids, retinol, alphatocopherol)
and tissue (carotenoids) levels after supplementation with
beta-carotene in subjects with precancerous and cancerous lesions of sig
moid colon.” Eur J Clin Nutr 51(10): 661-6.
(24) Mayne et al (1998), “Effect of supplemental beta-carotene
on plasma concentrations of carotenoids, retinol, and alpha-tocopherol in
humans.” Am J Clin Nutr 68(3): 642-7.
(25) Nierenberg et al (1997), “Effects of 4 y of oral supplementation
with beta-carotene on serum concentrations of retinol, tocopherol, and five
carotenoids.” Am J Clin Nutr 66(2): 315-9.
(26) Levin & Mokady (1994), “Antioxidant activity of 9-cis compared
to all-trans beta-carotene in vitro.” Free Radic Biol Med 17(1):
77-82.
IS YOUR BETA CAROTENE TOXIC?
pg.11
With the breakneck
speed of research into
nature’s pharmacy, radical
new discoveries seem to
appear almost every day.
Developments are occurring
so quickly that we only have
space in this issue for a brief
summary of a few of them.
But be warned: this new
science is on the razor’s edge
of research and development.
Waiting for official
recognition of the value of
these dietary substances by
government agencies or
medical orthodoxy gives
many people a reassuring
sense of certainty, but it also
means a long wait. Over thirty
years since Linus Pauling first
drew the attention of millions
to the protective powers of
vitamin C, the US Food and
Nutrition Board has just
raised its Dietary Reference
Intakes (DRIs) -- to a
whopping 90 mg daily for
men, and 75 mg daily for
women. It is up to each of us,
as individuals, weigh the
evidence, and decide whether
we will wait for a paternalistic
seal of approval, or embrace
Omega-3 fatty acids are already famous
for their ability to control
inflammation1. They do this because of
their effects on local cellular “hormones”
called eicosanoids (eye-KOSS-ah-noids).
Some (“bad”) eicosanoids promote
inflammation, while other (“good”)
eicosanoids serve a potent anti-inflammatory
function. Thus, our health depends in
large part on the body’s balance of “good”
and “bad” eicosanoids. This balance, in
turn, depends on two factors: which EFAs
(omega-3 and omega-6) are available as
building blocks for making eicosanoids, and
which enzymes are used to process those
EFAs. Like a factory which can make pasta
using one of two raw materials (either
whole wheat or white flour), and shape it
into spaghetti, manicotti, or pasta shells
depending on what machinery is used to
process it, the body’s eicosanoid factories
work with raw materials (EFAs) and
processing equipment (enzymes) to make
different finished products (“good” and
“bad” eicosanoids). By keeping the
machinery busy with the right raw materials
(the EFA input from your diet and
supplements), you can put those factories
to work for you instead of against you,
making more “good” and less “bad”
eicosanoids, thus preventing inflammation
before it starts.
One of the most powerful families of proinflammatory
eicosanoids are the
leukotrienes, such as leukotriene B4
(LTB4), which are formed from omega-6
EFAs using the enzyme 5-lypoxygenase
(5-LOX). The eicosanoids produced by 5-
lypoxygenase are the trigger for the pain
flareups in rheumatoid
arthritis (RA)2-4, causing
untold suffering to millions.
Leukotrienes are
also involved in other
inflammatory diseases, including asthma,
psoriasis, and ulcerative colitis6. Most
omega-3 supplements -- like the EPA and
DHA in salmon oil -- are unfortunately
not very effective in stopping the formation
of leukotrienes, because they aren’t good at
tying up the lypoxygenase enzyme
“machine”.
The medical establishment’s mainstay for
inflammation has for many years been the
nonsteroidal anti-inflammatory drugs
(NSAIDS, like aspirin, ibuprofen
[Advil®&91;, and naproxen [Anaprox®&91;).
These drugs do bring short-term relief to
many, but at a cost in side effects which
may include gastric ulcers, kidney and
liver damage, and (with a cruel irony)
long-term damage to the joints. These
drugs’ pain-relieving and ulcer-inducing
powers are both due to the fact that they
nonselectively block the formation of
nearly all eicosanoids -- “good” and ‘bad.”
Thus, at the same time that they are
blocking the formation of the eicosanoids
that trigger inflammation, they
simultaneously prevent the body from
making the eicosanoids which help
maintain the lining of the stomach.
These drugs have no direct ability to
inhibit 5-LOX, the enzyme responsible for
creating LTB4, the flareup-triggering
leukotriene. In fact, in some asthmatic
patients, NSAID therapy can actually
a new form of asthma marked by
increased leukotriene production5! The
pharmaceutical industry is now racing to
make new drugs which inhibit 5-LOX,
LTB-4, or the receptors for this master
inflammatory messenger. But now a new
EFA source stands ready to revolutionize
the use of omega-3s against inflammation.
The fatty acid extract of the Australian
green-lipped mussel (Perna canaliculus)
provides a rare blend of
unique omega-3 fatty
acids, most notably the
tongue-twistingeicosatetraenoic
acid (ETA),
which powerfully and
selectively blocks the formation of proinflammatory
eicosanoids. This EFA
acts like a laser-guided “smart” missile
against inflammation because of its powerful,
selective ability to keep the 5- and 12-
lypoxygenase enzyme machinery busy,
and thus prevent the formation of
leukotriene B-4. Researchers at the Queen
N ew
Suppleme
Revie
pg.12
Green mussel extract was
160% as effective as EPA and
over three times as effective
as evening primrose oil.
Elizabeth Hospital showed that the fatty
acid extract of the mussel powerfully
inhibits these enzymes, preventing the
formation of LTB4 and other “bad”
eicosanoids. Scientists at Australia’s
Queensland University
found that, of 37 products
tested on animals, this
extract had the most
powerful anti-inflammatory
effects7. In fact,
as compared to other EFA
oils, the fatty acid extract of the green
mussel was 160% as effective as EPA
and over three times as effective as
evening primrose oil -- using just -
of the required dose of other EFA
oils! Another green mussel product, which
is a crude extract not standardized to the
fatty acid content or extracted carefully to
protect the crucial omega-3s, had little or
no effect on inflammation. And a recent
double-blind trial8 reported improvements
in 76% of RA patients taking the green
mussel lipid extract, using measures such
as morning stiffness, grip strength, pain
scales, and joint functionality.
And the dangers of the 5- and 12-LOX
enzymes don’t stop with arthritis pain.
Other products of the LOX machinery
are used by many cancer cells to protect
themselves from apoptosis (the body’s
suicide mechanism for damaged or rogue
cells)11, to siphon off healthy cells’ blood
supply (through angiogenesis)9,, and to
spread to other parts of the body
(metastasis)10. Since it is a potent inhibitor
of these enzymes, it is not surprising that
Australian scientists announced that
the lipid extract of the green mussel
kills cancer cells in test tubes11a. All this
suggests that the extract may yet prove to
be powerful nutritional support against this
most insidious of diseases.
Phytosterols (plant sterols and
sterolins) are fatty components of plants
which are stripped from the diet by food
processing and cooking, and which support
human health in many ways. Various
combinations of sterols and sterolins have
been shown to improve
symptoms of benign prostatic hypertrophy
(BPH)12, improve some autoimm
u n e
disorders16, 17, lower
cholesterol when taken
with a meal18, and to possibly
prove helpful in
type II19 and type I20
diabetes. Women who
get more phytosterols in
their diet are less likely to develop breast
cancer21, and phytosterols slow the growth
and spread of human breast13,
prostate14, and colon15 cancer cells in animal
and test tube
models. They have anti-inflammatory
powers23, and are powerful immune
modulators21.
Unfortunately, most phytosterol
products utilize a poor extraction
process which reduces their bioavailability
and introduces an unnaturally low ratio of
sterolins to sterols. The most readily
available such product begins with a sterol
extract from one source (pine oil), using an
extraction method which almost
completely removes the natural sterolins,
and then adds in sterolins separately from
soy. The resulting amalgamation has one
hundred times as much sterol as the more
fragile sterolins, a ratio much lower than
is found in whole foods: natural sources
contain a 10% or better content of
sterolins, with some foods providing as
much as 80% sterolins by weight24. Such
low ratios become even worse upon
ingestion, because the body absorbs two
to five times less sterolin than it does
sterol24, so that a 100:1 sterol-to-sterolin
mixture may actually provide as unbalanced
a ratio as 200:1 or 500:1 in the body --
ratios far lower than those required for
optimal immune enhancement21.
These products are not useless, but they do
not live up to the potential of a more
natural phytosterol supplement. A ratio of
one milligram of sitosterols to 5-10
Women who get more
phytosterols in their diet
are less likely to develop
breast cancer.
pg.13
milligrams of plant sterols is optimal,
according to Dr. Karl Pegel of the
University of Natal, one foremost
authorities on the role of phytosterols in
human nutrition. These ratios can be
achieved by using a solvent-free,
whole-food plant extraction process
from sprouts. Studies performed at Pegel’s
institution affirm the higher
bioavailability of whole-food,
sprout-extracted phytosterols: such
sources have a bioavailability of 80% or
more, as compared to a much lower
bioavailability for other extraction
processes. Reports on the bioavailability of
unnaturally isolated phytosterols suggest
that their absorption may be as little as
5%25!
Coenzyme Q10 is a powerful fat-soluble
antioxidant which protects membranes
from free radicals and recycles the
vitamin E complex vitamins
(tocopherols and tocotrienols) to their
active antioxidant form after they are put
out of commission in fighting free radical
attackers. More importantly, it is
absolutely necessary to the body’s
ability to produce cellular energy in the
mitochondria -- the power plants of every
cell in your body. Without CoQ, cells
cannot produce the energy they need to
perform their functions, be they immune,
brain, or muscle cells. CoQ is most
well-known for its use in nutritional
support for heart disease -- especially
congestive heart failure. Thirty-four
controlled trials, as well as a multitude of
animal experiments and open trials, attest
to its power to rejuvenate the aging
heart26.
To get results from CoQ, however, one
must not just swallow a pill, but get the
CoQ10 into one’s system and into the
mitochondria where it is needed. Research
by Karl Folkers and Peter Langsjoen
established early on that a key plasma level
of 2.5 micrograms per milliliter is
required to see results inadvanced
cardiomyopathy27, 28. But achieving this
optimal level is harder than you might
New Salvos
think. Thus, some clinical trials using as
much as 200 mg of dry capsule CoQ10
daily have failed to raise levels to this
key therapeutic threshold29a. Another
study29b showed how much variation there
can be between individuals: subjects were
administered 300 mg CoQ daily as dry
capsules, and their plasma levels tested.
On average, this brought CoQ levels to 2.76
micg/mL, which is in the optimal zone;
however, the plasma levels of
varied wildly: while one subject
taking this high-dose dry capsule CoQ
increased his plasma levels to 5.44
micg/mL, another subject only
achieved plasma levels of 1.38
micg/mL!
This low absorption is due to way the body
must handle fat-soluble nutrients like
CoQ. As a fat-soluble compound, CoQ10
cannot pass directly into the blood, but
must first be dissolved in some fat. The
dissolved CoQ is then absorbed with the
fat, using micelles, which are tiny
absorption “packets” formed from bile.
But because of the high melting point
(48°) and relatively poor solubility of
CoQ, and because the digestive system
destroys some of the CoQ10 along the
way, it is difficult to ensure that much of
the CoQ in dry capsules will actually be
dissolved, even when taken with a fatty
meal. Further, because individuals vary
in bile secretion and intestinal
absorption, even well-dissolved CoQ may
not be taken up adequately by many.
The best way around these problems is
to enclose the CoQ10 in tiny
microspheres called . Liposomes
are microscopic membranes composed of
two layers of phospholipids (like
phosphatidylcholine (PC) and
phosphatidylserine (PS)). They are
similar to micelles, and also not unlike a
simplified version of the membrane of the
cell. Because they are soluble in water,
liposomes do not require dissolution in fat,
bile secretion, or micelle formation;
instead, liposomes pass almost directly
from the gut, through the intestinal wall,
and into the blood, bringing their CoQ
payload with them. Liposomes also
protect much of the CoQ10 from being
lost to digestive juices.
Just how effective are liposomes at getting
CoQ10 where it has to go? Research
performed by Dr. William V. Judy30, veteran
CoQ10 researcher31, 32, found that in just one
month, 90 mg a day of liposomal CoQ10
can raise plasma levels to 2.64
micrograms per milliliter -- levels barely
achieved using 600 mg of dry capsule
CoQ daily for eleven days29c, and not
achieved in in some studies
using 200 mg29a! The liposomal system not
only worked much better than dry capsules,
but also better than 90% of other
CoQs: better than softgels made by simply
dissolving CoQ in oil, and even better than
a micronized, hydrosoluble CoQ gel
capsule formula. Clearly, liposomal CoQ
helps ensure that you get the full
benefits of CoQ10.
Although new to Canadian health
consumers (it was first introduced to the
Canadian market in September of 1998),
Pantethine has been used in Italy, the
United States, and Japan since the 1980s,
primarily as a way to safely and effectively
support healthy cholesterol balance.
Pantethine is not the same as
pantothenic acid (vitamin B5), but they
are related: Pantethine is the active
coenzyme form of this vitamin. The body
doesn’t actually use pantothenic acid itself
to do anything; instead, it must convert
pantothenic acid into Pantethine to unlock
its potential. Pantethine, in turn, is the
active part of Coenzyme A (CoA). CoA
is everywhere in the body, and is involved in
many vital biological processes, from
energy production and fat metabolism,
to liver detoxification and the body’s
control of cholesterol synthesis . It’s an
exciting molecule which plays a key role in
human health.
The trouble is that the body’s ability to
make Pantethine from vitamin B5 is
very limited. Each person’s genes (and, to
a lesser extent, diet) places a “ceiling” on
how much Pantethine they will make at
any given time. But many people’s internal
Pantethine-making machinery runs at
far too low a level for optimal health.
The most extensively-researched example
of this is in Pantethine’s effects on
cholesterol. No amount of pantothenic
acid has significant impact on cholesterol
levels, precisely because the amount of
Pantethine a given person makes from B5
is held under tight genetic control. Thus,
some people’s Pantethine levels are already
high enough to keep their blood lipids in
healthy balance, and taking more B5
doesn’t change this fact; while others don’t
produce enough Pantethine to help
support cardiovascular health -- and taking
more B5 doesn’t change that, either.
Fortunately, if you have a Pantethinemaking
“deficiency,” you can add more
Pantethine into your system in the
form of a Pantethine dietary supplement,
thus correcting for an unhealthily low
steady state level.
A wealth of clinical evidence33-47, 51 shows
that pantethine supplementation
supports healthy cholesterol balance. In
adults33-46, 51 and children40, 47, in all tested
forms of dyslipidemia34, 42, 44, 45, 51 (Pantethine
has not been tested against the rare
Fredrickson’s Type I and V subgroups,
which develop pancreatitis rather than
cardiovascular disease), in dialysis patients35,
41 and diabetics34, 35, 38, 45, 46, as well as
survivors of previous heart attacks43,
Pantethine has proven itself to be a safe
and effective modulator of cholesterol
levels. The clinical trials have consistently
reported that subjects taking Pantethine
have lower total cholesterol, LDL, and
VLDL, but higher HDL; further,
Pantethine lowers triglycerides, a lipid
risk factor which is coming to the forefront
of health concern. Patients in one
double-blind, controlled crossover trial44
experienced decreases of 13.5% in total
cholesterol and LDL, while their in HDL
levels rose by 10%. While taking
Pantethine, patients also had decreases of
pg.14
N ew
Suppleme
Revie
13 to 30% in triglycerides, depending on
what sort of lipid disorder they had. The
other trials have reported similar results.
Pantethine also supports heart health in
other ways. It makes LDL cholesterol
less subject to attack by free radicals
mediated by copper48. This is important,
because we now know that LDL is much
more likely to be deposited in the arteries
when it becomes oxidized. Pantethine also
changes the EFA balance in platelets,
increasing their omega-3 content and
lowering their omega-650, 51; this may also
be important, because omega-6 EFAs in
platelets are more likely to cause blood
clots (thrombi), thus triggering a heart
attack or stroke, while omega-3s tend to
block this tendency52.
Science is acquiring knowledge at an
accelerating rate: today, our store of basic
biomedical knowledge is doubling every
three-and-a-half years. Advanced
Orthomolecular Research is committed
to keeping you up to date on the newest
developments, and of translating new
discoveries about natural substances into
usable nutraceutical technology.
Each capsule of Natur•Leaf™ contains 300mg of natural plant sterols and sitosterolins, plus 50mg of
enzymes. The 300mg sterols/sitosterolin blend comes from whole plant sprouts, which have been ground and
freeze-dried immediately after harvesting at a hydroponics farm in South Africa.
-p with a guarantee by Natal University of 80%-90% bioavailablilty. So,
in addition to the sterols andsitosterolins, the capsules contain vitamins, minerals and other
phytochemicals associated with the young plant sprouts.
The ratio of the sterols to their glucosides (sitosterolins) in Natur•Leaf™ is about 6:1, derived from a
variety of sprouts with natural ratios varying from 10:1 to 4:1. This ratio is important to understand,
becasue it is what is , with no introduction of outside glucosides (sitosterolins) to sterols. Other
sterol/sitosterolin products are derived from a chemical extraction process which eliminates or destroys the
glucosides, thus requiring an outside glucoside source to be added to the product.
•
• •
• •
Behold...
•
To the best of our knowledge, there is on other sterolin product on the earth which is more concentrated in its
sterol/glucoside ratio than Natur • Leaf™, and which offers such a high percentage of biovailability.
Holistic International is always one step ahead of the competition when it comes to new and innovative products. We were
the first to introduce to the Canadian market such products as Pantehtine, SAMet and Glucosamine Sulphate. For more
information on such ground- breaking products, give us a call and stock your shelves with tried and true quality!
Processing method affects whey protein
quality. Ion-exchange extraction,
although yeilding a high percentage of
protein, also reduces the amount of
important immune-enhancing peptides
(such as lactoferrin and glycomacropeptides)
and the highestquality
protein fraction (alphalactalbumin).
Ultrafilered wheys
preserve more of these important components
intact. Know what your buying!
Green Mussel Lipid Extract
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3. Grignani G, Zucchella M, Belai Beyene N, Brocchieri A, Saporiti
A, Cherie Ligniere EL. Levels of different metabolites of arachidonic
acid in synovial fluid of patients with arthrosis or rheumatoid arthritis.
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CoQ10
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33. Nomura H, Kimura Y, Okamoto O, Shiraishi G. Effects of
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34: Tonutti L, Taboga C, Noacco C. Comparison of the efficacy of
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35: Coronel F, Tornero F, Torrente J, Naranjo P, De Oleo P, Macia
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36: Binaghi P, Cellina G, Lo Cicero G, Bruschi F, Porcaro E, Penotti
M. Evaluation of the cholesterol-lowering effectiveness of pantethine in
women in perimenopausal age. Minerva Med. 1990 Jun; 81(6): 475-9.
37: Lu ZL. A double-blind clinical trial--the effects of pantethine on
serum lipids in patients with hyperlipidemia&91;.Chung Hua Hsin Hsueh
Kuan Ping Tsa Chih. 1989 Aug; 17(4): 221-3.
38: Donati C, Bertieri RS, Barbi G. Pantethine, diabetes mellitus and
atherosclerosis. Clinical study of 1045 patients. Clin Ter. 1989 Mar
31; 128(6): 411-22.
39: Borets VM, Lis MA, Pyrochkin VM, Kishkovich VP, Butkevich
ND. Therapeutic efficacy of pantothenic acid preparations in ischemic
heart disease patients. Vopr Pitan. 1987 Mar-Apr; (2): 15-7
40: Bertolini S, Donati C, Elicio N, Daga A, Cuzzolaro S,
Marcenaro A, Saturnino M, Balestreri R. Lipoprotein changes induced
by pantethine in hyperlipoproteinemic patients: adults and children. Int J
Clin Pharmacol Ther Toxicol. 1986 Nov; 24(11): 630-7.
41: Donati C, Barbi G, Cairo G, Prati GF, Degli Esposti E.
Pantethine improves the lipid abnormalities of chronic hemodialysis
patients: results of a multicenter clinical trial. Clin Nephrol. 1986 Feb;
25(2): 70-4.
42: Arsenio L, Bodria P, Magnati G, Strata A, Trovato R.
Effectiveness of long-term treatment with pantethine in patients with dys
lipidemia. Clin Ther. 1986; 8(5): 537-45.
43: Murai A, Miyahara T, Tanaka T, Sako Y, Nishimura N,
Kameyama M. The effects of pantethine on lipid and lipoprotein
abnormalities in survivors of cerebral infarction. Artery. 1985; 12(4):
234-43.
44: Gaddi A, Descovich GC, Noseda G, Fragiacomo C, Colombo L,
Craveri A, Montanari G, Sirtori CR. Controlled evaluation of pantethine,
a natural hypolipidemic compound, in patients with different
forms of hyperlipoproteinemia.Atherosclerosis. 1984 Jan; 50(1): 73-83.
45: Arsenio L, Caronna S, Lateana M, Magnati G, Strata A,
Zammarchi G. Hyperlipidemia, diabetes and atherosclerosis: efficacy of
treatment with pantethine. Acta Biomed Ateneo Parmense. 1984;
55(1): 25-42
46: Eto M, Watanabe K, Chonan N, Ishii K. Lowering effect of
pantethine on plasma beta-thromboglobulin and lipids in
diabetes mellitus. Artery. 1987; 15(1): 1-12.
47: Hoeg JM. Pharmacologic and surgical treatment of dyslipidemic children
and adolescents. Ann N Y Acad Sci. 1991; 623: 275-84.
48:Bon GB, Cazzolato G, Zago S, Avogaro P. Effects of pantethine
on in-vitro peroxidation of low density lipoproteins.
Atherosclerosis. 1985 Oct; 57(1): 99-106.
49: Vecsei L, Widerlov E. Preclinical and clinical studies with cysteamine
and pantethine related to the central nervous system. Prog
Neuropsychopharmacol Biol Psychiatry. 1990; 14(6): 835-62.
50: Prisco D, Rogasi PG, Matucci M, Paniccia R, Abbate R, Gensini
GF, Neri Serneri GG. Effect of oral treatment with pantethine on
platelet and plasma phospholipids in IIa hyperlipoproteinemia.
Angiology. 1987 Mar; 38(3): 241-7.
51: Gensini GF, Prisco D, Rogasi PG, Matucci M, Neri Serneri GG.
Changes in fatty acid composition of the single platelet phospholipids
induced by pantethine treatment. Int J Clin Pharmacol Res.
1985;5(5):309-18.
52: Ponte E, Cafagna D, Balbi M. Cardiovascular disease and
omega-3 fatty acids. Minerva Med. 1997 Sep; 88(9): 343-53.
N ew
Suppleme
Revie
pg.16
New Salvos
References
The raw material is flash-freeze-dried to
ensure potency. It is simply false to claim
that freeze drying causes protein
denaturation; in fact, the exact opposite is
the case! It is heat, not cold, which causes
protein denaturation; freeze-drying is the
preferred way of drying everything from in
backpacking foods to samples used in
scientific studies for exactly this reason.
Freeze-drying is done precisely because
it guards intact of the
immune-enhancing proteins from
denaturation, and preserves more of the
essential components of colostrum, than
does drying using either heat long drying
periods. Likewise, we do not use any
chemical solvents in the processing of
our colostrum. Since heat, long drying
periods, and solvents are the only ways
other than freeze-drying to provide a
properly dried product, this makes a
freeze-dried, high-quality, North American
product the clear choice for potency -- from
the dairy all the way to you.
Q: How do you pronounce “Jarrow”?
A: Good question! The “Jarrow” in
“Jarrow Formulas” and “JarroDophilus”
does not refer to the sticks used to throw the
I Ching, but to the founder of the company:
Jarrow Rogovin. Mr. Rogovin pronounces
his name with a hard “J,” not a soft “Y.”
We want to hear from you!
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Don’t forget to include your name and location.
Q: Another company has been
spreading around copies of a flyer on
colostrum. It makes some pretty wild
claims! Can you comment?
A: The flyer makes some good points
about quality issues in colostrum, but also
spreads a great deal of misinformation, and
makes comments which apply to other
colostrum sources, but not to ours. The raw
material for our All-Life Colostrum and
Jarrow Formulas’ Colostrum Specific
comes from a North American source. This
source provides us with colostrum from
cows which are free-range fed, not
exposed to rBGH or BST, are not
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Further, the raw colostrum is processed
under cGMP conditions. In these
respects, our colostrum is produced and
processed using methods identical to those
in New Zealand-sourced material.
However, there is one key difference
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and that from New Zealand: namely, the
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conditions cause cattle to produce greater
levels of immune-supporting compounds
than they do in more temperate zones. As a
result, All-Life Colostrum contains 25%
more immunoglobulins (Igs) than are
typically present in New Zealand
colostrum. Since boosting our levels of
such immune-supporting proteins is the
entire point of taking a colostrum
supplement, this makes colder-climate
colostrum the clear choice for supporting
health.
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For more information refer to this years catalogue and see what else they’ve got in store!
pg.17
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Access to the internet means fast access to an awesome amount of information. The internet
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just in time: the last decade has seen an explosion in the number of people are looking for new
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But the internet’s very freedom means that the quality of the information is mixed. The world
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pg.18
HEALTH ON THE INTERNET
Finding your way or stuck in the maze?
The old health care paradigm is dying. We
don’t look at our doctors as gods anymore.
In the new paradigm, each of us, as an
individual, is taking more responsibility for
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Unfortunately, many of us find that
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Holistic International is in contact with a
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they have all committed to supporting the
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Call us at 1-403-250-9997, and we’ll help
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]]> Holistic International
Box: 92 4404 12 Street N.E.
Calgary Alberta T2E 6K9
Canada
00
Holistic International™ is proud to be the formulator and distributer of the most advanced lines of supplements on Earth. Look for Advanced Orthomolecular Research, Jarrow Formulas, and Ayurved
formulas at finer health food stores near you.
You can’t remember where you put your keys. You wonder why you came into the kitchen. That word
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Cholinergic supernutrient
PS & Ginkgo in one pill
Well, all right: the headline is an
exaggeration -- but it’s not that as far from
the truth as you might think. Saw
palmetto is the most common herbal for
benign prostatic hyperplasia (BPH), the
noncancerous swelling of the prostate
gland which affects nearly all men to some
degree beginning in late middle age, leading
to discomfort, nocturia (the need to get
up in the middle of the night for a trip to
the bathroom), frequent and sudden
urges to urinate even when the bladder is
not full, intermittency (dribbling at the
end of the urinary stream), and
incomplete emptying of the bladder
when urinating. Saw palmetto, along with a
few other herbals, is reached for in health
food stores across North America almost
by reflex. And there is evidence that this
botanical is helpful for improving the
symptoms of BPH1. This can also be said of
β-sitosterol5, and to a lesser extent of such
herbals as 2 and stinging
nettle3,4, as well as the amino acid
combination Paraprost (glycine, alanine,
and glutamic acid)7, which is widely used for
prostate concerns in Japan. But (and this is a
big “but”) when it comes to the underlying
disease process itself, there is absolutely
no evidence that any of these natural
therapies actually reduces the of the
prostate -- that is, they fail to actually
address the underlying problem, as opposed
to its symptoms. Indeed, controlled trials
which have investigated this point have
specifically reported that there is no effect
on prostate volume from taking saw
palmetto1 or β-sitosterol6, the most
evidence-backed of the standard prostate
health botanicals.
By contrast, there is plenty of evidence that
finasteride (Proscar®), the most famous drug
therapy for BPH, can reduce prostate
Holistic International™
Box: 92 4404 12 Street N.E.
Calgary Alberta T2E 6K9
Canada
Phone Toll Free 1-800-387-0177
(403)-250-9997
Fax Toll Free 1-877-219-9974
(403)-250-9974
www.Holisticinternational.com
e-mail: Holistic@cadvision.com
Volume 1 Issue 2 August 2000
Preventative
Alternative
Ayurvedic
Holistic
Naturopathic
Orthomolecular
Cover Story
Throw your Saw
Palmetto out!
Defined Pollen Extract
for Prostate Health.
Pg.1
Breaking Health News
Is Beta-
Carotene toxic?
There is a difference!
Pg. 9
New Supplement
Review
A quick look at a
few new products that
shine! Pg. 12
A cut above the
rest
Holistic International
and Jarrow
Formulations’ hottest
new products. Pg. 17
I want to know!
We take your most difficult
questions. Pg. 18
pg.1
Image credit to Focus on Grain by Alan Blackwood 1986 from Focus on Resources series by Wayland Publishers Ltd.
volume. Unfortunately, finasteride is slow
(one year minimum) to take effect, does not
work with several classes of patients, is very
expensive, and has significant side effects,
including erectile dysfunction and loss
of libido. So men are left with a poor
choice: herbs which provide symptomatic
improvement with no halt to the loss of
prostate health, or a drug treatment which
addresses the core problem, but causes
problems of its own. But there is a way out
of this dilemma. A herbal remedy long
available in Europe is just now becoming
available in North America. It’s all-natural,
inexpensive, and free of significant side
effects; it improves symptoms; it works
faster than most other therapies, including
saw palmetto; it shows promise for more
prostate health concerns than just BPH;
and it has been proven to reduce prostate
volume in controlled clinical trials. It is a
defined pollen extract, sold under such
trade names as Cernitin, Cernilton, and
Prostaphil®, and it stands poised to
revolutionize the way many men approach
prostate health.
This substance should not be confused
with bee pollen. Bee pollen is a mixture of
whatever pollens with which the insects
happen to have come into contact. The
pollen extract, by contrast, is a mixture of
several specific pollen sources (primarily rye,
but also including timothy grass, corn,
hazel, sallow, aspen, oxye, and pine pollens).
Also, bee pollen in its raw form is covered
with a microscopic husk which prevents its
full assimilation by humans; by contrast, the
pollen extract discussed here is a
standardized extract, which incorporates a
specific 20:1 ratio of lipid- and
water-soluble components extracted under
low-temperature conditions to bypass the
pollen’s protective sheath.
Proven in Controlled Trials
Many people find it strange that something
as simple as flower pollen could have
powerful effects on prostate health. And
yet the clinical evidence is plain:
standardized pollen extract quickly
improves prostate symptoms and
reduces prostate volume. In one
double-blind, controlled study8, sixty men
with symptomatic BPH received either the
pollen extract or placebo for six months.
Sixty-nine percent of men receiving the
pollen extract showed improved overall
symptoms, compared to less than a third
of the placebo group; the differences were
statistically significant for such measures as
fewer incidences of nocturia, decreased
leftover urine in the bladder after
urination (“residual urine volume”), and
reductions in the volume of the prostate
as measured by ultrasound (see Figure 2).
Compared to the placebo group, there were
also more improvements reported by men
receiving the pollen extract in hesitancy
(inability to release urinary flow) and
intermittency, but these results were not
strong enough, in this small a group over
this short a period, to be statistically
meaningful.
Another double-blind, placebo-controlled
trial of the pollen extract was reported by
Becker and Ebeling9. Ninety-six men with
BPH completed the twelve-week trial,
during which the men were on either the
pollen extract or the placebo for one six
week period, and then “crossed over” to
the other pill. Statistically significant
results were experienced while the men
were taking the pollen extract in
nocturia and residual urine volume,
Volume 1, number 2
August 2000
Dr. Traj P.S. Nibber
Michael Rae
Danika Challand
Shebodo@Hotmail.com
Cindi Armstrong
Holistic International, manufacturers
and distributors of the most exciting
lines of envelope-pushing nutritional
supplements in Canada, welcomes you to
this issue of The Holistic Lifestyle,
published eight times a year. The Holistic
Lifestyle is designed to provide our
customers with essential information
and news of breakthrough research to
help you make the best decisions to meet
your health goals through supplements
and lifestyle choices.
The Holistic Lifestyle also provides news
about Holistic International and its
products, along with trade shows,
retailer information, and government
regulations and their impact on your
health freedom.
Comments? Questions?
We want to hear from you!
The Holistic Lifestyle
4404 - 12 Street North East Box #92
Calgary, Alberta Canada
T2E 6K9
The content of this newsletter is provided for
informational purposes only, and is not intended as
medical advice for individuals, which can only be
provided by a healthcare professional.
Contents © Holistic International™ 2000; Design ©
Danika Challand 2000.
pg.2
00
100
90
80
70
0
0 14 42 days
β−sitosterol
N = 20
R
Cornilton
N = 19
Figure 1: Significant reduction (p < 0.01) of the
serum PSA after 6 weeks' Defined Pollen
Extract. Redrawn from (17).
To date, no trial has directly compared the
therapeutic effect of the pollen extract to
saw palmetto. However, based on the
available evidence, it is clear that the pollen
extract is superior to saw palmetto on
several points. Most important is the fact,
noted above, that while it may improve
symptoms such as nocturia and peak flow
rate, saw palmetto has never been
shown to reduce prostate -- whereas
several trials, as we have seen, have
reported just this for the pollen extract.
This means that saw palmetto can only
address symptoms, while the defined
pollen extract can
actually help the
underlying disease. The
difference is crucial,
especially from the perspective of the
long-term prostate health of the men
taking these herbals, who may delay surgery
because of symptomatic relief. Also, it is
clear that saw palmetto does not work as
quickly, or for as many men, as does the
pollen extract: from the published
evidence1,18, it would appear that four to six
months are required to report significant
improvements in symptoms using saw
palmetto, whereas Becker and Ebeling10
could report improvement after only six
weeks! And, indeed, there is now some
question18, 19 as to whether saw palmetto
actually of any help at all in BPH; the
arguments are complex, and space is
limited, so we will not enter into this
debate.
Several other open trials of the efficacy of
standardized pollen extract against BPH
have been performed13, 14, 15, and these have
also been successful, but because of their
small size and uncontrolled design, we will
move on.
Other Prostate Concerns
BPH, of course, is not the only prostate
disorder that men may face. Another is
chronic prostatitis (CP), an ongoing
inflammation of the prostate gland,
reflected in the presence of markers of
inflammation in the prostate fluid. Chronic
along with borderline significant decreases
in daytime urinary frequency. The
investigating physicians reported “very
good” or “good” improvement during
the pollen phase of in 55.2% of the men,
whereas only 13% of the placebo-phase
men were so reported; and while “poor”
results were reported on placebo for
41.9% of the men, only 3.4% of the pollen
extract males’ progress was so rated. These
results were also significant from a
statistical perspective -- amazing results
over the course of a mere six weeks, with so
few men enrolled in the trial. When these
men were followed up for just twelve
additional weeks in an open-label study10,
the pollen extract also significantly
improved daytime urinary frequency,
while residual urine was decreased by
47%. Results which did not meet the
criteria for statistical significance included
reduced painful urination, urgency, and
discomfort, while 40.4% of men showed
reductions in prostatic volume (as
compared to 12.1% of the placebo group).
In a massive open-label observational
study11 on men with several prostate
disorders, including 1,116 with BPH, those
men with BPH and chronic prostatitis (see
below) experienced a 55.9% reduction in
prostate volume while on the pollen
extract, along with decreases in residual
urine, increases in urine flow rate, and
greater total urine volume with
decreased time taken to empty the
bladder. Both patients and physicians rated
the average improvement “good to very
good.”
Better than Other Botanicals
How do these results stack up to prostate
herbals the more common in North
America? Fortunately, controlled trials have
been performed to answer this question,
and the answer is “very well, thank you.” In
a head-to-head trial against Tadenan (the
best-studied and most famous brand of
in Europe), Dutkiewicz12
reported that 78% of the men in the
pollen extract group reported subjective
improvements, versus “only” 55% of
the group. Another trial16
compared it with Paraprost: significant
improvement in residual urinary
volume, flow rate, and (again, most
importantly) was seen in
the pollen extract group; the lenth of
time required to urinate was also better as
compared to the Paraprost group.
The most impressive comparison is that
with β-sitosterol -- both because
β-sitosterol is perhaps the most rigorously
studied of all the common prostate health
herbals, and because of
the unique insight the
trial yielded about the
power of the pollen
extract. The trial17 found that while there
were improvements in both groups for
subjective symptoms, painful urination,
and frequent urination, greater progress
was made in the pollen extract group,
while the groups equally demonstrated
improvements in straining, urinary
volume, residual volume, and
intermittency. This trial also measured
the levels of prostate-specific antigen
(PSA), a marker used to detect prostate
cancer, along with prostatic acid
phosphatase (PAP), a measure normally
elevated in many prostatic dysfunctions.
Measuring these markers was a first for
both botanicals. Both PAP and PSA were
significantly reduced in the defined
pollen extract group, whereas no
significant change was reported in
the β-sitosterol group (See figure 1).
Reductions in the volume
of the prostate as measpg.
3
suggested that the active ingredient in the
pollen extract might be a cyclic hydroxamic
acid called 2,4-dihydroxy-2H-1,4-benzox
azin-3(4H)-one (DIBOA).
Yet other investigators have disputed this
conclusion32: they found that DIBOA
could inhibit a breast cancer line,
and found compounds in the pollen extract
which were more more potent inhibitors
of the prostate cancer cell line. All of
these compounds appear to work by
inducing cell death in the cancer cells32.
Meanwhile, yet another group of
researchers has reported a whole new
category of tumor-inhibitory substances in
rye pollen: the secalosides43.
Thus, while DIBOA must play some role in
the anti-prostate cancer effect of the
defined pollen extract, it is not the only
active ingredient with anti-cancer power in
the test tube, and other compounds may be
responsible for the specific effect on prostate
cancer cells. Whatever the true active
ingredient, however, one thing is clear:
defined pollen extract may prove to be
potent nutritional support against
prostate -- and perhaps other -- cancers.
In this context, the lowering of PSA
levels experienced by men receiving the
pollen extract17 is very tantalizing. But we
cannot be certain that this means a
prostatitis is sometimes caused by
recurrent bacterial infection, but is often
present in the absence of such “nasties;” at
least some prostatitis may actually be caused
by unusual muscle tensions at the base of
the pelvis20, and a trial is being launched at
Stanford University to see if behavioral
therapy can help ease the symptoms where
this is the root problem. There is also
prostatodynia, which is distinct from CP
in that the chemical markers of
inflammation are not seen in the prostatic
fluid. It is very important to note that there
is no evidence that saw palmetto or the
other common herbals for BPH are
helpful for these conditions, with the
possible exception of Paraprost25. Because
the symptoms of these disorders sound
similar, many men with CP or prostatodynia
mistakenly self-medicate with saw palmetto,
with the result that their symptoms remain
and their health problem goes untreated.
Even when physicians are consulted (which
is always the best course of action), the
relative ignorance of many mainstream
MDs about the herbal pharmacy
leads them to give the
go-ahead for this useless
course of action. By
contrast, several open trials
have found the pollen
extract to be helpful for CP and
prostatodynia11, 21, 22, 23, 24. Rugendorff et al
ran one such trial21, in which 72 men with
CP or prostatodynia uncomplicated by
prostate stones or non-prostatic
complications like blockages of the bladder
“neck” were administered the defined
pollen extract. Examination by digital
rectal exam, urine flow, and white blood
cell count along with other immune
markers found that 78% of these men
were helped by defined pollen extract. A
second group of men whose CP was
complicated by the factors mentioned
above were not found to benefit, however.
Hope for Prostate Cancer
An even graver prostate health concern for
many men is prostate cancer. In men,
excluding skin cancer, prostate cancer is the
single most commonly-contracted cancer
form, with a new diagnosis every two
minutes in the United States and a new
death every fifteen minutes. The American
Cancer Society estimates that 180 400 men
will be diagnosed with prostate cancer in
the United States in this year alone -- and
diagnosed prostate cancer represents a
mere fraction of the total incidence of this
disease. Autopsy studies36, 37 show that 15
to 30% of men over 50, and 60 to 70
percent of men over the age of 80, have
latent, undiagnosed prostate cancer.
There has been exciting progress made in
the last few years in the discovery of
natural ways of reducing the risk of
prostate cancer, including successful
double-blind, placebo-controlled trials with
selenium26, alpha-tocopherol27, and the
carotenoid lycopene28. Preliminary
evidence now suggests that it is possible
that the defined pollen extract may yet
prove to be a safe, natural herb to help the
fight against the second greatest cause of
cancer death in men.
In the course of
attempts to discover
the components of the
extract which inhibit
prostate cell growth, a
fraction of the lipid-soluble extract in the
defined pollen extract (labelled FV-7) has
been discovered which appears to have the
power to halt the growth of prostate cancer
cells. In 1990, Habib at coworkers29 tested
defined pollen extract to see what its effects
would be on the growth (in test-tube
conditions) of nine cancerous and
noncancerous cell lines derived from
humans. They found that, of the cell lines
tested, the pollen extract would
inhibit the growth of prostate cell lines.
Further, it was noted that the growth
inhibition applied only to the epithelial cells
of the prostate (the gland itself), not the
stroma (the surrounding smooth muscle
cells). Later studies30, 31 on FV-7 found that
this subfraction of the defined pollen
extract inhibited the growth of a human
prostate cancer line. These investigators
Statistically significant results
were experienced while the men
were taking the pollen extract in
nocturia and residual urine volume.
pg.4
oxioreductase (HSORred) enzymes, which
convert DHT to the less-stimulating 3-α-
and 3-β-diol. In other words, the pollen
extract directly decreases both the synthesis
and the clearance of DHT. What the end
result of this would be is unclear, but the
net effect on DHT activity
levels in the prostate could
very well be zero. Clearly,
more studies are needed, but
direct inhibition of DHT may
not be a key mechanism of the pollen’s
activity.
Another possible mechanism of prostate
shrinkage by the pollen extract was
identified by Japanese researchers39. These
investigators subjected rats to high levels of
testosterone so that they would develop
BPH, and then administered the defined
pollen extract. While significantly reducing
the weight of the prostate, the pollen
extract elevated zinc levels in the gland
-- this, despite the fact that there is very
little zinc in the extract itself. When present
in the prostate, zinc has anti-5AR activity40,
and also reduces the binding of male
hormones41 and prolactin42 to the
prostate cell receptor, all of which would
be expected to reduce the growthtriggering
eggects of these hormones.
Since zinc levels are depressed in BPH and
prostate cancer44, simply taking zinc orally
may not increase zinc levels specifically in the
prostate, and may thus not be effective at
safe dosages.
Furthermore, the pollen extract inhibits
absorption of the toxic heavy metal
cadmium45, which is linked with prostate
cancer in many studies46 and which can
directly cause prostatic growth and cancer
in animal models47. Levels of cadmium are
increased in both BPH and prostate
cancer44. But while these effects on
mineral metabolism might help explain a
slowing of growth in the prostate, and enhance
any anti-cancer effect the pollen extract
may prove to have, they probably do not
explain the reported reductions in prostate
volume. Thus, while the fact of reduced
reduction in risk of prostate cancer:
Proscar®, for instance, also lowers PSA, but
does not appear to have any effect on this
terrible disease. Thus, it is possible that this
lowering of PSA may reduce the
usefulness of the PSA test as a marker for
prostate cancer (as is known to happen with
Proscar®); as with Proscar®, then, it seems
prudent to suggest that men should have
their PSA checked before starting on the
pollen extract, to establish a baseline from
which future tests can be evaluated. Though
the test-tube results will clearly have to be
confirmed in living humans, the forty-year
safety record of defined pollen extract and
its ability to lower PSA certainly make it
worth a second look by those concerned
with this deadliest and most intimate of
killers.
How Does it Work?
By now, many readers will be wondering how
exactly the defined pollen extract can exert
such profound effects on prostate health.
There are some hints in the literature, but
final answers still escape us. Partly, what we
are seeing is an anti-inflammatory effect:
in test tube studies, the pollen extract
inhibits the conversion of arachidonic
acid to series 2 eicosanoids, which are
local, cellular “hormones” which promote
inflammation. Because inflammation is the
key marker of chronic prostatitis, it is
obvious how this would be helpful in cases
of CP, but it may also enhance any
anticancer effects of the extract. This is
because cancer cells use series 2 eicosanoids
-- most notably prostaglandin E2 (PGE2)
-- to defend themselves from the body’s
immune system34, because PGE2 inhibits
natural killer cell activity. Thus, substances
which inhibit series-2 eicosanoid formation
may have anti-cancer effects as well as
anti-inflammatory ones.
Another mechanism at work in the
symptomatic improvement generated by
the pollen extract is its effects on smooth
muscle tone in the urinary tract. In
isolated urinary tract muscle cells57, 58, 59, and
one trial in humans35, it has been found that
the pollen extract balances the muscle tone
of the urethra and bladder, resulting in less
pinching off of the urine stream. This
would help explain the extract’s
improvement in such symptoms as
incomplete bladder emptying, hesitancy, or
intermittency. It may also
explain some of the results in
chronic prostatitis, since (as
noted above) unusual
muscular tensions may play a
role in much CP.
But the exact method by which the defined
pollen extract exerts its most exciting
influence on the prostate -- namely, its
ability to reduce the actual volume of the
prostate -- remains unknown. As noted
above, test-tube studies have shown29 that
the pollen extract does directly inhibit the
growth of prostate cells, but how exactly it
does this remains an enigma. One logical
assumption would be that the pollen extract
is exerting effects on the hormones which
drive BPH. Proscar®, the most successful
drug therapy for BPH, also reduces prostate
volume. It does so by inhibiting 5-α-
reductase (5AR), the enzyme which
converts testosterone into the much more
prostate-stimulating dihydrotestosterone
(DHT). Defined pollen extracts, likewise,
inhibit 5AR38; however, they also
inhibit the less-known hydroxysteroid
Both PAP and PSA were
significantly reduced in the
defined pollen extract
group.
pg.5
29
27
25
23
0
Figure 2: Prostate volume. Redrawn from (8).
31
mm
pre post
S.E.
S.E.
S.E.
S.E.
-4,6% Placebo (n=24) -18, 2% Cernilton (n=29)
prostate volume remains on solid ground,
the mechanisms of this revolutionary effect
remain elusive.
Not Just for the Prostate... And Not Just
for Men!
Most people taking the pollen extract are
using it for the health of their prostate,
which is by far the best-backed usage for
this botanical. Yet there are hints in the
literature of a broad range of other
applications which get much less attention.
One such property is detoxification and
liver protection. In addition to the
reduction in cadmium absorption
mentioned above45, investigators in Poland
have found that the defined pollen extract
provides protection against such toxins
as ammonium fluoride48, 49, paracetamol
(an anti-inflammatory and pain killer which
is among the drugs most commonly
consumed in toxic overdose)50, organic
solvents51, allyl alcohol52, 54, the deadly
carbon tetrachloride52, and
galctosamine52, 53 in lab animals. Some of
this protection may be due to the
antioxidant properties of the extract55,
along with its ability to increase levels of
liver detoxification enzymes56.
Another possible benefit from the pollen
extract may be protection from
atherosclerosis. In one study, animals fed
a high-fat diet along with defined pollen
extracts had lower cholesterol and
triglycerides compared to animals not
receiving the pollen extracts55. Another
study56 reported that such animals had
reduced total cholesterol and elevated
HDL (“good”) cholesterol, along with
reductions in atherosclerotic plaques:
the group receiving the high-fat diet alone
had a plaque intensity of 85.5%, while the
group which also received the defined
pollen extract had only a 33.7% plaque
intensity.
Finally, although we emphasize that the
evidence is purely anecdotal, in some parts of
the world more women buy defined pollen
extracts than men, because they have found
that the pollen extract helps with
urinary incontinence -- a result very
consistent with the improved bladder and
urethral smooth muscle tone balance35, 57-59
which the pollen extract is known to yield.
Funding is presently being sought to run a
controlled trial on this application.
The Future of Prostate Care
Proscar® and other drugs for BPH are
effective, but come with side effects and a
cost which make drug therapy unattractive
to many men. The natural alternatives most
common on Canadian health food store
shelves may help relieve symptoms, but do
not ultimately address the underlying
disease. But defined pollen extract has been
effectively helping European men with
many prostate health problems for decades
now, and is proven to do what no other
herbal can: shrink swollen prostates. As the
pollen itself is golden, so defined pollen
extract may open up a golden age for safe,
natural therapy for the most personal of
male health concerns.
pg.6
To the people of South America, it’s Chanca
Piedra, the “stone breaker.” In Ayurvedic
tradition, it’s Bahupatra . Botanists classify it as
Phyllanthus niruri. Hurricane Weed, Seed On
The Leaf, Feuilles de la Fievre, Child’s
Pick-a-back, Tamalaka, Turi Hutan ... whatever
you call it, this short tropical shrub is famed for
its healing powers.
Western science is beginning to confirm Chanca
Piedra’s ability to support the health of the
detoxification organs. From increasing the
flushing-out of the kidneys, to relaxing the
smooth muscles of the bladder, urethra, and
biliary tract, to guarding the liver against toxins
and the replication of some viruses, Chanca
Piedra may support the function of the body’s
detoxification systems in many ways ... and by
many names.
Traditional herbal medicine for:
-Kidney stones
-Gallstones
-Liver protection & detoxification
-Immune support and more!
A stone by any
other name ...
(42) Leake et al, “Interaction between prolactin and zinc in the human
prostate gland.” J Endocrinol. 1984 Jul; 102(1): 73-6.
(43) Jaton et al, “The secalosides, novel tumor cell growth inhibitory
glycosides from a pollen extract.” J Nat Prod. 1997 Apr; 60(4): 356-
60.
(44) Habib et al, "Metal-androgen interralationships in carcinoma and
hyperplasia of the human prostate." J Endocrinol 1976 Oct; 71(1):
133-41.
(45) Howaniec et al, “The role of cernitin in cadmium effect on the
absorption processes in rat small intestine.” Acta Physiol Pol. 1988
May-Jun; 39(3): 188-94.
(46) Waalkes & Rehm, “Cadmium and prostate cancer.” J Toxicol
Environ Health. 1994 Nov; 43(3): 251-69.
(47) Hoffmann et al, “Carcinogenic effects of cadmium on the prostate
of the rat.” J Cancer Res Clin Oncol. 1985; 109(3): 193-9.
(48) Humiczewska et al, “The effect of the pollen extracts quercitin and
cernitin on the liver, lungs, and stomach of rats intoxicated with
ammonium fluoride.” Folia Biol (Krakow). 1994; 42(3-4): 157-66.
(49) Mysliwiec , “Effect of pollen extracts (cernitin preparation) on
selected biochemical parameters of liver in the course of chronic
ammonium fluoride poisoning in rats.” Ann Acad Med Stetin. 1993;
39: 71-85.
(50) Juzwiak et al, “Experimental evaluation of the effect of pollen
extract on the course of paracetamol poisoning.” Ann Acad Med Stetin.
1993; 39: 57-69.
(51) Ceglecka, “Effect of pollen extract (cernitin) on the course of poisoning
with organic solvents.” Ann Acad Med Stetin 1992; 38: 79-95.
(52) Samochowiec & Wojcicki, “The effect of pollen on the changes in
the liver of laboratory rats evoked by ethionine, carbon tetrachloride, allyl
alcohol and galactosamine.” Arch Exp Veterinarmed 1989; 43(4):
521-32.
(53) Wojcicki et al, “The effect of Cernitins on galactosamine-induced
hepatic injury in rat.” Arch Immunol Ther Exp (Warsz). 1985; 33(2):
361-70.
(54) Wojcicki et al, “The protective effect of pollen extracts against allyl
alcohol damage of the liver.” Arch Immunol Ther Exp (Warsz). 1985;
33(6): 841-9.
(55) Wojcicki et al, “Study on the antioxidant properties of pollen
extracts.” Arch Immunol Ther Exp (Warsz) 1987; 35(5): 725-9.
(56) Wojcicki et al, “Effect of pollen extract on the development of
experimental atherosclerosis in rabbits.” Atherosclerosis 1986 Oct;
62(1): 39-45.
(57) Onodera et al, “Effects of cernitin pollen extract (CN-009) on the
isolated bladder smooth muscles and the intravesical pressure.” Nippon
Yakurigaku Zasshi 1991 May; 97(5): 267-76.
(58) Kimura et al, “Micturition activity of pollen extract: contractile
effects on bladder and inhibitory effects onurethral smooth muscle of
mouse and pig.” Planta Med.1986 Apr; 2: 148-151.
(59) Nakase et al, “Inhibitory effect and synergism of cernitin pollen
extract on the urethral smooth muscle and diaphragm of the rat.”
Nippon Yakurigaku Zasshi /Folia Pharmacol Japan. 1988 Jun; 91(6):
385-392.
(1) Wilt et al, “Saw palmetto extracts for treatment of benign prostatic
hyperplasia: a systematic review.” JAMA. 1998 Nov 11;280 (18):
1604-9.
(2) Breza et al, “Efficacy and acceptability of tadenan (Pygeum
africanum extract) in the treatment of benign prostatic hyperplasia
(BPH): a multicentre trial in central Europe.” Curr Med Res Opin.
1998;14(3):127-39.
(3) Romics, “Observations with Bazoton in the management of prostatic
hyperplasia.” Int Urol Nephrol. 1987; 19(3): 293-7.
(4) Vontobel et al, “Results of a double-blind study on the effectiveness of
ERU (extractum radicis Urticae) capsules in conservative treatment of
benign prostatic hyperplasia.” Urologe A. 1985 Jan; 24(1): 49-51.
(5) Wilt et al, “b-sitosterol for the treatment of benign prostatic hyperplasia:
a systematic review.” BJU Int. 1999 Jun; 83(9): 976-83.
(6) Berges et al, “Randomised, placebo-controlled, double-blind clinical
trial of beta-sitosterol in patients with benign prostatic hyperplasia. Betasitosterol
study group.” Lancet. 1995 Jun 17; 345(8964): 1529-32.
(7) Feinblatt & Gant, "Value of glycine, alanine and glutamic acid
combination." J Maine Med Assoc. 1958 Mar; 49(3).
(8) Buck et al, “Treatment of outflow tract obstruction due to benign
prostatic hyperplasia with the pollen extract, cernilton. A double-blind,
placebo-controlled study.” Br J Urol. 1990 Oct; 66(4): 398-404.
(9) Becker and Ebeling, “Conservative treatment of benign prostatic
hyperplasia (BPH) with cernilton N -- results of a placebo-controlled
double-blind study.” Urologe (B). 1988; 28: 301-6.
(10) Becker & Ebeling, “Phytotherapy of BPH with cernilton
N––results of a controlled prospective study.” Urologe (B). 1991; 31:
113-6.
(11) Ebeling, “Therapeutic results of defined pollen-extract in patients
with chronic prostatitis or BPH accompanied by chronic prostatitis.” in
Schmiedt et al (eds), Therapy of Prostatitis, (Munich: Zuckerschwerdt
Verlag, 1986): 154-160.
(12) Dutkiewicz, “Usefulness of cernilton in the treatment of benign
prostatic hyperplasia.” Int Urol Nephrol. 1996 96; 28(1): 49-53.
(13) Yasumoto et al, “Clinical evaluation of long-term treatment using
cernitin pollen extract in patients with benign prostatic hyperplasia.”
Clin Ther. 1995 Jan-Feb; 17(1): 82-7.
(14) Hayashi et al, “Clinical evaluation of cernilton in benign prostatic
hypertrophy&91;.” Hinyokika Kiyo. 1986 Jan; 32(1): 135-41.
(15) Ueda et al, “Clinical evaluation of cernilton on benign prostatic
hyperplasia.” Hinyokika Kiyo. 1985 Jan; 31(1): 187-91.
(16) Maekawa et al, “Clinical evaluation of rnilton on benign prostatic
hypertrophy--a multiple center double-blind study with Paraprost.”
Hinyokika Kiyo. 1990 Apr; 36(4): 495-516.
(17) Bräuer, “The treatment of benign prostate hyperplasia with
phytopharmaca. A comparative study of cernitin vs. beta-sitosterol.”
Therapiewoche. 1986; 36: 1686-96.
(18) Lowe & Ku, “Phytotherapy in treatment of benign prostatic
hyperplasia: a critical review.” Urology. 1996 Jul; 48(1): 12-20.
(19) Dreikorn & Schonhofer, “Status of phytotherapeutic drugs in treatment
of benign prostatic hyperplasia.” Urologe A. 1995 Mar;
34(2): 119-29.
(20) Zermann et al, “Chronic prostatitis: a myofascial pain syndrome?”
Infect Urol. 1999; 12(3):84-88.(21) Rugendorff et al, “Results of
treatment with pollen extract (cernilton N) in chronic prostatitis and
prostatodynia.”Br J Urol. 1993 Apr; 71(4): 433-8.
(22) Suzuki et al, “Clinical effect of cernilton in chronic prostatitis.”
Hinyokika Kiyo. 1992 Apr; 38(4): 489-94.
(23) Buck et al, “Treatment of chronic prostatitis and prostatodynia
with pollen extract.” Br J Urol. 1989 Nov; 64(5): 496-9.
(24) Jodai et al, “A long-term therapeutic experience with Cernilton in
chronic prostatitis.” Hinyokika Kiyo. 1988 Mar; 34(3): 561-8.
(25) Okada et al, “Clinical application of PPC for nonspecific chronic
prostatitis.” Hinyokika Kiyo. 1985 Jan; 31(1): 179-85.
(26) Clarket al, “Decreased incidence of prostate cancer with selenium
supplementation: results of adouble-blind cancer prevention trial.” Br J
Urol. 1998 May; 81(5): 730-4.
(27) Heinonen, “Prostate cancer and supplementation with alpha-tocopherol
and beta-carotene: incidence and mortality in a controlled trial.” J
Natl Cancer Inst. 1998 Mar 18; 90(6): 440-6.
(28) Kucuck et al , “Lycopene supplementation in men with localized
prostate cancer (PCa) reduces grade and volume of preneoplasia (PIN)
and tumor, decreases serum PSA, and modulates biomarkers of growth
and differentiation.” Meeting of the Am Assoc Cancer Res. 1999
April.
(29) Habib et al, “In vitro evaluation of the pollen extract, cernitin T-
60, in the regulation of prostate cell growth.” Br J Urol. 1990 Oct;
66(4): 393-7.
(30) Habib et al, “Identification of a prostate inhibitory substance in a
pollen extract.” Prostate. 1995 Mar; 26(3): 133-9.
(31) Zhang et al, “Isolation and characterization of a cyclic
hydroxamic acid from a pollen extract, which inhibits cancerous cell
growth in vitro.” J Med Chem. 1995 Feb 17; 38(4): 735-8.
(32) Roberts et al, “Cyclic hydroxamic acid inhibitors of prostate
cancer cell growth: selectivity andstructure activity relationships.”
Prostate. ce1998 Feb 1; 34(2): 92-9.
(33) Loschen & Ebeling, “Inhibition of arachidonic acid cascade by
extract of rye pollen.” Arzneimittelforschung. 1991 Feb; 41(2): 162-7.
(34) Uotila, “Inhibition of prostaglandin E2 formation and histamine
action in cancer immunotherapy.” Cancer Immunol Immunother. 1993
Sep; 37(4): 251-4.
(35) Takeuchi et al, “Quantitative evaluation of the effectiveness of
cernilton on benign prostatic hypertrophy.”Hinyokika Kiyo/Acta Urol
Jpn. 1981; 27: 317-326.
(36) Lundberg & Berge, “Prostate carcinoma: an autopsy study.” Scand
J Urol NephroI. 1970; 4(2): 93-7.
(37) Harvei, “Epidemiology of prostatic cancer.” Tidsskr Nor
Laegeforen. 1999 Oct 10; 119(24): 3589-94.
(38) Tunn & Krieg, ”Alterations in the intraprostatic hormonal
metabolism by the pollen extract cernilton N.” in Vahlensieck &
Rutishauser (eds), Benign Prostate Diseases. (New York: Thieme
Medical Publishers, 1992): 109-114.
(39) Ito et al, “Antiprostatic hypertrophic action of cernitin pollenextract
(cernilton).” Oyo Yakuri / Pharmacometrics 1986; 31(1): 1-
11.
(40) Leake et al, “The effect of zinc on the 5 alpha-reduction of
testosterone by the hyperplastic human prostate gland.” J Steroid
Biochem. 1984 Feb; 20(2): 651-5.
(41) Leake et al, “Subcellular distribution of zinc in the benign and
malignant human prostate: evidence for a direct zinc androgen
interaction.” Acta Endocrinol (Copenh). 1984 Feb; 105(2):281-8.
pg.7
www.holisticinternational.com
holistic@cadvision.com 1-800-387-0177 Box: 92 4404 12st
N.E. Calgary Alberta T2E 6K9 1-877-219-9974
The health of the prostate is something most
men never think about ... until they’re forced to. So
the fact that so many men are willing to take
drugs with known, serious side effects, or to even
undergo surgery, attests to how common, how
unpleasant, and how personal prostate health
concerns can be. Saw Palmetto, Stinging Nettle,
Pygeum africanum, Beta-sitosterol, and other
herbal formulas have become widely known as
natural ways to support the health of the
prostate, but research shows they don’t live up to
many mens’ expectations. And in some cases --
like Saw Palmetto -- it’s not even certain that
they’re of any help at all.
Prostaphil-2® may change all that. Used by men
for two generations in Europe, the power of this
proprietary pollen extract from Sweden is backed
by numerous clinical and experimental studies.
Research shows that this defined pollen extract
can support a healthy prostate, in ways that the
more common prostate herbals don’t. Look into
Prostaphil-2®. You may just find that you sleep
better at night.
Pollen Power for the Prostate
• Unique proprietary blend.
• Clinically proven.
• Safer and more effective than
---Saw Palmetto.
Beta-carotene, the main pigment which
gives the orange color to sweet potatoes
and carrots, is well-known and wellrepresented
in the daily supplement
regimen of nearly all health-conscious
North Americans. For many years, this
nutrient was thought to be simply a source
of provitamin A -- that is, a substance
from which the body could make vitamin A
itself (retinol). But all this began to change
in the early 1980s, when a powerful, largescale
epidemiologic study1 revealed an
astonishing connection between intake of
this carotenoid and lung cancer: men who
took in the greatest amount of
carotenes were seven to eight times less
likely to develop lung cancer than those
who took in the least -- a result
unaffected by their varying intake of retinol
or other nutrients. This result represented a
risk reduction so great as to indicate that
smokers with the highest carotene
intakes had the same relative risk for
lung cancer as non-smokers in
lower-intake groups. Since 1977, 53 of 135
epidemiological studies have found
significant reduction of risk for cancer
from β-carotene, measured as dietary
intake or plasma levels; fully half of the
remainder also found risk reductions, but
the results were not strong enough to be
considered statistically significant.
This result was in line with evidence
accumulated before and since on the role of
β-carotene as a potent antioxidant
(especially as a quencher of singlet
oxygen (1O2)) with anticarcinogenic
powers. Extensive experimental work in lab
animals5 and isolated cells6 indicated that
β-carotene can prevent the
development of cancer, and even stop
the growth of existing cancerous cells.
Cellular studies found that β-carotene
could decrease transformation of
benign tumors to malignant cancers,
increase the cell-to-cell communication
normally lost by cancer cells, prevent UV
damage, reduce chromosome
biochemistry is upset by the massive doses
of free radicals to which smoking exposes
smokers’ lungs and bodies. When a free
radical is quenched by an antioxidant, the
“lonely electron” is given a mate by the
antioxidant molecule. In the process,
however, the antioxidant itself becomes a free
radical. Progress is only possible because the
new free radical is less toxic than the old
one. The body’s antioxidant defenses are
designed to work as a team, with one
antioxidant quenching a free radical, and
then being itself quenched by another
antioxidant in turn, leading to progressively
less toxic byproducts, until vitamin C -- the
final acceptor -- is finally flushed out
through the kidneys. It’s like a game of
“hot potato,” with the potato cooling off
with each pass.
In smokers, however, this process is
interrupted, because smoking rapidly
depletes other antioxidants. As a result,
giving β-carotene alone to smokers may
have resulted in a high level of toxic
β-carotene “radicals” accumulating in the
lungs from contact with cigarette smoke,
with no vitamins C and E available to
detoxify them11. Interestingly, later analysis
of the ATBC and CARET
data suggested no risk, or
even a protective effect, for
β-carotene in light smokers
even as heavy smokers seemed
to show increased risk2,3. A more recent
trial using a combination of antioxidants4
found that β-carotene in combination
with selenium and vitamin E
significantly cut cancer risk; better
results might have been expected had
vitamin C been included. In fact, a new
Physicians’ Health Study13 is now under way
which will use a combination of E, C,
β-carotene, and a multivitamin against
cancer and cardiovascular disease; we await
the results with great optimism. In food, of
course -- the source of b-carotene in the
original epidemiological studies --
β-carotene always comes along with
vitamins C and E; supplement programs
should follow this pattern.
The ATBC subjects’ high intake of alcohol
may also have been a factor, because
high-dose alcohol interacts dangerously
with β-carotene because of their use of
common liver detoxification
instability induced by viruses, kill tumor
cells in some cancer lines, and even induce
differentiation, turning some cancer cells
into normal, healthy ones again6.
Excitement built, and double-blind,
randomized, placebo-controlled trials in
men at very high risk for lung cancer were
initiated: the Alpha-Tocopherol and
Beta-Carotene (ATBC) Cancer
Prevention Study, and the Carotene and
Retinol Efficacy Trial (CARET).
Unbelievable Results
The results came as a complete surprise.
The trials7,8 were called off early in 1995
and 1996, because preliminary analysis not
only failed to find any improvement in lung
cancer rates in the active groups, there was
a non-significant suggestion of an
in lung cancer rates! And while an
analysis published as a press release in the
New England Journal of Medicine declared
that another large β-carotene trial -- the
Physicians’ Health Study -- had found no
such risks, it found no benefit either.
On the one hand, the excess cancer
incidence was not statistically
significant, so there is the temptation to
ignore the results until better
data are available; but when
two seperate, large-trials seem
to show the same increased
risk, caution is in order. So
what might be going on here?
Flawed Trials
Actually, probably several things at once.
For one thing, there is the high-risk
populations used: ATBC and CARET
deliberately chose to study men who were
long-term smokers (and, in ATBC’s case,
also asbestos workers!) in order to get a
clear therapeutic result. But it now appears
from new human trials that, while
β-carotene can prevent the cells from
becoming cancerous (initiation)9, it may not
be able to halt the spread of existing
cancers (progression)10. Subjects at very
high risk may thus have already have
early-stage cancer when the trial began,
and β-carotene may not affected them.
Worse, it would appear that smoking may
make β-carotene a health hazard when
it is given . This is because the
teamwork involved in antioxidant
β-c i l
-
IS YOUR BETA
CAROTENE TOXIC?
The version in your multivitamin may be hazardous to
your health!
pg.9
marker of lipid peroxidation (free radical
damage to cell membranes, LDL, etc) were
measured. Not only did the all-trans
β-carotene fail to provide any measurable
antioxidant protection compared to the
dummy pill, but the group receiving
synthetic β-carotene actually had 13%
markers of free radical damage
than the placebo group! Although this
result was not statistically significant, it
contrasts sharply with the group receiving
the natural-source supplement, which
delivered a 76% reduction in
peroxidation markers. Similar results
were reported in a test-tube study by Levin
and Mokady26.
This lack of antioxidant ability is bad
enough in itself -- suggesting, as it does,
that the synthetic β-carotene administered
to the ATBC and CARET smokers could
not have helped them -- but further
investigation suggests a more chilling
conclusion. First is the possibility that
synthetic β-carotene supplements may
actually deplete the body of the natural
isomer. This is because both forms of
β-carotene use the same absorption
pathway, which only allows a limited
transport of this carotenoid at a given
time15, so that large-dose synthetic
β-carotene supplements may actually
inhibit absorption of the natural
- form of β-carotene. Ironically, in fact,
the liver appears to transport the trans form
more efficiently than the cis isomer18, so that
taking in one unit of synthetic β-carotene
might prevent more than one unit of the
pathways12.Nearly all of the apparent
excess lung cancer in the CARET
group was in a subpopulation with high
alcohol intake2; and, similarly, the risk of
cancer appeared to be higher in regular
drinkers than non-drinkers in ATBC3,
although this finding has recently been
disputed16.
The Wrong Molecule
But perhaps the most disastrous failure in
the design of the controlled trials is that
they used the wrong β-carotene. For
most supplements, whether they are
derived from cellular “factories” or
pharmaceutical ones makes no difference
to their chemical structure or biological
activity; natural versus synthetic vitamin E
is one of a very few exceptions to the rule.
Crucially, β-carotene is another.
The β-carotene used in CARET and ATBC
was synthetic β-carotene, which is
from the β-carotene
found in food. Synthetic β-carotene is
entirely in the “ ” form; by contrast,
natural β-carotene is a mixture of
and isomers. Many health-conscious
people are by now aware of the great
difference between the trans fatty acids in
partially hydrogenated vegetable oils and
the cis fats in natural EFA sources. In trans
bonds, the hydrogens attached to two
adjoining double-bonded carbons are on
opposite sides of the molecule, giving it a
flat molecular shape. Cis isomers, by
contrast, have one double bond in which
the two carbons’ hydrogens are on the same
side of the molecule’s backbone; and since
the two hydrogens repel one another
(because they both cary a positive charge --
an effect rather like two magnets aligned at
their “north” end), the molecule is bent at
this point (see Figure 3).
Synthetic β-carotene:
Not an Antioxidant
We do not want to bore you with detailed
chemistry, so let us get to the point: while
trans β-carotene can still be used to make
vitamin A, only the form is directly
useful as an antioxidant in the body! In
one trial14 , subjects were given either
natural β-carotene supplements from the
algae Dunaliella bardawil, synthetic
β-carotene, or a placebo, and levels of a
active antioxidant isomer from being
absorbed. To understand the problem,
think of a group of prank callers tying up
telephone lines of an organization,
preventing legitimate callers from making
contact. Now imagine that there are more
pranksters than callers with real reasons for
trying to get through. Now imagine that the
lines being tied up are used by 9-1-1
emergency operators ...
Some have speculated that the absorption
inhibition issue could be even more serious,
since an overload of synthetic β-carotene
might be expected to also reduce uptake of
other carotenoids such as lycopene,
lutein, and α-carotene. One preliminary
report on the ATBC subjects paradoxically
reported that lutein was, indeed, depressed
in those receiving synthetic β-carotene, but
that some other carotenoids were actually
increased in serum19. Several other reports,
however, have shown no association
between intake of the artificial supplement
and levels of any carotenoid other than
β-carotene itself 23, 24, 25.
Artificial β-carotene Damages Genes
An even greater reason to stay away from
the use of synthetic β-carotene
supplements was given by a recent study
which found that, while both natural and
synthetic β-carotene protected immune
cells from damage by gamma radiation,
synthetic β-carotene caused
chromosome damage in these cells,
with the number of damaged cells
increasing with the dosage17! By contrast,
natural β-carotene caused no such
spontaneous damage. In the same study,
natural β-carotene protected cells from
DNA cross-linking induced by the
antibiotic mitomycin C, which the
synthetic form was not reported to do.
A small trial reported just before the ATBC
alarm sounded shows that these are not just
theoretical concerns. The trial was
conducted patients with precancerous cells
in their stomachs. It assigned the patients to
receive one of three supplements: natural
β-carotene, synthetic β-carotene, or a
placebo. When the researchers looked at
the results, they found that only the
natural supplement had reduced the
abnormal cellular development21.
IS YOUR BETA CAROTENE TOXIC?
pg.10
Thus, the synthetic β-carotene used in
ATBC, CARET, and most β-carotene
supplements available on the market appear
to simultaneously inhibit the absorption of
beneficial cis β-carotene, and to be
themselves possible carcinogens. In sum,
synthetic β-carotene supplements may
be worse than useless: they may
actually be harmful, especially to
high-risk populations like those in the large
trials. The only reason we can see for the
use of the artificial supplement in CARET
and ATBC is its low cost; in retrospect, as a
letter to the New England Journal of
Medicine put it, the use of this supplement
“is neither hard to understand nor easy to
forgive.”22
Choosing the Right β-Carotene
To recap: there are many reasons to believe
that the results of the large-scale trials of
β-carotene were the results of flawed
design, and that we should trust the
extensive epidemiological, animal, and
cellular evidence that β-carotene can
prevent the development of cancer. The
evidence strongly suggests that a central
flaw in the ATBC and CARET trials may
have been the use of synthetic (all-trans)
supplements. Fortunately, the problem of
synthetic β-carotene is not inescapable:
while most multivitamins, ACES
combinations, and stand-alone β-carotene
supplements still use the artificial molecule,
supplements are available which
contain natural β-carotene exclusively,
usually derived from marine algae. These
supplements deliver β-carotene in the
natural form, with the vital cis isomers
present. But we have to learn from the
trials’ other mistakes as well. It is important
to ensure that you are also taking a
spectrum of antioxidants with your
β-carotene, especially vitamins C and E. It
may also be important to avoid excessive
consumption of alcohol -- a wise policy
in any case. And, most important of all --
for your own sake, quit smoking.
Your body can only absorb fat-soluble
vitamins (like CoQ10, betacarotene,
tocotrienols, and
lycopene) when they’re dissolved in
fat. To get
maximum benefits make sure there’s
a little fat in the meal when you
swallow the pill-- and never take
them on an empty stomach!
References
(1) Shekelle et al (1981), “ Dietary vitamin A and risk of cancer in the
Western Electric study.” Lancet 2(8257): 1185-90.
(2) Omenn et al (1996), “Risk factors for lung cancer and for
intervention effects in CARET.” J Natl Cancer Inst 88: 1550-9
[revised conclusions&91;.
(3) Albanes et al (1996), “Alpha tocopherol and beta carotene
supplements in the Alpha Tocopherol and Beta Carotene trial: effects of
baseline characteristics and study compliance.” J Natl Cancer Inst 88:
1560-70 [revised conclusions&91;.
(4) Blot et al (1993), “Nutrition intervention trials in Linxian, China:
supplementation with specific vitamin/mineral combinations, cancer
incidence, and disease-specific mortality in the general population.” J
Natl Cancer Inst 85(18): 1483-92.
(5) Toma et al (1995), “Effectiveness of beta-carotene in cancer
hemoprevention.” Eur J Cancer Prev 4(3): 213-24.
(6) Krinksy (1996), “Cellular aspects of carotenoid actions.” In
Cadenas & Packer (eds), Handbook of Antioxidants (Antioxidants in
Health & Disease): 315-36. INSERT CITY: Marcel Dekker.
(7) Albanes et al (1995), “Effects of alpha-tocopherol and beta-carotene
supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene
Cancer Prevention Study.” Am J Clin Nutr 62(6 Suppl): 1427S-
1430S.
(8) Omenn et al (1996), “Effects of a combination of beta carotene and
vitamin A on lung cancer and cardiovascular disease.” N Engl J Med
334(18):1150-5.
(9) van Poppel et al (1992), “Beta-carotene supplementation in smokers
reduces the frequency of micronuclei in sputum.” Br J Cancer 66(6):
1164-8.
(10) van Poppel et al (1992), “No influence of beta-carotene on
smoking-induced DNA damage as reflected by sister chromatid
exchanges.” Int J Cancer 51(3): 355-8.
(11) Wang & Russell (1999), “Procarcinogenic and anticarcinogenic
effects of beta-carotene.” Nutr Rev 57(9 Pt 1): 263-72.
(12) Leo & Lieber (1999), “Alcohol, vitamin A, and beta-carotene:
adverse interactions, including hepatotoxicity and carcinogenicity. Am J
Clin Nutr 69(6): 1071-85.
(13) Christen et al (2000), “Design of Physicians' Health Study II--a
randomized trial of beta-carotene, vitamins E and C, and multivitamins,
in prevention of cancer, cardiovascular disease, and eye disease, and review
of results of completed trials.” Ann Epidemiol 10(2): 125-34.
(14) Ben-Amotz & Levy (1996), “Bioavailability of a natural isomer
mixture compared with synthetic all-trans beta-carotene in human
serum.” Am J Clin Nutr 63(5): 729-34.
(15) Erdman et al (1993), “Absorption and transport of carotenoids.”
Ann N Y Acad Sci 691: 76-85.
(16) Woodson et al (1999), “Association between alcohol and lung cancer
in the alpha-tocopherol, beta-carotene cancer prevention study in
Finland.” Cancer Causes Control 10(3): 219-26.
(17) Xue et al (1998), “Comparative studies on genotoxicity and
antigenotoxicity of natural and synthetic beta-carotene stereoisomers.”
Mutat Res 418(2-3): 73-8.
(18) Erdman et al (1998), “All-trans beta-carotene is absorbed
preferentially to 9-cis beta-carotene, but the latter accumulates in the
tissues of domestic ferrets (Mustela putorius puro).” J Nutr 128(11):
2009-13.
(19) Albanes et al (1997), “Effects of supplemental beta-carotene, cigarette
smoking, and alcohol consumption on serum carotenoids in the
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.” Am J
Clin Nutr 66(2): 366-72.
(20) Neuman et al (1999), “Prevention of exercise-induced asthma by
a natural isomer mixture of beta-carotene.” Ann Allergy Asthma
Immunol 82(6): 549-53.
(21) Yeum et al (1995), “B-carotene intervention trial in premalignant
gastric lesions.” J Am Coll Nutr 14(5): 536.
(22) von Eggers-Doering (1996), “Antioxidant vitamins, cancer, and
cardiovascular disease.” N Engl J Med 335(14): 1065.
(23) Pappalardo (1997), “Plasma (carotenoids, retinol, alphatocopherol)
and tissue (carotenoids) levels after supplementation with
beta-carotene in subjects with precancerous and cancerous lesions of sig
moid colon.” Eur J Clin Nutr 51(10): 661-6.
(24) Mayne et al (1998), “Effect of supplemental beta-carotene
on plasma concentrations of carotenoids, retinol, and alpha-tocopherol in
humans.” Am J Clin Nutr 68(3): 642-7.
(25) Nierenberg et al (1997), “Effects of 4 y of oral supplementation
with beta-carotene on serum concentrations of retinol, tocopherol, and five
carotenoids.” Am J Clin Nutr 66(2): 315-9.
(26) Levin & Mokady (1994), “Antioxidant activity of 9-cis compared
to all-trans beta-carotene in vitro.” Free Radic Biol Med 17(1):
77-82.
IS YOUR BETA CAROTENE TOXIC?
pg.11
With the breakneck
speed of research into
nature’s pharmacy, radical
new discoveries seem to
appear almost every day.
Developments are occurring
so quickly that we only have
space in this issue for a brief
summary of a few of them.
But be warned: this new
science is on the razor’s edge
of research and development.
Waiting for official
recognition of the value of
these dietary substances by
government agencies or
medical orthodoxy gives
many people a reassuring
sense of certainty, but it also
means a long wait. Over thirty
years since Linus Pauling first
drew the attention of millions
to the protective powers of
vitamin C, the US Food and
Nutrition Board has just
raised its Dietary Reference
Intakes (DRIs) -- to a
whopping 90 mg daily for
men, and 75 mg daily for
women. It is up to each of us,
as individuals, weigh the
evidence, and decide whether
we will wait for a paternalistic
seal of approval, or embrace
Omega-3 fatty acids are already famous
for their ability to control
inflammation1. They do this because of
their effects on local cellular “hormones”
called eicosanoids (eye-KOSS-ah-noids).
Some (“bad”) eicosanoids promote
inflammation, while other (“good”)
eicosanoids serve a potent anti-inflammatory
function. Thus, our health depends in
large part on the body’s balance of “good”
and “bad” eicosanoids. This balance, in
turn, depends on two factors: which EFAs
(omega-3 and omega-6) are available as
building blocks for making eicosanoids, and
which enzymes are used to process those
EFAs. Like a factory which can make pasta
using one of two raw materials (either
whole wheat or white flour), and shape it
into spaghetti, manicotti, or pasta shells
depending on what machinery is used to
process it, the body’s eicosanoid factories
work with raw materials (EFAs) and
processing equipment (enzymes) to make
different finished products (“good” and
“bad” eicosanoids). By keeping the
machinery busy with the right raw materials
(the EFA input from your diet and
supplements), you can put those factories
to work for you instead of against you,
making more “good” and less “bad”
eicosanoids, thus preventing inflammation
before it starts.
One of the most powerful families of proinflammatory
eicosanoids are the
leukotrienes, such as leukotriene B4
(LTB4), which are formed from omega-6
EFAs using the enzyme 5-lypoxygenase
(5-LOX). The eicosanoids produced by 5-
lypoxygenase are the trigger for the pain
flareups in rheumatoid
arthritis (RA)2-4, causing
untold suffering to millions.
Leukotrienes are
also involved in other
inflammatory diseases, including asthma,
psoriasis, and ulcerative colitis6. Most
omega-3 supplements -- like the EPA and
DHA in salmon oil -- are unfortunately
not very effective in stopping the formation
of leukotrienes, because they aren’t good at
tying up the lypoxygenase enzyme
“machine”.
The medical establishment’s mainstay for
inflammation has for many years been the
nonsteroidal anti-inflammatory drugs
(NSAIDS, like aspirin, ibuprofen
[Advil®&91;, and naproxen [Anaprox®&91;).
These drugs do bring short-term relief to
many, but at a cost in side effects which
may include gastric ulcers, kidney and
liver damage, and (with a cruel irony)
long-term damage to the joints. These
drugs’ pain-relieving and ulcer-inducing
powers are both due to the fact that they
nonselectively block the formation of
nearly all eicosanoids -- “good” and ‘bad.”
Thus, at the same time that they are
blocking the formation of the eicosanoids
that trigger inflammation, they
simultaneously prevent the body from
making the eicosanoids which help
maintain the lining of the stomach.
These drugs have no direct ability to
inhibit 5-LOX, the enzyme responsible for
creating LTB4, the flareup-triggering
leukotriene. In fact, in some asthmatic
patients, NSAID therapy can actually
a new form of asthma marked by
increased leukotriene production5! The
pharmaceutical industry is now racing to
make new drugs which inhibit 5-LOX,
LTB-4, or the receptors for this master
inflammatory messenger. But now a new
EFA source stands ready to revolutionize
the use of omega-3s against inflammation.
The fatty acid extract of the Australian
green-lipped mussel (Perna canaliculus)
provides a rare blend of
unique omega-3 fatty
acids, most notably the
tongue-twistingeicosatetraenoic
acid (ETA),
which powerfully and
selectively blocks the formation of proinflammatory
eicosanoids. This EFA
acts like a laser-guided “smart” missile
against inflammation because of its powerful,
selective ability to keep the 5- and 12-
lypoxygenase enzyme machinery busy,
and thus prevent the formation of
leukotriene B-4. Researchers at the Queen
N ew
Suppleme
Revie
pg.12
Green mussel extract was
160% as effective as EPA and
over three times as effective
as evening primrose oil.
Elizabeth Hospital showed that the fatty
acid extract of the mussel powerfully
inhibits these enzymes, preventing the
formation of LTB4 and other “bad”
eicosanoids. Scientists at Australia’s
Queensland University
found that, of 37 products
tested on animals, this
extract had the most
powerful anti-inflammatory
effects7. In fact,
as compared to other EFA
oils, the fatty acid extract of the green
mussel was 160% as effective as EPA
and over three times as effective as
evening primrose oil -- using just -
of the required dose of other EFA
oils! Another green mussel product, which
is a crude extract not standardized to the
fatty acid content or extracted carefully to
protect the crucial omega-3s, had little or
no effect on inflammation. And a recent
double-blind trial8 reported improvements
in 76% of RA patients taking the green
mussel lipid extract, using measures such
as morning stiffness, grip strength, pain
scales, and joint functionality.
And the dangers of the 5- and 12-LOX
enzymes don’t stop with arthritis pain.
Other products of the LOX machinery
are used by many cancer cells to protect
themselves from apoptosis (the body’s
suicide mechanism for damaged or rogue
cells)11, to siphon off healthy cells’ blood
supply (through angiogenesis)9,, and to
spread to other parts of the body
(metastasis)10. Since it is a potent inhibitor
of these enzymes, it is not surprising that
Australian scientists announced that
the lipid extract of the green mussel
kills cancer cells in test tubes11a. All this
suggests that the extract may yet prove to
be powerful nutritional support against this
most insidious of diseases.
Phytosterols (plant sterols and
sterolins) are fatty components of plants
which are stripped from the diet by food
processing and cooking, and which support
human health in many ways. Various
combinations of sterols and sterolins have
been shown to improve
symptoms of benign prostatic hypertrophy
(BPH)12, improve some autoimm
u n e
disorders16, 17, lower
cholesterol when taken
with a meal18, and to possibly
prove helpful in
type II19 and type I20
diabetes. Women who
get more phytosterols in
their diet are less likely to develop breast
cancer21, and phytosterols slow the growth
and spread of human breast13,
prostate14, and colon15 cancer cells in animal
and test tube
models. They have anti-inflammatory
powers23, and are powerful immune
modulators21.
Unfortunately, most phytosterol
products utilize a poor extraction
process which reduces their bioavailability
and introduces an unnaturally low ratio of
sterolins to sterols. The most readily
available such product begins with a sterol
extract from one source (pine oil), using an
extraction method which almost
completely removes the natural sterolins,
and then adds in sterolins separately from
soy. The resulting amalgamation has one
hundred times as much sterol as the more
fragile sterolins, a ratio much lower than
is found in whole foods: natural sources
contain a 10% or better content of
sterolins, with some foods providing as
much as 80% sterolins by weight24. Such
low ratios become even worse upon
ingestion, because the body absorbs two
to five times less sterolin than it does
sterol24, so that a 100:1 sterol-to-sterolin
mixture may actually provide as unbalanced
a ratio as 200:1 or 500:1 in the body --
ratios far lower than those required for
optimal immune enhancement21.
These products are not useless, but they do
not live up to the potential of a more
natural phytosterol supplement. A ratio of
one milligram of sitosterols to 5-10
Women who get more
phytosterols in their diet
are less likely to develop
breast cancer.
pg.13
milligrams of plant sterols is optimal,
according to Dr. Karl Pegel of the
University of Natal, one foremost
authorities on the role of phytosterols in
human nutrition. These ratios can be
achieved by using a solvent-free,
whole-food plant extraction process
from sprouts. Studies performed at Pegel’s
institution affirm the higher
bioavailability of whole-food,
sprout-extracted phytosterols: such
sources have a bioavailability of 80% or
more, as compared to a much lower
bioavailability for other extraction
processes. Reports on the bioavailability of
unnaturally isolated phytosterols suggest
that their absorption may be as little as
5%25!
Coenzyme Q10 is a powerful fat-soluble
antioxidant which protects membranes
from free radicals and recycles the
vitamin E complex vitamins
(tocopherols and tocotrienols) to their
active antioxidant form after they are put
out of commission in fighting free radical
attackers. More importantly, it is
absolutely necessary to the body’s
ability to produce cellular energy in the
mitochondria -- the power plants of every
cell in your body. Without CoQ, cells
cannot produce the energy they need to
perform their functions, be they immune,
brain, or muscle cells. CoQ is most
well-known for its use in nutritional
support for heart disease -- especially
congestive heart failure. Thirty-four
controlled trials, as well as a multitude of
animal experiments and open trials, attest
to its power to rejuvenate the aging
heart26.
To get results from CoQ, however, one
must not just swallow a pill, but get the
CoQ10 into one’s system and into the
mitochondria where it is needed. Research
by Karl Folkers and Peter Langsjoen
established early on that a key plasma level
of 2.5 micrograms per milliliter is
required to see results inadvanced
cardiomyopathy27, 28. But achieving this
optimal level is harder than you might
New Salvos
think. Thus, some clinical trials using as
much as 200 mg of dry capsule CoQ10
daily have failed to raise levels to this
key therapeutic threshold29a. Another
study29b showed how much variation there
can be between individuals: subjects were
administered 300 mg CoQ daily as dry
capsules, and their plasma levels tested.
On average, this brought CoQ levels to 2.76
micg/mL, which is in the optimal zone;
however, the plasma levels of
varied wildly: while one subject
taking this high-dose dry capsule CoQ
increased his plasma levels to 5.44
micg/mL, another subject only
achieved plasma levels of 1.38
micg/mL!
This low absorption is due to way the body
must handle fat-soluble nutrients like
CoQ. As a fat-soluble compound, CoQ10
cannot pass directly into the blood, but
must first be dissolved in some fat. The
dissolved CoQ is then absorbed with the
fat, using micelles, which are tiny
absorption “packets” formed from bile.
But because of the high melting point
(48°) and relatively poor solubility of
CoQ, and because the digestive system
destroys some of the CoQ10 along the
way, it is difficult to ensure that much of
the CoQ in dry capsules will actually be
dissolved, even when taken with a fatty
meal. Further, because individuals vary
in bile secretion and intestinal
absorption, even well-dissolved CoQ may
not be taken up adequately by many.
The best way around these problems is
to enclose the CoQ10 in tiny
microspheres called . Liposomes
are microscopic membranes composed of
two layers of phospholipids (like
phosphatidylcholine (PC) and
phosphatidylserine (PS)). They are
similar to micelles, and also not unlike a
simplified version of the membrane of the
cell. Because they are soluble in water,
liposomes do not require dissolution in fat,
bile secretion, or micelle formation;
instead, liposomes pass almost directly
from the gut, through the intestinal wall,
and into the blood, bringing their CoQ
payload with them. Liposomes also
protect much of the CoQ10 from being
lost to digestive juices.
Just how effective are liposomes at getting
CoQ10 where it has to go? Research
performed by Dr. William V. Judy30, veteran
CoQ10 researcher31, 32, found that in just one
month, 90 mg a day of liposomal CoQ10
can raise plasma levels to 2.64
micrograms per milliliter -- levels barely
achieved using 600 mg of dry capsule
CoQ daily for eleven days29c, and not
achieved in in some studies
using 200 mg29a! The liposomal system not
only worked much better than dry capsules,
but also better than 90% of other
CoQs: better than softgels made by simply
dissolving CoQ in oil, and even better than
a micronized, hydrosoluble CoQ gel
capsule formula. Clearly, liposomal CoQ
helps ensure that you get the full
benefits of CoQ10.
Although new to Canadian health
consumers (it was first introduced to the
Canadian market in September of 1998),
Pantethine has been used in Italy, the
United States, and Japan since the 1980s,
primarily as a way to safely and effectively
support healthy cholesterol balance.
Pantethine is not the same as
pantothenic acid (vitamin B5), but they
are related: Pantethine is the active
coenzyme form of this vitamin. The body
doesn’t actually use pantothenic acid itself
to do anything; instead, it must convert
pantothenic acid into Pantethine to unlock
its potential. Pantethine, in turn, is the
active part of Coenzyme A (CoA). CoA
is everywhere in the body, and is involved in
many vital biological processes, from
energy production and fat metabolism,
to liver detoxification and the body’s
control of cholesterol synthesis . It’s an
exciting molecule which plays a key role in
human health.
The trouble is that the body’s ability to
make Pantethine from vitamin B5 is
very limited. Each person’s genes (and, to
a lesser extent, diet) places a “ceiling” on
how much Pantethine they will make at
any given time. But many people’s internal
Pantethine-making machinery runs at
far too low a level for optimal health.
The most extensively-researched example
of this is in Pantethine’s effects on
cholesterol. No amount of pantothenic
acid has significant impact on cholesterol
levels, precisely because the amount of
Pantethine a given person makes from B5
is held under tight genetic control. Thus,
some people’s Pantethine levels are already
high enough to keep their blood lipids in
healthy balance, and taking more B5
doesn’t change this fact; while others don’t
produce enough Pantethine to help
support cardiovascular health -- and taking
more B5 doesn’t change that, either.
Fortunately, if you have a Pantethinemaking
“deficiency,” you can add more
Pantethine into your system in the
form of a Pantethine dietary supplement,
thus correcting for an unhealthily low
steady state level.
A wealth of clinical evidence33-47, 51 shows
that pantethine supplementation
supports healthy cholesterol balance. In
adults33-46, 51 and children40, 47, in all tested
forms of dyslipidemia34, 42, 44, 45, 51 (Pantethine
has not been tested against the rare
Fredrickson’s Type I and V subgroups,
which develop pancreatitis rather than
cardiovascular disease), in dialysis patients35,
41 and diabetics34, 35, 38, 45, 46, as well as
survivors of previous heart attacks43,
Pantethine has proven itself to be a safe
and effective modulator of cholesterol
levels. The clinical trials have consistently
reported that subjects taking Pantethine
have lower total cholesterol, LDL, and
VLDL, but higher HDL; further,
Pantethine lowers triglycerides, a lipid
risk factor which is coming to the forefront
of health concern. Patients in one
double-blind, controlled crossover trial44
experienced decreases of 13.5% in total
cholesterol and LDL, while their in HDL
levels rose by 10%. While taking
Pantethine, patients also had decreases of
pg.14
N ew
Suppleme
Revie
13 to 30% in triglycerides, depending on
what sort of lipid disorder they had. The
other trials have reported similar results.
Pantethine also supports heart health in
other ways. It makes LDL cholesterol
less subject to attack by free radicals
mediated by copper48. This is important,
because we now know that LDL is much
more likely to be deposited in the arteries
when it becomes oxidized. Pantethine also
changes the EFA balance in platelets,
increasing their omega-3 content and
lowering their omega-650, 51; this may also
be important, because omega-6 EFAs in
platelets are more likely to cause blood
clots (thrombi), thus triggering a heart
attack or stroke, while omega-3s tend to
block this tendency52.
Science is acquiring knowledge at an
accelerating rate: today, our store of basic
biomedical knowledge is doubling every
three-and-a-half years. Advanced
Orthomolecular Research is committed
to keeping you up to date on the newest
developments, and of translating new
discoveries about natural substances into
usable nutraceutical technology.
Each capsule of Natur•Leaf™ contains 300mg of natural plant sterols and sitosterolins, plus 50mg of
enzymes. The 300mg sterols/sitosterolin blend comes from whole plant sprouts, which have been ground and
freeze-dried immediately after harvesting at a hydroponics farm in South Africa.
-p with a guarantee by Natal University of 80%-90% bioavailablilty. So,
in addition to the sterols andsitosterolins, the capsules contain vitamins, minerals and other
phytochemicals associated with the young plant sprouts.
The ratio of the sterols to their glucosides (sitosterolins) in Natur•Leaf™ is about 6:1, derived from a
variety of sprouts with natural ratios varying from 10:1 to 4:1. This ratio is important to understand,
becasue it is what is , with no introduction of outside glucosides (sitosterolins) to sterols. Other
sterol/sitosterolin products are derived from a chemical extraction process which eliminates or destroys the
glucosides, thus requiring an outside glucoside source to be added to the product.
•
• •
• •
Behold...
•
To the best of our knowledge, there is on other sterolin product on the earth which is more concentrated in its
sterol/glucoside ratio than Natur • Leaf™, and which offers such a high percentage of biovailability.
Holistic International is always one step ahead of the competition when it comes to new and innovative products. We were
the first to introduce to the Canadian market such products as Pantehtine, SAMet and Glucosamine Sulphate. For more
information on such ground- breaking products, give us a call and stock your shelves with tried and true quality!
Processing method affects whey protein
quality. Ion-exchange extraction,
although yeilding a high percentage of
protein, also reduces the amount of
important immune-enhancing peptides
(such as lactoferrin and glycomacropeptides)
and the highestquality
protein fraction (alphalactalbumin).
Ultrafilered wheys
preserve more of these important components
intact. Know what your buying!
Green Mussel Lipid Extract
1. Kremer JM. n-3 fatty acid supplements in rheumatoid arthritis. Am
J Clin Nutr. 2000 Jan; 71(1 Suppl):349S-51S.
2. Sperling RI. Eicosanoids in rheumatoid arthritis. Rheum Dis Clin
North Am. 1995 Aug; 21(3): 741-58.
3. Grignani G, Zucchella M, Belai Beyene N, Brocchieri A, Saporiti
A, Cherie Ligniere EL. Levels of different metabolites of arachidonic
acid in synovial fluid of patients with arthrosis or rheumatoid arthritis.
Minerva Med. 1996 Mar; 87(3): 75-9.
4. Gursel T, Firat S, Ercan ZS. Increased serum leukotriene B4 level
in the active stage of rheumatoid arthritis in children. Prostaglandins
Leukot Essent Fatty Acids. 1997 Mar; 56(3): 205-7.
5. Szczeklik A, Stevenson DD. Aspirin-induced asthma: advances in
pathogenesis and management. J Allergy Clin Immunol. 1999 Jul;
104(1): 5-13.
6. Henderson WR Jr. The role of leukotrienes in inflammation. Ann
Intern Med. 1994 Nov 1; 121(9): 684-97.
7. Whitehouse MW, Roberts MS, Brooks PM. Over the counter
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8. Gibson SLM, Gibson RG. The treatment of arthritis with a lipid
extract of Perna canaliculus: a randomized trial. Compl Ther Med.
1998; 6: 122-6.
9. Nie D, Tang K, Szekeres K, Li L, Honn KV. Eicosanoid
regulation of angiogenesis in human prostate carcinoma and its therapeutic
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10. Tang K, Honn KV. 12(S)-HETE in cancer metastasis. Adv Exp
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11. Tang DG, Chen YQ, Honn KV. Arachidonate lipoxygenases as
essential regulators of cell survival and apoptosis.PNAS. 1996 May
28; 93(11): 5241-6.
11a. Masters, C. The cure for cancer? The New Zealand Herald,
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Phytosterols
12. Wilt TJ, MacDonald R, Ishani A. beta-sitosterol for the treatment
of benign prostatic hyperplasia: a systematic review. BJU Int. 1999 Jun;
83(9): 976-83.
13. Awad AB, Downie A, Fink CS, Kim U. Dietary phytosterol
inhibits the growth and metastasis of MDA-MB-231 human
breast cancer cells grown in SCID mice. Anticancer Res. 2000
Mar-Apr; 20(2A): 821-4.
14. von Holtz RL, Fink CS, Awad AB. beta-Sitosterol activates the
sphingomyelin cycle and induces apoptosis in LNCaP
human prostate cancer cells. Nutr Cancer. 1998; 32(1): 8-12.
15. Awad AB, von Holtz RL, Cone JP, Fink CS, Chen YC.
beta-Sitosterol inhibits growth of HT-29 human colon cancer cells by
activating the sphingomyelin cycle. Anticancer Res. 1998 Jan-Feb;
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16. Ramakrishanamacharya CH, Krishnaswamy MR, Rao RB,
Viswanathan S. Anti-inflammatory efficacy of Melothria
madraspatana in active rheumatoid arthritis. Clin Rheumatol. 1996
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17. Zorn J. New aspects in rheumatism therapy. Experiences with a
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32(4): 135-8.
18. Law M. Plant sterol and stanol margarines and health. BMJ. 2000
Mar 25; 320(7238):861-4.
19. Sutherland WH, Scott RS, Lintott CJ, Robertson MC, Stapely
SA, Cox C. Plasma non-cholesterol sterols in patients with non-insulin
dependent diabetes mellitus. Horm Metab Res. 1992 Apr;24(4):172-5.
20. Ivorra MD, DO’Con MP, Paya M, Villar A. Anti-hyperglycemica
and insulin releasing effects of beta-sitosterol 3-B-D-glucoside and its
aglycone beta-sitosterol. Arch Int Pharmacodyn Ther. 1988 April; 296:
224-31.
21. Bouic PJ, Etsebeth S, Liebenberg RW, Albrecht CF, Pegel K, Van
Jaarsveld PP. beta-Sitosterol and beta-sitosterol glucoside stimulate
human peripheral blood lymphocyte proliferation: implications for their
use as an immunomodulatoryvitamin combination. Int J
Immunopharmacol. 1996 Dec; 18(12):693-700.
22. Ronco A, De Stefani E, Boffetta P, Deneo-Pellegrini H,
Mendilaharsu M, Leborgne F. Vegetables, fruits, and related nutrients
and risk of breast cancer: a case-control study in Uruguay. Nutr Cancer.
1999; 35(2): 111-9.
23. Gupta MB, Nath R, Srivastava N, Shanker K, Kishor K,
Bhargava KP. Anti-inflammatory and antipyretic activities of beta-sitos
terol. Planta Med. 1980 Jun; 39(2): 157-63.
24. Pegel KH. The importance of sitosterol and sitosterolin in human
and animal nutrition. S Afr J Sci. 1997 June; 93: 263-8.
25. Salen G, Ahrens EH Jr, Grundy SM. Metabolism of beta-sitosterol
in man. J Clin Invest. 1970 May; 49(5): 952-67.
CoQ10
26. Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in
cardiovascular disease. Biofactors. 1999; 9(2-4): 273-84.
27. Langsjoen PH, Folkers K, Lyson K, Muratsu K, Lyson T,
Langsjoen P. Effective and safe therapy with coenzyme Q10 for cardiomyopathy.
Klin Wochenschr. 1988 Jul 1; 66(13): 583-90.
28. Langsjoen PH, Langsjoen PH, Folkers K. Long-term efficacy and
safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy.
Am J Cardiol. 1990 Feb 15; 65(7): 521-3.
29a. Khatta M, Alexander BS, Krichten CM, Fisher ML,
Freudenberger R, Robinson SW, Gottlieb SS. The effect of coenzyme
Q10 in patients with congestive heart failure. Ann Intern Med. 2000
Apr 18; 132(8): 636-40.
29b. Mohr D, Bowry VW, Stocker R. Dietary supplementation with
coenzyme Q10 results in increased levels of ubiquinol-10 within
circulating lipoproteins and increased resistance of human low-density
lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta.
1992 Jun 26; 1126(3): 247-54.
29c. Shults CW, Beal MF, Fontaine D, Nakano K, Haas RH.
Absorption, tolerability, and effects on mitochondrial activity of oral
coenzyme Q10 in parkinsonian patients. Neurology. 1998 Mar; 50(3):
793-5.
30. Judy WV. “Coenzyme Q10 absorption study (Jarrow Formulas).”
and “Dry powder and softgel CoQ10 formulations: absorption studies.”
1999; Southeastern Institute of Biomedical Reasearch: Bradenton, FL.
31. Folkers K, Brown R, Judy WV, Morita M. Survival of cancer
patients on therapy with coenzyme Q10. Biochem Biophys Res Commun.
1993 Apr 15; 92(1): 241-5.
32. Judy WV, Stogsdill WW, Folkers K. Myocardial preservation by
therapy with coenzyme Q10 during heart surgery. Clin Investig. 1993;
71(8 Suppl): S155-61.
Pantethine
33. Nomura H, Kimura Y, Okamoto O, Shiraishi G. Effects of
antihyperlipidemic drugs and diet plus exercise therapy in the treatment
of patients with moderate hypercholesterolemia. Clin Ther. 1996 May-
Jun; 18(3): 477-82.
34: Tonutti L, Taboga C, Noacco C. Comparison of the efficacy of
pantethine, acipimox, and bezafibrate on plasma lipids and index of
cardiovascular risk in diabetics with dyslipidemia. Minerva Med. 1991
Oct; 82(10): 657-63.
35: Coronel F, Tornero F, Torrente J, Naranjo P, De Oleo P, Macia
M, Barrientos A. Treatment of hyperlipemia in diabetic patients on
dialysis with a physiological substance. Am J Nephrol. 1991; 11(1): 32-
6.
36: Binaghi P, Cellina G, Lo Cicero G, Bruschi F, Porcaro E, Penotti
M. Evaluation of the cholesterol-lowering effectiveness of pantethine in
women in perimenopausal age. Minerva Med. 1990 Jun; 81(6): 475-9.
37: Lu ZL. A double-blind clinical trial--the effects of pantethine on
serum lipids in patients with hyperlipidemia&91;.Chung Hua Hsin Hsueh
Kuan Ping Tsa Chih. 1989 Aug; 17(4): 221-3.
38: Donati C, Bertieri RS, Barbi G. Pantethine, diabetes mellitus and
atherosclerosis. Clinical study of 1045 patients. Clin Ter. 1989 Mar
31; 128(6): 411-22.
39: Borets VM, Lis MA, Pyrochkin VM, Kishkovich VP, Butkevich
ND. Therapeutic efficacy of pantothenic acid preparations in ischemic
heart disease patients. Vopr Pitan. 1987 Mar-Apr; (2): 15-7
40: Bertolini S, Donati C, Elicio N, Daga A, Cuzzolaro S,
Marcenaro A, Saturnino M, Balestreri R. Lipoprotein changes induced
by pantethine in hyperlipoproteinemic patients: adults and children. Int J
Clin Pharmacol Ther Toxicol. 1986 Nov; 24(11): 630-7.
41: Donati C, Barbi G, Cairo G, Prati GF, Degli Esposti E.
Pantethine improves the lipid abnormalities of chronic hemodialysis
patients: results of a multicenter clinical trial. Clin Nephrol. 1986 Feb;
25(2): 70-4.
42: Arsenio L, Bodria P, Magnati G, Strata A, Trovato R.
Effectiveness of long-term treatment with pantethine in patients with dys
lipidemia. Clin Ther. 1986; 8(5): 537-45.
43: Murai A, Miyahara T, Tanaka T, Sako Y, Nishimura N,
Kameyama M. The effects of pantethine on lipid and lipoprotein
abnormalities in survivors of cerebral infarction. Artery. 1985; 12(4):
234-43.
44: Gaddi A, Descovich GC, Noseda G, Fragiacomo C, Colombo L,
Craveri A, Montanari G, Sirtori CR. Controlled evaluation of pantethine,
a natural hypolipidemic compound, in patients with different
forms of hyperlipoproteinemia.Atherosclerosis. 1984 Jan; 50(1): 73-83.
45: Arsenio L, Caronna S, Lateana M, Magnati G, Strata A,
Zammarchi G. Hyperlipidemia, diabetes and atherosclerosis: efficacy of
treatment with pantethine. Acta Biomed Ateneo Parmense. 1984;
55(1): 25-42
46: Eto M, Watanabe K, Chonan N, Ishii K. Lowering effect of
pantethine on plasma beta-thromboglobulin and lipids in
diabetes mellitus. Artery. 1987; 15(1): 1-12.
47: Hoeg JM. Pharmacologic and surgical treatment of dyslipidemic children
and adolescents. Ann N Y Acad Sci. 1991; 623: 275-84.
48:Bon GB, Cazzolato G, Zago S, Avogaro P. Effects of pantethine
on in-vitro peroxidation of low density lipoproteins.
Atherosclerosis. 1985 Oct; 57(1): 99-106.
49: Vecsei L, Widerlov E. Preclinical and clinical studies with cysteamine
and pantethine related to the central nervous system. Prog
Neuropsychopharmacol Biol Psychiatry. 1990; 14(6): 835-62.
50: Prisco D, Rogasi PG, Matucci M, Paniccia R, Abbate R, Gensini
GF, Neri Serneri GG. Effect of oral treatment with pantethine on
platelet and plasma phospholipids in IIa hyperlipoproteinemia.
Angiology. 1987 Mar; 38(3): 241-7.
51: Gensini GF, Prisco D, Rogasi PG, Matucci M, Neri Serneri GG.
Changes in fatty acid composition of the single platelet phospholipids
induced by pantethine treatment. Int J Clin Pharmacol Res.
1985;5(5):309-18.
52: Ponte E, Cafagna D, Balbi M. Cardiovascular disease and
omega-3 fatty acids. Minerva Med. 1997 Sep; 88(9): 343-53.
N ew
Suppleme
Revie
pg.16
New Salvos
References
The raw material is flash-freeze-dried to
ensure potency. It is simply false to claim
that freeze drying causes protein
denaturation; in fact, the exact opposite is
the case! It is heat, not cold, which causes
protein denaturation; freeze-drying is the
preferred way of drying everything from in
backpacking foods to samples used in
scientific studies for exactly this reason.
Freeze-drying is done precisely because
it guards intact of the
immune-enhancing proteins from
denaturation, and preserves more of the
essential components of colostrum, than
does drying using either heat long drying
periods. Likewise, we do not use any
chemical solvents in the processing of
our colostrum. Since heat, long drying
periods, and solvents are the only ways
other than freeze-drying to provide a
properly dried product, this makes a
freeze-dried, high-quality, North American
product the clear choice for potency -- from
the dairy all the way to you.
Q: How do you pronounce “Jarrow”?
A: Good question! The “Jarrow” in
“Jarrow Formulas” and “JarroDophilus”
does not refer to the sticks used to throw the
I Ching, but to the founder of the company:
Jarrow Rogovin. Mr. Rogovin pronounces
his name with a hard “J,” not a soft “Y.”
We want to hear from you!
Send all questions to:
“I want to know” column
Holistic International
c/o The Holistic Lifestyle
Box: 92 4404 12 Street N.E.
Calgary Alberta
T2E 6K9
Canada
Don’t forget to include your name and location.
Q: Another company has been
spreading around copies of a flyer on
colostrum. It makes some pretty wild
claims! Can you comment?
A: The flyer makes some good points
about quality issues in colostrum, but also
spreads a great deal of misinformation, and
makes comments which apply to other
colostrum sources, but not to ours. The raw
material for our All-Life Colostrum and
Jarrow Formulas’ Colostrum Specific
comes from a North American source. This
source provides us with colostrum from
cows which are free-range fed, not
exposed to rBGH or BST, are not
routinely treated with antibiotics, etc.
Further, the raw colostrum is processed
under cGMP conditions. In these
respects, our colostrum is produced and
processed using methods identical to those
in New Zealand-sourced material.
However, there is one key difference
between the colostrum used in our product
and that from New Zealand: namely, the
superiority of the colostrum produced at
more extreme latitudes. Harsher winter
conditions cause cattle to produce greater
levels of immune-supporting compounds
than they do in more temperate zones. As a
result, All-Life Colostrum contains 25%
more immunoglobulins (Igs) than are
typically present in New Zealand
colostrum. Since boosting our levels of
such immune-supporting proteins is the
entire point of taking a colostrum
supplement, this makes colder-climate
colostrum the clear choice for supporting
health.
The satisfaction of a pasta meal... and the
nodding off three hours later. The rush of a
quick sugar fix ... and the crash when it’s all
burned up. The bulging waistline. The stern
look from your doctor. The craving for carb.
Blood glucose is needed to fuel our brains and
provide easily accessible energy. But carb is
like a drug: it’s addictive, it’s got side effects,
and it’s got a real withdrawal syndrome. The
mills of the agrobusiness have pumped us full
of high-glycemic carb for decades, until we’ve
become sugar junkies,strung out on carb.
Glucose Optimizer is formulated to deliver
nutrients and herbs which help fight the sugar
fix.
Supports healthy insulin function
Reduces enzyme warping by sugars (AGEs)
Helps with blood sugar balance
A wide variety of Jarrow Formulations™ products are available through Holistic International™.
For more information refer to this years catalogue and see what else they’ve got in store!
pg.17
Lyprinol
A wonder from the sea:
a rare omega-3 fatty acid
supplement from the
Austrialian green-liped
mussel.
Natur • Leaf
Phytosterol supplement
with natural ratios of
sterols and sterolins.
Very well-absorbed.
Maxxum 4
Our best multivitamin/
multimineral, with a full
spectrum of antioxidant
carotenoids. Includes
natural beta-carotene!
Think-Well
Hard-to-find “smart
nutrients” like Choline
Alfoscerate, vinpocetine,
huperzine A, and more!
Q-Sorb
Pharmaceutical-grade
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Maximun absorption for
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Acti-Cyclase
Contains forskolin, of a
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Decades of research and
Ayurvedic tradition.
Check out the next generation of
cutting-edge supplements...
Access to the internet means fast access to an awesome amount of information. The internet
opens us up to a new world of free-flowing ideas about health and fitness, unfiltered by official
approval from the usual sources: government, the medical establishment, and the media. And
just in time: the last decade has seen an explosion in the number of people are looking for new
information on health and nutrition.
But the internet’s very freedom means that the quality of the information is mixed. The world
wide web feeds our information hunger, but the new “marketplace of ideas,” like a grocery
megastore, can be overwhelming and hard to navigate; more importantly, it offers a lot more
“junk food” information than wholesome fare. Health-conscious people want to know: “where
can I get the information that matters most? Where will I find readable, cutting-edge
summaries of new research on natural health products -- supplements that can support me in
sickness and in health?”
At Holistic International, we’re committed to providing just that. We’ve worked to make
www.holisticinternational.com
a reliable source of quality information on the most advanced nutritional supplements
available.
Cut through the tangles of the web. Find the center of the labyrinth. Visit our site today.
pg.18
HEALTH ON THE INTERNET
Finding your way or stuck in the maze?
The old health care paradigm is dying. We
don’t look at our doctors as gods anymore.
In the new paradigm, each of us, as an
individual, is taking more responsibility for
his or her own health. We’re eating right,
exercising, and taking supplements to keep
healthy; we’re reading, talking, trying new
approaches, and questioning conventional
wisdom.
Unfortunately, many of us find that
old-school doctors are more of an impediment
to this process than a help. Healthconscious
individuals need the kind of
physician that supports our health
pro-actively, rather than waiting until we’re
are sick and pumping us full of drugs. We
need doctors who respect our health
freedom, and want to work with us to
maintain or restore our health. Most of all,
we want a physician who understands the
healing power of Nature, and who is keeping
up with the cresting wave of research into
nutrients and herbs and their role in
keeping us youthful, vibrant, and alive.
Holistic International is in contact with a
network of such physicians. While we
cannot look into the practices of each of
these doctors individually, and cannot
reccomend or endorse any one of them,
they have all committed to supporting the
health of their patients through safe,
natural approaches. If you’re having trouble
finding a doctor that can really support
your health decisions and work with you to
bring you to a personal health peak, these
physicians are a good place to start looking.
Call us at 1-403-250-9997, and we’ll help
you find some of the integrative physicians
-- Naturophathic Doctors, Doctors of
Chiropractic, and nutritionally-oriented
MDs -- closest to you.
ADoctor from
the New
Schoo
has generated a lot of excitement,
and with good reason: it’s an incredibly
powerful antioxidant (the head of the
body’s antioxidant network) which detoxifies
the liver, improves insulin function and blood
sugar levels, and makes old mitochondria
(cellular “power plants”) act young again.
The good news is, it’s quickly and efficiently
absorbed into tissues; the bad news is, studies
show that it’s just as quickly flushed back
out again, leaving you back where you started
from in as little as an hour and a half!
There’s two solutions to this problem: take
your lipoic acid six to ten times a day, or take
our new formula.
is a true sustained-release lipoic acid, providing
continous protection over a six hour delivery
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oe
r i ic Acid love y a d l ave you?
her do sage a r e v ue
• ha m c tical - gr ade raw a r
r
u l ustaine -re a e sy tem.

]]> http://www.vitaminpost.ca/news/164/Latest-Science-in-Vitamin-%26-Mineral-Research-.html Sun, 12 Jul 2009 04:59:58 +0000 http://www.vitaminpost.ca/news/164/Latest-Science-in-Vitamin-%26-Mineral-Research-.html pg. 1 ADVANCES in orthomolecular research
Call it the supplement paradox.
A huge body of careful, prospective scientific research into
the relationship between peoples’ lifestyles and their longterm
health has confirmed, again and again, that eating a
diet rich in fruits and vegetables will lead you to a longer
life, and lower your risk of chronic disease.
The most obvious thing about such diets is that they’re rich in
essential vitamins and minerals. And yet time and time
again, controlled clinical trials of nutritional
supplementation with vitamin and minerals – including key
antioxidant nutrients like “vitamin E,” vitamin C, and
beta-carotene – has failed to protect people from killer
diseases.
Whether it’s “vitamin E” against heart disease,1 or betacarotene
against cancer,2-4 or antioxidant “cocktails” against
atherosclerosis5 or death from any cause,6,7 again and again
the results have come back negative. Either there’s no effect
at all … or the results are too ambiguous to pin your hopes
on … or there’s been a suggestion that the people taking
their assigned pills were worse off than people taking the
placebo stand-ins.
It’s a pretty sad record.
How can this be? Before the results of these trials came in,
many health-conscious people had their faith in their
multivitamins boosted by the simple fact that these trials had
even managed to get off the ground in the face of extreme
skepticism from much of the medical establishment. Now
those skeptics feel justified in their condescension – and the
forces that oppose health freedom have been given
ammunition in their anti-supplement attacks.
The reaction from most supplement companies has been
disappointing. Many companies are in the business for no
other reason than to make a quick buck, and have chosen to
simply ignore these trials, hoping that the unsettling results
will not reach the ears of their customers and cut off access
to a reliable cash cow. Other companies are sincere in their
belief in the value of supplementation – but they base this
belief on blind faith, playing hear no evil, see no evil when
large-scale, carefully-controlled, rigorous clinical studies fail
to confirm a pre-established credo. Such companies have
failed to respond to the latest discoveries in the rapidlyaccelerating
field of nutritional science, continuing instead to
design their products based on accepted health-food-store
dogmas.
Health-conscious people can’t afford to be blinded by
wishful thinking, or to rely on formulas based on outmoded
theories and fuzzy-headed, pseudoscientific notions. The
fact is that the conventional wisdom underlying ‘basic’
nutritional supplementation has been disproved. If we
are to gain the benefits that we expect from our
supplement programs, we have to be ready to listen to what
science is actually saying today instead of what it suggested
twenty years ago.We will have to clear the ground, looking
at the science with our old blinders removed, questioning our
assumptions, turning over the graves of the ‘authorities’ of
yesteryear, and laying the foundation for a genuinely new
approach to nutritional supplementation.
Latest Science in
Vitamin & Mineral
Principles In Formulating The
Optimal Multi
Nutritional supplementation with
“vitamin E,” vitamin C,
and beta-carotene –
has failed to protect
people from killer diseases
But where to begin? With what we already know. We know
that healthy diets support longer, healthier life. And we know
that supplements based on old-school thinking do not. Once
we accept these two facts, the way forward becomes clear:
compare the contents of a health-promoting diet to typical
multivitamin/multinutrient products, and see what’s so
fundamentally different between the two. And once you
start looking, the contrast is so sharp that it strikes you like
a barrel of ice water. Multivitamin supplements which should
have been designed to be, in effect, super-concentrated
versions of an optimal diet are revealed instead to be gross
caricatures of those diets, distorting and unbalancing the real
picture of preventive nutrition.
Let’s see where previous products have gone wrong … and
how we can get it right for the future.
First, Do No Harm
The most extreme disconnect between health-giving foods
and badly-designed pills, is cases where a multivitamin not
only doesn’t protect the health of its users, but actively harms
them. We are accustomed to thinking of nutritional
supplements as fundamentally safe; and certainly, no
multivitamin has ever caused the kind of killer toxicity we
see from some xenobiotic drugs (except in cases of
overdose resulting from sloppy manufacturing, or from
accidental or intentional swallowing of too many pills). But
there’s now strong evidence that nearly all multivitamin
products contain one or more nutrient overdoses or
imbalances extreme enough to cause real, long-term
damage to the health of those swallowing them.
One well-documented, crippling result of long-term, chronic
supplement overdose is the association between excessive
preformed vitamin A (retinol/retinyl esters) and the loss
of bone health. It’s long been known, from animal studies,
that getting too much vitamin A is bad for the skeletal
system. In recent years, these findings have been confirmed
in humans. Several large, well-designed population studies
(and a few smaller and less rigorous ones) have now
reported that men and women with the highest intake8,9
or serum levels10,11 of retinol are at the greatest risk of
suffering a fracture; taking in the most retinol also
associates with having the lowest bone mineral density
(BMD).8,12-14 (It’s important to understand that this refers to
preformed vitamin A: beta-carotene and other ‘provitamin
A’ carotenoids have not been associated with loss of
bone health).
Frighteningly, the amount of preformed vitamin A which
these studies have found to put consumers at risk of broken
bones is right in the ballpark found in many – and perhaps
most – multivitamins: “just” 1.5 milligrams (5000 IU) in one
study,8 and a similar 6 600 IU in another9 is enough to
roughly double your risk of a fracture. It’s extremely
unlikely that you’d get dosages like these from food – you’d
have to spend all day gorging on liver, eggs, and fortified
milk – but it’s all too easy to exceed the safety limit if you’re
taking the kind of multivitamin designed around an
unthinking ‘more is better’ paradigm. And indeed, nearly no
one in these studies would have reached the extreme levels
of intake associated with increased fracture risk if it were
not for the badly thought-out supplements they were letting
into their systems.
But this doesn’t mean that you should avoid all intake of
retinol, or depend entirely on carotenoids to get your
vitamin A. The rate of conversion of “provitamin A”
carotenoids into retinol varies nearly ninefold from person to
person,15 and can be altered by age, genes, body weight,
and alpha-tocopherol intake. Remember that retinol is an
absolutely essential nutrient – and in fact, one of its most
important functions in the body is in normal skeletal
metabolism! Indeed, some of the same studies that
reported the impairment of bone health caused by years of
retinol overdose have found that people with the lowest
vitamin A levels11 or intake12 also suffer an elevated
fracture risk11 and lower BMD.12 It appears that the ideal
retinol intake – from diet and supplements combined – is in
the ballpark of 2000 IU.
But remember that, because of government-mandated
fortification, a single serving of low-fat milk or yogurt
contains between about 500 and 750 IU of vitamin A,
and a standard 85g (3 oz) slice of liver contains an
astounding 22 000 IU!
Men and women with the
of are at the r
of suffering a
So it’s very easy to overshoot your safe vitamin A intake if
your supplement contains more than 1000 IU of retinol. The
goal of supplementation should be to put you into that
happy medium where bone health is optimized; supporting
the balance of the diet instead of overbalancing it with
levels you’d never get from well-chosen foods.
Another source of long-term health theft resulting from
sloppily-designed supplements is overbalanced zinc-tocopper
ratios. The body’s metabolism of these two minerals
is inextricably intertwined because of their similar atomic
structure: they resemble each other so closely that they can
compete with one another for absorption and transport, and
interfere with one another’s binding to enzymes, if one is
present in excess. Getting too much of either nutrient creates
a functional deficiency of the other. So keeping the two
minerals in proper balance is important if you’re going to
reap the health benefits of either – or even to avoid doing
yourself damage.
pg. 3 ADVANCES in orthomolecular research
fig 1. Retinol intake and bone mineral density in the elderly. Modified
from reference 54.
Both animal and human evidence suggests that, for optimal
utilization of both minerals, the balance between zinc and
copper should be about ten-to-one.16 But most supplement
formulators seem to have been dazzled by the exciting
research which documents the importance of getting
adequate zinc in your diet – so much so, that they’ve
ignored the crucial place of copper in the equation. As a
result, it’s common for multivitamins to include very high
doses of zinc, but little or no copper, so that many –
perhaps most – multivitamin and multimineral formulas
contain potentially harmful zinc-to-copper imbalances.
Such imbalances are more than just a theoretical concern. In
a series of human studies, using a ratio between zinc and
copper of 23.5-to-one (and sometimes lower) – common
zinc-to-copper ratios, found in many multivitamins –
resulted in wide-ranging metabolic disturbances,
including reduced levels of the copper-based antioxidants
enzymes cytosolic superoxide dismutase and
ceruloplasmin, high total and LDL (“bad”) cholesterol,
reductions in the body’s levels of enkephalins (natural painkilling
molecules), and abnormal cardiac function (including
rhythm disturbances and even heart attacks)!16-18
And these are just the metabolic derangements observed
over the course of a few weeks or months. Over years of
functional copper deficiency created by excessive zinc
intake, it seems inescapable that other problems known to
result from ‘simple’ copper deficiency – such as impaired
bone metabolism, poor glucose control, and increased
levels of Advanced Glycation Endproducts (AGE) – would
also manifest themselves.
The most bitterly ironic twist in the black comedy of zincmad
pill design has only recently appeared. Many men
take zinc supplements to support the health of their
prostates, because of some evidence suggests that low zinc
levels are associated with prostate cancer and other
prostate disorders.19 But a large new study,20 which tracked
the health habits of nearly 50 000 American male health
professionals for 14 years, found that extreme zinc oversupplementation
was associated with a more than
doubled risk of developing advanced prostate cancer,
especially if continued for more than 10 years.
All of this has lead to alarm amongst researchers who have
devoted their academic careers to documenting the
importance of copper in human health. Dr. Leslie M. Klevay,
for instance, has warned of the “hazards of zinc
supplements.”17 But the problem is not zinc supplements, but
the excessive zinc dosages, and/or unbalanced zinc-tocopper
ratios, found in far too many multivitamins. A
properly-designed core nutritional program will work to
ensure optimal intake of both nutrients – individually, and in
balance.
Yet another example of “megadose mania,” for which the
evidence is disturbing if not yet conclusive, is the probable
neurological damage caused by excessive manganese
supplementation. It’s well-established that workers in
industries where inhaling manganese is common (such as
manganese miners and welders) are at greater risk for
neurological syndromes resembling Parkinson’s disease,
and animal studies clearly show that excessive manganese
intake leads to neurological damage.21 Furthermore, in a
study that compared the level of manganese present in the
drinking water in different communities with the rates of
neurological symptoms amongst their residents,22 it was
found that neurological symptoms were more common
amongst the elderly in high-manganese areas. (Another
study, however, did not report an association23).
But the best evidence that manganese oversupplementation
really is an issue worthy of our concern is
a study which compared the manganese intake from diet
and supplements of people with Parkinson’s disease with
those of people without the disease.24 The study found that
people with high dietary intake of manganese are about
70% more likely to fall prey to this neurological disorder
– and that the risk was further increased among people who
also consumed manganese-containing supplements, or who
also had a very high intake of iron.
It’s not clear exactly how much manganese is too much, in
large part because of the different bioavailabilities and
distribution in the body of manganese coming from fumes,
water, food, and supplements. And it’s hard to detect the
early symptoms of manganese excess, because they are so
nonspecific: loss of appetite, impaired reproduction,
anemia, and retarded growth in children.
A review of the evidence by the National Academy of
Sciences’ Institute of Medicine found that the lowest level of
total manganese intake at which suggestions of harm could
be documented was at manganese intake from diet of 15
milligrams; they cautiously suggest that the safe upper limit
of manganese consumption from all sources is 11 mg.25When
you consider that unusually manganese-rich diets can
contain between 6.325 and 826 milligrams of the mineral, the
idea of adding an additional five, ten, or even more
milligrams of manganese in the form of a badly-thoughtout
multivitamin becomes an increasingly bad notion – yet
such dosages are common.
Again, this doesn’t mean that you should treat manganese
like a nutritional pariah, or a toxin like lead or cadmium.
Manganese is an essential nutrient, needed for healthy skin,
bone, and cartilage, for maintaining glucose tolerance, and
for the formation of the mitochondrial form of the
antioxidant enzyme superoxide dismutase (SOD). But the
bottom line is that there’s no good evidence that getting
more than a few milligrams of manganese makes you any
healthier, and there is some pretty suggestive research
indicating that a very high intake could ultimately do you
harm. It seems clear that supplements should contain enough
manganese to ensure that you aren’t deficient, but not much
more: a couple of milligrams is safe, and will meet your
nutritional needs.
Nutritional Bait-And-Switch
But the problems with multivitamins extend into subtler
territories than frank overdose. Another is using the wrong
molecule. When studies show that people whose diets are
chock-full of some key nutrient are protected against a
ravaging disease, you’d think that it’d be a no-brainer to
create supplements which contain that same nutrient. Far too
often, however, supplement companies have cheated
health-conscious consumers by substituting counterfeit
versions of these molecules for the real thing – versions
with fundamentally different effects on the body.
One example that we’ve previously documented in detail is
lipoic acid: unless they say otherwise, supplement
companies replace R(+)-lipoic acid – the form of this
nutrient produced by the body for its own use – with an
adulterated, 50-50 “racemic mixture” of R(+)-lipoic acid
and the purely artificial S(-)-form of the molecule. Studies
show that the artificial S(-)-lipoic acid is not just less potent
than the natural R(+)-form, but in some cases actually
interferes with, or has the opposite effect of, R(+)-lipoic
acid. (For a review of some of the research on R(+)-lipoic
acid, see “Your Two-Faced Lipoic Acid” in Advances 2(1), or
visit http://www.R-Lipoic.com).
This same problem is common to many keystone nutritional
supplements. One excellent example is beta-carotene. The
studies designed to test the ability of beta-carotene to
prevent cancer and heart disease were based on the very
strong evidence that people whose diets contain more betacarotene
had a lower risk of lung (and other) cancers.27 But
when companies began making beta-carotene supplements,
the form of ‘beta-carotene’ that they produced – and that
was used in nearly all of the trials – was not the same
‘beta-carotene’ that occurs in food.
Beta-carotene from food contains two structural forms
(isomers) of the molecule: all-trans and 9,cis-beta-carotene
(see Figure 1). But the beta-carotene used in nearly all
supplements has been entirely composed of the all-transform
of the molecule.
The difference is important to all of us, not just organic
chemists. Studies have clearly shown that the effects of
natural and synthetic beta-carotene are fundamentally
different. Synthetic beta-carotene has much lower
antioxidant activity;28-30 more alarmingly, studies performed
in human white blood cells have revealed that the synthetic
beta-carotene used in most supplements causes genetic
damage to the cells!31 Natural beta-carotene, by contrast,
does not have this effect.31 So perhaps it’s no surprise that
the studies designed to test the ability of beta-carotene
supplements have actually found that the pills not only fail
to protect users against cancer,2-4 but may actually increase
the cancer risk:2,4 all of these studies used the synthetic, alltrans
form of the molecule.
Another example of molecular mismatch is “vitamin E.”
Numerous studies in the health habits of large populations
have found that the “vitamin E” in food provides protection
against cardiovascular disease (CVD)32-34 and Alzheimer’s
disease.35-37 Yet these same studies have reported that users
of “vitamin E” supplements have not been given protection.32-
37 In fact, a “meta-analysis” study which pooled the results
of 19 high-quality controlled trials found that high-dose
alpha-tocopherol supplements actually increase
mortality in patients with existing cardiovascular disease!1
Scientists now have a very good explanation for this: again,
the “vitamin E” in food is very different from the “vitamin E”
contained in nearly all supplements.
We’re not just talking about the difference between socalled
“natural” “vitamin E” (d-alpha-tocopherol, or more
properly RRR-alpha-tocopherol) and “synthetic” “vitamin E,”
(dl- or all-rac-alpha-tocopherol). The only real difference
between d- and dl-alpha tocopherol is in its strength: it
takes more dl-alpha-tocopherol to get the same effect you
get from d-alpha.38
No, the real distinction between the “vitamin E” you get from
a healthy diet, and the “vitamin E” you’ll find in most pills, is
not one of degree, but of kind. While the “vitamin E” in food
does contain d-alpha-tocopherol, this molecule actually
makes up only a minor fraction of the vitamin E in healthy
diets. “Vitamin E” is not this one molecule, but a complex,
composed of eight distinct molecules – four tocopherols, and
four tocotrienols. And in fact, the single largest amount of
“vitamin E” in healthy diets appears as gamma-tocopherol,
not its alpha cousin.39-43
Again, this isn’t just trivia for biochemistry geeks. The
different members (or “vitamers”) of the E complex have
different functions in the body, just as different B vitamins
do. Recently, the unique properties of gamma-tocopherol,
have become a particular focus of researchers’ attention,44,45
but the unique benefits of the “other” E vitamins are clearly
also important. Some of these unique health properties
were discussed in “There’s No Such Thing as Vitamin E,” in
The Holistic Lifestyle 1(4), and we hope to go into more
detail in a future issue of Advances.
To jump to the punch line, however: these newly-discovered
properties of gamma-tocopherol, tocotrienols, and other
natural E vitamins explain why the “vitamin E” in food
protects against chronic disease where supplements keep
failing.32-37 And indeed, by looking at levels of E vitamers in
the body, the importance of the distinction becomes clear:
high levels of gamma- – and not alpha- – tocopherol is
associated with reduced risk of CVD46-49 and heart attack,50
and that the same is true of prostate cancer.51,52 Likewise,
evidence exists for a selective gamma-tocopherol depletion
in the brains of people with Alzheimer’s
disease.53,54
And the real problem with unbalanced alpha-tocopherol
supplements is not just that they’re missing these other E
vitamers, and therefore fail to provide their unique
benefits. Astoundingly, alpha-tocopherol, at doses typical
of most supplements, actually interferes with the body’s
ability to hold onto and use of the other E complex
members!
Because of its specific importance to reproduction, and
because a natural diet contains comparatively little of this
specific E vitamin, evolution equipped the body to hang onto
its supplies of alpha-tocopherol – even at the expense of
other E vitamins. As a result, when you flood yourself with
unbalanced alpha-tocopherol supplements, you actually
deplete your body of other E-complex members (see
Figure 3).55-59
It doesn’t take a lot of unbalanced alpha-tocopherol to
drive down your gamma-tocopherol supply: five months of
swallowing just 150 IU of isolated alpha-tocopherol per
day robs your body of 63% of its plasma gammatocopherol
levels, leaving you with lower levels than you
would have had if you were taking no supplement at all.55
And the effect can be long-lasting: after one year of highdose
(1200 IU) alpha-tocopherol supplementation, tissue
gamma-tocopherol levels take two years of “cold turkey” to
recover to the level they were at before supplementation
began.58
And don’t think that the “natural mixed tocopherols” added
in as an afterthought to some “vitamin E” supplements will
make up for this imbalance. These products throw in no more
than 20% as much of the tocopherols other than alphatocopherol,
almost as an afterthought – and they contain no
tocotrienols. But it’s been shown that it takes a lot more of
the “other” E vitamins to make up for the alpha-tocopherol
overdoses found in these pills. For example, if you take 371
milligrams of alpha-tocopherol into your body every day,
you’ll still suffer a 30% loss of gamma-tocopherol in plasma
even if you try to balance it out with more than 400
milligrams of gamma-tocopherol and other E complex
members.59
In fact, careful examination of studies involving the
cholesterol-balancing effects of tocotrienols reveals that the
body needs at least twice as much of the “other” E
vitamins to prevent alpha-tocopherol from canceling out
their benefits.60-62 It should come as no surprise that this ratio
is similar to what’s found in a balanced diet of whole
foods.39-43
Yet another example of the kind of nutritional bait-andswitch
at work in common multivitamin formulations is the
ongoing use of inferior forms of selenium. Extensive
research demonstrates that Se-Methylselenocysteine
(SeMC) is the most effective cancer-fighting form of
selenium available.63-65 (We reviewed the revolution in
selenium cancer research of the last decade in the Spring
2003 issue of Advances). Not surprisingly, foods with known
cancer-fighting powers – such as high-selenium broccoli,
garlic, and onions – contain much of their selenium in this
form, whereas selenomethionine and other common selenium
forms predominate in foods like beef and wheat – foods
which are not particularly noted as being protective against
cancer. Yet most companies continue to put
selenomethionine, selenate, selenite, or selenium yeast into
their pills.
extreme zinc
over-supplementation was
associated with a more than
doubled risk of developing advanced
prostate cancer
ADVANCES in orthomolecular research pg. 6
Figure 2: All-trans and 9,cis-beta-carotene.
Take, again, the difference between menatetrenone (MK-
4, the form of vitamin K2 biosynthesized by mammals) and
phylloquinone (vitamin K1 – the form used in nearly all
supplements). We know that menatetrenone delivers
superior skeletal,66 brain,67 and cardiovascular68,69 health
benefits. Yet supplements continue to use vitamin K1 – or
sometimes bacterial menaquinones (such as
menaquinone-7 (MK-7) – the main bacterial form of K2),
which are not the same molecule (see figure 4).
There’s also the greater bioavailability and stronger
clinical evidence for calcium citrate-malate compared with
other vegetarian calcium sources (regular calcium citrate is
not equivalent!70). And we could go into other examples. But
the point, by now, should be obvious. When evidence
suggests that high intakes of a nutrient found in healthy
foods supports vibrant health, make sure that your
supplement contains the same molecule, and not an
impostor or second-best.
Emerging Essentials
Official government nutrition panels recognize only 13
essential vitamins and 15 essential minerals. But in recent
years, it’s become increasingly clear that a few other
substances are just as indispensable for your health. It was
only recently that chromium was recognized by the Institute
of Medicine to be necessary for your health. But the
evidence is compelling that boron, silicon, lithium, and
vanadium are as necessary to your health as the
“official” essential minerals, such as calcium, magnesium,
or zinc, and that a little-known redox factor called
pyrroloquinoline quinone (PQQ) is being considered as a
vitamin just as essential to your health as vitamin C or
pantothenic acid (vitamin B5).
Boron appears to be an essential to normal brain function,71
a key factor in preserving the health of the skeleton and
joints,72 and has been linked to reduced risk of prostate
cancer;73 recent studies in the homeostatic control of boron
concentration in the body74 and in breast milk75 show that the
body is actively regulating levels, demonstrating its
essentiality in the body, and a failure of this control is
observed in mothers who subsequently undergo premature
labor.75
Silicon has been shown to be essential to normal bone
formation in animal studies,76,77 and epidemiological
studies,78 and preliminary clinical trials79 suggest that it builds
stronger bones in humans, too, apparently through a
cofactor role in collagen synthesis. And vanadium appears
to have a key role in thyroid function, as well as having a
“pharmacological” effect on glucose metabolism at
extremely high doses.80
Perhaps the most remarkable rise of a newly-identified
mineral in recent years has been lithium.81 Although most
people think of this mineral as a “drug” to used treat
bipolar disorder, lithium is a trace mineral found in “hard”
water and food: typical diets contain between 0.650 and
3.1 milligrams of lithium per day, coming mostly from
grains and vegetables.
Animal studies have shown that lithium is an essential
mineral in mammals. Lithium-deficient laboratory rodents
have impaired reproductive function and abnormal lipid
metabolism. When USDA scientists sat down to reformulate
the standard rodent chow used in laboratory experiments in
1997, one of the key changes to the diet was to fortify its
lithium content beyond the amount that occurs naturally in
the elements of the diet.81
Similarly, studies in goats show that lithium-deficient animals
suffer depressed immune systems, chronic inflammation,
splenic atrophy, excessive iron buildup in their tissues, and
calcium deposits in their blood vessels; moreover, the
activity of the enzymes involved in their mitochondrial
energy production is depressed, and they develop “benign”
tumors of the breast, salivary glands, and adrenal glands,
as well as ovarian cysts.81
But the most fascinating research on lithium’s role in health
has come from studies comparing the health of people
living in areas with higher and lower amounts of lithium in
the rain or tap water, and individuals with higher and lower
levels of the mineral in their hair, scalp, and urine. These
studies have found that people living in areas with low
lithium have higher rates of neurosis, schizophrenia,
psychosis, psychiatric ward admissions, homicide,
suicide, forcible sexual assault, burglary, and
runaways.81
Supplement companies have
substituted counterfeit
versions with fundamentally different
effects on the body.
Based on the amount of lithium found in typical diets, and
the amounts known to support brain health when consumed
in the diet and drinking water, nutrition researchers are
now suggesting an ‘RDA’ of lithium in the range of 0.400
to 1 milligram per day.81 Lithium supplements are now
becoming more readily available in the United States;
unfortunately, the Canadian authorities continue to insist that
even nutritional doses of organic lithium is a “drug,” and
threaten fines and imprisonment to anyone making it
available except by prescription.
Plant Protectors
The most consistent finding in all of the science of
epidemiology is that diets rich in fruits and vegetables are
associated with reduced risk of cancer, heart disease, and
age-related disability. Fruits and veggies are the best
source of many vitamins and minerals, of course, but there’s
a lot more in a healthy diet than just these essential
nutrients. For more than half a century, scientists have known
that when experimental animals are fed highly-refined
diets which contain all the protein, essential fats, vitamins,
and minerals known to be essential to their normal growth
and development, they are still more vulnerable to cancer
than animals containing similar levels of all essential
nutrients, but composed primarily of unrefined or semirefined
food sources.82-87 The explanation for this
phenomenon lies mostly in phytochemicals.
Strictly speaking, any biologically-active substance
produced in plants can be called a “phytochemical.” But the
term is most often used to refer to those protective, diseasepreventing
bioactive compounds which – while not
“essential” in the same sense as vitamin C or magnesium –
none the less play a major role in the benefits of a good
diet. In recent years, researchers have made rapid strides
in teasing out the biological effects of these biomolecules –
and every now and then, a phytochemical has been
identified as being crucial to the health-promoting effects of
individual foods, or groups of food, which have been
singled out as especially potent medicines in Nature’s
pharmacy. Each of these discoveries reveals a critical
element of good nutrition that has been missing from
narrowly-defined “multivitamin” formulas.
Figure 3: Unbalanced alpha-tocopherol supplements deplete your body of
gamma-tocopherol. Redrawn from (55).
But there are literally thousands of biologically active
substances in plants: over 5 000 have been identified, many
of them only recently.88 But while some of them are
important contributors to the health of people consuming
them, others are needed by the plant, but are of no value
to us when we eat them – and some of these compounds
(even if found in healthy foods) are known to be toxic.
The research on phytochemicals demands a new approach
to nutritional supplementation. Those bioactive plant
molecules which will help you reach a longer, healthier life
need to be identified and placed on the “A” list for the core
nutritional supplement of tomorrow. But other such
compounds are helpful to only a few people with unique
health concerns, and therefore should not be in a
multinutrient formulation designed to be taken by every
health-conscious person. Still others are of no nutritional
value, and ultimately only of interest to agronomists. And a
few are even harmful. So how do you know which is which?
After decades of research, such an “A” list of
phytochemicals has emerged. The process was long and
painstaking, but its conclusions are proportionally solid. It
began by narrowing down the broad category of “fruits
and vegetables,” and carefully looking at which plant foods
have the most consistent associations with good health. The
conclusion: while there are no doubt health benefits from all
fruits and vegetables, and while any given plant food or
phytochemical may catch a headline here and there, the
most powerful, consistent evidence points to cruciferous
vegetables (such as broccoli, cabbage, and mustard
greens); Allium vegetables (such as garlic and onions);
green, leafy vegetables; citrus fruits, tomatoes, carrots,
and raw vegetables generally, as being especially
powerful in promoting good health.89-96
High-dose alpha-tocopherol
supplements actually mortality
When you flood yourself with
unbalanced alpha-tocopherol
supplements, you actually deplete your
body of other E-complex members
0.15
0.14
0.13
0.12
0.11
0.10
0.09
0.08
0.07
0.06
0.05
0.04
0.03
0.02
Plasma γ- Tocopherol (mg/dl)
-4 0 1 3 7 14 21
28 29 30 31 32
36
Days
SUPPLEMENTATION PERIOD
D-α-tocopherol
pg. 7 ADVANCES in orthomolecular research
Researchers next turned their attention to the question of
why these particular plant foods should be more effective in
keeping you healthy than others. In the case of carrots, the
most likely player is its range of mixed carotenoids,
including lutein and alpha-carotene. But they found that the
other fruits and vegetables contain specific phytochemicals
which are either unique to these foods, or are found in much
higher amounts in these plant foods than in others. And by
exploring these phytochemicals’ effects on the body in
experimental animals and cellular studies, science has
vetted a phytochemical dream team.
The key plant bioactives are the isothiocyanates (most
importantly sulforaphane) and indoles (especially indole-
3-carbinol (I3C)), which appear as glucosinolates in
cruciferous vegetables; the Allium vegetables’ allyl
sulfides (the most potent of which is diallyl disulfide
(DADS)); the limonene and related monoterpenes found in
citrus (and especially citrus peel); the lycopene that comes
overwhelmingly from tomatoes and tomato products; transresveratrol,
found in red wine; green tea’s key polyphenol
EgCG; and chlorophyll, which gives the hue to green, leafy
vegetables. (The importance of raw vegetables probably
comes from the fact that the enzymes which liberate
sulforaphane and I3C from their storage forms are
inactivated by longer, higher-temperature cooking, leading
to reduced bioavailability of these cancer-fighting
nutrients97,98). While it’s currently not possible to put all of
these phytochemicals into a single multivitamin formulation
because of various interactions that make some of the
specific combinations technically impossible or undesirable,
it’s clear that a supplement program designed to closely
mimic an optimal diet must include as many of these phytopowerhouses
as possible.
A review of the scientific literature shows how consistently
the consensus has crystallized around the central
importance of these phytochemical elite.90-96 One can
certainly point to still other substances found in plants which
might have health benefits, but none of them have this
powerful weight of epidemiological, experimental,
mechanistic, and in some cases clinical99-101 evidence to back
them.
So, for instance, test-tube studies on the effects of ellagic
acid on DNA adduct formation are intriguing, but no studies
in the health habits of large human populations show that
people consuming lots of ellagic-acid-rich strawberries or
raspberries are less likely to develop cancer than people
eating other fruits and vegetables. The available results are
intriguing – but not strong enough to justify designating it a
critical phytonutrient which should be a part of every
health-conscious person’s supplement program. (In fact, the
same objection applies to many other polyphenols. For one
of the key reasons underlying many such disconnects, see
For Biochemistry Geeks Only!).
There are also many phytochemicals which have benefits to
people with serious health problems – but that aren’t
necessarily helpful to basically-healthy people looking to
further enhance and protect their health. In many cases,
these phytochemicals come from herbs and other botanicals
which are not a part of the regular, habitual diets of
anyone in the world: they should – and traditionally have
been – regarded as medicines for people with specific health
needs, not healthy foods that contribute to the well-being of
health-conscious people.
Figure 4 : Structural representation of Vit K1 and Vitamin K2.
Silymarin from milk thistle, for instance, is of great benefit
to people with some kinds of liver disease, mostly because
it fights the oxidative stress, membrane damage, and
inflammation of the liver that’s associated with cirrhosis
(scarring) of the organ,124,125 and also perhaps by increasing
the amount of protein-biosynthesis “instructions” coming out
of the tissue’s DNA code.125 All of this gives the cirrhotic liver
the opportunity to heal itself – but there’s no evidence that
healthy people, with undamaged livers, will get “superhealthy”
livers by taking this herb.
Since, in fact, we know virtually nothing about the effects of
these kinds of herbs on otherwise-healthy people; it’s hard
to see the idea of taking these powerful extracts regularly
as anything but an unnecessary gamble with your health.
They do not belong in a core multinutrient formulation,
designed to be taken by everybody, every day, for the rest
of your life.
Your Body’s “Detergent”
While these phytochemicals exert a wide range of
important effects on cellular metabolism, most of them share
the common feature that they modulate the balance of the
ADVANCES in orthomolecular research pg. 8
K1
K2
body’s detoxification enzymes. Your body neutralizes toxic
chemicals and many internal waste products using a twostep
biochemical breakdown process. In phase I
detoxification, ‘procarcinogen’ compounds are first made
more chemically reactive using a group of enzymes known
as the cytochrome P450s or mixed-function oxidases.
Think of phase I detoxification enzymes as “agents
provocateurs,” who infiltrate an enemy group to incite the
more dangerous elements in an organization to show their
cards. It’s then the job of the phase II detoxification system
to play the role of more conventional law enforcement,
“arresting” those fired-up (more reactive) “cellular
terrorists” and “handcuffing” them with molecules
(conjugates) that make them easier to safely excrete
through the urine or the bile.
The danger spot is in the step between, in which the
“activated” procarcinogens are potentially even more
dangerous, until they are “handcuffed” by the phase II
system. This is where many phytochemicals lend a hand.
Broadly, many of the best-documented phytochemicals
increase the activity of the phase II system, while reducing
down the activity of phase I. This slows the overproduction
of activated procarcinogens, and ensures that there is
enough phase II activity to ensure that activated
procarcinogens are all bound up and sent packing.126
But of course, for phase II detoxification to take place, your
phase II enzymes need an adequate supply of the
“handcuffs” (conjugates) that render the procarcinogens
tame. So it’s important to ensure that your diet and
supplement program contains plenty of key conjugation
factors such as acetic acid, glycine, taurine,
trimethylglycine, and sulfur sources such as NAcetylcysteine
(NAC).
Random Dosages
Almost every week, a new study comes out linking a diet rich
in some key nutrient with a longer, healthier life. And when
the popular press reports the story, they put it something like
this: “the people whose diets contained the most of this
nutrient were only two-thirds as likely to get breast cancer”
– or heart attack, or Alzheimer’s disease, or any of the
myriad assaults of “normal” aging. The problem with these
stories is that they rarely tell you how much of the nutrient in
question the people eating those diets were consuming. Too
often, in fact, the medical abstracts of the original scientific
papers don’t give you this information either. If you want to
find out, you have to take a jaunt down to a medical library
and dig up the full-text article.
But few people have the time to take this trouble, especially
granted the wide range of individual ingredients in their
core nutrient formulas, plus their “add-on” supplements. So,
most of us depend on the formulators of these products, not
just to include the right ingredients in their products, but to
include a research-backed dose.
Too often, this just doesn’t happen. In fact, comparing major
research papers to the ingredients lists on typical
supplement bottles, you’ll be forced to wonder if the
designers of such products used a dice roll to determine
their dosages.
Let’s take a couple of examples. There is powerful support
for the ability of the carotenoid lycopene to reduce the risk
of cancer – prostate cancer in particular,92,99,100 but also
cancers at many other sites in the body.92 But how much
lycopene is associated with cancer protection? Studies in
large populations show that high-lycopene diets, rich in
tomato paste and other good sources of the carotenoid,
provide from 13127 or 14,128 through 18,129,130 to as high as
24131 milligrams of lycopene a day. (Earlier studies, which
reported lower intakes (such as 6.5132 or 9133 mg/day) were
using an outdated carotenoid database which neglected
many lycopene-containing foods and which relied on an
obsolete analysis method that low-balled the foods’
carotenoid content134,135).
So a supplement designed to support the protective effects
of high-lycopene diets should also contain these same
established, protective amounts. Instead, nearly no
multinutrient products contain more than 3 milligrams of this
crucial carotenoid – and some contain as little as a tenth of
this paltry amount! To put this into its full, damning
perspective: because tomatoes and tomato products are
consumed even by people eating very poor diets (in the
form of ketchup on their MacGreaseburgers and a little
tomato sauce on the occasional slice of ’za), even the bottom
20% of diets provide lycopene in doses such as 2.3131 to
3.4129 or even as much as 4.4130 or 4.5128 milligrams of
lycopene on an average day!
Where do these senselessly low doses come from? Some
formulators just formulate their products in ignorance,
without bothering to dig into the original research; others
know full well that the measly dose they’re including won’t
do anyone any good, but cynically throw a token quantity
of lycopene into their products for no other reason than to
catch your eye as you scan their labels. Neither is providing
you with anything like the amount of lycopene that the
research says is needed to shield your body from the
ravages of cancer.
pg. 9 ADVANCES in orthomolecular research
Flavonoids of which there are several
thousands are abundant polyphenols in the human diet
and are divided into six main classes:
( ) (e.g. Catechins), (e.g.
Quercetin), (e.g. Luteolin),
(Naringin), (e.g. Genistein) and
(e.g. cyanidin)
Now let’s look at the other – and more disturbing – extreme.
While enthusiasm for beta-carotene has dampened thanks
to the spectacular failures of several large trials, at one
time most ‘premium’ multivitamins contained 25 to 50
milligrams (41 625 to 83 250 IU) of synthetic beta-carotene
in a daily dose; indeed, many antioxidant combination
products still contain such overdoses. (If you’re doublechecking
a supplement label for its carotenoid content,
you’ll want to look for the absolute milligram potency,
because many supplements list IU potencies using old,
outdated conversion factors;25 indeed, the proper way to
make this conversion remains controversial today.136
Milligram potencies are the clearest and best way to get
this information on a label).
We’ve already seen that the use of synthetic beta-carotene
was a disaster in the waiting; however, the use of these
massive amounts of the stuff can only have made things
worse. Because the strong evidence from epidemiological
and experimental studies that beta-carotene protects you
from cancer27 never supported such huge doses – and since
then, animal research has shown that the overkill quantities
of beta-carotene used in too many supplements actually
increase cancer risk when you’re exposed to cigarette
smoke.
Incredible – some would say unconscionable – but true.
When we turn again to research using the latest carotenoid
database to document the amount of beta-carotene being
consumed by people whose diets are rich in this carotenoid
– diets strongly and consistently associated with lower
cancer risk27 – we see that even the richest diets contain from
as little as 6.8,128 through 8.95129 or 9.8,131 and not more than
11.4127 milligrams of beta-carotene per day. In other words,
the amounts of beta-carotene which, in the diet, is
associated with reduced risk of cancer is only about a third
to one half of the amount used in far too many supplements
– and also in the unsuccessful clinical trials of beta-carotene
to prevent cancer.2-4
And recent studies suggest that this beta-carotene
overdosing isn’t just a matter of wasted money. At these
extreme doses, scientists have observed that the body’s
carcinogen-detoxifying systems become unbalanced137,138
and genes related to the cancer process become
activated.139 One study in ferrets (whose metabolism of
beta-carotene is much more like that of humans than is other
rodents’) compared animals exposed to cigarette smoke
alone to animals exposed to the smoke plus beta-carotene
supplements at one of two doses: one designed to reflect
the levels of beta-carotene present in a diet emphasizing
this nutrient, and the other reflecting the kinds of mega
doses typical of many antioxidant and multivitamin
products.
The results: the “rich-diet” beta-carotene supplement dose
resulted in lower levels of squamous metaplasia
(precancerous lesions) of the lung – but giving the same
animals the equivalent of a 30 milligram (49 950 IU)
synthetic beta-carotene supplement led to the activation of
several pro-cancer genes, and to the animals suffering more
precancerous lung lesions than did those exposed to
cigarette smoke alone!139
Along with the use of synthetic (all-trans-) rather than natural
(9-cis-containing) forms of the molecule, these findings
provide one of the likely reasons for the suggestion of
higher cancer risk in smokers given the equivalent,
unjustifiable doses of beta-carotene in the disastrously
failed clinical trials.2-4,134 And the proof in the pudding has
come from the massive SU.VI.MAX trial. This randomized,
double-blind, placebo-controlled study tested effects of an
antioxidant supplement containing doses that reflect the
amounts found in good diets – including 6 mg of beta
carotene and 120 mg of vitamin C, along with vitamin E,
selenium, and zinc – in 13 017 healthy, middle-aged French
men and women. After following the two groups for 7.5
years, it was found that supplements of beta-carotene and
other antioxidants, at doses typical of good diets,
reduced cancer incidence by 31%, and death from all
causes by 37%– although there was no reduction observed
in the women, apparently linked to fact that the women had
higher levels of antioxidant nutrients to begin with.140
Without hammering the point to death, let’s look at one
more example. It’s important to take all of the B vitamins,
not only because they’re essential nutrients but because they
work as a complex, with their metabolism dependent on one
another and an excess of one sometimes creates a
deficiency of another.141,142 But has it ever occurred to you
how weird it is that so many multivitamins and B-complex
vitamins contain exactly as much thiamin as niacin as
riboflavin, and so on – the same 50 mg or 100 mg for each
and every B vitamin except folic acid, all the way down the
list? Does it physiologically make sense that the body would
optimally use exactly the same amount of half a dozen
different B vitamins, each with its own unique, irreplaceable
functions in the body?
Well, of course, it doesn’t. The numbers used are arbitrary,
with no physiological justification. Someone, years ago,
Science has vetted a phytochemical
dream team: sulforaphane, indole-3-
carbinol (I3C), limonene, lycopene, transresveratrol,
EgCG, and chlorophyll
ADVANCES in orthomolecular research pg. 10
Comparing major research papers
to the ingredients lists on typical
supplement bottles, you ll wonder if the designers used a
dice roll to
determine their dosages.
Those Fickle Flavonoids
With so many phytochemicals showing favorable-looking results in test tube and animal studies, it’s a bit surprising to see how few
have been linked to better health in large population studies or clinical trials. In many cases, it’s likely that this has to do with the
way the body – and in particular, the human body – metabolizes these substances.
Polyphenols (including flavonoids and phenolic acids), in particular, undergo a whole series of complex biotransformations
which make it difficult to predict their effects in the body based on their effects in the test tube. Both the probiotic bacteria in
your intestinal tract, and your body’s own detoxification systems, really “go to town” on polyphenols, so that the original molecule
will go through several cycles of having old conjugates
cleaved and new ones added before it is finally excreted,
creating diverse and largely unpredictable array of
metabolites along the way (see Figure 5).102-104
With most nutrients, you can expect that the effects in
humans will be similar to the effects in experimental
animals. But in the case of flavonoids, this often doesn’t
pan out. Humans metabolize many flavonoids differently –
and often much more heavily – than rodents do,102 so that
extrapolation from rodent studies becomes an extremely
uncertain, speculative exercise.
Some of the metabolites of a given flavonoid will not be
absorbed at all; others will be absorbed, but their
biological activity will be much different from that seen in
test-tube studies using the original, un-metabolized
compound. It’s these metabolites – and not the parent
molecule – that will determine the real effect of flavonoids
in the body: good, bad, or indifferent.102
Let’s take a few examples. The absorption and metabolism
of epigallocatechin gallate (EgCG) in green tea is
well-characterized,105-112 the effects of its metabolites have been explored,113 and there is extensive epidemiological evidence
showing that people consuming high amounts (most consistently, ten servings of Japanese sencha green tea live longer,114 develop
less cancer,114-118 and possibly suffer fewer heart attacks.118, 119 Therefore, we can be confident that there really is value in bringing
EgCG into your diet and supplement program. By contrast, we’re only just beginning to get a handle on what the body does with
apigenin,120 luteolin,121 or the flavonoids in strawberries,122 and there is only very weak evidence to
suggest a specific health benefit in people whose diets contain high amounts of foods rich in these particular polyphenols, as
opposed to other plant foods.
This may also explain why research on the effects of flavonoids as a class in humans has been so conflicting. As one recent review
of the field put it, “Some studies support a protective effect of flavonoid consumption in
cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm.”123 The
bottom line: with such varying bioavailabilities and biological activities, you can’t really generalize from one polyphenol to
another – and you can’t rely on work in the test tube, or even experimental animals. Human clinical and epidemiological data for
specific foods and food flavonoids must be our touchstone.
Figure 5: Factors Affecting Flavonoid Absorption. Redrawn from (102).
ADVANCES in orthomolecular research pg. 12
plucked these numbers out of thin air – and somehow, they
stuck. The irrationality of these numbers can clearly be seen
in the case of thiamin.
The conventional form of thiamin cannot pass directly across
cell membranes: it requires a special shuttle system to pump
it across the intestinal wall and (later) into the cell. There are
enough “seats” on the shuttles to ensure that you’ll absorb
the small doses typically found in food … but most of a 50
milligram dose gets left waiting at the harbor as the ship
pulls away. And while a small amount of additional
absorption occurs via diffusion into the fluid that bathes the
cells, this adds little to total bioavailability: no
matter how much thiamin you take, you
don’t materially increase plasma levels
beyond what you get from the first
12 milligrams of the dose.143-147
Even greater problems occur in
getting thiamin into the cells to do
its job. While some thiamin crosses the
intestinal wall through diffusion into the
fluid surrounding the cells of the intestinal
tract, the cells themselves (except for red blood cells) cannot
absorb conventional thiamin except through the active
transport system.147,148
The strictness of the limits of this system can be seen when
you bypass the limited intestinal absorption of thiamin by
injecting it directly into the blood. When 5 milligrams are
injected, most of the dose is taken up by the cells, and the
kidneys will excrete only 25% of the original dose. But
increasing the dose does not increase the cellular
absorption. The more thiamin you inject, the more ends up
simply passing out through the urine, and at 100 milligrams
or more, 100% of the additional thiamin is excreted in the
urine.149
There’s certainly no harm to taking this extra thiamin – but
no point to it, either. This is one case where the old skeptic’s
taunt is true: you really are flushing most of that extra
thiamin down the toilet! And the same is true of a lot of
the other B vitamins you’re taking. Doses should be based
on science – not nice, round numbers.
When the Mix Won’t Match
There are plenty of health-promoting substances out there
that you may want to seriously consider taking in
supplemental form, but that you wouldn’t want to have
included in your multivitamin for one reason or another.
Many people, for instance, take supplemental IP6 (inositol
hexaphosphate or “phytate”), a nutrient found in many
plant foods which plenty of evidence suggests is a powerful
nutrient protector against the horrors of cancer.150 And it
would certainly be convenient to get this important
supplement along with your other core nutrients in one
formula. We’ve even seen IP6 included in some multivitamin
and immune-boosting formulas. The problem with doing this
lies in a key chemical property of IP6: its ability to react
with many minerals – including calcium and zinc – to form
tightly-bound, insoluble, un-absorbable complexes. The
result: when you mix IP6 with calcium in your gut, you
lose much of the benefit of both the IP6 and these
minerals!
This problem is even seen in some IP6-
rich grain foods. On the one hand,
bone disorders – including
osteomalacia, rickets, and
osteoporosis – are commonplace
in populations where unleavened
breads and similar foods provide
the bulk of the energy in the
diet;151-153 and on the other hand,
studies show that animals
receiving a diet high in wheat bran
experience two thirds less cancer protection than
animals given the same amount of IP6 in their drinking
water,154 where it doesn’t come in contact with the nutrients in
their food.
The key green tea polyphenol EgCG (epigallocatechin
gallate) is a similar case. Green tea polyphenols inhibit
the absorption of many minerals. The most famous case is
iron: green tea extracts clearly reduce its bioavailability,155
and it’s clear that people who drink a lot of tea and who
have marginal iron status are at higher risk of anemia.156-159
Tea polyphenols may also inhibit absorption of calcium160,161
and zinc,161,162 although the effects appear to be minor and
perhaps transient.
Of course, you may not want to absorb all of the iron in your
diet, particularly if you’re a man or a postmenopausal
woman or eat a high-meat diet. Excess iron levels are
associated with oxidative DNA damage163 and may increase
risk of several age-related diseases, including neurological
disease,24,164 diabetes,165-167 and possibly heart disease.168 But
while most people don’t need an iron supplement, people
who are conscious about their diet – particularly if they
don’t eat much red meat – have little to gain from actively
inhibiting their iron absorption. Overall, it just makes sense
to take your green tea supplements away from meals –
and thus separately from your main nutritional supplement.
The overkill quantities
of beta-carotene
used in too many
supplements actually increase
cancer risk
pg. 13 ADVANCES in orthomolecular research
Get Back to “Basics”
Oftentimes, people become so excited about the potential
of exotic botanicals or emerging orthomolecular compounds
to impact their health, that they pay less attention to the
basic, essential nutrients. Maybe it’s a case of “familiarity
breeding contempt:” we’re so familiar with zinc, copper, or
vitamin C that we neglect to pay them any attention. But you
can’t expect to enjoy optimized health from advanced
supplementation if your body is lacking the basic nutrient
cofactors required for its essential biochemical processes.
And on the flip side, as we’ve seen, it’s all too easy to
mistakenly imbalance yourself on these same nutrients or to
fail to reap their full benefits, if you aren’t paying enough
attention to just what and how much you’re taking.
Instead of just taking your supplements based on “one size
fits all” nutritional formula, it’s worthwhile to take careful
stock of where you’re at, nutritionally, from your diet alone.
If your diet is particularly healthy, you may not need a full
daily dose of a multivitamin formula; and if you have a diet
that is especially strong on a specific nutrient, you may not
need to add on extra nutrition on top of your multi as others
might. Do you drink a lot of milk? Then you probably don’t
need a full 1000 milligrams of calcium from supplements
alone. Are you absolutely addicted to oysters? Your zinc is
likely covered. And so on.
For those wishing to personalize their supplement program
to the greatest possible degree, there are many software
packages available that will actually tell you how much of
the essential nutrients you’re taking in each day. One of the
best is http://www.nutritiondata.com , which is free,
available online, and gives great, user-friendly graphical
output. The time required to plug in the foods you eat every
day for a couple of weeks will be worth it if it tells you
where key deficiencies or imbalances may lie – and where
you can rest on your nutritional laurels.
So the first rule of supplementation is: begin at the
beginning. With this base, you can consider moving up to a
more advanced multinutrient formula, incorporating key
phytochemicals from the “superstar” team identified above,
and then adding in additional, more advanced supplements
such as powerful phytochemicals or cutting-edge
orthomolecules like benfotiamine or extended release
R(+)-Lipoic Acid based on your own priorities and health
concerns. Once you have a well-laid foundation, you can
build up a solid nutritional fortress.
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death
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]]> pg. 1 ADVANCES in orthomolecular research
Call it the supplement paradox.
A huge body of careful, prospective scientific research into
the relationship between peoples’ lifestyles and their longterm
health has confirmed, again and again, that eating a
diet rich in fruits and vegetables will lead you to a longer
life, and lower your risk of chronic disease.
The most obvious thing about such diets is that they’re rich in
essential vitamins and minerals. And yet time and time
again, controlled clinical trials of nutritional
supplementation with vitamin and minerals – including key
antioxidant nutrients like “vitamin E,” vitamin C, and
beta-carotene – has failed to protect people from killer
diseases.
Whether it’s “vitamin E” against heart disease,1 or betacarotene
against cancer,2-4 or antioxidant “cocktails” against
atherosclerosis5 or death from any cause,6,7 again and again
the results have come back negative. Either there’s no effect
at all … or the results are too ambiguous to pin your hopes
on … or there’s been a suggestion that the people taking
their assigned pills were worse off than people taking the
placebo stand-ins.
It’s a pretty sad record.
How can this be? Before the results of these trials came in,
many health-conscious people had their faith in their
multivitamins boosted by the simple fact that these trials had
even managed to get off the ground in the face of extreme
skepticism from much of the medical establishment. Now
those skeptics feel justified in their condescension – and the
forces that oppose health freedom have been given
ammunition in their anti-supplement attacks.
The reaction from most supplement companies has been
disappointing. Many companies are in the business for no
other reason than to make a quick buck, and have chosen to
simply ignore these trials, hoping that the unsettling results
will not reach the ears of their customers and cut off access
to a reliable cash cow. Other companies are sincere in their
belief in the value of supplementation – but they base this
belief on blind faith, playing hear no evil, see no evil when
large-scale, carefully-controlled, rigorous clinical studies fail
to confirm a pre-established credo. Such companies have
failed to respond to the latest discoveries in the rapidlyaccelerating
field of nutritional science, continuing instead to
design their products based on accepted health-food-store
dogmas.
Health-conscious people can’t afford to be blinded by
wishful thinking, or to rely on formulas based on outmoded
theories and fuzzy-headed, pseudoscientific notions. The
fact is that the conventional wisdom underlying ‘basic’
nutritional supplementation has been disproved. If we
are to gain the benefits that we expect from our
supplement programs, we have to be ready to listen to what
science is actually saying today instead of what it suggested
twenty years ago.We will have to clear the ground, looking
at the science with our old blinders removed, questioning our
assumptions, turning over the graves of the ‘authorities’ of
yesteryear, and laying the foundation for a genuinely new
approach to nutritional supplementation.
Latest Science in
Vitamin & Mineral
Principles In Formulating The
Optimal Multi
Nutritional supplementation with
“vitamin E,” vitamin C,
and beta-carotene –
has failed to protect
people from killer diseases
But where to begin? With what we already know. We know
that healthy diets support longer, healthier life. And we know
that supplements based on old-school thinking do not. Once
we accept these two facts, the way forward becomes clear:
compare the contents of a health-promoting diet to typical
multivitamin/multinutrient products, and see what’s so
fundamentally different between the two. And once you
start looking, the contrast is so sharp that it strikes you like
a barrel of ice water. Multivitamin supplements which should
have been designed to be, in effect, super-concentrated
versions of an optimal diet are revealed instead to be gross
caricatures of those diets, distorting and unbalancing the real
picture of preventive nutrition.
Let’s see where previous products have gone wrong … and
how we can get it right for the future.
First, Do No Harm
The most extreme disconnect between health-giving foods
and badly-designed pills, is cases where a multivitamin not
only doesn’t protect the health of its users, but actively harms
them. We are accustomed to thinking of nutritional
supplements as fundamentally safe; and certainly, no
multivitamin has ever caused the kind of killer toxicity we
see from some xenobiotic drugs (except in cases of
overdose resulting from sloppy manufacturing, or from
accidental or intentional swallowing of too many pills). But
there’s now strong evidence that nearly all multivitamin
products contain one or more nutrient overdoses or
imbalances extreme enough to cause real, long-term
damage to the health of those swallowing them.
One well-documented, crippling result of long-term, chronic
supplement overdose is the association between excessive
preformed vitamin A (retinol/retinyl esters) and the loss
of bone health. It’s long been known, from animal studies,
that getting too much vitamin A is bad for the skeletal
system. In recent years, these findings have been confirmed
in humans. Several large, well-designed population studies
(and a few smaller and less rigorous ones) have now
reported that men and women with the highest intake8,9
or serum levels10,11 of retinol are at the greatest risk of
suffering a fracture; taking in the most retinol also
associates with having the lowest bone mineral density
(BMD).8,12-14 (It’s important to understand that this refers to
preformed vitamin A: beta-carotene and other ‘provitamin
A’ carotenoids have not been associated with loss of
bone health).
Frighteningly, the amount of preformed vitamin A which
these studies have found to put consumers at risk of broken
bones is right in the ballpark found in many – and perhaps
most – multivitamins: “just” 1.5 milligrams (5000 IU) in one
study,8 and a similar 6 600 IU in another9 is enough to
roughly double your risk of a fracture. It’s extremely
unlikely that you’d get dosages like these from food – you’d
have to spend all day gorging on liver, eggs, and fortified
milk – but it’s all too easy to exceed the safety limit if you’re
taking the kind of multivitamin designed around an
unthinking ‘more is better’ paradigm. And indeed, nearly no
one in these studies would have reached the extreme levels
of intake associated with increased fracture risk if it were
not for the badly thought-out supplements they were letting
into their systems.
But this doesn’t mean that you should avoid all intake of
retinol, or depend entirely on carotenoids to get your
vitamin A. The rate of conversion of “provitamin A”
carotenoids into retinol varies nearly ninefold from person to
person,15 and can be altered by age, genes, body weight,
and alpha-tocopherol intake. Remember that retinol is an
absolutely essential nutrient – and in fact, one of its most
important functions in the body is in normal skeletal
metabolism! Indeed, some of the same studies that
reported the impairment of bone health caused by years of
retinol overdose have found that people with the lowest
vitamin A levels11 or intake12 also suffer an elevated
fracture risk11 and lower BMD.12 It appears that the ideal
retinol intake – from diet and supplements combined – is in
the ballpark of 2000 IU.
But remember that, because of government-mandated
fortification, a single serving of low-fat milk or yogurt
contains between about 500 and 750 IU of vitamin A,
and a standard 85g (3 oz) slice of liver contains an
astounding 22 000 IU!
Men and women with the
of are at the r
of suffering a
So it’s very easy to overshoot your safe vitamin A intake if
your supplement contains more than 1000 IU of retinol. The
goal of supplementation should be to put you into that
happy medium where bone health is optimized; supporting
the balance of the diet instead of overbalancing it with
levels you’d never get from well-chosen foods.
Another source of long-term health theft resulting from
sloppily-designed supplements is overbalanced zinc-tocopper
ratios. The body’s metabolism of these two minerals
is inextricably intertwined because of their similar atomic
structure: they resemble each other so closely that they can
compete with one another for absorption and transport, and
interfere with one another’s binding to enzymes, if one is
present in excess. Getting too much of either nutrient creates
a functional deficiency of the other. So keeping the two
minerals in proper balance is important if you’re going to
reap the health benefits of either – or even to avoid doing
yourself damage.
pg. 3 ADVANCES in orthomolecular research
fig 1. Retinol intake and bone mineral density in the elderly. Modified
from reference 54.
Both animal and human evidence suggests that, for optimal
utilization of both minerals, the balance between zinc and
copper should be about ten-to-one.16 But most supplement
formulators seem to have been dazzled by the exciting
research which documents the importance of getting
adequate zinc in your diet – so much so, that they’ve
ignored the crucial place of copper in the equation. As a
result, it’s common for multivitamins to include very high
doses of zinc, but little or no copper, so that many –
perhaps most – multivitamin and multimineral formulas
contain potentially harmful zinc-to-copper imbalances.
Such imbalances are more than just a theoretical concern. In
a series of human studies, using a ratio between zinc and
copper of 23.5-to-one (and sometimes lower) – common
zinc-to-copper ratios, found in many multivitamins –
resulted in wide-ranging metabolic disturbances,
including reduced levels of the copper-based antioxidants
enzymes cytosolic superoxide dismutase and
ceruloplasmin, high total and LDL (“bad”) cholesterol,
reductions in the body’s levels of enkephalins (natural painkilling
molecules), and abnormal cardiac function (including
rhythm disturbances and even heart attacks)!16-18
And these are just the metabolic derangements observed
over the course of a few weeks or months. Over years of
functional copper deficiency created by excessive zinc
intake, it seems inescapable that other problems known to
result from ‘simple’ copper deficiency – such as impaired
bone metabolism, poor glucose control, and increased
levels of Advanced Glycation Endproducts (AGE) – would
also manifest themselves.
The most bitterly ironic twist in the black comedy of zincmad
pill design has only recently appeared. Many men
take zinc supplements to support the health of their
prostates, because of some evidence suggests that low zinc
levels are associated with prostate cancer and other
prostate disorders.19 But a large new study,20 which tracked
the health habits of nearly 50 000 American male health
professionals for 14 years, found that extreme zinc oversupplementation
was associated with a more than
doubled risk of developing advanced prostate cancer,
especially if continued for more than 10 years.
All of this has lead to alarm amongst researchers who have
devoted their academic careers to documenting the
importance of copper in human health. Dr. Leslie M. Klevay,
for instance, has warned of the “hazards of zinc
supplements.”17 But the problem is not zinc supplements, but
the excessive zinc dosages, and/or unbalanced zinc-tocopper
ratios, found in far too many multivitamins. A
properly-designed core nutritional program will work to
ensure optimal intake of both nutrients – individually, and in
balance.
Yet another example of “megadose mania,” for which the
evidence is disturbing if not yet conclusive, is the probable
neurological damage caused by excessive manganese
supplementation. It’s well-established that workers in
industries where inhaling manganese is common (such as
manganese miners and welders) are at greater risk for
neurological syndromes resembling Parkinson’s disease,
and animal studies clearly show that excessive manganese
intake leads to neurological damage.21 Furthermore, in a
study that compared the level of manganese present in the
drinking water in different communities with the rates of
neurological symptoms amongst their residents,22 it was
found that neurological symptoms were more common
amongst the elderly in high-manganese areas. (Another
study, however, did not report an association23).
But the best evidence that manganese oversupplementation
really is an issue worthy of our concern is
a study which compared the manganese intake from diet
and supplements of people with Parkinson’s disease with
those of people without the disease.24 The study found that
people with high dietary intake of manganese are about
70% more likely to fall prey to this neurological disorder
– and that the risk was further increased among people who
also consumed manganese-containing supplements, or who
also had a very high intake of iron.
It’s not clear exactly how much manganese is too much, in
large part because of the different bioavailabilities and
distribution in the body of manganese coming from fumes,
water, food, and supplements. And it’s hard to detect the
early symptoms of manganese excess, because they are so
nonspecific: loss of appetite, impaired reproduction,
anemia, and retarded growth in children.
A review of the evidence by the National Academy of
Sciences’ Institute of Medicine found that the lowest level of
total manganese intake at which suggestions of harm could
be documented was at manganese intake from diet of 15
milligrams; they cautiously suggest that the safe upper limit
of manganese consumption from all sources is 11 mg.25When
you consider that unusually manganese-rich diets can
contain between 6.325 and 826 milligrams of the mineral, the
idea of adding an additional five, ten, or even more
milligrams of manganese in the form of a badly-thoughtout
multivitamin becomes an increasingly bad notion – yet
such dosages are common.
Again, this doesn’t mean that you should treat manganese
like a nutritional pariah, or a toxin like lead or cadmium.
Manganese is an essential nutrient, needed for healthy skin,
bone, and cartilage, for maintaining glucose tolerance, and
for the formation of the mitochondrial form of the
antioxidant enzyme superoxide dismutase (SOD). But the
bottom line is that there’s no good evidence that getting
more than a few milligrams of manganese makes you any
healthier, and there is some pretty suggestive research
indicating that a very high intake could ultimately do you
harm. It seems clear that supplements should contain enough
manganese to ensure that you aren’t deficient, but not much
more: a couple of milligrams is safe, and will meet your
nutritional needs.
Nutritional Bait-And-Switch
But the problems with multivitamins extend into subtler
territories than frank overdose. Another is using the wrong
molecule. When studies show that people whose diets are
chock-full of some key nutrient are protected against a
ravaging disease, you’d think that it’d be a no-brainer to
create supplements which contain that same nutrient. Far too
often, however, supplement companies have cheated
health-conscious consumers by substituting counterfeit
versions of these molecules for the real thing – versions
with fundamentally different effects on the body.
One example that we’ve previously documented in detail is
lipoic acid: unless they say otherwise, supplement
companies replace R(+)-lipoic acid – the form of this
nutrient produced by the body for its own use – with an
adulterated, 50-50 “racemic mixture” of R(+)-lipoic acid
and the purely artificial S(-)-form of the molecule. Studies
show that the artificial S(-)-lipoic acid is not just less potent
than the natural R(+)-form, but in some cases actually
interferes with, or has the opposite effect of, R(+)-lipoic
acid. (For a review of some of the research on R(+)-lipoic
acid, see “Your Two-Faced Lipoic Acid” in Advances 2(1), or
visit http://www.R-Lipoic.com).
This same problem is common to many keystone nutritional
supplements. One excellent example is beta-carotene. The
studies designed to test the ability of beta-carotene to
prevent cancer and heart disease were based on the very
strong evidence that people whose diets contain more betacarotene
had a lower risk of lung (and other) cancers.27 But
when companies began making beta-carotene supplements,
the form of ‘beta-carotene’ that they produced – and that
was used in nearly all of the trials – was not the same
‘beta-carotene’ that occurs in food.
Beta-carotene from food contains two structural forms
(isomers) of the molecule: all-trans and 9,cis-beta-carotene
(see Figure 1). But the beta-carotene used in nearly all
supplements has been entirely composed of the all-transform
of the molecule.
The difference is important to all of us, not just organic
chemists. Studies have clearly shown that the effects of
natural and synthetic beta-carotene are fundamentally
different. Synthetic beta-carotene has much lower
antioxidant activity;28-30 more alarmingly, studies performed
in human white blood cells have revealed that the synthetic
beta-carotene used in most supplements causes genetic
damage to the cells!31 Natural beta-carotene, by contrast,
does not have this effect.31 So perhaps it’s no surprise that
the studies designed to test the ability of beta-carotene
supplements have actually found that the pills not only fail
to protect users against cancer,2-4 but may actually increase
the cancer risk:2,4 all of these studies used the synthetic, alltrans
form of the molecule.
Another example of molecular mismatch is “vitamin E.”
Numerous studies in the health habits of large populations
have found that the “vitamin E” in food provides protection
against cardiovascular disease (CVD)32-34 and Alzheimer’s
disease.35-37 Yet these same studies have reported that users
of “vitamin E” supplements have not been given protection.32-
37 In fact, a “meta-analysis” study which pooled the results
of 19 high-quality controlled trials found that high-dose
alpha-tocopherol supplements actually increase
mortality in patients with existing cardiovascular disease!1
Scientists now have a very good explanation for this: again,
the “vitamin E” in food is very different from the “vitamin E”
contained in nearly all supplements.
We’re not just talking about the difference between socalled
“natural” “vitamin E” (d-alpha-tocopherol, or more
properly RRR-alpha-tocopherol) and “synthetic” “vitamin E,”
(dl- or all-rac-alpha-tocopherol). The only real difference
between d- and dl-alpha tocopherol is in its strength: it
takes more dl-alpha-tocopherol to get the same effect you
get from d-alpha.38
No, the real distinction between the “vitamin E” you get from
a healthy diet, and the “vitamin E” you’ll find in most pills, is
not one of degree, but of kind. While the “vitamin E” in food
does contain d-alpha-tocopherol, this molecule actually
makes up only a minor fraction of the vitamin E in healthy
diets. “Vitamin E” is not this one molecule, but a complex,
composed of eight distinct molecules – four tocopherols, and
four tocotrienols. And in fact, the single largest amount of
“vitamin E” in healthy diets appears as gamma-tocopherol,
not its alpha cousin.39-43
Again, this isn’t just trivia for biochemistry geeks. The
different members (or “vitamers”) of the E complex have
different functions in the body, just as different B vitamins
do. Recently, the unique properties of gamma-tocopherol,
have become a particular focus of researchers’ attention,44,45
but the unique benefits of the “other” E vitamins are clearly
also important. Some of these unique health properties
were discussed in “There’s No Such Thing as Vitamin E,” in
The Holistic Lifestyle 1(4), and we hope to go into more
detail in a future issue of Advances.
To jump to the punch line, however: these newly-discovered
properties of gamma-tocopherol, tocotrienols, and other
natural E vitamins explain why the “vitamin E” in food
protects against chronic disease where supplements keep
failing.32-37 And indeed, by looking at levels of E vitamers in
the body, the importance of the distinction becomes clear:
high levels of gamma- – and not alpha- – tocopherol is
associated with reduced risk of CVD46-49 and heart attack,50
and that the same is true of prostate cancer.51,52 Likewise,
evidence exists for a selective gamma-tocopherol depletion
in the brains of people with Alzheimer’s
disease.53,54
And the real problem with unbalanced alpha-tocopherol
supplements is not just that they’re missing these other E
vitamers, and therefore fail to provide their unique
benefits. Astoundingly, alpha-tocopherol, at doses typical
of most supplements, actually interferes with the body’s
ability to hold onto and use of the other E complex
members!
Because of its specific importance to reproduction, and
because a natural diet contains comparatively little of this
specific E vitamin, evolution equipped the body to hang onto
its supplies of alpha-tocopherol – even at the expense of
other E vitamins. As a result, when you flood yourself with
unbalanced alpha-tocopherol supplements, you actually
deplete your body of other E-complex members (see
Figure 3).55-59
It doesn’t take a lot of unbalanced alpha-tocopherol to
drive down your gamma-tocopherol supply: five months of
swallowing just 150 IU of isolated alpha-tocopherol per
day robs your body of 63% of its plasma gammatocopherol
levels, leaving you with lower levels than you
would have had if you were taking no supplement at all.55
And the effect can be long-lasting: after one year of highdose
(1200 IU) alpha-tocopherol supplementation, tissue
gamma-tocopherol levels take two years of “cold turkey” to
recover to the level they were at before supplementation
began.58
And don’t think that the “natural mixed tocopherols” added
in as an afterthought to some “vitamin E” supplements will
make up for this imbalance. These products throw in no more
than 20% as much of the tocopherols other than alphatocopherol,
almost as an afterthought – and they contain no
tocotrienols. But it’s been shown that it takes a lot more of
the “other” E vitamins to make up for the alpha-tocopherol
overdoses found in these pills. For example, if you take 371
milligrams of alpha-tocopherol into your body every day,
you’ll still suffer a 30% loss of gamma-tocopherol in plasma
even if you try to balance it out with more than 400
milligrams of gamma-tocopherol and other E complex
members.59
In fact, careful examination of studies involving the
cholesterol-balancing effects of tocotrienols reveals that the
body needs at least twice as much of the “other” E
vitamins to prevent alpha-tocopherol from canceling out
their benefits.60-62 It should come as no surprise that this ratio
is similar to what’s found in a balanced diet of whole
foods.39-43
Yet another example of the kind of nutritional bait-andswitch
at work in common multivitamin formulations is the
ongoing use of inferior forms of selenium. Extensive
research demonstrates that Se-Methylselenocysteine
(SeMC) is the most effective cancer-fighting form of
selenium available.63-65 (We reviewed the revolution in
selenium cancer research of the last decade in the Spring
2003 issue of Advances). Not surprisingly, foods with known
cancer-fighting powers – such as high-selenium broccoli,
garlic, and onions – contain much of their selenium in this
form, whereas selenomethionine and other common selenium
forms predominate in foods like beef and wheat – foods
which are not particularly noted as being protective against
cancer. Yet most companies continue to put
selenomethionine, selenate, selenite, or selenium yeast into
their pills.
extreme zinc
over-supplementation was
associated with a more than
doubled risk of developing advanced
prostate cancer
ADVANCES in orthomolecular research pg. 6
Figure 2: All-trans and 9,cis-beta-carotene.
Take, again, the difference between menatetrenone (MK-
4, the form of vitamin K2 biosynthesized by mammals) and
phylloquinone (vitamin K1 – the form used in nearly all
supplements). We know that menatetrenone delivers
superior skeletal,66 brain,67 and cardiovascular68,69 health
benefits. Yet supplements continue to use vitamin K1 – or
sometimes bacterial menaquinones (such as
menaquinone-7 (MK-7) – the main bacterial form of K2),
which are not the same molecule (see figure 4).
There’s also the greater bioavailability and stronger
clinical evidence for calcium citrate-malate compared with
other vegetarian calcium sources (regular calcium citrate is
not equivalent!70). And we could go into other examples. But
the point, by now, should be obvious. When evidence
suggests that high intakes of a nutrient found in healthy
foods supports vibrant health, make sure that your
supplement contains the same molecule, and not an
impostor or second-best.
Emerging Essentials
Official government nutrition panels recognize only 13
essential vitamins and 15 essential minerals. But in recent
years, it’s become increasingly clear that a few other
substances are just as indispensable for your health. It was
only recently that chromium was recognized by the Institute
of Medicine to be necessary for your health. But the
evidence is compelling that boron, silicon, lithium, and
vanadium are as necessary to your health as the
“official” essential minerals, such as calcium, magnesium,
or zinc, and that a little-known redox factor called
pyrroloquinoline quinone (PQQ) is being considered as a
vitamin just as essential to your health as vitamin C or
pantothenic acid (vitamin B5).
Boron appears to be an essential to normal brain function,71
a key factor in preserving the health of the skeleton and
joints,72 and has been linked to reduced risk of prostate
cancer;73 recent studies in the homeostatic control of boron
concentration in the body74 and in breast milk75 show that the
body is actively regulating levels, demonstrating its
essentiality in the body, and a failure of this control is
observed in mothers who subsequently undergo premature
labor.75
Silicon has been shown to be essential to normal bone
formation in animal studies,76,77 and epidemiological
studies,78 and preliminary clinical trials79 suggest that it builds
stronger bones in humans, too, apparently through a
cofactor role in collagen synthesis. And vanadium appears
to have a key role in thyroid function, as well as having a
“pharmacological” effect on glucose metabolism at
extremely high doses.80
Perhaps the most remarkable rise of a newly-identified
mineral in recent years has been lithium.81 Although most
people think of this mineral as a “drug” to used treat
bipolar disorder, lithium is a trace mineral found in “hard”
water and food: typical diets contain between 0.650 and
3.1 milligrams of lithium per day, coming mostly from
grains and vegetables.
Animal studies have shown that lithium is an essential
mineral in mammals. Lithium-deficient laboratory rodents
have impaired reproductive function and abnormal lipid
metabolism. When USDA scientists sat down to reformulate
the standard rodent chow used in laboratory experiments in
1997, one of the key changes to the diet was to fortify its
lithium content beyond the amount that occurs naturally in
the elements of the diet.81
Similarly, studies in goats show that lithium-deficient animals
suffer depressed immune systems, chronic inflammation,
splenic atrophy, excessive iron buildup in their tissues, and
calcium deposits in their blood vessels; moreover, the
activity of the enzymes involved in their mitochondrial
energy production is depressed, and they develop “benign”
tumors of the breast, salivary glands, and adrenal glands,
as well as ovarian cysts.81
But the most fascinating research on lithium’s role in health
has come from studies comparing the health of people
living in areas with higher and lower amounts of lithium in
the rain or tap water, and individuals with higher and lower
levels of the mineral in their hair, scalp, and urine. These
studies have found that people living in areas with low
lithium have higher rates of neurosis, schizophrenia,
psychosis, psychiatric ward admissions, homicide,
suicide, forcible sexual assault, burglary, and
runaways.81
Supplement companies have
substituted counterfeit
versions with fundamentally different
effects on the body.
Based on the amount of lithium found in typical diets, and
the amounts known to support brain health when consumed
in the diet and drinking water, nutrition researchers are
now suggesting an ‘RDA’ of lithium in the range of 0.400
to 1 milligram per day.81 Lithium supplements are now
becoming more readily available in the United States;
unfortunately, the Canadian authorities continue to insist that
even nutritional doses of organic lithium is a “drug,” and
threaten fines and imprisonment to anyone making it
available except by prescription.
Plant Protectors
The most consistent finding in all of the science of
epidemiology is that diets rich in fruits and vegetables are
associated with reduced risk of cancer, heart disease, and
age-related disability. Fruits and veggies are the best
source of many vitamins and minerals, of course, but there’s
a lot more in a healthy diet than just these essential
nutrients. For more than half a century, scientists have known
that when experimental animals are fed highly-refined
diets which contain all the protein, essential fats, vitamins,
and minerals known to be essential to their normal growth
and development, they are still more vulnerable to cancer
than animals containing similar levels of all essential
nutrients, but composed primarily of unrefined or semirefined
food sources.82-87 The explanation for this
phenomenon lies mostly in phytochemicals.
Strictly speaking, any biologically-active substance
produced in plants can be called a “phytochemical.” But the
term is most often used to refer to those protective, diseasepreventing
bioactive compounds which – while not
“essential” in the same sense as vitamin C or magnesium –
none the less play a major role in the benefits of a good
diet. In recent years, researchers have made rapid strides
in teasing out the biological effects of these biomolecules –
and every now and then, a phytochemical has been
identified as being crucial to the health-promoting effects of
individual foods, or groups of food, which have been
singled out as especially potent medicines in Nature’s
pharmacy. Each of these discoveries reveals a critical
element of good nutrition that has been missing from
narrowly-defined “multivitamin” formulas.
Figure 3: Unbalanced alpha-tocopherol supplements deplete your body of
gamma-tocopherol. Redrawn from (55).
But there are literally thousands of biologically active
substances in plants: over 5 000 have been identified, many
of them only recently.88 But while some of them are
important contributors to the health of people consuming
them, others are needed by the plant, but are of no value
to us when we eat them – and some of these compounds
(even if found in healthy foods) are known to be toxic.
The research on phytochemicals demands a new approach
to nutritional supplementation. Those bioactive plant
molecules which will help you reach a longer, healthier life
need to be identified and placed on the “A” list for the core
nutritional supplement of tomorrow. But other such
compounds are helpful to only a few people with unique
health concerns, and therefore should not be in a
multinutrient formulation designed to be taken by every
health-conscious person. Still others are of no nutritional
value, and ultimately only of interest to agronomists. And a
few are even harmful. So how do you know which is which?
After decades of research, such an “A” list of
phytochemicals has emerged. The process was long and
painstaking, but its conclusions are proportionally solid. It
began by narrowing down the broad category of “fruits
and vegetables,” and carefully looking at which plant foods
have the most consistent associations with good health. The
conclusion: while there are no doubt health benefits from all
fruits and vegetables, and while any given plant food or
phytochemical may catch a headline here and there, the
most powerful, consistent evidence points to cruciferous
vegetables (such as broccoli, cabbage, and mustard
greens); Allium vegetables (such as garlic and onions);
green, leafy vegetables; citrus fruits, tomatoes, carrots,
and raw vegetables generally, as being especially
powerful in promoting good health.89-96
High-dose alpha-tocopherol
supplements actually mortality
When you flood yourself with
unbalanced alpha-tocopherol
supplements, you actually deplete your
body of other E-complex members
0.15
0.14
0.13
0.12
0.11
0.10
0.09
0.08
0.07
0.06
0.05
0.04
0.03
0.02
Plasma γ- Tocopherol (mg/dl)
-4 0 1 3 7 14 21
28 29 30 31 32
36
Days
SUPPLEMENTATION PERIOD
D-α-tocopherol
pg. 7 ADVANCES in orthomolecular research
Researchers next turned their attention to the question of
why these particular plant foods should be more effective in
keeping you healthy than others. In the case of carrots, the
most likely player is its range of mixed carotenoids,
including lutein and alpha-carotene. But they found that the
other fruits and vegetables contain specific phytochemicals
which are either unique to these foods, or are found in much
higher amounts in these plant foods than in others. And by
exploring these phytochemicals’ effects on the body in
experimental animals and cellular studies, science has
vetted a phytochemical dream team.
The key plant bioactives are the isothiocyanates (most
importantly sulforaphane) and indoles (especially indole-
3-carbinol (I3C)), which appear as glucosinolates in
cruciferous vegetables; the Allium vegetables’ allyl
sulfides (the most potent of which is diallyl disulfide
(DADS)); the limonene and related monoterpenes found in
citrus (and especially citrus peel); the lycopene that comes
overwhelmingly from tomatoes and tomato products; transresveratrol,
found in red wine; green tea’s key polyphenol
EgCG; and chlorophyll, which gives the hue to green, leafy
vegetables. (The importance of raw vegetables probably
comes from the fact that the enzymes which liberate
sulforaphane and I3C from their storage forms are
inactivated by longer, higher-temperature cooking, leading
to reduced bioavailability of these cancer-fighting
nutrients97,98). While it’s currently not possible to put all of
these phytochemicals into a single multivitamin formulation
because of various interactions that make some of the
specific combinations technically impossible or undesirable,
it’s clear that a supplement program designed to closely
mimic an optimal diet must include as many of these phytopowerhouses
as possible.
A review of the scientific literature shows how consistently
the consensus has crystallized around the central
importance of these phytochemical elite.90-96 One can
certainly point to still other substances found in plants which
might have health benefits, but none of them have this
powerful weight of epidemiological, experimental,
mechanistic, and in some cases clinical99-101 evidence to back
them.
So, for instance, test-tube studies on the effects of ellagic
acid on DNA adduct formation are intriguing, but no studies
in the health habits of large human populations show that
people consuming lots of ellagic-acid-rich strawberries or
raspberries are less likely to develop cancer than people
eating other fruits and vegetables. The available results are
intriguing – but not strong enough to justify designating it a
critical phytonutrient which should be a part of every
health-conscious person’s supplement program. (In fact, the
same objection applies to many other polyphenols. For one
of the key reasons underlying many such disconnects, see
For Biochemistry Geeks Only!).
There are also many phytochemicals which have benefits to
people with serious health problems – but that aren’t
necessarily helpful to basically-healthy people looking to
further enhance and protect their health. In many cases,
these phytochemicals come from herbs and other botanicals
which are not a part of the regular, habitual diets of
anyone in the world: they should – and traditionally have
been – regarded as medicines for people with specific health
needs, not healthy foods that contribute to the well-being of
health-conscious people.
Figure 4 : Structural representation of Vit K1 and Vitamin K2.
Silymarin from milk thistle, for instance, is of great benefit
to people with some kinds of liver disease, mostly because
it fights the oxidative stress, membrane damage, and
inflammation of the liver that’s associated with cirrhosis
(scarring) of the organ,124,125 and also perhaps by increasing
the amount of protein-biosynthesis “instructions” coming out
of the tissue’s DNA code.125 All of this gives the cirrhotic liver
the opportunity to heal itself – but there’s no evidence that
healthy people, with undamaged livers, will get “superhealthy”
livers by taking this herb.
Since, in fact, we know virtually nothing about the effects of
these kinds of herbs on otherwise-healthy people; it’s hard
to see the idea of taking these powerful extracts regularly
as anything but an unnecessary gamble with your health.
They do not belong in a core multinutrient formulation,
designed to be taken by everybody, every day, for the rest
of your life.
Your Body’s “Detergent”
While these phytochemicals exert a wide range of
important effects on cellular metabolism, most of them share
the common feature that they modulate the balance of the
ADVANCES in orthomolecular research pg. 8
K1
K2
body’s detoxification enzymes. Your body neutralizes toxic
chemicals and many internal waste products using a twostep
biochemical breakdown process. In phase I
detoxification, ‘procarcinogen’ compounds are first made
more chemically reactive using a group of enzymes known
as the cytochrome P450s or mixed-function oxidases.
Think of phase I detoxification enzymes as “agents
provocateurs,” who infiltrate an enemy group to incite the
more dangerous elements in an organization to show their
cards. It’s then the job of the phase II detoxification system
to play the role of more conventional law enforcement,
“arresting” those fired-up (more reactive) “cellular
terrorists” and “handcuffing” them with molecules
(conjugates) that make them easier to safely excrete
through the urine or the bile.
The danger spot is in the step between, in which the
“activated” procarcinogens are potentially even more
dangerous, until they are “handcuffed” by the phase II
system. This is where many phytochemicals lend a hand.
Broadly, many of the best-documented phytochemicals
increase the activity of the phase II system, while reducing
down the activity of phase I. This slows the overproduction
of activated procarcinogens, and ensures that there is
enough phase II activity to ensure that activated
procarcinogens are all bound up and sent packing.126
But of course, for phase II detoxification to take place, your
phase II enzymes need an adequate supply of the
“handcuffs” (conjugates) that render the procarcinogens
tame. So it’s important to ensure that your diet and
supplement program contains plenty of key conjugation
factors such as acetic acid, glycine, taurine,
trimethylglycine, and sulfur sources such as NAcetylcysteine
(NAC).
Random Dosages
Almost every week, a new study comes out linking a diet rich
in some key nutrient with a longer, healthier life. And when
the popular press reports the story, they put it something like
this: “the people whose diets contained the most of this
nutrient were only two-thirds as likely to get breast cancer”
– or heart attack, or Alzheimer’s disease, or any of the
myriad assaults of “normal” aging. The problem with these
stories is that they rarely tell you how much of the nutrient in
question the people eating those diets were consuming. Too
often, in fact, the medical abstracts of the original scientific
papers don’t give you this information either. If you want to
find out, you have to take a jaunt down to a medical library
and dig up the full-text article.
But few people have the time to take this trouble, especially
granted the wide range of individual ingredients in their
core nutrient formulas, plus their “add-on” supplements. So,
most of us depend on the formulators of these products, not
just to include the right ingredients in their products, but to
include a research-backed dose.
Too often, this just doesn’t happen. In fact, comparing major
research papers to the ingredients lists on typical
supplement bottles, you’ll be forced to wonder if the
designers of such products used a dice roll to determine
their dosages.
Let’s take a couple of examples. There is powerful support
for the ability of the carotenoid lycopene to reduce the risk
of cancer – prostate cancer in particular,92,99,100 but also
cancers at many other sites in the body.92 But how much
lycopene is associated with cancer protection? Studies in
large populations show that high-lycopene diets, rich in
tomato paste and other good sources of the carotenoid,
provide from 13127 or 14,128 through 18,129,130 to as high as
24131 milligrams of lycopene a day. (Earlier studies, which
reported lower intakes (such as 6.5132 or 9133 mg/day) were
using an outdated carotenoid database which neglected
many lycopene-containing foods and which relied on an
obsolete analysis method that low-balled the foods’
carotenoid content134,135).
So a supplement designed to support the protective effects
of high-lycopene diets should also contain these same
established, protective amounts. Instead, nearly no
multinutrient products contain more than 3 milligrams of this
crucial carotenoid – and some contain as little as a tenth of
this paltry amount! To put this into its full, damning
perspective: because tomatoes and tomato products are
consumed even by people eating very poor diets (in the
form of ketchup on their MacGreaseburgers and a little
tomato sauce on the occasional slice of ’za), even the bottom
20% of diets provide lycopene in doses such as 2.3131 to
3.4129 or even as much as 4.4130 or 4.5128 milligrams of
lycopene on an average day!
Where do these senselessly low doses come from? Some
formulators just formulate their products in ignorance,
without bothering to dig into the original research; others
know full well that the measly dose they’re including won’t
do anyone any good, but cynically throw a token quantity
of lycopene into their products for no other reason than to
catch your eye as you scan their labels. Neither is providing
you with anything like the amount of lycopene that the
research says is needed to shield your body from the
ravages of cancer.
pg. 9 ADVANCES in orthomolecular research
Flavonoids of which there are several
thousands are abundant polyphenols in the human diet
and are divided into six main classes:
( ) (e.g. Catechins), (e.g.
Quercetin), (e.g. Luteolin),
(Naringin), (e.g. Genistein) and
(e.g. cyanidin)
Now let’s look at the other – and more disturbing – extreme.
While enthusiasm for beta-carotene has dampened thanks
to the spectacular failures of several large trials, at one
time most ‘premium’ multivitamins contained 25 to 50
milligrams (41 625 to 83 250 IU) of synthetic beta-carotene
in a daily dose; indeed, many antioxidant combination
products still contain such overdoses. (If you’re doublechecking
a supplement label for its carotenoid content,
you’ll want to look for the absolute milligram potency,
because many supplements list IU potencies using old,
outdated conversion factors;25 indeed, the proper way to
make this conversion remains controversial today.136
Milligram potencies are the clearest and best way to get
this information on a label).
We’ve already seen that the use of synthetic beta-carotene
was a disaster in the waiting; however, the use of these
massive amounts of the stuff can only have made things
worse. Because the strong evidence from epidemiological
and experimental studies that beta-carotene protects you
from cancer27 never supported such huge doses – and since
then, animal research has shown that the overkill quantities
of beta-carotene used in too many supplements actually
increase cancer risk when you’re exposed to cigarette
smoke.
Incredible – some would say unconscionable – but true.
When we turn again to research using the latest carotenoid
database to document the amount of beta-carotene being
consumed by people whose diets are rich in this carotenoid
– diets strongly and consistently associated with lower
cancer risk27 – we see that even the richest diets contain from
as little as 6.8,128 through 8.95129 or 9.8,131 and not more than
11.4127 milligrams of beta-carotene per day. In other words,
the amounts of beta-carotene which, in the diet, is
associated with reduced risk of cancer is only about a third
to one half of the amount used in far too many supplements
– and also in the unsuccessful clinical trials of beta-carotene
to prevent cancer.2-4
And recent studies suggest that this beta-carotene
overdosing isn’t just a matter of wasted money. At these
extreme doses, scientists have observed that the body’s
carcinogen-detoxifying systems become unbalanced137,138
and genes related to the cancer process become
activated.139 One study in ferrets (whose metabolism of
beta-carotene is much more like that of humans than is other
rodents’) compared animals exposed to cigarette smoke
alone to animals exposed to the smoke plus beta-carotene
supplements at one of two doses: one designed to reflect
the levels of beta-carotene present in a diet emphasizing
this nutrient, and the other reflecting the kinds of mega
doses typical of many antioxidant and multivitamin
products.
The results: the “rich-diet” beta-carotene supplement dose
resulted in lower levels of squamous metaplasia
(precancerous lesions) of the lung – but giving the same
animals the equivalent of a 30 milligram (49 950 IU)
synthetic beta-carotene supplement led to the activation of
several pro-cancer genes, and to the animals suffering more
precancerous lung lesions than did those exposed to
cigarette smoke alone!139
Along with the use of synthetic (all-trans-) rather than natural
(9-cis-containing) forms of the molecule, these findings
provide one of the likely reasons for the suggestion of
higher cancer risk in smokers given the equivalent,
unjustifiable doses of beta-carotene in the disastrously
failed clinical trials.2-4,134 And the proof in the pudding has
come from the massive SU.VI.MAX trial. This randomized,
double-blind, placebo-controlled study tested effects of an
antioxidant supplement containing doses that reflect the
amounts found in good diets – including 6 mg of beta
carotene and 120 mg of vitamin C, along with vitamin E,
selenium, and zinc – in 13 017 healthy, middle-aged French
men and women. After following the two groups for 7.5
years, it was found that supplements of beta-carotene and
other antioxidants, at doses typical of good diets,
reduced cancer incidence by 31%, and death from all
causes by 37%– although there was no reduction observed
in the women, apparently linked to fact that the women had
higher levels of antioxidant nutrients to begin with.140
Without hammering the point to death, let’s look at one
more example. It’s important to take all of the B vitamins,
not only because they’re essential nutrients but because they
work as a complex, with their metabolism dependent on one
another and an excess of one sometimes creates a
deficiency of another.141,142 But has it ever occurred to you
how weird it is that so many multivitamins and B-complex
vitamins contain exactly as much thiamin as niacin as
riboflavin, and so on – the same 50 mg or 100 mg for each
and every B vitamin except folic acid, all the way down the
list? Does it physiologically make sense that the body would
optimally use exactly the same amount of half a dozen
different B vitamins, each with its own unique, irreplaceable
functions in the body?
Well, of course, it doesn’t. The numbers used are arbitrary,
with no physiological justification. Someone, years ago,
Science has vetted a phytochemical
dream team: sulforaphane, indole-3-
carbinol (I3C), limonene, lycopene, transresveratrol,
EgCG, and chlorophyll
ADVANCES in orthomolecular research pg. 10
Comparing major research papers
to the ingredients lists on typical
supplement bottles, you ll wonder if the designers used a
dice roll to
determine their dosages.
Those Fickle Flavonoids
With so many phytochemicals showing favorable-looking results in test tube and animal studies, it’s a bit surprising to see how few
have been linked to better health in large population studies or clinical trials. In many cases, it’s likely that this has to do with the
way the body – and in particular, the human body – metabolizes these substances.
Polyphenols (including flavonoids and phenolic acids), in particular, undergo a whole series of complex biotransformations
which make it difficult to predict their effects in the body based on their effects in the test tube. Both the probiotic bacteria in
your intestinal tract, and your body’s own detoxification systems, really “go to town” on polyphenols, so that the original molecule
will go through several cycles of having old conjugates
cleaved and new ones added before it is finally excreted,
creating diverse and largely unpredictable array of
metabolites along the way (see Figure 5).102-104
With most nutrients, you can expect that the effects in
humans will be similar to the effects in experimental
animals. But in the case of flavonoids, this often doesn’t
pan out. Humans metabolize many flavonoids differently –
and often much more heavily – than rodents do,102 so that
extrapolation from rodent studies becomes an extremely
uncertain, speculative exercise.
Some of the metabolites of a given flavonoid will not be
absorbed at all; others will be absorbed, but their
biological activity will be much different from that seen in
test-tube studies using the original, un-metabolized
compound. It’s these metabolites – and not the parent
molecule – that will determine the real effect of flavonoids
in the body: good, bad, or indifferent.102
Let’s take a few examples. The absorption and metabolism
of epigallocatechin gallate (EgCG) in green tea is
well-characterized,105-112 the effects of its metabolites have been explored,113 and there is extensive epidemiological evidence
showing that people consuming high amounts (most consistently, ten servings of Japanese sencha green tea live longer,114 develop
less cancer,114-118 and possibly suffer fewer heart attacks.118, 119 Therefore, we can be confident that there really is value in bringing
EgCG into your diet and supplement program. By contrast, we’re only just beginning to get a handle on what the body does with
apigenin,120 luteolin,121 or the flavonoids in strawberries,122 and there is only very weak evidence to
suggest a specific health benefit in people whose diets contain high amounts of foods rich in these particular polyphenols, as
opposed to other plant foods.
This may also explain why research on the effects of flavonoids as a class in humans has been so conflicting. As one recent review
of the field put it, “Some studies support a protective effect of flavonoid consumption in
cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm.”123 The
bottom line: with such varying bioavailabilities and biological activities, you can’t really generalize from one polyphenol to
another – and you can’t rely on work in the test tube, or even experimental animals. Human clinical and epidemiological data for
specific foods and food flavonoids must be our touchstone.
Figure 5: Factors Affecting Flavonoid Absorption. Redrawn from (102).
ADVANCES in orthomolecular research pg. 12
plucked these numbers out of thin air – and somehow, they
stuck. The irrationality of these numbers can clearly be seen
in the case of thiamin.
The conventional form of thiamin cannot pass directly across
cell membranes: it requires a special shuttle system to pump
it across the intestinal wall and (later) into the cell. There are
enough “seats” on the shuttles to ensure that you’ll absorb
the small doses typically found in food … but most of a 50
milligram dose gets left waiting at the harbor as the ship
pulls away. And while a small amount of additional
absorption occurs via diffusion into the fluid that bathes the
cells, this adds little to total bioavailability: no
matter how much thiamin you take, you
don’t materially increase plasma levels
beyond what you get from the first
12 milligrams of the dose.143-147
Even greater problems occur in
getting thiamin into the cells to do
its job. While some thiamin crosses the
intestinal wall through diffusion into the
fluid surrounding the cells of the intestinal
tract, the cells themselves (except for red blood cells) cannot
absorb conventional thiamin except through the active
transport system.147,148
The strictness of the limits of this system can be seen when
you bypass the limited intestinal absorption of thiamin by
injecting it directly into the blood. When 5 milligrams are
injected, most of the dose is taken up by the cells, and the
kidneys will excrete only 25% of the original dose. But
increasing the dose does not increase the cellular
absorption. The more thiamin you inject, the more ends up
simply passing out through the urine, and at 100 milligrams
or more, 100% of the additional thiamin is excreted in the
urine.149
There’s certainly no harm to taking this extra thiamin – but
no point to it, either. This is one case where the old skeptic’s
taunt is true: you really are flushing most of that extra
thiamin down the toilet! And the same is true of a lot of
the other B vitamins you’re taking. Doses should be based
on science – not nice, round numbers.
When the Mix Won’t Match
There are plenty of health-promoting substances out there
that you may want to seriously consider taking in
supplemental form, but that you wouldn’t want to have
included in your multivitamin for one reason or another.
Many people, for instance, take supplemental IP6 (inositol
hexaphosphate or “phytate”), a nutrient found in many
plant foods which plenty of evidence suggests is a powerful
nutrient protector against the horrors of cancer.150 And it
would certainly be convenient to get this important
supplement along with your other core nutrients in one
formula. We’ve even seen IP6 included in some multivitamin
and immune-boosting formulas. The problem with doing this
lies in a key chemical property of IP6: its ability to react
with many minerals – including calcium and zinc – to form
tightly-bound, insoluble, un-absorbable complexes. The
result: when you mix IP6 with calcium in your gut, you
lose much of the benefit of both the IP6 and these
minerals!
This problem is even seen in some IP6-
rich grain foods. On the one hand,
bone disorders – including
osteomalacia, rickets, and
osteoporosis – are commonplace
in populations where unleavened
breads and similar foods provide
the bulk of the energy in the
diet;151-153 and on the other hand,
studies show that animals
receiving a diet high in wheat bran
experience two thirds less cancer protection than
animals given the same amount of IP6 in their drinking
water,154 where it doesn’t come in contact with the nutrients in
their food.
The key green tea polyphenol EgCG (epigallocatechin
gallate) is a similar case. Green tea polyphenols inhibit
the absorption of many minerals. The most famous case is
iron: green tea extracts clearly reduce its bioavailability,155
and it’s clear that people who drink a lot of tea and who
have marginal iron status are at higher risk of anemia.156-159
Tea polyphenols may also inhibit absorption of calcium160,161
and zinc,161,162 although the effects appear to be minor and
perhaps transient.
Of course, you may not want to absorb all of the iron in your
diet, particularly if you’re a man or a postmenopausal
woman or eat a high-meat diet. Excess iron levels are
associated with oxidative DNA damage163 and may increase
risk of several age-related diseases, including neurological
disease,24,164 diabetes,165-167 and possibly heart disease.168 But
while most people don’t need an iron supplement, people
who are conscious about their diet – particularly if they
don’t eat much red meat – have little to gain from actively
inhibiting their iron absorption. Overall, it just makes sense
to take your green tea supplements away from meals –
and thus separately from your main nutritional supplement.
The overkill quantities
of beta-carotene
used in too many
supplements actually increase
cancer risk
pg. 13 ADVANCES in orthomolecular research
Get Back to “Basics”
Oftentimes, people become so excited about the potential
of exotic botanicals or emerging orthomolecular compounds
to impact their health, that they pay less attention to the
basic, essential nutrients. Maybe it’s a case of “familiarity
breeding contempt:” we’re so familiar with zinc, copper, or
vitamin C that we neglect to pay them any attention. But you
can’t expect to enjoy optimized health from advanced
supplementation if your body is lacking the basic nutrient
cofactors required for its essential biochemical processes.
And on the flip side, as we’ve seen, it’s all too easy to
mistakenly imbalance yourself on these same nutrients or to
fail to reap their full benefits, if you aren’t paying enough
attention to just what and how much you’re taking.
Instead of just taking your supplements based on “one size
fits all” nutritional formula, it’s worthwhile to take careful
stock of where you’re at, nutritionally, from your diet alone.
If your diet is particularly healthy, you may not need a full
daily dose of a multivitamin formula; and if you have a diet
that is especially strong on a specific nutrient, you may not
need to add on extra nutrition on top of your multi as others
might. Do you drink a lot of milk? Then you probably don’t
need a full 1000 milligrams of calcium from supplements
alone. Are you absolutely addicted to oysters? Your zinc is
likely covered. And so on.
For those wishing to personalize their supplement program
to the greatest possible degree, there are many software
packages available that will actually tell you how much of
the essential nutrients you’re taking in each day. One of the
best is http://www.nutritiondata.com , which is free,
available online, and gives great, user-friendly graphical
output. The time required to plug in the foods you eat every
day for a couple of weeks will be worth it if it tells you
where key deficiencies or imbalances may lie – and where
you can rest on your nutritional laurels.
So the first rule of supplementation is: begin at the
beginning. With this base, you can consider moving up to a
more advanced multinutrient formula, incorporating key
phytochemicals from the “superstar” team identified above,
and then adding in additional, more advanced supplements
such as powerful phytochemicals or cutting-edge
orthomolecules like benfotiamine or extended release
R(+)-Lipoic Acid based on your own priorities and health
concerns. Once you have a well-laid foundation, you can
build up a solid nutritional fortress.
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supplement
led to more precancerous lung
lesions than those exposed to
cigarette smoke alone!
Supplements of betacarotene
and other
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typical of good diets, reduced
death
from all causes by 3 7 %
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166 Jiang R, Manson JE, Meigs JB, et al. Body iron stores in relation to risk of type 2 diabetes in
apparently healthy women. JAMA. 2004 Feb 11;291(6):711-7.
167 Ford ES, Cogswell ME. Diabetes and serum ferritin concentration among U.S. adults. Diabetes
Care. 1999 Dec;22(12):1978-83.
168 de Valk B, Marx JJ. Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med. 1999 Jul
26;159(14):1542-8.

]]> http://www.vitaminpost.ca/news/163/Is-Total-E-the-Answer%3F-.html Sun, 12 Jul 2009 04:57:58 +0000 http://www.vitaminpost.ca/news/163/Is-Total-E-the-Answer%3F-.html ADVANCES in orthomolecular research pg. 22
In December 2004, the Annals of Internal Medicine
announced the pre-press results of a new study on the
effects of high-dose “vitamin E” supplements on the death
rate in patients at high cardiovascular risk.1 Pooling the
results of 19 randomized, controlled trials of “vitamin E”
supplements, the authors concluded that “High-dosage (400
IU/d) vitamin E supplements may increase all-cause
mortality and should be avoided.”
If you’ll pardon the gallows humor: many supplement users
nearly had a heart attack.
How could this be? Vitamin E is, along with vitamin C,
probably the most widely-used antioxidant supplement in
the world, taken daily as a stand-alone supplement by
22% of American adults over 55 years of age.2 And its role
in heart health has been taken as health-food-store dogma
for decades. Even medical doctors – amongst the most
conservative people when it comes to the benefits of
supplements – take vitamin E pills at about the same rate
as the population at large.3,4
If you’ve listened to the mainstream press for
the last decade or so, you’ve probably
heard at least a few press reports on
studies that failed to find a benefit to vitamin
E in heart patients. But to suggest that
vitamin E might actually increase the death
rate is straight out of left field. It can’t be right.
Can it?
Well, yes, it can. All of those studies reporting “no effect”
have actually been finding very small increases in the death
rate in people taking the “vitamin E” supplements
compared to those taking the placebo dummy pills. But the
difference between the two groups has been so small as to
be statistically insignificant. No responsible scientist would
report a result that appeared to be nothing more than a
statistical fluke as a real increase in mortality.
It’s only when these many trials were combined into one
“supertrial” (meta-analysis) that it became clear. The
assembled trials showed no harmful effect from low-dose
(less than 50 IU per day) “vitamin E” supplements. In fact,
there even appeared to be a small benefit – but it’s hard
to say, because most of these low-dose studies (the Linxian,
MIN.VIT.AOX., and SU.VI.MAX. trials) also included
selenium and other beneficial nutrients that might have
been responsible for the positive results. But the pooled
results for the “high dose” (>400 IU) trials were clear:
people taking 400 IU or more of alpha-tocopherol a day
are actually increasing their risk of death (Figure 1)!1
If all you’ve heard about vitamin E and heart health has
come from the mainstream press and “establishment”
supplement companies, then this result will come as a
complete shock. But if
you’ve been watching
the research that’s been
accumulating on “vitamin
E” for the last decade or
so a bit more carefully,
you’ve spent much of the last decade waiting for this
second shoe to drop.
Alpha Tocopherol is Not “Vitamin E”
The starting point for an understanding of this apparent
In The News “Alpha-
Tocopherol Kills”?
“Vitamin E Kills”? Is
Total E The Answer?
Making Sense of the New Study
People taking 400 IU or more of
alpha-tocopherol a day are actually
increasing their risk of death.
Figure 1: Death from all causes goes up with increasing
doses of unbalanced alpha-tocopherol. Redrawn from (1).
pg. 23 ADVANCES in orthomolecular research
hairpin turn is to realize that supplements commonly
labeled “vitamin E” – including the ones used in the clinical
trials underlying the newly-discovered increase in death
rate from high-dose supplementation – are mislabeled.
They do not contain “vitamin E,” because there’s no such
thing. Alpha-tocopherol is no more “vitamin E” than
pyridoxine is “vitamin B.” Like “vitamin B,” vitamin E is a
complex – a family of eight molecules: four tocopherols and
four tocotrienols. These eight E-complex family members
work together in the body to support its health.
Even vitamin E “with mixed tocopherols” still leaves you
missing half of the E-complex: the tocotrienols. On top of
this, the proportions of the different tocopherols
contained in most “mixed tocopherol” supplements are
completely unbalanced. These products typically contain
five times as much alpha-tocopherol as the other three
tocopherols combined – a heavy-handed formulation which
guarantees that you won’t gain any health benefits from
these “other” vitamin E molecules.
It’s now known that taking too much alpha-tocopherol
actually depletes your body of other E-complex
vitamins,5-9 denying you of their benefits. In fact, when
alpha-tocopherol is taken at doses typical of most “vitamin
E” supplements, even counterbalancing it with an equal
amount of
the “other” E
vitamers isn’t
enough to
prevent this
supplementinduced
deficiency: the excessive alpha-tocopherol still
drives out gamma-, leaving your levels 30% below
what they would naturally be if you just ate a
regular diet.9 And in addition to lowering the level of
other E-complex molecules in your body,
supplements containing too much
alpha-tocopherol can directly counteract some of the
unique effects of the other E vitamins!10-12
The Blocked Benefits
In contrast to the results of trials using alpha-tocopherol
supplements, studies of the health of large populations of
people consistently find that people getting plenty of the
“vitamin E” in food enjoy a reduced risk of heart disease
and heart attacks.13-15 In fact, some studies have specifically
found that a high intake of the “vitamin E” in food is
protective against heart disease, but alpha-tocopherol
supplements are not.14,15
Why the seeming paradox? Perhaps, again, the form of
“vitamin E” is to blame. The vitamin E in food is a mixture of
the whole E complex, while most “vitamin E” supplements
are overloaded with alpha-tocopherol. And as we’ve
emphasized, supplements weighted toward alpha-tocopherol
deplete the body of other E vitamins, and can even
counteract their effects.5-9 So it may be that
conventional “vitamin E” supplements can’t protect your
heart because of all of the vitamin E molecules that are
missing from, or drowned out in, such supplements.
Since gamma-tocopherol is the single largest component of
the vitamin E in the diet,16-20 it makes sense to look into the
role that this E-complex member might play in the
protective effect of the vitamin E family against heart
disease. Such a role would make sense in the context of our
new understanding of the key role played by inflammation
in the development and progression of heart disease.21,22
That’s because of the differing effects of alpha- and
gamma-tocopherol against a class of free radicals known
as “reactive nitrogen species,” such as peroxynitrite,
nitroxyl, and nitrogen dioxide.
Alpha-tocopherol (and alpha-tocotrienol) are the most
important and effective
antioxidants
when it comes to
protecting your biological
membranes
from free radicals whose structure is based on oxygen23,24 –
but they’re almost useless in defending you against the
threat posed by reactive nitrogen species.25-27 And there’s
now significant evidence that much of the damage that
inflammation inflicts on the body is mediated by
reactive nitrogen species.
Unlike alpha-tocopherol, gamma-tocopherol is very
effective in trapping reactive nitrogen species – many
times more effective than its alpha- cousins.25-27 As well,
some evidence suggests that alpha-tocopherol can play a
role in dealing with nitrogen-based free radicals – not
directly, but by lending a helping hand to
gamma-tocopherol, restoring it to active duty after it is
“injured” in the battle against the reactive nitrogen foe.28
And the connection between reactive nitrogen and heart
disease – and the protective role of gamma-tocopherol – is
Too much
alpha-tocopherol actually
depletes your body of other
E-complex vitamins
alpha-tocopherol can directly
counteract some of the unique effects
of the other E vitamins
ADVANCES in orthomolecular research pg. 24
much more than just a reasonable-sounding theory. Plenty
of studies have found that people who have just suffered
a heart attack29 or who are afflicted with heart disease30-
33 have low plasma levels of gamma-tocopherol, while
their alpha-tocopherol levels are normal.
The question of just why heart patients’ gamma-tocopherol
levels are so low may have been answered by a recent
study34 which measured the levels of
5-NO2-gama-tocopherol in such people. (You’ll recall that
the 5-NO2 marker is the telltale residue that’s left over
when gamma-tocopherol detoxifies nitrogen-based free
radicals. High levels of this marker thus indicate that the
body’s gamma-tocopherol is being used up in the fight
against a brutal
onslaught of
reactive nitrogen
species). When
scientists measured
levels of
this waste product
in the bodies
of people suffering
with
c l o g g e d - u p
arteries, they
found that, on top of having somewhat lower levels of
gamma-tocopherol itself, people with coronary heart
disease have three times more used-up
gamma-tocopherol in their plasma than do healthy
people!34 Furthermore, these researchers found similarly
high levels of wasted gamma-tocopherol in the
atherosclerotic plaque itself, tying the suspect directly to the
scene of the crime.33
Other research shows us that gamma-tocopherol has many
heart-health benefits which reach beyond protecting the
body from reactive nitrogen species. For instance, a study
with experimental animals35 found that gamma-tocopherol
is superior to alpha-tocopherol in slowing down the
formation of potentially killer blood clots – clots which
can get stuck in a narrowed blood vessel and trigger a
stroke. The same study found gamma-tocopherol to be better
at preventing free radicals from making “bad” (LDL)
cholesterol more prone to form arteriosclerotic plaque
through oxidative modification, and at boosting levels of
the protective enzyme superoxide dismutase (SOD).
In another study,36 the same researchers tested the ability of
two different “vitamin E” preparations to protect heart cells
from the massive spike in free radicals that occurs when the
heart’s oxygen supply is restored after a period of having
been cut off – a model of “reperfusion injury,” which
causes much of the damage to the brain after a stroke, or
to the heart after a heart attack. One group of heart cells
was first pretreated with plain alpha-tocopherol. A second
group had its defenses bolstered with 62%
gamma-tocopherol blend (the remainder contained 25%
delta-tocopherol and just 13% alpha-tocopherol). And a
third group was not given any protective E vitamins. Then,
the cells were subjected to the crisis of simulated
reperfusion.
When heart cells are damaged by free radicals or various
other assaults, an enzyme called lactate dehydrogenase
(LDH) is leaked into the surrounding fluid at higher
concentrations than normal. This lets scientists use LDH levels
as a measure of damage to the heart after reperfusion
injury. In the unprotected cells, reperfusion savaged the
cells, causing levels of LDH in the surrounding medium to
double. As measured by the release of LDH, pretreatment
with alpha-tocopherol somewhat reduced the amount of
damage to the heart cells … but in the cells given the
high-gamma-tocopherol pretreatment, the injury was
People who are afflicted with
heart disease
have low plasma levels of
gamma-tocopherol,
while their
alpha-tocopherol levels
are normal
fig 2. Data on time to thrombus formation and platelet aggregation
from control group, alpha tocopherol and gamma tocopherol. Redrawn
from (1) .
fig 3. Oxidation of LDL by PMA-stimulated leukocytes. Redrawn from
(1).
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pg. 27 ADVANCES in orthomolecular research
nearly abolished (see Figure 2 & 3). The gamma-tocopherol
blend also provided superior protection against an
aggravated inflammatory response (as measured by the
levels and activity of the inflammatory enzyme inducible
nitric oxide synthase (iNOS)), and did a better job of
keeping the defensive SOD enzyme active (whereas
reperfusion normally forces its activity down).36
Toasting the Tocotrienols
Another group of E vitamins not included in standard
“vitamin E” supplements, and likely contributing to the
heart-health benefits of vitamin E-rich diets, are the
tocotrienols. Numerous randomized, double-blind,
placebo-controlled trials have shown that, in combination
with a diet low in
saturated fat, high
doses (usually 200
m i l l i g r a m s ) ,
tocotrienols lower
total and LDL
(“bad”) cholesterol
levels over
and above the
effects of a
heart-healthy diet
alone37-42 – typically
by an additional
10 to 20%.
Tocotrienols do this
through a mechanism
similar to – but
not the same as – the “statin” drugs (such as atorvastatin
(Lipitor®) and simvastatin (Zocor®)), modulating the effects
of an enzyme called hydroxymethylglutaryl CoA
reductase (or HMG-CoA reductase, if you don’t have all
day to spit it out).43,44 By contrast, alpha-tocopherol is unable
to favorably modulate the HMG-CoA enzyme. And in fact,
studies in animals10,11 and humans12 have found that when
tocotrienol supplements contain more than one-third
alpha tocopherol, the cholesterol-balancing benefits of
the tocotrienols are lost!
In the most exciting test of tocotrienols’ heart-health
benefits to date,45 fifty men and women with high
cholesterol and advanced atherosclerotic disease took
either 240 milligrams of tocotrienols or a dummy pill for a
year and a half, without either the patients or their doctors
knowing who got what. Before starting the trial, and every
six months thereafter, scientists used ultrasound to monitor
both groups’ disease status, measuring the thickening of the
main artery leading from the heart to the brain. As you
might expect, 40% of the people taking the placebo got
worse over the course of the trial, and none improved. But
astoundingly, not only did only 8% of the tocotrienol group
suffer any further thickening, but 28% of the people
taking the tocotrienol supplement experienced an actual
reversal of the thickening of their arteries!
This is a far cry from the total failure of alpha-tocopherol
to protect heart health seen in previous studies. The
difference is most striking when you compare these results
with the recent VEPAS trial,58 which found that supplements
containing alpha-tocopherol alone may actually increase
the thickening of your arteries!
Bring the Balance Back
So it’s easy to see how regular, unbalanced
alpha-tocopherol supplementation, by driving down levels
of gamma-tocopherol and the tocotrienols, could negate
these E vitamins’ benefits – leaving people swallowing these
pills at higher risk of heart disease and heart attack. So
let’s say that you’ve decided that you want to take advantage
of this new research, to restore – and even enhance –
the protective role of these “other” vitamin E molecules with
a complete, balanced E-complex formula.
This still leaves you with some questions. How much of the
various vitamin E family members should you take? The
research on the many E-complex vitamers is still just a tiny
exploratory expedition into a vast, largely unexplored
frontier, so the optimal amounts and ratios of these
molecules remain far from nailed down. And different
people, with different concerns and priorities, will benefit
from different E-complex supplement plans. But we can
gain some clues from the research that’s available to us.
First, obviously, to get the full benefits of the E-complex,
you’ll want to ensure that your supplement contains the
full spectrum of eight E-complex vitamins: four tocopherols
and four tocotrienols, with no missing molecules. Second,
because of its depleting effect on other E-complex
molecules, it’s important that the total amount of
E-complex molecules other than alpha-tocopherol should
significantly exceed the amount of alpha-tocopherol
itself.
In particular, based on what we know about the content of
different tocopherols in a healthy diet,9-13 and of the
28% of the people taking
the tocotrienol supplement
experienced an actual reversal of the
thickening of their arteries!
When tocotrienol supplements
contain more than one-third alpha
tocopherol, the cholesterol-balancing benefits
of the tocotrienols are lost
Palm, Source of
tocotreinols.
depleting effects of excessive alpha-tocopherol,2-6
gamma-tocopherol should make the single greatest
contribution to your E-complex fortification: there should
be at least twice as much gamma- as alpha-tocopherol
in your total supplement plan. Be sure to have a look at
all of your supplements. You may find that your
multivitamin, your antioxidant formula, or a supplement that
you take to address some specific health concern are all
laced with alpha-tocopherol. You’ll want to apply these
rules on the sum of your alpha-tocopherol intake, making
sure that you’re getting enough of the rest of the E-complex
to balance out that “hidden” alpha.
But there will be people who are particularly concerned
with reaping the specific benefits of high-dose tocotrienols.
Such persons might include people looking to restore a
healthy lipoprotein pattern in their blood, or who are at
high risk of breast cancer, or who have existing heart
disease. If you’re one of these people, the research
suggests you’ll want to take considerably more tocotrienols
than would be felt necessary by basically healthy people
who are simply looking to preserve and enhance their
overall health. For people whose situations push them
toward tocotrienols, a separate, high-dose tocotrienol
supplement is an obvious solution. For such use, be sure that
the amount of alpha-tocopherol you’re taking (in
milligrams) does not make up more than 30% of the sum of
alpha-tocopherol plus total tocotrienols combined,10-12
remembering to include the alpha-tocopherol in all of your
supplements in the equation.
Unfortunately, most multivitamin or antioxidant supplements
are formulated in ignorance of this research, with the result
that they often contain hundreds of IUs of alpha-tocopherol
and little to nothing of the rest of the complex. If you can,
it’s probably best to avoid such products altogether; if you
can’t, or choose not to, then you’ll want to take extra
tocotrienols and gamma-tocopherol to meet the guidelines
we’ve discussed. (Since alpha-tocopherol is usually given in
IUs instead of milligrams, you’ll need to multiply the IU
value of alpha-tocopherol by 0.66 to get the true number
of milligrams of alpha-tocopherol in these supplements).
The IU Lies!
And that brings up another point. People making the switch
from conventional alpha-tocopherol or “mixed tocopherol”
vitamin E formulas to a complete E-complex or tocotrienol
supplement often expect to see the “other” vitamin E
molecules measured in the familiar international unit (IU).
But IUs are an inaccurate way to measure vitamin E
activity. The IU only measures one specific function of
vitamin E: its ability to prevent animals from spontaneously
resorbing their fetuses.
Alpha-tocopherol exerts the strongest influence on this
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pg. 29 ADVANCES in orthomolecular research
process, and thus is assigned the highest IU potency per
milligram.What the IU does not measure is the many unique
contributions to your health made by the other E-complex
molecules – contributions that go beyond the maintenance
of basic reproductive functions, which can be met in humans
by 15 milligrams of alpha-tocopherol per day. This means
that measuring vitamin E activity in IU distorts the
contributions made by different E molecules,
exaggerating the importance of alpha-tocopherol and
downplaying the contributions unique to the other E
molecules. It’s as if you were asked to pay for works of
sculpture by the pound, irrespective of the subject or the
sculptor: the real value is obscured by an artificial common
currency.
For too long, health-conscious people have been subjected
to a game of “bait-and-switch,” with the staid old guard of
the supplement industry dangling forth the benefits of the
complete E complex in the diet to sell unbalanced
alpha-tocopherol supplements.
With the new meta-analysis,1 the true costs of these
marketing campaigns have become clear. Complete,
balanced E-complex supplements hold forth the promise of
delivering the full potential of this nutritional “broken
family.”
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28 Goss SP, Hogg N, Kalyanaraman B. The effect of alpha-tocopherol on the nitration of
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29 Ruiz Rejon F, Martin-Pena G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla B. Plasma status
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30 Nojiri S, Daida H, Mokuno H, Iwama Y, Mae K, Ushio F, Ueki T. Association of serum
antioxidant capacity with coronary artery disease in middle-aged men. Jpn Heart J. 2001
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31 Kontush A, Spranger T, Reich A, Baum K, Beisiegel U. Lipophilic antioxidants in blood
plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol.
Atherosclerosis. 1999 May;144(1):117-22.
32 Kristenson M, Zieden B, Kucinskiene Z, Elinder LS, Bergdahl B, Elwing B, Abaravicius A,
Razinkoviene L, Calkauskas H, Olsson AG. Antioxidant state and mortality from coronary heart
disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50. BMJ.
1997 Mar 1;314(7081):629-33.
33 Ohrvall M, Sundlof G, Vessby B. Gamma, but not alpha, tocopherol levels in serum are
reduced in coronary heart disease patients. J Intern Med. 1996 Feb;239(2):111-7.
34 Morton LW, Ward NC, Croft KD, Puddey IB. Evidence for the nitration of gamma-tocopherol
in vivo: 5-nitro-gamma-tocopherol is elevated in the plasma of subjects with coronary heart
disease. Biochem J. 2002 Jun 15;364(Pt 3):625-8.
35 Saldeen T, Li D, Mehta JL. Differential effects of alpha- and gamma-tocopherol on
low-density ipoprotein oxidation, superoxide activity, platelet aggregation and arterial
thrombogenesis. J Am Coll Cardiol. 1999 Oct;34(4):1208-15.
36 Chen H, Li D, Saldeen T, Romeo F, Mehta JL. Mixed tocopherol preparation is superior to
alpha-tocopherol alone against hypoxia-reoxygenation injury. Biochem Biophys Res Commun.
2002 Feb 22;291(2):349-53.
37 Qureshi AA, Bradlow BA, Salser WA, Brace LD. Novel tocotrienols of rice bran modulate
cardiovascular disease risk parameters of hypercholesteorlemic humans. J Nutr Biochem. 1997
May;8(5):290-8.
38 Qureshi AA, Qureshi N, Wright JJ, Shen Z, Kramer G, Gapor A, Chong YH, DeWitt G, Ong
A, Peterson DM, et al. Lowering of serum cholesterol in hypercholesterolemic humans by
tocotrienols (palmvitee). Am J Clin Nutr. 1991 Apr;53(4 Suppl):1021S-1026S.
39 Qureshi AA, Sami SA, Salser WA, Khan FA. Dose-dependent suppression of serum
cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans.
Atherosclerosis. 2002 Mar;161(1):199-207.
40 Qureshi AA, Sami SA, Salser WA, Khan FA. Synergistic effect of tocotrienol-rich fraction
(TRF(25)) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans. J Nutr
Biochem. 2001 Jun;12(6):318-329.
41 Qureshi AA, Bradlow BA, Brace L, Manganello J, Peterson DM, Pearce BC, Wright JJ, Gapor
A, Elson CE. Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids.
1995 Dec;30(12):1171-7.
42 Tan DT, Khor HT, Low WH, Ali A, Gapor A. Effect of a palm-oil-vitamin E concentrate on the
serum and lipoprotein lipids in humans. Am J Clin Nutr. 1991 Apr;53(4 Suppl):1027S-1030S.
43 Parker RA, Pearce BC, Clark RW, Gordon DA, Wright JJ. Tocotrienols regulate cholesterol
production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-
coenzyme A

]]> ADVANCES in orthomolecular research pg. 22
In December 2004, the Annals of Internal Medicine
announced the pre-press results of a new study on the
effects of high-dose “vitamin E” supplements on the death
rate in patients at high cardiovascular risk.1 Pooling the
results of 19 randomized, controlled trials of “vitamin E”
supplements, the authors concluded that “High-dosage (400
IU/d) vitamin E supplements may increase all-cause
mortality and should be avoided.”
If you’ll pardon the gallows humor: many supplement users
nearly had a heart attack.
How could this be? Vitamin E is, along with vitamin C,
probably the most widely-used antioxidant supplement in
the world, taken daily as a stand-alone supplement by
22% of American adults over 55 years of age.2 And its role
in heart health has been taken as health-food-store dogma
for decades. Even medical doctors – amongst the most
conservative people when it comes to the benefits of
supplements – take vitamin E pills at about the same rate
as the population at large.3,4
If you’ve listened to the mainstream press for
the last decade or so, you’ve probably
heard at least a few press reports on
studies that failed to find a benefit to vitamin
E in heart patients. But to suggest that
vitamin E might actually increase the death
rate is straight out of left field. It can’t be right.
Can it?
Well, yes, it can. All of those studies reporting “no effect”
have actually been finding very small increases in the death
rate in people taking the “vitamin E” supplements
compared to those taking the placebo dummy pills. But the
difference between the two groups has been so small as to
be statistically insignificant. No responsible scientist would
report a result that appeared to be nothing more than a
statistical fluke as a real increase in mortality.
It’s only when these many trials were combined into one
“supertrial” (meta-analysis) that it became clear. The
assembled trials showed no harmful effect from low-dose
(less than 50 IU per day) “vitamin E” supplements. In fact,
there even appeared to be a small benefit – but it’s hard
to say, because most of these low-dose studies (the Linxian,
MIN.VIT.AOX., and SU.VI.MAX. trials) also included
selenium and other beneficial nutrients that might have
been responsible for the positive results. But the pooled
results for the “high dose” (>400 IU) trials were clear:
people taking 400 IU or more of alpha-tocopherol a day
are actually increasing their risk of death (Figure 1)!1
If all you’ve heard about vitamin E and heart health has
come from the mainstream press and “establishment”
supplement companies, then this result will come as a
complete shock. But if
you’ve been watching
the research that’s been
accumulating on “vitamin
E” for the last decade or
so a bit more carefully,
you’ve spent much of the last decade waiting for this
second shoe to drop.
Alpha Tocopherol is Not “Vitamin E”
The starting point for an understanding of this apparent
In The News “Alpha-
Tocopherol Kills”?
“Vitamin E Kills”? Is
Total E The Answer?
Making Sense of the New Study
People taking 400 IU or more of
alpha-tocopherol a day are actually
increasing their risk of death.
Figure 1: Death from all causes goes up with increasing
doses of unbalanced alpha-tocopherol. Redrawn from (1).
pg. 23 ADVANCES in orthomolecular research
hairpin turn is to realize that supplements commonly
labeled “vitamin E” – including the ones used in the clinical
trials underlying the newly-discovered increase in death
rate from high-dose supplementation – are mislabeled.
They do not contain “vitamin E,” because there’s no such
thing. Alpha-tocopherol is no more “vitamin E” than
pyridoxine is “vitamin B.” Like “vitamin B,” vitamin E is a
complex – a family of eight molecules: four tocopherols and
four tocotrienols. These eight E-complex family members
work together in the body to support its health.
Even vitamin E “with mixed tocopherols” still leaves you
missing half of the E-complex: the tocotrienols. On top of
this, the proportions of the different tocopherols
contained in most “mixed tocopherol” supplements are
completely unbalanced. These products typically contain
five times as much alpha-tocopherol as the other three
tocopherols combined – a heavy-handed formulation which
guarantees that you won’t gain any health benefits from
these “other” vitamin E molecules.
It’s now known that taking too much alpha-tocopherol
actually depletes your body of other E-complex
vitamins,5-9 denying you of their benefits. In fact, when
alpha-tocopherol is taken at doses typical of most “vitamin
E” supplements, even counterbalancing it with an equal
amount of
the “other” E
vitamers isn’t
enough to
prevent this
supplementinduced
deficiency: the excessive alpha-tocopherol still
drives out gamma-, leaving your levels 30% below
what they would naturally be if you just ate a
regular diet.9 And in addition to lowering the level of
other E-complex molecules in your body,
supplements containing too much
alpha-tocopherol can directly counteract some of the
unique effects of the other E vitamins!10-12
The Blocked Benefits
In contrast to the results of trials using alpha-tocopherol
supplements, studies of the health of large populations of
people consistently find that people getting plenty of the
“vitamin E” in food enjoy a reduced risk of heart disease
and heart attacks.13-15 In fact, some studies have specifically
found that a high intake of the “vitamin E” in food is
protective against heart disease, but alpha-tocopherol
supplements are not.14,15
Why the seeming paradox? Perhaps, again, the form of
“vitamin E” is to blame. The vitamin E in food is a mixture of
the whole E complex, while most “vitamin E” supplements
are overloaded with alpha-tocopherol. And as we’ve
emphasized, supplements weighted toward alpha-tocopherol
deplete the body of other E vitamins, and can even
counteract their effects.5-9 So it may be that
conventional “vitamin E” supplements can’t protect your
heart because of all of the vitamin E molecules that are
missing from, or drowned out in, such supplements.
Since gamma-tocopherol is the single largest component of
the vitamin E in the diet,16-20 it makes sense to look into the
role that this E-complex member might play in the
protective effect of the vitamin E family against heart
disease. Such a role would make sense in the context of our
new understanding of the key role played by inflammation
in the development and progression of heart disease.21,22
That’s because of the differing effects of alpha- and
gamma-tocopherol against a class of free radicals known
as “reactive nitrogen species,” such as peroxynitrite,
nitroxyl, and nitrogen dioxide.
Alpha-tocopherol (and alpha-tocotrienol) are the most
important and effective
antioxidants
when it comes to
protecting your biological
membranes
from free radicals whose structure is based on oxygen23,24 –
but they’re almost useless in defending you against the
threat posed by reactive nitrogen species.25-27 And there’s
now significant evidence that much of the damage that
inflammation inflicts on the body is mediated by
reactive nitrogen species.
Unlike alpha-tocopherol, gamma-tocopherol is very
effective in trapping reactive nitrogen species – many
times more effective than its alpha- cousins.25-27 As well,
some evidence suggests that alpha-tocopherol can play a
role in dealing with nitrogen-based free radicals – not
directly, but by lending a helping hand to
gamma-tocopherol, restoring it to active duty after it is
“injured” in the battle against the reactive nitrogen foe.28
And the connection between reactive nitrogen and heart
disease – and the protective role of gamma-tocopherol – is
Too much
alpha-tocopherol actually
depletes your body of other
E-complex vitamins
alpha-tocopherol can directly
counteract some of the unique effects
of the other E vitamins
ADVANCES in orthomolecular research pg. 24
much more than just a reasonable-sounding theory. Plenty
of studies have found that people who have just suffered
a heart attack29 or who are afflicted with heart disease30-
33 have low plasma levels of gamma-tocopherol, while
their alpha-tocopherol levels are normal.
The question of just why heart patients’ gamma-tocopherol
levels are so low may have been answered by a recent
study34 which measured the levels of
5-NO2-gama-tocopherol in such people. (You’ll recall that
the 5-NO2 marker is the telltale residue that’s left over
when gamma-tocopherol detoxifies nitrogen-based free
radicals. High levels of this marker thus indicate that the
body’s gamma-tocopherol is being used up in the fight
against a brutal
onslaught of
reactive nitrogen
species). When
scientists measured
levels of
this waste product
in the bodies
of people suffering
with
c l o g g e d - u p
arteries, they
found that, on top of having somewhat lower levels of
gamma-tocopherol itself, people with coronary heart
disease have three times more used-up
gamma-tocopherol in their plasma than do healthy
people!34 Furthermore, these researchers found similarly
high levels of wasted gamma-tocopherol in the
atherosclerotic plaque itself, tying the suspect directly to the
scene of the crime.33
Other research shows us that gamma-tocopherol has many
heart-health benefits which reach beyond protecting the
body from reactive nitrogen species. For instance, a study
with experimental animals35 found that gamma-tocopherol
is superior to alpha-tocopherol in slowing down the
formation of potentially killer blood clots – clots which
can get stuck in a narrowed blood vessel and trigger a
stroke. The same study found gamma-tocopherol to be better
at preventing free radicals from making “bad” (LDL)
cholesterol more prone to form arteriosclerotic plaque
through oxidative modification, and at boosting levels of
the protective enzyme superoxide dismutase (SOD).
In another study,36 the same researchers tested the ability of
two different “vitamin E” preparations to protect heart cells
from the massive spike in free radicals that occurs when the
heart’s oxygen supply is restored after a period of having
been cut off – a model of “reperfusion injury,” which
causes much of the damage to the brain after a stroke, or
to the heart after a heart attack. One group of heart cells
was first pretreated with plain alpha-tocopherol. A second
group had its defenses bolstered with 62%
gamma-tocopherol blend (the remainder contained 25%
delta-tocopherol and just 13% alpha-tocopherol). And a
third group was not given any protective E vitamins. Then,
the cells were subjected to the crisis of simulated
reperfusion.
When heart cells are damaged by free radicals or various
other assaults, an enzyme called lactate dehydrogenase
(LDH) is leaked into the surrounding fluid at higher
concentrations than normal. This lets scientists use LDH levels
as a measure of damage to the heart after reperfusion
injury. In the unprotected cells, reperfusion savaged the
cells, causing levels of LDH in the surrounding medium to
double. As measured by the release of LDH, pretreatment
with alpha-tocopherol somewhat reduced the amount of
damage to the heart cells … but in the cells given the
high-gamma-tocopherol pretreatment, the injury was
People who are afflicted with
heart disease
have low plasma levels of
gamma-tocopherol,
while their
alpha-tocopherol levels
are normal
fig 2. Data on time to thrombus formation and platelet aggregation
from control group, alpha tocopherol and gamma tocopherol. Redrawn
from (1) .
fig 3. Oxidation of LDL by PMA-stimulated leukocytes. Redrawn from
(1).
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pg. 27 ADVANCES in orthomolecular research
nearly abolished (see Figure 2 & 3). The gamma-tocopherol
blend also provided superior protection against an
aggravated inflammatory response (as measured by the
levels and activity of the inflammatory enzyme inducible
nitric oxide synthase (iNOS)), and did a better job of
keeping the defensive SOD enzyme active (whereas
reperfusion normally forces its activity down).36
Toasting the Tocotrienols
Another group of E vitamins not included in standard
“vitamin E” supplements, and likely contributing to the
heart-health benefits of vitamin E-rich diets, are the
tocotrienols. Numerous randomized, double-blind,
placebo-controlled trials have shown that, in combination
with a diet low in
saturated fat, high
doses (usually 200
m i l l i g r a m s ) ,
tocotrienols lower
total and LDL
(“bad”) cholesterol
levels over
and above the
effects of a
heart-healthy diet
alone37-42 – typically
by an additional
10 to 20%.
Tocotrienols do this
through a mechanism
similar to – but
not the same as – the “statin” drugs (such as atorvastatin
(Lipitor®) and simvastatin (Zocor®)), modulating the effects
of an enzyme called hydroxymethylglutaryl CoA
reductase (or HMG-CoA reductase, if you don’t have all
day to spit it out).43,44 By contrast, alpha-tocopherol is unable
to favorably modulate the HMG-CoA enzyme. And in fact,
studies in animals10,11 and humans12 have found that when
tocotrienol supplements contain more than one-third
alpha tocopherol, the cholesterol-balancing benefits of
the tocotrienols are lost!
In the most exciting test of tocotrienols’ heart-health
benefits to date,45 fifty men and women with high
cholesterol and advanced atherosclerotic disease took
either 240 milligrams of tocotrienols or a dummy pill for a
year and a half, without either the patients or their doctors
knowing who got what. Before starting the trial, and every
six months thereafter, scientists used ultrasound to monitor
both groups’ disease status, measuring the thickening of the
main artery leading from the heart to the brain. As you
might expect, 40% of the people taking the placebo got
worse over the course of the trial, and none improved. But
astoundingly, not only did only 8% of the tocotrienol group
suffer any further thickening, but 28% of the people
taking the tocotrienol supplement experienced an actual
reversal of the thickening of their arteries!
This is a far cry from the total failure of alpha-tocopherol
to protect heart health seen in previous studies. The
difference is most striking when you compare these results
with the recent VEPAS trial,58 which found that supplements
containing alpha-tocopherol alone may actually increase
the thickening of your arteries!
Bring the Balance Back
So it’s easy to see how regular, unbalanced
alpha-tocopherol supplementation, by driving down levels
of gamma-tocopherol and the tocotrienols, could negate
these E vitamins’ benefits – leaving people swallowing these
pills at higher risk of heart disease and heart attack. So
let’s say that you’ve decided that you want to take advantage
of this new research, to restore – and even enhance –
the protective role of these “other” vitamin E molecules with
a complete, balanced E-complex formula.
This still leaves you with some questions. How much of the
various vitamin E family members should you take? The
research on the many E-complex vitamers is still just a tiny
exploratory expedition into a vast, largely unexplored
frontier, so the optimal amounts and ratios of these
molecules remain far from nailed down. And different
people, with different concerns and priorities, will benefit
from different E-complex supplement plans. But we can
gain some clues from the research that’s available to us.
First, obviously, to get the full benefits of the E-complex,
you’ll want to ensure that your supplement contains the
full spectrum of eight E-complex vitamins: four tocopherols
and four tocotrienols, with no missing molecules. Second,
because of its depleting effect on other E-complex
molecules, it’s important that the total amount of
E-complex molecules other than alpha-tocopherol should
significantly exceed the amount of alpha-tocopherol
itself.
In particular, based on what we know about the content of
different tocopherols in a healthy diet,9-13 and of the
28% of the people taking
the tocotrienol supplement
experienced an actual reversal of the
thickening of their arteries!
When tocotrienol supplements
contain more than one-third alpha
tocopherol, the cholesterol-balancing benefits
of the tocotrienols are lost
Palm, Source of
tocotreinols.
depleting effects of excessive alpha-tocopherol,2-6
gamma-tocopherol should make the single greatest
contribution to your E-complex fortification: there should
be at least twice as much gamma- as alpha-tocopherol
in your total supplement plan. Be sure to have a look at
all of your supplements. You may find that your
multivitamin, your antioxidant formula, or a supplement that
you take to address some specific health concern are all
laced with alpha-tocopherol. You’ll want to apply these
rules on the sum of your alpha-tocopherol intake, making
sure that you’re getting enough of the rest of the E-complex
to balance out that “hidden” alpha.
But there will be people who are particularly concerned
with reaping the specific benefits of high-dose tocotrienols.
Such persons might include people looking to restore a
healthy lipoprotein pattern in their blood, or who are at
high risk of breast cancer, or who have existing heart
disease. If you’re one of these people, the research
suggests you’ll want to take considerably more tocotrienols
than would be felt necessary by basically healthy people
who are simply looking to preserve and enhance their
overall health. For people whose situations push them
toward tocotrienols, a separate, high-dose tocotrienol
supplement is an obvious solution. For such use, be sure that
the amount of alpha-tocopherol you’re taking (in
milligrams) does not make up more than 30% of the sum of
alpha-tocopherol plus total tocotrienols combined,10-12
remembering to include the alpha-tocopherol in all of your
supplements in the equation.
Unfortunately, most multivitamin or antioxidant supplements
are formulated in ignorance of this research, with the result
that they often contain hundreds of IUs of alpha-tocopherol
and little to nothing of the rest of the complex. If you can,
it’s probably best to avoid such products altogether; if you
can’t, or choose not to, then you’ll want to take extra
tocotrienols and gamma-tocopherol to meet the guidelines
we’ve discussed. (Since alpha-tocopherol is usually given in
IUs instead of milligrams, you’ll need to multiply the IU
value of alpha-tocopherol by 0.66 to get the true number
of milligrams of alpha-tocopherol in these supplements).
The IU Lies!
And that brings up another point. People making the switch
from conventional alpha-tocopherol or “mixed tocopherol”
vitamin E formulas to a complete E-complex or tocotrienol
supplement often expect to see the “other” vitamin E
molecules measured in the familiar international unit (IU).
But IUs are an inaccurate way to measure vitamin E
activity. The IU only measures one specific function of
vitamin E: its ability to prevent animals from spontaneously
resorbing their fetuses.
Alpha-tocopherol exerts the strongest influence on this
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pg. 29 ADVANCES in orthomolecular research
process, and thus is assigned the highest IU potency per
milligram.What the IU does not measure is the many unique
contributions to your health made by the other E-complex
molecules – contributions that go beyond the maintenance
of basic reproductive functions, which can be met in humans
by 15 milligrams of alpha-tocopherol per day. This means
that measuring vitamin E activity in IU distorts the
contributions made by different E molecules,
exaggerating the importance of alpha-tocopherol and
downplaying the contributions unique to the other E
molecules. It’s as if you were asked to pay for works of
sculpture by the pound, irrespective of the subject or the
sculptor: the real value is obscured by an artificial common
currency.
For too long, health-conscious people have been subjected
to a game of “bait-and-switch,” with the staid old guard of
the supplement industry dangling forth the benefits of the
complete E complex in the diet to sell unbalanced
alpha-tocopherol supplements.
With the new meta-analysis,1 the true costs of these
marketing campaigns have become clear. Complete,
balanced E-complex supplements hold forth the promise of
delivering the full potential of this nutritional “broken
family.”
References
1 Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E
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2 Millen AE, Dodd KW, Subar AF. Use of vitamin, mineral, nonvitamin, and nonmineral
supplements in the United States: The 1987, 1992, and 2000 National Health Interview Survey
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3 : Muntwyler J, Hennekens CH, Manson JE, et al. Vitamin supplement use in a low-risk
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4 Frank E, Bendich A, Denniston M. Use of vitamin-mineral supplements by female physicians in
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14 Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM. Dietary antioxidant vitamins
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16 Lehmann J, Martin HL, Lashley EL, Marshall MW, Judd JT. Vitamin E in foods from high and
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17 Qureshi N, Qureshi AA. Tocotrienols: novel hypocholesterolemic agents with antioxidant
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Dekker, 247-67..
18 Heinonen M, Piironen V. The tocopherol, tocotrienol, and vitamin E content of the average
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19 McLaughlin PJ, Weihrauch JL. Vitamin E content of foods. J Am Diet Assoc. 1979
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20 Bieri JG. Sources and consumption of antioxidants in the diet. JAOCS. 1984
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21 Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore JR, Pepys MB.
Low grade inflammation and coronary heart disease: prospective study and updated
meta-analyses. BMJ. 2000 Jul 22;321(7255):199-204.
22 Lusis AJ. Atherosclerosis. Nature. 2000 Sep 14;407(6801):233-41.
23 Serbinova E, Kagan V, Han D, Packer L. Free radical recycling and intramembrane mobility
in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol. Free Radic Biol Med.
1991;10(5):263-75.
24 Kamal-Eldin A, Appelqvist LA. The chemistry and antioxidant properties of tocopherols and
tocotrienols. Lipids. 1996 Jul;31(7):671-701.
25 Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN.
Gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements
alpha-tocopherol: physiological implications. PNAS. 1997 Apr 1;94(7):3217-22.
26 Cooney RV, Harwood PJ, Franke AA, Narala K, Sundstrom AK, Berggren PO, Mordan LJ.
Products of gamma-tocopherol reaction with NO2 and their formation in rat insulinoma
(RINm5F) cells. Free Radic Biol Med. 1995 Sep;19(3):259-69.
27 Cooney RV, Franke AA, Harwood PJ, Hatch-Pigott V, Custer LJ, Mordan LJ.
Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol. PNAS.
1993 Mar 1;90(5):1771-5.
28 Goss SP, Hogg N, Kalyanaraman B. The effect of alpha-tocopherol on the nitration of
gamma-tocopherol by peroxynitrite. Arch Biochem Biophys. 1999 Mar 15;363(2):333-40.
29 Ruiz Rejon F, Martin-Pena G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla B. Plasma status
of retinol, alpha- and gamma-tocopherols, and main carotenoids to first myocardial infarction:
case control and follow-up study. Nutrition. 2002 Jan;18(1):26-31.
30 Nojiri S, Daida H, Mokuno H, Iwama Y, Mae K, Ushio F, Ueki T. Association of serum
antioxidant capacity with coronary artery disease in middle-aged men. Jpn Heart J. 2001
Nov;42(6):677-90.
31 Kontush A, Spranger T, Reich A, Baum K, Beisiegel U. Lipophilic antioxidants in blood
plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol.
Atherosclerosis. 1999 May;144(1):117-22.
32 Kristenson M, Zieden B, Kucinskiene Z, Elinder LS, Bergdahl B, Elwing B, Abaravicius A,
Razinkoviene L, Calkauskas H, Olsson AG. Antioxidant state and mortality from coronary heart
disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50. BMJ.
1997 Mar 1;314(7081):629-33.
33 Ohrvall M, Sundlof G, Vessby B. Gamma, but not alpha, tocopherol levels in serum are
reduced in coronary heart disease patients. J Intern Med. 1996 Feb;239(2):111-7.
34 Morton LW, Ward NC, Croft KD, Puddey IB. Evidence for the nitration of gamma-tocopherol
in vivo: 5-nitro-gamma-tocopherol is elevated in the plasma of subjects with coronary heart
disease. Biochem J. 2002 Jun 15;364(Pt 3):625-8.
35 Saldeen T, Li D, Mehta JL. Differential effects of alpha- and gamma-tocopherol on
low-density ipoprotein oxidation, superoxide activity, platelet aggregation and arterial
thrombogenesis. J Am Coll Cardiol. 1999 Oct;34(4):1208-15.
36 Chen H, Li D, Saldeen T, Romeo F, Mehta JL. Mixed tocopherol preparation is superior to
alpha-tocopherol alone against hypoxia-reoxygenation injury. Biochem Biophys Res Commun.
2002 Feb 22;291(2):349-53.
37 Qureshi AA, Bradlow BA, Salser WA, Brace LD. Novel tocotrienols of rice bran modulate
cardiovascular disease risk parameters of hypercholesteorlemic humans. J Nutr Biochem. 1997
May;8(5):290-8.
38 Qureshi AA, Qureshi N, Wright JJ, Shen Z, Kramer G, Gapor A, Chong YH, DeWitt G, Ong
A, Peterson DM, et al. Lowering of serum cholesterol in hypercholesterolemic humans by
tocotrienols (palmvitee). Am J Clin Nutr. 1991 Apr;53(4 Suppl):1021S-1026S.
39 Qureshi AA, Sami SA, Salser WA, Khan FA. Dose-dependent suppression of serum
cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans.
Atherosclerosis. 2002 Mar;161(1):199-207.
40 Qureshi AA, Sami SA, Salser WA, Khan FA. Synergistic effect of tocotrienol-rich fraction
(TRF(25)) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans. J Nutr
Biochem. 2001 Jun;12(6):318-329.
41 Qureshi AA, Bradlow BA, Brace L, Manganello J, Peterson DM, Pearce BC, Wright JJ, Gapor
A, Elson CE. Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids.
1995 Dec;30(12):1171-7.
42 Tan DT, Khor HT, Low WH, Ali A, Gapor A. Effect of a palm-oil-vitamin E concentrate on the
serum and lipoprotein lipids in humans. Am J Clin Nutr. 1991 Apr;53(4 Suppl):1027S-1030S.
43 Parker RA, Pearce BC, Clark RW, Gordon DA, Wright JJ. Tocotrienols regulate cholesterol
production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-
coenzyme A

]]> http://www.vitaminpost.ca/news/162/There%27s-No-Such-Thing-as-%22Vitamin-E%22%21.html Sun, 12 Jul 2009 04:48:08 +0000 http://www.vitaminpost.ca/news/162/There%27s-No-Such-Thing-as-%22Vitamin-E%22%21.html There's No Such Thing as "Vitamin E"!

AOR Total E - 60 softgels

What's Missing from Your "Natural Vitamin E" Supplement

Imagine walking into your local health food store and
seeing a bottle on the shelf labeled simply "Vitamin B."
You'd be a little puzzled, wouldn't you? Maybe even curious
enough to pick up the bottle and see just what the label
meant.

Next imagine that it turned out that the pills in the bottle
contained just one B vitamin: thiamin. What would you think?
That the manufacturers didn't know what they were doing?
That someone was trying to dupe the gullible? That it was a
typo - that they had accidentally missed the "1" in "Vitamin
B1" (thiamin)?
Sure, you'd think, thiamin is one B vitamin, but what about
the rest of the B-complex? There's no such thing as just
"Vitamin B."
Exactly. While there are B vitamins, there is no one "vitamin
B." Instead, the B vitamins are a family: the "B complex." Just
because you're getting plenty of one B vitamin - niacin, say,
or riboflavin - doesn't mean that your needs for
pantothenate, or folic acid, or the rest of the B-complex are
being met. Not only does each B vitamin have its own unique
role to play in supporting your health, but the B complex
also works together, as a synergistic whole. You need the full
team on your side to enjoy the health benefits of the Bfamily
vitamins. In fact, supplementation with just part of the
B complex can even create an artificial deficiency in other
B vitamins.1
Most health-conscious people already know all of this. The
irony is that nearly every one of us falls into the exact same
trap when we buy "vitamin E."
Introducing the E Complex
Have a look at your "Natural Vitamin E" supplement. The
label probably reads something like this: "d-alpha
tocopherol ... 400 IU." That may seem perfectly
appropriate: after all, that's what vitamin E is, right?
Well, no - it's not. Alpha-tocopherol is no more "vitamin E"
than pyridoxine is "vitamin B." Like "vitamin B," vitamin E is
a complex - a family of eight molecules: four tocopherols
and four tocotrienols. These eight E-complex family
members work together in the body to support its health. As
we'll see, each member of the family has its own, unique
functions. No one family member can fully substitute for
another.
"But," you may say, "the vitamin E I bought says it contains

'Natural Mixed Tocopherols.' So it's complete, right?"

AOR Total E - 60 softgels

Unfortunately not - for two reasons.
First, even vitamin E "with mixed tocopherols" still leaves you
missing half of the E-complex: the tocotrienols. (We'll get
into the difference between tocopherols and tocotrienols -
and some of the reasons you'll want to be sure that you're
getting enough of this half of the vitamin E family - a little
later on). Second, the proportions of the different
tocopherols contained in most "mixed tocopherol"
supplements are completely unbalanced. These products
typically contain five times as much alpha-tocopherol as the
other three tocopherols combined - a heavy-handed
formulation which guarantees that you won't gain any
health benefits from these "other" vitamin E molecules.
It's now known that taking too much alpha-tocopherol
actually depletes your body of other E-complex vitamins.2-6
This fact is an unfortunate side-effect of our evolutionary
history. In the Darwinian struggle to pass on genes, there is
a powerful evolutionary pressure at work which selects traits
that ensure successful reproduction - sometimes even at the
expense of putting long-term health at risk. And of all the
members of t he E family, alpha-tocopherol contributes the
most to ensuring that pregnant animals successfully bring
their fetuses to term.7,8
But alpha-tocopherol makes up only a fraction of the total
vitamin E in food - and much of that is in the germ of
grains,9-13 which played no part in the diet that shaped our
evolution.14 So in order to ensure their reproductive fitness,
most animals - including humans - have evolved mechanisms
of selectively holding onto the small amount of alphatocopherol
found in our natural diets, at the expense of the
other E vitamins.15,16
This selective retention of alpha-tocopherol is a critical
evolutionary advantage if you're a Paleolithic huntergatherer,
living with the reality that your unborn child may
be lost to a simple nutritional deficiency in times of drought.
But it's a disaster if you're a modern human with access to a
reliable food supply - and to supplements that contain so
much alpha-tocopherol that they will rob your body of the
long-term health benefits of the other E-complex vitamins.
Vitamin E Special ADVANCES in orthomolecular research 1
2 ADVANCES in orthomolecular research Vitamin E Special
The best-studied example of this problem is alphatocopherol's
effect on gamma-tocopherol, which is the most
plentiful single E vitamin in food (as opposed to
supplements)9-13 and which holds out the most exciting
promise out of the tocopherol side of the vitamin E family.
After just three days of supplementing with 400 IU of
alpha-tocopherol, peoples' gamma-tocopherol levels
plummet by more than two-thirds (see Figure 1).3 In fact, as
little as 100 IU of alpha-tocopherol can force your gammatocopherol
levels down to 30% below what they would be
if you were taking no supplement at all.2 And after one
year of alpha-tocopherol supplementation, it may take as
much as two years to fully restore the body's alpha-togamma-
tocopherol ratio!5
Figure 1: Unbalanced alpha-tocopherol supplements deplete
your body of gamma-tocopherol. Redrawn from (2).
When alpha-tocopherol is taken at doses typical of most
"vitamin E" supplements, even counterbalancing it with an
equal amount of the "other" E vitamers isn't enough to
prevent this supplement-induced deficiency: the excessive
alpha-tocopherol still drives out gamma-, leaving your
levels 30% below what they would naturally be if you just
ate a regular diet.6 So the token amount of total tocopherols
other than alpha- contained in "mixed tocopherol" pills can't
hope to staunch the bleeding of this critical E vitamin from
your body. By contrast, even taking gamma-tocopherol
alone does not lower your alpha-tocopherol levels,17 and
taking supplemental tocotrienols actually boosts the alphatocopherol
level in your body.18,19
And (as we'll see), in addition to lowering the level of other
E-complex molecules in your body, supplements containing
too much alpha-tocopherol can directly counteract some of
the unique effects of the other E vitamins!
So what exactly can these "other" vitamin E molecules do
that alpha-tocopherol can't? The full answer to that question
will only come after many more years of research into this
emerging field of science. But we already have a lot of the
answers when it comes to two hot spots of vitamin E
research: gamma-tocopherol and the tocotrienols.
Gamma-Tocopherol
And the Smog Within
While we often tend to talk about "free radicals" as if they
were one faceless, undifferentiated horde of oxidative
enemies, they're actually more of a rag-tag mob than a
uniform army. Different free radicals are formed in
different ways, attack different targets, and are best
blocked by different antioxidants. CoQ10, for instance,
provides extremely effective defense against "lipid
peroxides" in cell membranes - but it's useless in defending
the body's proteins from "carbonylation" mediated by
unbound transition metals.
So one important reason to make sure that you're getting
the full spectrum of E vitamins is the fact that the unique
chemical structures of each of the vitamin E family members
gives them differing antioxidant roles in the body. For
instance, alpha-tocopherol and alpha-tocotrienol are the
most important and effective antioxidants when it comes to
protecting your biological membranes from free radicals
whose structure is based on oxygen20,21 - but they're almost
useless in defending you against the threat posed by
"reactive nitrogen species," such as peroxynitrite, nitroxyl,
and nitrogen dioxide.22-24
These nitrogen-based molecular vandals are the main class
of free radicals found in smog and cigarette smoke, and are
produced by the body during inflammation. As you may
know, there's a growing consensus in the scientific community
that inflammation lies at the heart of many age-related,
degenerative diseases: not just obvious ones like rheumatoid
arthritis, but also heart disease,25,26 cancer,27 and agerelated
neurodegenerative disorders (most notably
Alzheimer's disease).28 And there's now significant evidence
that much of the damage that inflammation inflicts on the
body is mediated by reactive nitrogen species.
But while the chemical structures of the "alpha-Es" make
them nearly powerless against these cellular arsonists,
gamma-tocopherol is very effective in trapping reactive
nitrogen species - many times more effective than its alphacousins.
22-24 As well, some evidence suggests that alphatocopherol
can play a role in dealing with nitrogen-based
Vitamin E Special ADVANCES in orthomolecular research
free radicals - not directly, but by lending a helping hand
to gamma-tocopherol, restoring it to active duty after it is
"injured" in the battle against the reactive nitrogen foe.29
Even when all they had to go on were the results of a few
test-tube studies and some anomalies in the previous vitamin
E research, the importance of fighting off reactive nitrogen
species led pioneering gamma-tocopherol researchers at
the University of California to suggest that "Because alphatocopherol
supplementation suppresses gamma-tocopherol
levels, a combination of the two tocopherols that better
reflects the ratios found in our diet may be more useful as
a supplement than the formulations currently available."22
Just a few years later, documentation has replaced
educated speculation as, one after another, studies have
reached the conclusion that gamma-tocopherol protects
against age-related, inflammation-linked degenerative
disease where alpha-tocopherol fails.
Gamma-Tocopherol Against Prostate Cancer
Older studies of alpha-tocopherol's effects on a man's risk
of prostate cancer have been rife with seeming
contradictions. One large study (the ATBC trial)30 found that
a low-dose (50 milligram) alpha-tocopherol supplement
reduced the risk of prostate cancer. Yet the results of a
previous study suggest that high-dose alpha-tocopherol
may actually increase prostate cancer risk.31,32 The
suggestion of a greater vulnerability was there at doses
exceeding 100 IU of alpha-tocopherol, and it became
stronger when scientists looked at a subgroup of men taking
400 IU.31
The latest study to investigate the subject33 may have
resolved the issue - by looking at the whole vitamin E
picture, instead of at alpha-tocopherol in isolation. This
study found that men who have the most gamma-tocopherol
in their blood are an astounding five times less likely to
develop prostate cancer than men whose blood gammatocopherol
levels are lowest. In the same study, alphatocopherol
and selenium levels were also found to be
protective, but only in men whose gamma-tocopherol levels
were also high: if gamma-tocopherol was low, then neither
of these other nutrients provided any benefits!
When researchers then looked back at the results of a
previous epidemiological study, they re-analyzed the results
and uncovered the same association.34 This result was also
consistent with a previous study in Japanese men,35 which
seemed to hint that gamma-tocopherol - but not alphatocopherol
- made men less likely to fall prey to this deadly
disease.
Why would gamma-tocopherol be so important in warding
off cancer of the prostate? No one can say for sure yet, but
a good bet is that there's a connection with reactive nitrogen
species.31 As we've already seen, chronic inflammation has
been linked to many different kinds of cancer,27 including
cancer of the prostate.36 A lot of inflammation's collateral
damage is inflicted directly by reactive nitrogen species ...
and gamma-tocopherol is an effective detoxifier of this
class of free radicals.

AOR Total E - 60 softgels
And there's more evidence linking nitrogen-based free
radicals to prostate cancer: the unique prostate-protecting
effects of the carotenoid lycopene. Carotenoids - such as
beta-carotene, lutein, and cryptoxanthin - are the plant
pigments that give many vegetables their colors. Numerous
studies have investigated the possibility that a diet rich in
carotenoids can protect a man from prostate cancer. When
this idea has been tested by looking at the dietary practices
of large populations of men, only lycopene has consistently
been found to be associated with reduced risk.37 And the
evidence is now building closer to a definitive conclusion, as
lycopene's prostate-protecting potency has now been
supported by preliminary controlled trials.38,39
Why only lycopene, and not its carotenoid cousins? Perhaps
it's because lycopene is much more effective against
reactive nitrogen species than are the other
carotenoids.22,40,41 If this is the key to lycopenes prostateprotecting
powers, then the promise of gamma-tocopherol
would be even greater, since even lycopene's ability to fight
off nitrogen-based free radicals is actually much weaker
than gamma-tocopherol's!22
The new information about prostate cancer, reactive
nitrogen species, and gamma-tocopherol may tie up the
loose ends in the vitamin E/prostate cancer story, giving
scientists an unified explanation of how low-dose alphatocopherol
could buffer the risk of prostate cancer,30 even
though high-dose alpha-tocopherol may possibly put men at
greater risk.31,32 Remember, while alpha-tocopherol alone is
almost impotent against the nitrogen-based free radical
assault,22-24 a small amount of alpha-tocopherol may help
keep gamma-tocopherol up and running, protecting you
against their onslaught.29 But a high intake of alphatocopherol
can force gamma-tocopherol out of your body,
denying you its protection altogether.2,5,6 So we would
expect that alpha-tocopherol would only be helpful against
prostate cancer at a dose low enough to allow gammatocopherol
levels to also be high - which is just what the
latest study found.33
But new research, published just before this article was
going to press, now suggests that there's more to the
protective power of gamma-tocopherol than its ability to
hose down reactive nitrogen species. In this new study,42
3
4 ADVANCES in orthomolecular research Vitamin E Special
scientists at the University of Bern's Institute of Biochemistry
and Molecular Biology investigated the ability the
tocopherols to prevent two different lines of prostate cancer
from advancing from the G1 ("Gap 1") phase (in which the
cancer cell increases its volume in preparation for
replicating its DNA) to the "S (Synthesis) phase" (in which
DNA is actually synthesized). The move from G1 phase to S
phase is a critical juncture in cancer cell proliferation:
slowing down this transition keeps the tumor from growing.
The differences were remarkable. In one cell line, gammatocopherol
slowed prostate cancer cell transition from G1 to
S by 86%, versus only 50% for alpha-tocopherol; the huge
efficacy gap was also seen in another prostate cancer line
(74% versus 48%), and also in a bone cancer cell line (13%
and 4%, respectively). By looking at the cells' production of
key proteins regulating the cell cycle, the scientists were
even able to track down this inhibition of growth to its
source: gamma-tocopherol significantly inhibited the cancer
cells' production of cyclins D1 and E - proteins that fuel
tumor growth by forcing cancer cells to undergo the G1-to-
S transition.42
This new research further reinforces the urgency of the
recommendations of the researchers who unraveled the
differing effects of the two tocopherols on mens' prostate
cancer risk: as they put it,33 "Since supplementation with
alpha-tocopherol may lower gamma-tocopherol
concentrations in plasma and tissues, consideration should
be given to supplementation with combined alpha- and
gamma-tocopherols in future prostate cancer prevention
trials."

AOR Total E - 60 softgels
Brain Smog Alzheimer's disease is now known to be a state
characterized by chronic inflammation: a slow flame that
gradually blackens the brain.28 Accordingly, people taking
anti-inflammatory drugs for more than two years have been
consistently found to have a dramatically lower risk of
developing the disease.43 Evidence has accumulated that, as
in other inflammatory disorders, much of the damage to the
brain of the Alzheimer victim is directly caused by nitrogenbased
free radicals generated by the inflammatory
process.44-46 The same appears to be true of several other
neurological disorders, including Parkinson's disease.45,46
The latest, strongest support for this hypothesis is a recent
study47 in which scientists looked at the amount of damage
in the brains of people with Alzheimer's disease that was
specifically caused by reactive nitrogen species. They found
that areas of the brain which degenerate in Alzheimer's
disease are riddled with the biochemical debris left over
when proteins are damaged by nitrogen-based free
radicals. In fact, these Alzheimer's-sensitive parts of the
brain had five to eight times as much of this kind of damage
as was found in areas of the brain which are less affected
by Alzheimer's pathology.
By tracing the smoky haze that clouds the brains of people
with Alzheimer's disease back to the flames of reactive
nitrogen, this study suggests that gamma-tocopherol might
be our first-line fire extinguisher. Scientists have just
released an ingenious study showing exactly that.48
As in a previous study,49 these investigators found that
alpha-tocopherol levels are the same in the brains of the
Alzheimer's victims as in the brains of people free from the
disease. But gamma-tocopherol levels are depleted
throughout the brains of people with Alzheimer's disease
compared to the brains of those without it, including a
significant decrease of over 50% in the cerebellum. These
depleted levels of gamma-tocopherol correspond with
increased levels of 5-NO2-gama-tocopherol - the leftover
husk of a molecule of gamma-tocopherol that has been
consumed in fighting nitrogen-based free radicals.48
What this shows is that there is a selective drain on gammatocopherol
in areas of the brain affected by Alzheimer's
disease, suggesting that this specific form of vitamin E is
being used up faster in the brains of people with the
disease than in healthy people. And you can almost hear the
second shoe dropping when researchers report that the
region-by-region pattern of used-up gamma-tocopherol
followed the pattern of nitrogen-based free radical
damage already established in the earlier study.47
To get a better idea of what gamma-tocopherol might
actually do to defend the cellular structures of the brain, the
same team tested gamma-tocopherol's capacity to protect
the enzyme alpha-ketoglutarate dehydrogenase complex
(KGDC) from damage by nitrogen-based free radicals,
comparing its power with alpha-tocopherol's performance.
KGDC is known to be destroyed by the nitrogen radical
peroxynitrite, and the brains of Alzheimer's patients have
50 to 75% less KGDC than do the brains of people who are
free of the disease. The researchers again confirmed the
protective power of gamma-tocopherol: as much as 55% of
the peroxynitrite damage to this Alzheimer's-sensitive
enzyme was prevented by gamma-tocopherol, while alphatocopherol
offered only a 15% reduction, even at the most
effective concentration.48
The implications of these detailed biochemical investigations
are supported by the results of recent studies comparing the
effectiveness of different sources of vitamin E in protecting
people against neurodegenerative diseases. In the last two
years, three separate studies of the risk of Alzheimer's
disease in large populations have found that high intakes of
the vitamin E in food - which is richest in gamma-tocopherol
- is associated with reduced risk of Alzheimer's disease,
while the use of alpha-tocopherol supplements provides no
protective benefits.50-52 A similar study of more general agerelated
cognitive decline reached the same conclusion.53
And the news keeps coming in, confirming that something
about food vitamin E is fundamentally different from the
vitamin E in supplements. As this article was approaching
press time, we were alerted to the results of a new study54
on the protective effects of "vitamin E" against Parkinson's
disease - a neurological disorder which, like Alzheimer's,
has been linked to reactive nitrogen species.45,46 In this
study,54 the diet and supplement habits of over 47 000 male
health professionals and nearly 80 000 nurses were
probed, and then their risk of Parkinson's was followed over
the course of the ensuing 12 to 14 years. Roughly one in five
of these health care workers was using a "vitamin E"
supplement (whether from alpha-tocopherol alone, or with
an cosmetic dash of "mixed tocopherols") - but these
supplements offered no protection. Yet those who got the
most of the vitamin E found in food, which is largely gamma
tocopherol, had their risk of Parkinson's disease knocked
down by one third.
The research all points in one direction. In fact, the scientists
who performed the landmark biochemical studies in
Alzheimer's patients' brains go further, suggesting that, since
"Dietary supplementation with alpha-tocopherol will
decrease plasma levels of gamma-tocopherol ... it is
conceivable that the beneficial effects of alpha-tocopherol
supplementation are confounded by a diminuition of
gamma-tocopherol pools in [Alzheimer's disease&91; ... A better
clinical paradigm might entail cosupplementation with
gamma-tocopherol [all emphasis ours&91;."48 As we've already
seen, these researchers are part of a growing chorus of
scientists calling for a fundamental shift in vitamin E
supplements: a shift away from alpha-tocopherol
hegemony, and toward a balance of E complex molecules,
giving preeminence to gamma-tocopherol.
Smoldering Arteries
Despite high hopes, many large-scale, double-blind,
placebo-controlled studies have now brought home an
inescapable conclusion: alpha-tocopherol supplements do
not give any protection against death from a heart attack
or other heart hazards in people at high risk, whether
alpha-tocopherol is taken alone (as in the HOPE,55 GISSI,56
CHAOS,57 Primary Prevention Project (PPP),58 and recent
VEAPS59 trials) or even in combination with other
antioxidants (as in the HATS60 and MRC/BHF Heart
Protection Studies61).
And late in 2004, the results of a new study combining these
and other trials into one "supertrial" (meta-analysis) made
the true impact of overdosing on alpha-tocopherol clear.62
The assembled trials showed no harmful effect from lowdose
(less than 50 IU per day) "vitamin E" supplements. In
fact, there even appeared to be a small benefit - but it's
hard to say, because most of these low-dose studies (the
Linxian, MIN.VIT.AOX., and SU.VI.MAX. trials) also included
selenium and other beneficial nutrients that might have been
responsible for the positive results. But the pooled results for
the "high dose" (>400 IU) trials were clear: people taking
400 IU or more of alpha-tocopherol a day are actually
increasing their risk of death!62
In contrast to the results of trials using alpha-tocopherol
supplements, studies of the health of large populations of
people consistently find that people getting plenty of the
"vitamin E" in food experience reduced risk of heart disease
and heart attacks.63-65 In fact, some studies64,65 have
specifically found that a high intake of the "vitamin E" in
food is protective against heart disease, but alphatocopherol
supplements are not.
Why the seeming paradox? Perhaps, again, the form of
"vitamin E" is to blame. Remember, the vitamin E in the diet
is fundamentally different from that in most so-called
"vitamin E" supplements. The vitamin E in food is a mixture
of the whole E complex, while most "vitamin E" supplements
are overloaded with alpha-tocopherol. And as we've
emphasized, supplements weighted toward alphatocopherol
deplete the body of other E vitamins, and can
even counteract their effects.2-6 So it may be that
conventional "vitamin E" supplements can't protect your
heart because of all of the vitamin E molecules that are
missing from, or drowned out in, such supplements.
Since gamma-tocopherol is the single largest component of
the vitamin E in the diet,9-13 it makes sense to look into the
role that this E-complex member might play in the protective
effect of the vitamin E family against heart disease. Such a
role would make sense in the context of our new
understanding of the key role played by inflammation in the
development and progression of heart disease,25,26 and of
reactive nitrogen species as one of the main ways that
inflammation can damage the body. And the connection
between reactive nitrogen and heart disease - and the
protective role of gamma-tocopherol - is much more than
just a reasonable-sounding theory. Plenty of studies have
found that people who have just suffered a heart attack66
Vitamin E Special AADDVVAANNCCEESS iinn oorrtthhoommoolleeccuullaarr rreesseeaarrcchh 5
6 ADVANCES in orthomolecular research Vitamin E Special
or who are afflicted with heart disease67-70 have low plasma
levels of gamma-tocopherol, while their alpha-tocopherol
levels are normal.
The question of just why heart patients' gamma-tocopherol
levels are so low may have been answered by a recent
study71 which measured the levels of 5-NO2-gamatocopherol
in such people. (You'll recall that the 5-NO2
marker is the telltale residue that's left over when gammatocopherol
detoxifies nitrogen-based free radicals. High
levels of this marker thus indicate that the body's gammatocopherol
is being used up in the fight against a brutal
onslaught of reactive nitrogen species). When scientists
measured levels of this waste product in the bodies of
people suffering with clogged-up arteries, they found that,
on top of having somewhat lower levels of gammatocopherol
itself, people with coronary heart disease have
three times more used-up gamma-tocopherol in their plasma
than do healthy people!71 Furthermore, these researchers
found similarly high levels of wasted gamma-tocopherol in
the atherosclerotic plaque itself, tying the suspect directly to
the scene of the crime.70
But other research shows us that gamma-tocopherol has
many heart-health benefits which reach beyond protecting
the body from reactive nitrogen species. For instance, a
study with experimental animals72 found that gammatocopherol
is superior to alpha-tocopherol in slowing down
the formation of potentially killer blood clots - clots which
can get stuck in a narrowed blood vessel and trigger a
stroke. The same study found gamma-tocopherol to be
better at preventing free radicals from making "bad" (LDL)
cholesterol more prone to form arteriosclerotic plaque
through oxidative modification, and at boosting levels of the
protective enzyme superoxide dismutase (SOD).
In another study,73 the same researchers tested the ability of
two different "vitamin E" preparations to protect heart cells
from the massive spike in free radicals that occurs when the
heart's oxygen supply is restored after a period of having
been cut off - a model of "reperfusion injury," which causes
much of the damage to the brain after a stroke, or to the
heart after a heart attack. One group of heart cells was
first pretreated with plain alpha-tocopherol. A second
group had its defenses bolstered with 62% gammatocopherol
blend (the remainder contained 25% deltatocopherol
and just 13% alpha-tocopherol). And a third
group was not given any protective E vitamins. Then, the
cells were subjected to the crisis of simulated reperfusion.
When heart cells are damaged by free radicals or various
other assaults, an enzyme called lactate dehydrogenase
(LDH) is leaked into the surrounding fluid at higher
concentrations than normal. This lets scientists use LDH levels
as a measure of damage to the heart after reperfusion
injury. In the unprotected cells, reperfusion savaged the cells,
causing levels of LDH in the surrounding medium to double.
As measured by the release of LDH, pretreatment with
alpha-tocopherol somewhat reduced the amount of
damage to the heart cells ... but in the cells given the highgamma-
tocopherol pretreatment, the injury was nearly
abolished (see Figure 2). The gamma-tocopherol blend also
provided superior protection against an aggravated
inflammatory response (as measured by the levels and
activity of the inflammatory enzyme inducible nitric oxide
synthase (iNOS)), and did a better job of keeping the
defensive SOD enzyme active (whereas reperfusion
normally forces its activity down).73
Figure 2: Gamma-tocopherol-rich mixture provides heart cells
with far more protection than alpha-tocopherol against
reperfusion injury, as measured by LDH. Redrawn from (73).
And there's more. While our attention has been focused on
its ability to protect the body from the downstream effects
of inflammation (by quenching reactive nitrogen species),
recent evidence shows that gamma-tocopherol can also
intervene in the inflammation process itself.
COX-2 Inhibitor
Cyclo-oxygenase (COX) is an enzyme involved in making a
class of cellular micro-hormones called prostanoids. There
are two varieties of this enzyme, called (reasonably
enough) COX-1 and COX-2. The prostanoids made by the
two forms of COX have very different effects on the body.
The prostanoids made by COX-1 are needed by cells to
perform essential, day-to-day "housekeeping functions"
such as producing mucin in the stomach, while the
prostanoids derived from COX-2 are involved in
inflammatory reactions. So when COX-2 is kept from
making its prostanoids, inflammation is blocked.
Many older anti-inflammatory drugs (such as aspirin and
Non-Steroidal Anti-inflammatory Drugs (NSAIDs) like
ibuprofen) work by inhibiting the inflammatory COX-2
enzyme. Unfortunately, these drugs also interfere with COX-
1, which prevents it from carrying out its important
n=5
*P<0.01 vs Control
†P<0.05 vs H-R
§P<0.05 vs a-T+H-R
Control
H-R
α-T+H-R
m-T+H-R
α-T+
Normoxia
m-T+
Normoxia
*
†
LDH Levels in Media (U/L)
40
20
0
† §
"housekeeping functions." It's this anti-COX-1 problem that
causes the ulcers, kidney damage, and other side effects
associated with these drugs. The new "COX-2" inhibitor
drugs (such as celecoxib (Celebrex(r)) and rofecoxib
(Vioxx(r))) put the damper on the fires of COX-2, but
without hampering th