N-ACETYL-L-CARNOSINE EYEDROPS
A Revolution in Orthomolecular Eye Health!

The excitement surrounding the dipeptide Carnosine began when researchers at the Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia's premier scientific research center painstakingly documented the unthinkable: that carnosine can not only slow down, but actually reverse, cellular senescence - the process of "aging" at the cellular level.

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Based on their results, scientists "propose that carnosine is an important component of cellular maintenance mechanisms," and "favor the view that it may have a very important role in controlling cellular homeostasis" - that is, in keeping cells in the tightly-regulated condition that optimizes their function.

Taking Out the Trash
But how Carnosine exerts these effects remains a mystery. In test-tube studies, Carnosine protects cells and biomolecules against a sweeping range of toxic insults. The one protective effect that's probably received the most attention in the life extension community is its ability to protect proteins against glycation - the process through which sugars bind to proteins and warp their structure, turning functional proteins into dysfunctional Advanced Glycation Endproducts (AGEs). But this effect has only been shown to happen in test tubes: it's not really clear that the same thing would happen in a living person, and in fact there's good reason to believe that it won't.

Instead, it appears that Carnosine may attack the same problem from a different angle, actually boosting the cell's ability to clear out damaged proteins once they're formed. One of the problems with damaged proteins is that their mangled structures often don't give easy access to the enzymes that normally digest worn-out cellular components, making it difficult for the cell to remove them. Experimental studies have found that Carnosine reacts with proteins which have already been damaged by glycation and other assaults on their structural/functional integrity, forming "carnosylated" complexes which appear to be more easily removed than the original, warped protein.

At the same time, other such studies suggest that Carnosine revs up the proteasome - the cell's "recycling center" for malformed proteins. Instead of blocking the formation of AGEs, in other words, Carnosine might actually help the body to eliminate glycated and other dysfunctional proteins.

The results at the cellular level are enticing. The question that begs to be answered next is: how do these effects translate out on a larger scale - on the health of our tissues and organs - when you supplement with Carnosine?

Eyes Syruped Shut
Misshapen proteins accumulate across the entire structure of the eye with "normal" aging, interfering with visual functioning. AGEs, in particular, play a major role in the universal age-related loss of eye structure and function, as well as in the more specific degenerative diseases of the aging eye, such as cataracts, glaucoma, and age-related macular degeneration (AMD).

Delivering Carnosine directly to the eye itself, then, would be predicted to be the ideal real-world test case for the test-tube finding that Carnosine can protect against - and perhaps even actually undo - the damage wrought by glycation and other protein-warping mechanisms of aging. New human trials have shown that topical Carnosine delivers on this promise.

• In an open study protocol, scientists gave Carnosine supplements to patients in late middle age who had varying degrees of visual impairment, but no symptomatic cataracts. Over the course of two to six months, the scientists observed that the use of topical Carnosine supplementation "appears to alleviate eye tiredness and ... obviously improve eyesight, giving more clear vision." Users found that topical Carnosine "could brighten and relax their eyes." The improvements were statistically significant.

• In clinical studies involving 109 patients, these scientists found Carnosine effective in cases of primary and secondary corneal dystrophy, corneal erosions, trophic keratitis, and bullous keratopathy, as well as corneal ulcerations and other damage wrought on the cornea by viral and bacterial infections. The Russian government accordingly approved topical Carnosine supplementation for these uses as early as 1997.

• 21 people, with a total of 27 affected eyes, who had suffered corneal haze following Photorefractive Keratectomy (PRK - a form of laser surgery) (27 eyes were affected), were given topical Carnosine three times a day for two months. Fully 57.9% of people using the Carnosine eye drops experienced a reduction in corneal haze intensity, accompanied by an improvement in visual acuity; only 14% of users' eyes continued to worsen. The positive results appeared in patients with low to moderate myopia, who had developed moderate haze (1 to 1.5 on a 3-point scale) within a month of surgery; there are no known treatments which are effective for late corneal haze of a higher grade than this.

• In a second, larger, and more rigorous trial, patients who had just undergone PRK (41 patients (including 73 affected eyes)) or LASIK ("LAser in-Situ Keratomileusis" - 34 people, 60 eyes) were given the same thrice-daily regimen of topical Carnosine as was used in the first trial, while corresponding control groups (41 PRK patients and 34 LASIK recipients) received Carnosine-free dummy eye drops. Compared with people applying the placebo solution, the healing of the corneal epithelium of people supplementing with Carnosine eye drops took 35 hours less time to regrow - a speeding of the epithelial re-growth process of nearly a day and a half. Even better, users of topical Carnosine supplements following LASIK were one-third less likely to suffer corneal haze than those using the un-supplemented eye drops!

• In an open investigation, 96 senior citizens who had suffered with senile cataracts for as little as two to as much as twenty-one years applied topical Carnosine supplements to their eyes three or four times a day, for periods ranging from three to six months. At the end of the study, the researchers found that Carnosine eye drops lead to improvements in eyesight and lens transparency in the great majority of patients. They saw improvements in every single one of the people suffering with early-stage cataracts; and even in mature senile cataract, a remarkable 80% of the topical Carnosine users experienced a benefit. The investigators went on to expand on these preliminary results with the sequential treatment of nearly a thousand cataract patients - to similar success and with no side effects observed.

Instead of using Carnosine itself, more recent trials have used N-acetyl-L-Carnosine, a metabolite of Carnosine, which the body slowly converts back into free Carnosine, allowing for slower, more thorough delivery of free Carnosine into the eye's tissues and access to areas of the eye where Carnosine itself cannot penetrate.

• In a randomized, double-blind, placebo-controlled study, scientists first evaluated the baseline state of cataract victims' eyes. The scientists then randomly handed out either topical N-Acetyl-L-Carnosine supplements (as a 1% solution) or an identical-looking placebo solution. A third group of cataract patients received no eye drops at all.

After just six months, ninety percent of the eyes of people supplementing with N-Acetyl-L-Carnosine eye drops saw their visual acuity improve, with the strength of the effect ranging from a modest gain to a full 100% recovery. In the same period, only 5.7 percent of the eyes of people using the stand-in eye drops were judged to have improved visual acuity, while over a third (34.7%) suffered a worsening of acuity, and most (60%) simply retained the same impaired vision with which they had begun the study. In a two-year extension, N-Acetyl-L-Carnosine eye drop users were shown to maintain their improved vision, while the eyesight of those not receiving the supplement continues to deteriorate.

• On top of the gains in visual acuity, researchers observed that N-Acetyl-L-Carnosine topical supplementation also clearly improves glare sensitivity, with 88.9% of N-Acetyl-L-Carnosine eye drop users' eyes seeing improvements ranging from 27 to 100% after just six months; again, the divide separating supplementers from non-supplementers was unequivocal, with over half (56.3%) of nonusers' eyes deteriorating and none getting any better. The glare sensitivity tests were not repeated at the two-year mark.

• At the end of the full two-year trial, the image analyses showed that 47.8% of the lenses of N-Acetyl-L-Carnosine topical supplement users were clearer than they were at the beginning of the trial - and none had worsened. Meanwhile, none of the people whose eye drops did not contain N-Acetyl-L-Carnosine showed improvements on the image analysis, while a predictable 47.4% of the lenses continuing the hazy slide into blindness.

• Another randomized, placebo-controlled study tested the effects of N-Acetyl-L-Carnosine on glare disability in drivers. Glare disability is excessive luminance or a problematic distribution of luminance which disturbs vision. Elderly drivers often experience this problem at night from oncoming headlights. The problem increases with age, and is one of the first complaints of drivers with initial cataracts. Drivers aged 65-69 years have the second highest fatality rate per mile traveled (exceeded only by the youngest drivers), even though they travel fewer miles per year. In this study, N-Acetyl-L-Carnosine eye drops were given to 65 older drivers with a cataract in at least one eye, and to 72 adult drivers with no cataracts for 4 months. Eyes treated with N-Acetyl-L-Carnosine had a statistically significant improvement in visual acuity and glare sensitivity compared to the control group. N-Acetyl-L-Carnosine improved the drivers' vision whether or not they had cataracts, but the improvements were especially noticeable in those with cataracts.

For the first time, a simple topical treatment was proved to actually reverse the clouding of the cataracted lens - and the treatment was not a drug, but a natural substance naturally present in healthy cells.

The Rest of Us
The results of the many human trials constitute proof-of-concept for the wider concept that the use of topical Carnosine - and especially the unique Carnosine metabolite N-Acetyl-L-Carnosine, a biological "delivery system" for Carnosine - can help the eyes to heal from damage, and allow the body to remove dysfunctional proteins from the eye. When you put that together with the fact that malformed proteins are implicated in nearly every aspect of age-related visual decline, these studies clearly point to the potential of Carnosine/N-Acetyl-L-Carnosine eye drops to support the maintenance of normal, healthy eye structure and function in people whose eyes are just fine - and whose owners want to keep them that way.

An Important Note About Formulation
In all of the clinical trials, N-Acetyl-L-Carnosine has been used by itself, with no added antioxidants or other ingredients other than other than formulants (such as buffering agents) required to make a viable N-Acetyl-L-Carnosine ophthalmic solution. The metabolism of N-Acetyl-L-Carnosine into Carnosine depends on enzymes in the body (N-acetylesterase and N-acetyltransferase), which accomplish this transformation as part of their normal biological function. The activity of these enzymes can be significantly changed by the presence of antioxidants other than N-Acetyl-L-Carnosine in the area.

Therefore, mixing N-Acetyl-L-Carnosine with other antioxidants - such as vitamin A or alpha-tocopherol - in the same formula is asking for trouble. Under these circumstances, the conversion of N-Acetyl-L-Carnosine into Carnosine will be altered, with unpredictable results on the levels of free Carnosine delivered to different tissues within the eye.

The results observed in clinical trials flow from the natural, unmodified kinetics of these enzymes. Products which adulterate N-Acetyl-L-Carnosine with unnecessary additional antioxidants are untested, potentially ineffective, and may theoretically even damage your vision in the long term by leading to the inappropriate tissue-specific release of Carnosine, conversion to histamine, and resultant chronic, low-level inflammation. Ensure that any N-Acetyl-L-Carnosine supplement you use is free of extraneous antioxidants.

References

Babizhayev MA. Rejuvenation of Visual Functions in Older Adult Drivers and Drivers with Cataract During a Short-Term Administration of N-Acetylcarnosine Lubricant Eye Drops. Rejuvenation Research. 2004;7(3):186-198.

Kourenkov VV, Cheloudtchenko VM, Sergienko VI, Formazyuk VE, Beuerman RW, Maitchouk DY. Beta-alanyl-L-histidine (Carnosine) in the management of the healing process during and after excimer laser refractive surgery. Invest Ophthalmol Vis Sci. 1999 Mar 15; 40(4): 584(Abs544).

Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc). 2000 Jul; 65(7): 869-71.

Maichuk IuF, Formaziuk VE, Sergienko VI. Development of carnosine eye drops and assessing their efficacy in corneal diseases. Vestn Oftalmol. 1997 Nov-Dec; 113(6): 27-31.

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides. 2001 Jun; 22(6): 979-94.