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Suggested Use
Take one or two capsules per day with food, or as directed by a qualified health care practitioner.
Main Applications
* Calcium absorption
* Bone health
* Auto Immune Disorders
* Immune support
* Normal cellular growth and differentiation
Pregnancy / Nursing
No studies, best to avoid.
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*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
| The term vitamin as applied to vitamin D is inaccurate because it is synthesized by the skin following exposure to sunlight. Synthesis is dependent upon numerous factors including the type of ultraviolet and intensity, duration of exposure, skin pigmentation, age, altitude, latitude, hour of day and time of season.
Vitamin D deficiency is widespread across all population groups. Most physicians recognize that the elderly population is at risk, however it is less appreciated that children, young adults and middle age groups are also at risk. |
|
Studies have shown that children in Madrid, Spain to Maine, New York were approximately 50% deficit in vitamin D in the winter months. Apart from equilateral regions where people make sufficient vitamin D, people everywhere else (particularly latitudes of 40N and 40S) make little vitamin D. In Edmonton, which is 52N, vitamin D synthesis is impaired from October through to March. This problem is further accentuated by misinformation and inappropriate statements of avoiding sun and overuse of sunscreen by public health services. No doubt sun over exposure is associated strongly with skin cancer but too little vitamin D synthesis also has its own unique health problems.
UVB exposure to the skin epidermis produces vitamin D, which then undergoes hydroxylation (addition of OH or hydroxyl group) first in the liver and then in the kidneys to produce the active hormone 1, 25-dihydroxy vitamin D.
1, 25(OH) D is responsible for not only the bone development and growth in children and maintenance of bone in adults, but also for the prevention of osteoporosis and fractures in the elderly.
Vitamin D deficiency in children results in rickets and osteomalacia in adults. Both conditions are characterized by inadequate bone mineralization. Vitamin D is essential for the efficient utilization of dietary calcium. Blood calcium levels are tightly regulated. In a vitamin D deficient state, the amount of calcium absorbed is inadequate to satisfy the body's requirement, this causes the body to release the hormone PTH (parathyroid hormone) which activates the cells (osteoclasts) to breakdown the bone to get the much needed calcium. This results in osteopenia and osteoporosis. Additionally, PTH causes the kidneys to excrete phosphate and the overall net result is a decrease in calcium phosphate, the major mineral required for mineralizing bone. The bone building cells-osteoblasts continue to deposit collagen matrix, resulting in rubbery matrix which expands upon hydration and causes pressure and a low grade unrelenting pain often misdiagnosed as fibromyalgia.
Vitamin D is also important in the function of muscles. Muscle weakness, pain and changes in gait have been described in vitamin D insufficiency. This may be the reason that the elderly have more falls and consequently increased fracture rates.
One study found low levels of vitamin D in one in four patients who suffer from chronic pain. Patients with inadequate levels of vitamin D required nearly twice the dose of morphine that was used by patients with normal levels, and the vitamin D deficiency group used morphine for an average of 71.1 months compared to 43.8 months for non-deficient patients. These results led the researchers to hypothesize that while vitamin D is not the principle cause of chronic pain, it may be a contributing factor, and one that can be alleviated by supplementation.
Vitamin D3 deficiencies have been associated with increased hypertension, increased auto-immune diseases and various forms of cancer including breast, prostate and ironically skin. Low Vitamin D is associated with premenstrual syndrome (PMS), poor immune system, diabetes and the so called syndrome X and seasonally affective disorders.
References
• Hooten WM. Vitamin D inadequacy may exacerbate chronic pain. American Society of Anesthesiologists. 2007.
Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures
Ann Intern Med. 2008;149(4):242-250.
Cauley JA, LaCroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD, Robbins JA, Wu C, Stanczyk FZ, LeBoff MS, Wactawski-Wende J, Sarto G, Ockene J, Cummings SR
Background: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear. Objective: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women.
Design: Nested case-control study.
Setting: 40 clinical centers in the United States.
Participants: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture.
Measurements: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures.
Results: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD,20.28] vs. 59.60 nmol/L [SD, 18.05]; P 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption.
Limitations: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis.
Conclusion: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture.
25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population.
Arch Intern Med. 2008;168(15):1629-1637.
Melamed ML, Michos ED, Post W, Astor B.
BACKGROUND: In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced mortality. Observational data suggests that low 25-hydroxyvitaminDlevels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown.
METHODS:Wetested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition Examination Survey (NHANES III) linked mortality files. Participant vitaminDlevels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000.
RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, 17.8 ng/mL [to convert to nanomoles per liter, multiply by 2.496]), while greater physical activity, vitaminDsupplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models (adjusted for baseline demographics, season, and traditional and novel CVD risk factors), compared with the highest quartile, being in the lowest quartile (25[OH]D levels 17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The adjusted models ofCVDand cancer mortality revealed a higher risk, which was not statistically significant.
CONCLUSION: The lowest quartile of 25(OH)D level (17.8 ng/mL) is independently associated with all-cause mortality in the general population.
Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality.
Arch Intern Med. 2008;168(12):1340-1349.
Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm B, Weihrauch G, Maerz W.
BACKGROUND: In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25- hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality.
METHODS: Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25- hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths.
RESULTS: During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for allcause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29- 2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels).
CONCLUSIONS: Low 25-hydroxyvitamin D and 1,25- dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.
Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey.
Am J Clin Nutr 2008;87:136-41.
Suzanne E Judd, Mark S Nanes, Thomas R Ziegler, Peter WF Wilson, and Vin Tangpricha
Background: The prevalences of both hypertension and vitamin D insufficiency are high in the United States. Recent clinical trials and animal studies have suggested that vitamin D insufficiency may be associated with elevated blood pressure. Objective: With cross-sectional data, we sought to determine whether vitamin D concentrations were related to systolic blood pressure (SBP) in the third National Health and Nutrition Examination Survey (1988 -1992).
Design: Blood pressure was classified with 5 categories from the Joint National Committee 7 with a sixth category added to distinguish participants with normotensive SBP (110 mm Hg) from those with high-normal SBP (110-119 mm Hg). We used predicted marginals to estimate the conditional means of serum 25 hydroxyvitamin D [25(OH)D] and to test for trend across blood pressure categories. We used linear regression to explore the association between vitamin D, blood pressure, and age.
Results: Lower 25(OH)D concentrations were associated with a higher blood pressure category in whites (P 0.001); however, when controlling for age, the association was no longer significant. Concentrations of 25(OH)D80 nmol/L decreased the age-related increase in SBP by 20% compared with participants having 25(OH)D concentrations 50 nmol/L (P 0.001). Only 8% of blacks had 25(OH)D concentrations 80 nmol/L.
Conclusions: SBP is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. This observation provides a rationale for studies on the potential effects of vitamin D supplementation as a method to reduce SBP in persons at risk of hypertension.
Vitamin D Deficiency and Risk of Cardiovascular Disease.
Circulation published online Jan 7, 2008.
Thomas J. Wang, Michael J. Pencina, Sarah L. Booth, Paul F. Jacques, Erik Ingelsson, Katherine Lanier, Emelia J. Benjamin, Ralph B. DAgostino, Myles Wolf and Ramachandran S. Vasan
Background-Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes. A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking.
Methods and Results-We studied 1739 Framingham Offspring Study participants (mean age 59 years; 55% women; all white) without prior cardiovascular disease. Vitamin D status was assessed by measuring 25-dihydroxyvitamin D (25-OH D) levels. Prespecified thresholds were used to characterize varying degrees of 25-OH D deficiency (15 ng/mL, 10 ng/mL). Multivariable Cox regression models were adjusted for conventional risk factors. Overall, 28% of individuals had levels 15 ng/mL, and 9% had levels 10 ng/mL. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. Individuals with 25-OH D 15 ng/mL had a multivariable-adjusted hazard ratio of 1.62 (95% confidence interval 1.11 to 2.36, P0.01) for incident cardiovascular events compared with those with 25-OH D 15 ng/mL. This effect was evident in participants with hypertension (hazard ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those without hypertension (hazard ratio 1.04, 95% confidence interval 0.55 to 1.96). There was a graded increase in cardiovascular risk across categories of 25-OH D, with multivariable-adjusted hazard ratios of 1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to 15 ng/mL and 1.80 (95% confidence interval 1.05 to 3.08) for levels 10 ng/mL (P for linear trend 0.01). Further adjustment for C-reactive protein, physical activity, or vitamin use did not affect the findings.
Conclusions-Vitamin D deficiency is associated with incident cardiovascular disease. Further clinical and experimental studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease.
Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women.
Am J Clin Nutr. 2007 Nov;86(5):1420-1425.
Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, Aviv A.
BACKGROUND: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation.
OBJECTIVE: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL. DESIGN: Serum vitamin D concentrations were measured in 2160 women aged 18-79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.
RESULTS: Age was negatively correlated with LTL (r = -0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation.
CONCLUSION: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.
Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study.
Cancer Causes Control. 2007 Sep;18(7):775-82.
Robien K, Cutler GJ, Lazovich D.
Vitamin D, a prosteroid hormone with anti-proliferative and pro-differentiation activity, is thought to act as a cancer chemopreventive agent. This study evaluated the association between vitamin D intake and breast cancer risk among women in a large prospective cohort study. A total of 34,321 postmenopausal women who had completed a questionnaire that included diet and supplement use were followed for breast cancer incidence from 1986 to 2004. Adjusted relative risks (RR) for breast cancer were calculated for dietary, supplemental, and total vitamin D intake among all women. The adjusted RR of breast cancer for women consuming >800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77-1.03). RRs were stronger among women with negative than positive ER or PR status. The association of high vitamin D intake with breast cancer was strongest in the first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46-0.94 compared with lowest-intake group), and diminished over time. Changes in vitamin D intake over time might have contributed to the diminished association observed in later years. Vitamin D intake of >800 IU/day appears to be associated with a small decrease in risk of breast cancer among postmenopausal women. Studies evaluating all sources of vitamin D, especially sun exposure, are needed to fully understand the association between vitamin D and breast cancer risk.
Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.
Am J Clin Nutr. 2007 Jun;85(6):1586-91.
Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP.
BACKGROUND: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking.
OBJECTIVE: The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types.
DESIGN: This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged >55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo.
RESULTS: When analyzed by intention to treat, cancer incidence was lower in the Ca + D women than in the placebo control subjects (P < 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk.
CONCLUSIONS: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170.
Association between Vitamin D Receptor Gene Polymorphism and Alzheimer's Disease.
Tohoku J Exp Med. 2007 Jul;212(3):275-82.
Gezen-Ak D, Dursun E, Ertan T, Hanagasi H, Gürvit H, Emre M, Eker E, Oztürk M, Engin F, Yilmazer S.
Vitamin D(3) is known to be involved in neuroprotection and exert its neuroprotective effects by modulating neuronal calcium homeostasis and production of neurotrophins. The single nucleotide polymorphisms (SNP) in vitamin D receptor (VDR) gene which can influence the affinity of vitamin D(3) to its receptor may be related to neurodegenerative diseases and neuronal damage by altering the vitamin D-mediated pathways. In this study, our aim was to determine whether there is an association between VDR gene and late-onset Alzheimer's disease (AD) in order to see if vitamin D contributes to AD or not. One hundred and four cases of dementia of Alzheimer type and 109 age-matched controls were genotyped according to ApaI (a: + restriction site and A: no restriction site) and TaqI (t: + restriction site and T: no restriction site) sites in intron 8 and exon 9 of the ligand-binding site of VDR gene. When the controls and patients were compared for their ApaI genotypes, the frequency of the patients with Aa genotype was significantly higher than the frequency of the healthy individuals with the same genotype (p = 0.008, chi(2) = 9.577, OR = 2.30). Thus, the "Aa" genotype may increase the risk of developing AD 2.3 times when compared with the "AA" genotype. On the other hand, the "AT" haplotype was significantly higher in controls (p = 0.006) indicating a protective role of the "AT" haplotype in AD. Consequently, this study provides evidence for a possible link between AD and vitamin D.
Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis.
Arthritis Rheum. 2007 Jun 28;56(7):2143-2149
Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D.
OBJECTIVE: Previous in vitro and animal studies have suggested that vitamin D, in particular, its metabolite 25-hydroxyvitamin D (25[OH]D), may have immunomodulatory effects. To study further the potential immunomodulatory effects of vitamin D in humans, we explored the hypothesis that serum vitamin D metabolites may be inversely associated with current disease activity, severity, and functional disability in patients with early inflammatory polyarthritis (IP).
METHODS: We studied 206 consecutive patients with IP who were enrolled in the Norfolk Arthritis Register between January 2000 and November 2003 inclusive. Patients were studied within 6 months of symptom onset. None of the patients was taking steroids, and all had received <6 weeks of disease-modifying therapy. Associations between serum levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25[OH](2)D) at baseline and the swollen and tender joint counts, Health Assessment Questionnaire (HAQ) scores, C-reactive protein (CRP) levels, and the Disease Activity Score 28-joint assessment (DAS28) scores at baseline and 1 year were assessed.
RESULTS: The median age at symptom onset was 59 years (range 20-88 years), with a median disease duration of 4 months. At baseline, there was an inverse relationship between 25(OH)D levels and the tender joint count, DAS28 score, and HAQ score. The only inverse relationship with 1,25(OH)(2)D was with the HAQ score. Each 10-ng/ml increase in the level of 25(OH)D was associated with a decrease in the DAS28 score of 0.3 and in the CRP level of approximately 25%. At 1 year, the only significant result was an inverse association between baseline vitamin D metabolite levels and the HAQ score; that is, those with higher metabolite levels had lower HAQ scores.
CONCLUSION: These data provide further support that vitamin D plays an immunomodulatory role in inflammatory arthritis. This association needs to be examined in other cohorts of patients with early IP, as well as in longitudinal studies. If confirmed, the clinical response to vitamin D supplementation should be examined in early IP.
Vitamin D-deficiency rickets among children in Canada.
CMAJ. 2007 Jun 28
Ward LM, Gaboury I, Ladhani M, Zlotkin S.
BACKGROUND: Based on regional and anecdotal reports, there is concern that vitamin D deficiency rickets is persistent in Canada despite guidelines for its prevention. We sought to determine the incidence and clinical characteristics of vitamin D deficiency rickets among children living in Canada.
METHODS: A total of 2325 Canadian pediatricians were surveyed monthly from July 1, 2002, to June 30, 2004, through the Canadian Paediatric Surveillance Program to determine the incidence, geographic distribution and clinical profiles of confirmed cases of vitamin D-deficiency rickets. We calculated incidence rates based on the number of confirmed cases over the product of the length of the study period (2 years) and the estimates of the population by age group.
RESULTS: There were 104 confirmed cases of vitamin Dâ deficiency rickets during the study period. The overall annual incidence rate was 2.9 cases per 100 000. The incidence rates were highest among children residing in the the north (Yukon Territory, Northwest Territories and Nunavut). The mean age at diagnosis was 1.4 years (standard deviation [SD] 0.9, minâmax 2 weeksâ6.3 years). Sixty-eight children (65%) had lived in urban areas most of their lives, and 57 (55%) of the cases were identified in Ontario. Ninety-two (89%) of the children had intermediate or darker skin. Ninety-eight percent (94%) had been breastfed, and 3 children (2.9%) had been fed standard infant formula. None of the breast-fed infants had received vitamin D supplementation according to current guidelines (400 IU/d). Maternal risk factors included limited sun exposure and a lack of vitamin D from diet or supplements during pregnancy and lactation. The majority of children showed clinically important morbidity at diagnosis, including hypocalcemic seizures (20 cases, 19%).
INTERPRETATION: Vitamin Dâdeficiency rickets is persistent in Canada, particularly among children who reside in the north and among infants with darker skin who are breastfed without appropriate vitamin D supplementation. Since there were no reported cases of breast-fed children having received regular vitamin D (400 IU/d) from birth who developed rickets, the current guidelines for rickets prevention can be effective but are not being consistently implemented. The exception appears to be infants, including those fed standard infant formula, born to mothers with a profound vitamin D deficiency, in which case the current guidelines may not be adequate to rescue infants from the vitamin D-deficient state.
1,25-dihydroxyvitamin D(3) reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking.
J Neurosci Res. 2007 Jun 28
Pedersen LB, Nashold FE, Spach KM, Hayes CE.
Multiple sclerosis (MS) is a complex neurodegenerative disease whose pathogenesis involves genetic and environmental risk factors leading to an aberrant, neuroantigen-specific, CD4(+) T cell-mediated autoimmune response. In support of the hypothesis that vitamin D(3) may reduce MS risk and severity, we found that vitamin D(3) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) inhibited induction of experimental autoimmune encephalomyelitis (EAE), an MS model. To investigate how 1,25-(OH)(2)D(3) could carry out anti-inflammatory functions, we administered 1,25-(OH)(2)D(3) or a placebo to mice with EAE, and subsequently analyzed clinical disease, chemokines, inducible nitric oxide synthase (iNOS), and recruitment of dye-labeled monocytes. The 1,25-(OH)(2)D(3) treatment significantly reduced clinical EAE severity within 3 days. Sharp declines in chemokines, inducible iNOS, and CD11b(+) monocyte recruitment into the central nervous system (CNS) preceded this clinical disease abatement in the 1,25-(OH)(2)D(3)-treated animals. The 1,25-(OH)(2)D(3) did not directly and rapidly inhibit chemokine synthesis in vivo or in vitro. Rather, the 1,25-(OH)(2)D(3) rapidly stimulated activated CD4(+) T cell apoptosis in the CNS and spleen. Collectively, these results support a model wherein inflammation stimulates a natural anti-inflammatory feedback loop. The activated inflammatory cells produce 1,25-(OH)(2)D(3), and this hormone subsequently enhances the apoptotic death of inflammatory CD4(+) T cells, removing the driving force for continued inflammation. In this way, the sunlight-derived hormone could reduce the risk of chronic CNS inflammation and autoimmune-mediated neurodegenerative disease. (c) 2007 Wiley-Liss, Inc.
Vitamin D and its implications for musculoskeletal health in women: An update.
Maturitas. 2007 Jun 28;
Pérez-López FR.
Vitamin D is a hormone that controls phosphorus, calcium, and bone metabolism and neuromuscular function. Vitamin D synthesis is a process in which the skin, liver, and kidney are sequentially involved. The vitamin D pool is completed by the amount taken with food and supplements. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes a painful disease, osteomalacia, and increases muscle weakness, which worsens the risk of falls and fractures. A high prevalence of vitamin D insufficiency exists in the apparently healthy population, osteoporotic patients, and patients with prior fractures. Factors contributing to low vitamin D levels include low sunlight exposure, decreased skin synthesis and intestinal absorption, and inadequate diet. The simplest way to correct hypovitaminosis is adequate nutrition and supplements. However, few patients with osteoporosis and/or fractures, receive adequate supplements. Vitamin D insufficiency may alter the regulatory mechanisms of parathyroid hormone and may induce a secondary hyperparathyroidism that increases the risk of osteoporosis and fractures, although the necessary degree of this is not established. Monitoring of serum 25-hydroxyvitamin D levels is the only way to assess vitamin D status. The ideal healthy blood levels of 25-hydroxyvitamin D are controversial, although a range from 30 to 60ng/mL is widely accepted. The role of vitamin D supplementation is to provide humans with the nutrient in an amount closer to the biological norm for our species. This amount of vitamin D results in optimal function of many aspects of health, including balance and muscle strength, thus reducing the risk of fracture beyond what is possible via the quality and quantity of bone itself.
Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes.
Diabetes. 2007 Jul 2
Bailey R, Cooper JD, Zeitels L, Smyth DJ, Yang JH, Walker NM, Hyppönen E, Dunger DB, Ramos-Lopez E, Badenhoop K, Nejentsev S, Todd JA.
Objective Epidemiological studies have linked vitamin D deficiency with the susceptibility to type 1 diabetes. Higher levels of the active metabolite, 1alpha,25-dihydroxyvitamin D, could protect from immune destruction of the pancreatic beta cells. 1alpha,25-dihydroxyvitamin D is derived from its precursor 25-hydroxyvitamin D by the enzyme 1alpha-hydroxylase encoded by the CYP27B1 gene, and is inactivated by 24-hydroxylase encoded by the CYP24A1 gene. Our aim was to study the association between the CYP27B1 and CYP24A1 gene polymorphisms and type 1 diabetes. Research Design and Methods We studied 7,854 patients with type 1 diabetes and 8,758 controls from Great Britain and 2,774 affected families. We studied four CYP27B1 variants, including common polymorphisms -1260C>A (rs10877012) and +2838T>C (rs4646536), and 16 tag polymorphisms in the CYP24A1 gene. Results We found evidence of association with type 1 diabetes for CYP27B1 -1260 and +2838 polymorphisms, which are in perfect linkage disequilibrium. The common C allele of CYP27B1 -1260 was associated with an increased disease risk in the case-control analysis (OR = 1.07, P = 2.9 x 10(-3)), and in the fully independent collection of families (RR = 1.11, P = 6.4 x 10(-3)). The combined support of an association for CYP27B1 -1260 is P = 3.8 x 10(-6). For the CYP24A1 gene we found no evidence of association with type 1 diabetes (multilocus test P = 0.23). Conclusions The present data provides evidence that common inherited variation in the vitamin D metabolism affects susceptibility to type 1 diabetes.
Pharmacological treatment of osteoporosis for people over 70.
Aging Clin Exp Res. 2007 Jun;19(3):246-54.
Moro Alvarez MJ, Díaz-Curiel M.
Osteoporosis has been defined as "a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture". The impact of osteoporosis is most pronounced in elderly populations who run the greatest risk of fractures. The probability of developing mainly hip, vertebral and other non-vertebral fractures (for example, a Colles fracture) not only depends on bone mineral density (BMD) but also on age. Older patients are more susceptible to fracture than younger patients with the same BMD T-score. As the older population increases, the incidence of osteoporotic fractures is expected to rise dramatically over the next few decades. Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss and kyphosis. These changes may result in significant declines in physical performance, function and, ultimately, loss of independence. The challenge for physicians is to prevent bone loss, to diagnose and treat osteoporosis before fractures occur, and to treat patients who have already experienced a fracture to prevent recurrent fractures. The objective of this review is to analyze the capacity to reduce fractures as the key element to evaluate the effectiveness of available medications: calcium and Vitamin D, bone formation drugs, antiresortive drugs, and dualeffect drugs. In view of the paucity of information about treatment of osteoporosis in the elderly population, available studies were not designed with this objective, so that this article reviews data mostly deriving from post-hoc analysis or sub-analysis of the main phase III clinical trials of each of the tested medications.
Correlation between vitamin D(3) deficiency and insulin resistance in pregnancy.
Diabetes Metab Res Rev. 2007 Jul 2;
Maghbooli Z, Hossein-Nezhad A, Karimi F, Shafaei AR, Larijani B.
BACKGROUND: The serum level of 25-hydroxyvitamin D deficiency has long been suspected as a risk factor for glucose intolerance and perhaps 1,25-dihydroxyvitamin D has a role in the regulation of insulin secretion. This study investigates the relation between 25-hydroxyvitamin D concentrations and insulin resistance in pregnant women.
METHODS: A cross-sectional study was conducted on 741 pregnant women referred to five educating hospital clinics. Universal screening was performed with a GCT-50 g, and those with plasma glucose levels >/= 7.2 mmol/L were diagnosed as GDM if they had an impaired GTT-100 g based on Carpenter and Coustan criteria. The levels of insulin and C-peptide were measured during OGTT-100 g test. The homeostasis model assessment index (HOMA) equation was used as the insulin resistance index. The concentrations of 25-hydroxyvitamin D, and PTH were also measured.
RESULTS: Total prevalence of vitamin D deficiency (<25 nmol/L) was found in 70.6% of pregnant women. Prevalence of severe vitamin D deficiency (<12.5) in GDM patients was higher than in normoglycaemic pregnancies. The regression model revealed a strong correlation between the HOMA index and serum levels of vitamin D.
CONCLUSIONS: These results show that a positive correlation of 25(OH) vitamin D concentrations with insulin sensitivity and vitamin D deficiency could be a confirmative sign of insulin resistance. Copyright (c) 2007 John Wiley & Sons, Ltd.
Prevalence of vitamin D insufficiency in elderly ambulatory outpatients in Denver, Colorado.
Am J Geriatr Pharmacother. 2007 Mar;5(1):1-8.
Linnebur SA, Vondracek SF, Griend JP, Ruscin JM, McDermott MT.
BACKGROUND: Vitamin D insufficiency is common in the elderly. However, previous studies have utilized 25-hydroxvvitamin D (25[OH]D) concentrations as low as <16 ng/mL for defining vitamin D insufficiency. Moreover, most of the studies have been conducted in European patients, in certain geographic areas of the United States, or in institutionalized elderly.
OBJECTIVE: The goal of this study was to characterize vitamin D concentrations in ambulatory elderly living in metropolitan Denver, Colorado, utilizing 25(OH)D concentrations <32 ng/mL as the definition for vitamin D insufficiency.
METHODS: Ambulatory older adults (aged 65-89 years) with clinic visits during December 2005 and January 2006 were enrolled. Serum concentrations of 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, creatinine, and albumin were measured; height and weight were also measured. Data regarding dietary and over-the-counter vitamin D intake were collected, as well as information on body mass index, history of osteoporosis, osteoporosis treatment, and history of falls and fractures.
RESULTS: Eighty patients (mean [SD] age, 77.8 [5.3] years; age range, 66-89 years) completed the study; there were no dropouts. The majority of patients were white (88%) and female (68%). Fifty-nine (74%) were found to have vitamin D insufficiency. Mean total and over-the-counter vitamin D intake was significantly higher in sufficient (P < 0.01) and insufficient (P < 0.05) patients compared with deficient patients, but dietary intake did not differ significantly between groups. The majority of patients who were vitamin D insufficient consumed more than the recommended 400 to 600 IU/d of vitamin D. Obese patients were found to have significantly lower 25(OH)D concentrations (P < 0.001) and higher PTH concentrations (P = 0.04) than nonobese patients.
CONCLUSIONS: Vitamin D insufficiency is prevalent in ambulatory, and especially obese, elderly living in Denver, Colorado, despite vitamin D intake consistent with national recommendations. Dietary intake of vitamin D appeared to be unreliable to prevent insufficiency. Based on our results, along with other published data, we feel that national recommendations for vitamin D intake in the elderly should be increased to at least 800 to 1000 IU/d of over-the-counter supplemental cholecalciferol.
Vitamin D2 is much less effective than vitamin D3 in humans.
J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91.
Armas LA, Hollis BW, Heaney RP.
Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market.The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline.The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1.Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).
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