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Vitamin D and type 2 diabetes: are we ready for a prevention trial? Scragg R. Diabetes. 2008 Oct;57(10):2565-6. PMID: 18820212 doi: 10.2337/db08-0879 Despite evidence from the current article (3) and the Finnish study (17), doubts still remain about whether low vitamin status is a cause of type 2 diabetes. Further cohort studies are required, assessing baseline vitamin D status using blood 25(OH)D to be sure that the Ely and Finnish studies are not false-positive results. Glucose clamp studies are also required because we are still not sure of the mechanism influenced by vitamin D-whether it is insulin resistance, secretion, or both. But most importantly, given that nearly three decades have passed since the first studies linking vitamin D with insulin metabolism (6,7), well-designed clinical trials of the effect of vitamin D supplementation on glycemia status and diabetes risk are urgently required to settle this question. And they need to prevent past mistakes. In particular, the vitamin D dose given in such trials needs to be high enough-above 2,000 IU per day (19)-to raise blood 25(OH)D levels above 80 nmol/l because diabetes risk is lowest at this level (9,20). If well-designed trials are carried out and confirm a protective effect from vitamin D, it could be used by the general population as a simple and cheap solution to help prevent the diabetes epidemic.

Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Diabetes Care. 2007 Oct;30(10):2569-70. Epub 2007 Jul 12. PMID: 17626891 doi: 10.2337/dc07-0292 We found a significant inverse association between serum 25OHD and risk of type 2 diabetes in the simple model. However, the association was attenuated in the multivariate analysis, adjusting for potential risk factors of type 2 diabetes. To our knowledge, this is the first cohort study investigating the association between serum 25OHD and incidence of type 2 diabetes. Our results are in line with those from the Nurses' Health Study (5), where an inverse association was observed for the intake of vitamin D supplements. We could not differentiate whether the results depended on the effect of vitamin D deficiency on β-cell function or on insulin resistance. In summary, the results are in line with the hypothesis that a high serum 25OHD concentration may reduce the risk of type 2 diabetes. Further research is needed to confirm the association and to distinguish between the independent role of vitamin D and the role of healthy dietary and lifestyle patterns in reducing the risk of type 2 diabetes.

Statins and vitamin D. Aloia JF, Li-Ng M, Pollack S. Am J Cardiol. 2007 Oct 15;100(8):1329. Epub 2007 Jul 5. No abstract available. PMID: 17920383 A total of 208 women were randomized to receive vitamin D3 (n=104) or placebo (n=104). 51 women were on statins. At baseline, the subjects on statins had a significantly higher 25-OHD level than the subjects who were not on statins (51.2 ± 20.1 nmol/L versus 43.2 ± 18.0 nmol/L respectively, p=0.008). This was also true when averaging 25-OHD levels across the 3-year study period and looking at active and placebo patients separately. 185 subjects had follow-up 25-OHD levels drawn every 6 months during the study. Higher levels were seen in the statin use subgroup whether they were on placebo or active vitamin D (Figure 1Figure 1). There was no interaction seen between vitamin D use and statin use, i.e. the impacts are additive (p=0.5502). This significant difference is comparable to the increase in 25-OHD levels seen in Pérez-Castrillón's study (41 ± 19 versus 47 ± 19 nmol/L, p=0.003) [1]. Although Pérez-Castrillón et al found a statistically significant relation between total cholesterol and 25-OHD (r=0.277, p=0.002), we did not find a significant relation between total cholesterol and 25-OHD in our study population.

"For what reason I don't know, but this January 2009 editorial by William Faloon of the Life Extension Foundation is making the rounds. Perhaps it just came available on the web. It's a good read, particularly in light of the billions and trillions of dollars the thieves & thugs in DC are about to flush down the crapper on your behalf. Some notable excerpts. A large number of new vitamin D studies have appeared in the scientific literature since I wrote my plea to the federal government. These studies don't just confirm what we knew 16 months ago-they show that optimizing vitamin D intake will save even more lives than what we projected. For instance, a study published in June 2008 showed that men with low vitamin D levels suffer 2.42 times more heart attacks. Now look what this means in actual body counts. Each year, about 157,000 Americans die from coronary artery disease-related heart attacks. Based on this most recent study, if every American optimized their vitamin D status, the number of deaths prevented from this kind of heart attack would be 92,500. To put the number of lives saved in context, tens of millions of dollars are being spent to advertise that Lipitor® reduces heart attacks by 37%. This is certainly a decent number, but not when compared with how many lives could be saved by vitamin D. According to the latest study, men with the higher vitamin D levels had a 142% reduction in heart attacks."

25-Hydroxyvitamin D and functional outcomes in adolescents. Lamberg-Allardt CJ, Viljakainen HT. Am J Clin Nutr. 2008 Aug;88(2):534S-536S. Review. PMID: 18689396 CONCLUSIONS Cross-sectional studies have shown a relation among serum 25(OH)D concentration, serum PTH concentration, and BMD in adolescents. Long-term randomized controlled intervention studies have shown that vitamin D3 supplementation has a positive effect on BMD in adolescence; some of these studies found an effect with doses as small as 5 µg (200 IU) to 10 µg (400 IU) per day, or without supplemental calcium.

Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Hyppönen E, Power C. Am J Clin Nutr. 2007 Mar;85(3):860-8. PMID: 17344510 Conclusion: Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level. Data from the 1958 birth cohort suggest that, at different cutoffs for hypovitaminosis D, a substantial public health problem exists in British whites. Obese participants and those living in Scotland were at the highest risk of hypovitaminosis D. However, the prevalence in the general population was very high during the winter and spring, which suggests that, to improve the situation, action is required at a population level rather than at a risk-group level. In the United States, calls have gone out for an increase in vitamin D fortification of foods (11), and the data from the current study suggest that such action is also warranted in the United Kingdom. Vitamin D is currently available without prescription as a dietary supplement only as part of cod liver oil or multivitamin products; hence, a need clearly exists to consider increased availability of over-the-counter supplements. Hypovitaminosis D has been implicated in the development of serious conditions, including diabetes, various types of cancer, and cardiovascular diseases, in addition to its essential role in maintaining bone health (1, 2). The high rates of hypovitaminosis D reported in this study suggest that immediate action is needed to improve the vitamin D status of the British population.

A New Zealand study has found that South Asian women with insulin resistance improved markedly after taking vitamin D supplements Nutrition researcher Pamela von Hurst of the Institute of Food, Nutrition and Human Health at Albany, said while diet and exercise played a major part in the onset of type-2 diabetes, her findings reinforced the importance of vitamin D from the sun and supplements to prevent type-2 diabetes. Initial screening of 235 Auckland women from India, Pakistan and Sri Lanka aged 20 and older, revealed 47 per cent were insulin deficient and 84 per cent were vitamin D deficient. The 81 recruited for the study were split into two groups for a randomised controlled trial and given a vitamin D supplement or placebo. As well as an improvement in insulin resistance among those who took vitamin D for six months, Ms Von Hurst said post-menopausal women in the study also showed a reduced rate of bone breakdown.

Assessment of dietary vitamin D requirements during pregnancy and lactation. Hollis BW, Wagner CL. Am J Clin Nutr. 2004 May;79(5):717-26. Review. PMID: 15113709 We found that high-dose maternal vitamin D supplementation not only improves the nutritional vitamin D status of breastfeeding infants but also elevates the maternal concentrations into the mid-normal range. Thus, a dual benefit is achieved from high-dose maternal supplementation. It is noteworthy that in the Finnish study, the authors added a disclaimer, "A sufficient supply of vitamin D to the breastfed infant is achieved only by increasing the maternal supplementation up to 2000 IU/d. Such a dose is far higher than the RDA [DRI] for lactating mothers [and therefore] its safety over prolonged periods is not known and should be examined by further study." This point of concern was valid when this study was conducted in 1986 (92); however, on the basis of the current findings of Vieth et al (2) and of Heaney et al (3)-which showed that vitamin D intakes <= 10 000 IU/d (250 µg) are safe for prolonged periods (up to 5 mo)-we believe that it is time to reexamine the understated DRI of vitamin D for lactating mothers. This work is now being conducted in our clinics and laboratory.

High-dose vitamin D3 supplementation in a cohort of breastfeeding mothers and their infants: a 6-month follow-up pilot study. Wagner CL, Hulsey TC, Fanning D, Ebeling M, Hollis BW. Breastfeed Med. 2006 Summer;1(2):59-70. PMID: 17661565 doi:10.1089/bfm.2006.1.59. Objective: To examine the effect of high-dose maternal vitamin D3 (vitD) supplementation on the nutritional vitD status of breastfeeding (BF) women and their infants compared with maternal and infant controls receiving 400 and 300 IU vitD/day, respectively. Design: Fully lactating women (n = 19) were enrolled at 1-month postpartum into a randomized- control pilot trial. Each mother received one of two treatments for a 6-month study period: 0 or 6000 IU vitD3 plus a prenatal vitamin containing 400 IU vitD3. The infants of mothers assigned to the control group received 300 IU vitD3/day; those infants of mothers in the high-dose group received 0 IU (placebo). Maternal serum and milk vitD and 25(OH)D were measured at baseline then monthly; infant serum vitD and 25(OH)D were measured at baseline, and months 4 and 7. Urinary calcium/creatinine ratios were measured monthly in both mothers and infants. Dietary and BF history and outdoor activity questionnaires were completed at each visit. Changes in skin pigmentation were measured by spectrophotometry. Data were analyzed using chi-square, t-test, and analysis of variance (ANOVA) on an intent-to-treat basis. Conclusion: With limited sun exposure, an intake of 400 IU/day vitamin D3 did not sustain circulating maternal 25(OH)D levels, and thus, supplied only extremely limited amounts of vitamin D to the nursing infant via breast milk. Infant levels achieved exclusively through maternal supplementation were equivalent to levels in infants who received oral vitamin D supplementation. Thus, a maternal intake of 6400 IU/day vitamin D elevated circulating 25(OH)D in both mother and nursing infant.

"Women from India, Pakistan and Sri Lanka with insulin resistance showed marked improvement after taking vitamin D supplements, says a study. Von Hurst, nutrition lecturer at the Institute of Food, Nutrition and Human Health at Albany, conducted the study for her doctoral thesis. Insulin resistance is largely symptom-free and sufferers are unaware of their condition. 'Once it has fully developed into type-2 diabetes, it can be treated, but not cured,' says Von Hurst. Von Hurst says that while diet and exercise play a major part in the onset of type-2 diabetes, her findings reinforce the importance of vitamin D from the sun and supplements to prevent type-2 diabetes. She also found evidence of vitamin D increasing bone strength in older women. "

Pharmacokinetics of a single, large dose of cholecalciferol. Ilahi M, Armas LA, Heaney RP. Am J Clin Nutr. 2008 Mar;87(3):688-91. PMID: 1832660 Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline. Our study highlights that 100 000 IU cholecalciferol is a safe, efficient, and cost-effective means to increase calcidiol concentrations in the elderly. From this study we can safely recommend 100 000 IU cholecalciferol dosed every 2 mo in persons with moderate baseline calcidiol concentrations. However, in those persons with baseline calcidiol concentrations < 20 ng/mL, even this large dose will not adequately raise their calcidiol concentrations.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects

Serum 25-hydroxyvitamin D status of vegetarians, partial vegetarians, and nonvegetarians: the Adventist Health Study-2. Chan J, Jaceldo-Siegl K, Fraser GE. Am J Clin Nutr. 2009 May;89(5):1686S-1692S. Epub 2009 Apr 1. PMID: 19339396 Conclusions: s25(OH)D concentrations were not associated with vegetarian status. Other factors, such as vitamin D supplementation, degree of skin pigmentation, and amount and intensity of sun exposure have greater influence on s25(OH)D than does diet.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D ≤ 80 nmol or 32 µg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. Hollis BW. J Nutr. 2005 Feb;135(2):317-22. Review. PMID: 15671234 [

A large number of new vitamin D studies have appeared in the scientific literature since I wrote my plea to the federal government. These studies don't just confirm what we knew 16 months ago-they show that optimizing vitamin D intake will save even more lives than what we projected. Vitamin D More Effective Than Previously Known For instance, a study published in June 2008 showed that men with low vitamin D levels suffer 2.42 times more heart attacks. Now look what this means in actual body counts.

A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, Albanes D. Cancer Res. 2006 Oct 15;66(20):10213-9. PMID: 17047087 Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer (highest versus lowest quintile, >65.5 versus <32.0 nmol/L: OR, 2.92; 95% CI, 1.56-5.48, Ptrend = 0.001) that remained after excluding cases diagnosed early during follow-up. Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status. Our findings need to be replicated in other populations and caution is warranted in their interpretation and implication. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer. In conclusion, contrary to expectation, subjects with higher 25(OH)D concentrations were at greater risk for pancreatic cancer compared with those with lower concentrations in our prospective study with long-term follow-up. Caution is warranted in the interpretation and implication of our findings, however, as vitamin D inadequacy is an important public health problem and adequate status is desirable to prevent bone and other diseases (5). Our results, however, are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF; Elizabeth Glaser Pediatric Research Network Obesity Study Group. Am J Clin Nutr. 2009 Sep;90(3):459-67. Epub 2009 Jul 29. PMID: 19640956 RESULTS: The mean (+/-SD) age of the adolescents was 14.9 +/- 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (+/-SD) body mass index (in kg/m(2)) was 36 +/- 5, FM was 40.0 +/- 5.5%, and VAT was 12.4 +/- 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 +/- 0.22 ng/mL per 1% increment in FM (beta +/- SE, P = 0.05), whereas PTH decreased by 0.78 +/- 0.29 pg/mL per 1% increment in VAT (P = 0.01). CONCLUSIONS: To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (+/-2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors

Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth R, Milojevic S, Peltekova V. J Nutr. 2000 Mar;130(3):578-84. PMID: 10702588 We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite. When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D. If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.

Sweat gland epithelial and myoepithelial cells are vitamin D targets. Koike N, Stumpf WE. Exp Dermatol. 2007 Feb;16(2):94-7. PMID: 17222221 DOI: 10.1111/j.1600-0625.2006.00513.x Nuclear receptor binding of 1,25(OH)2-vitamin D3 (vitamin D) in skin keratinocytes of epidermis, hair sheaths and sebaceous glands was discovered through receptor microscopic autoradiography. Extended experiments with 3H-1,25(OH)2-vitamin D3 and its analog 3H-oxacalcitriol (OCT) now demonstrate nuclear receptor binding in sweat gland epithelium of secretory coils and ducts as well as in myoepithelial cells, as studied in paws of nude mice after i.v. injection. The results suggest genomic regulation of cell proliferation and differentiation, as well as of secretory and excretory functions, indicating potential therapies for impaired secretion as in hypohidrosis of aged and diseased skin.