Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Lancet. 2001 Nov 3;358(9292):1500-3. PMID: 11705562 doi:10.1016/S0140-6736(01)06580-1 INTERPRETATION: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes.

Aging decreases the capacity of human skin to produce vitamin D3. MacLaughlin J, Holick MF. J Clin Invest. 1985 Oct;76(4):1536-8. PMID: 2997282

25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS. J Am Soc Nephrol. 2009 Aug;20(8):1805-12. Epub 2009 May 14. PMID: 19443637 doi: 10.1681/ASN.2008111157 "In conclusion, lower 25-hydroxyvitamin D concentrations associate with increased risk for incident CAC. Accelerated development of atherosclerosis may underlie, in part, the increased cardiovascular risk associated with vitamin D deficiency."

A German group has now shown that the important inflammatory marker, tumor necrosis factor (TNF), is also reduced by vitamin D supplementation. Many studies have implicated increased TNF levels in promoting cancer. In this study, a modest vitamin D dose of 3320 units (83 micrograms) was given vs. placebo. The 25-hydroxy D level reached in the treated group was 34.2 ng/ml (85.5 nmol/L), which resulted in a 26.5% reduction in TNF compared with 18.7% reduction (?) in the placebo group.

Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. Tarcin O, Yavuz DG, Ozben B, Telli A, Velioglu Ogunc A, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. J Clin Endocrinol Metab. 2009 Jul 7. [Epub ahead of print] PMID: 19584181 doi:10.1210/jc.2008-1212 Conclusions: This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D associated endothelial dysfunction may predispose to higher cardiovascular disease in the winter.

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.

Vitamin D status predicts physical performance and its decline in older persons. Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, Knol DL, Lips P. J Clin Endocrinol Metab. 2007 Jun;92(6):2058-65. Epub 2007 Mar 6. PMID: 17341569 doi:10.1210/jc.2006-1525 ONCLUSIONS: Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women. Because almost 50% of the population had serum 25-OHD below 20 ng/ml, public health strategies should be aimed at this group.

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8. PMID: 17398180 In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. The mechanism by which atorvastatin increases vitamin D levels is related to inhibition of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol is synthesized from 7-dehydrocholesterol, which is also a precursor of vitamin D3. For this reason, we initially observed a statistically significant relation between total cholesterol and vitamin D. HMG-CoA enzyme reductase is key to the synthesis of cholesterol, whereas ultraviolet radiation causes the formation of 25-hydroxyvitamin D. Inhibition of the enzyme may increase levels of 7-dehydrocholesterol and increase the synthesis of 25-hydroxycholecalciferol, thereby increasing vitamin D levels,10 although we observed no relation between lower cholesterol and increased vitamin D. In addition, 25-hydroxyvitamin D has been shown to inhibit HMG-CoA enzyme reductase activity in in vitro studies.11 A greater concentration of vitamin D could increase enzymatic inhibition, acting in synergy with the statin in decreasing total cholesterol.

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.

Estimation of the dietary requirement for vitamin D in free-living adults >=64 y of age. Cashman KD, Wallace JM, Horigan G, Hill TR, Barnes MS, Lucey AJ, Bonham MP, Taylor N, Duffy EM, Seamans K, Muldowney S, Fitzgerald AP, Flynn A, Strain JJ, Kiely M. Am J Clin Nutr. 2009 May;89(5):1366-74. Epub 2009 Mar 18. PMID: 19297462 doi:10.3945/ajcn.2008.27334 Conclusion: To ensure that the vitamin D requirement is met by the vast majority (>97.5%) of adults aged ≥64 y during winter, between 7.9 and 42.8 µg vitamin D/d is required, depending on summer sun exposure and the threshold of adequacy of 25(OH)D. .

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Am J Clin Nutr. 2008 Jun;87(6):1952-8. PMID: 18541590 The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.

Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Trivedi DP, Doll R, Khaw KT. BMJ. 2003 Mar 1;326(7387):469. PMID: 12609940 CONCLUSION: Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Bischoff HA, Stähelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. J Bone Miner Res. 2003 Feb;18(2):343-51. PMID: 12568412 A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

Vitamin D supplementation improves neuromuscular function in older people who fall. Dhesi JK, Jackson SH, Bearne LM, Moniz C, Hurley MV, Swift CG, Allain TJ. Age Ageing. 2004 Nov;33(6):589-95. PMID: 15501836 doi:10.1093/ageing/afh20 9 CONCLUSIONS: vitamin D supplementation, in fallers with vitamin D insufficiency, has a significant beneficial effect on functional performance, reaction time and balance, but not muscle strength. This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function, which may in part explain the mechanism whereby vitamin D reduces falls and fractures.

How much vitamin D3 do the elderly need? Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Lamberg-Allardt C. J Am Coll Nutr. 2006 Oct;25(5):429-35. PMID: 17031013 Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 µg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status

A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Li-Ng M, Aloia JF, Pollack S, Cunha BA, Mikhail M, Yeh J, Berbari N. Epidemiol Infect. 2009 Mar 19:1-9. [Epub ahead of print] PMID: 19296870

White Europeans could have evolved as recently as 5,500 years ago, according to research which suggests that the early humans who populated Britain and Scandinavia had dark skins for millenniums. It was only when early humans gave up hunter-gathering and switched to farming about 5,500 years ago that white skin began to be favoured, say the researchers. This is because farmed food was deficient in vitamin D, a vital nutrient. Humans can make this in their skin when exposed to sunlight, but dark skin is much less efficient at it.

A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D William B. Grant Dermato-Endocrinology. Volume 1, Issue 1 January/February 2009 Pages: 25 - 33 The International Agency for Research on Cancer (IARC) released a report, Vitamin D and Cancer, on November 25, 2008. The report focused on the current state of knowledge and level of evidence of a causal association between vitamin D status and cancer risk. Although presenting and evaluating evidence for the beneficial role of UVB and vitamin D in reducing the risk of cancer, it discounted or omitted important evidence in support of the efficacy of vitamin D. The report largely dismissed or ignored ecological studies on the grounds that confounding factors might have affected the findings. The report accepted a preventive role of vitamin D in colorectal cancer but not for breast cancer.

Dietary Reference Intakes for Vitamin D and Calcium An IOM committee has been named to undertake a study to assess current relevant data and update as appropriate the DRIs for vitamin D and calcium. The review will include consideration of chronic and non-chronic disease indicators. The study will also incorporate, as appropriate, systematic evidence-based reviews of the literature and an assessment of potential indicators of adequacy and of excess intake. Indicators for adequacy and excess will be selected based on the strength and quality of the evidence and the demonstrated public health significance, taking into consideration sources of uncertainty in the evidence.

The second committee meeting was held August 4-5, 2009 in Washington, DC and included an Information-Gathering Workshop on August 4, 2009. The agenda for this workshop is below, along with the PowerPoint presentations that were used by the speakers during the workshop. Please note, online presentations from this meeting are subject to copyright protection. Permission from the speaker is required prior to any copying, reproducing, or rebroadcasting any portion of the speaker's presentations. Additional copyright and legal policies of The National Academies can be read in the National Academies Legal Statement.