Vitamin D

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.

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

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

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.

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.

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.

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 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.

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.

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."

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

Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. Ish-Shalom S, Segal E, Salganik T, Raz B, Bromberg IL, Vieth R. J Clin Endocrinol Metab. 2008 Sep;93(9):3430-5. Epub 2008 Jun 10. PMID: 18544622 doi:10.1210/jc.2008-0241 CONCLUSIONS: Supplementation with vitamin D can be achieved equally well with daily, weekly, or monthly dosing frequencies. Therefore, the choice of dose frequency can be based on whichever approach will optimize an individual's adherence with long-term vitamin D supplementation.

Annual injection of vitamin D and fractures of aged bones. Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, Kokko AM, Kolho LA, Rajala SA. Calcif Tissue Int. 1992 Aug;51(2):105-10. PMID: 1422948

Serum vitamin D level after an annual intramuscular injection of ergocalciferol. Heikinheimo RJ, Haavisto MV, Harju EJ, Inkovaara JA, Kaarela RH, Kolho LA, Rajala SA. Calcif Tissue Int. 1991;49 Suppl:S87. PMID: 1933611 An annual intramuscular injection of ergocalciferol (150,000 IU) normalized low serum (25(OH)D concentrations in elderly people for 1 year. The treatment had a slight effect on serum 24,25(OH)2D levels but no effect on 1,25(OH)2D levels.

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data. Diamond TH, Ho KW, Rohl PG, Meerkin M. Med J Aust. 2005 Jul 4;183(1):10-2. PMID: 15992330 Conclusions: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.

25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. Am J Clin Nutr. 2008 Jun;87(6):1738-42. PMID: 18541563 Conclusions: At physiologic inputs, there is rapid conversion of precursor to product at low vitamin D3 concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D3 inputs and serum concentrations, there is very little native cholecalciferol in the body, and 25(OH)D constitutes the bulk of vitamin D reserves. However, at supraphysiologic inputs, large quantities of vitamin D3 are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.

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.

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.

Vitamin D and disease prevention with special reference to cardiovascular disease. Zittermann A. Prog Biophys Mol Biol. 2006 Sep;92(1):39-48. Epub 2006 Feb 28. Review. PMID: 1660034