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A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Wintertime vitamin D supplementation inhibits seasonal variation of calcitropic hormones and maintains bone turnover in healthy men. Viljakainen HT, Väisänen M, Kemi V, Rikkonen T, Kröger H, Laitinen EK, Rita H, Lamberg-Allardt C. J Bone Miner Res. 2009 Feb;24(2):346-52. PMID: 18847321

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. Epub 2007 Dec 18. PMID: 18089691 Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Am J Clin Nutr. 1998 Oct;68(4):854-8. PMID: 9771862 Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

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.

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 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

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.

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.

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. .

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.

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.

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

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.

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.

Vitamin D3 and calcium to prevent hip fractures in the elderly women. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ. N Engl J Med. 1992 Dec 3;327(23):1637-42. PMID: 1331788 CONCLUSIONS. Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Matsuoka, L. Y., Wortsman, J., Hanifan, N. & Holick, M. F. (1988) Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D: a preliminary study. Arch. Dermatol. 124:1802-1804

In vivo threshold for cutaneous synthesis of vitamin D3. Matsuoka LY, Wortsman J, Haddad JG, Hollis BW. J Lab Clin Med. 1989 Sep;114(3):301-5. PMID: 2549141