Vitamin D

Vitamin D deficiency and risk of cardiovascular disease. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Circulation. 2008 Jan 29;117(4):503-11. Epub 2008 Jan 7. PMID: 18180395 doi: 10.1161/CIRCULATIONAHA.107.706127 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.

Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Arch Intern Med. 2008 Jun 23;168(12):1340-9. PMID: 18574092 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.

25-hydroxyvitamin D3 is an active hormone in human primary prostatic stromal cells. Lou YR, Laaksi I, Syvälä H, Bläuer M, Tammela TL, Ylikomi T, Tuohimaa P. FASEB J. 2004 Feb;18(2):332-4. Epub 2003 Dec 4. PMID: 14657005

25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Giovannucci E, Liu Y, Hollis BW, Rimm EB. Arch Intern Med. 2008 Jun 9;168(11):1174-80. PMID: 18541825 Conclusion Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

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. Judd SE, Nanes MS, Ziegler TR, Wilson PW, Tangpricha V. Am J Clin Nutr. 2008 Jan;87(1):136-41. PMID: 18175747 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.

Sunlight and vitamin D: both good for cardiovascular health. Holick MF. J Gen Intern Med. 2002 Sep;17(9):733-5. PMID: 12220371 doi: 10.1046/j.1525-1497.2002.20731.x.

Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, Arcaro G. Clin Endocrinol (Oxf). 2006 Nov;65(5):593-7. PMID: 17054459 DOI: 10.1111/j.1365-2265.2006.02633.x CONCLUSIONS: Hypovitaminosis D is highly prevalent in type 2 diabetic adults and is strongly and independently associated with increased carotid IMT. Further investigation into whether vitamin D may play a role in the prevention of atherosclerosis appears to be warranted. In conclusion, our results show that type 2 diabetic adults have significant reductions in serum 25(OH)D concentrations (vs matched controls) that predict preclinical atherosclerosis, independent of classical risk factors, renal function tests, inflammatory markers, use of medications and presence of the metabolic syndrome. These findings suggest the need for ongoing evaluation of the possible protective role of vitamin D3 supplementation in the development of atherosclerosis.

Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Islam T, Gauderman WJ, Cozen W, Mack TM. Neurology. 2007 Jul 24;69(4):381-8. PMID: 17646631 Conclusion: Early sun avoidance seems to precede the diagnosis of multiple sclerosis (MS). This protective effect is independent of genetic susceptibility to MS.

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

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.

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.

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.

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.

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.