Vitamin d: popular cardiovascular supplement but benefit must be evaluated.
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Vitamin D deficiency is prevalent in the United States. Understanding any relationship between this deficiency and cardiovascular disease is essential. Vitamin D, as used, refers to both D(2) and D(3); both are present in over-the-counter supplements, whereas D(2) is the prescription product in the United States. In the liver, both D(2) and D(3) are converted to 25-hydroxyvitamin D, the major circulating metabolite that is measured to assess activity. The actual active form at a cellular level is 1,25-dihydroxyvitamin D; however, it does not correlate well with overall activity. Estimated vitamin D deficiency is, at times, more than 50%. Despite absence of placebo-controlled randomized trials, much information associates vitamin D deficiency with cardiovascular risk and supports benefit from vitamin D supplementation. There are also reports that explain how this benefit from vitamin D may occur. Vitamin D appears to cause only minimal changes in low- and high-density lipoprotein levels. Therefore, any cardiovascular benefit that may exist from vitamin D probably has an explanation other than an effect on levels of these lipoproteins. There is more association of vitamin D deficiency with metabolic syndrome components such as an increase in blood pressure, elevated plasma triglycerides, and impaired insulin metabolism. Possible documentation of cardiovascular benefit from vitamin D includes some evidence for endothelial stabilization and decreased inflammation in arteries. If the clinician decides that recommendation of vitamin D supplementation is warranted, it is reassuring that toxicity is rare. Furthermore, this toxicity involves doses exceeding those of most clinical trials and mainly has involved hypercalcemia. Vitamin D supplementation is easy and can be taken as a dose of 2000 IU daily on an indefinite basis. In 1997, the Food and Nutrition Board of the U.S. Institute of Medicine considered this the safe tolerable upper limit, but this is not based on current evidence. Some practitioners, especially endocrinologists, recommend vitamin D at a dose of 50,000 IU per week for 8 weeks, repeated if necessary to achieve a normal level of vitamin D. It appears appropriate to assess low vitamin D as a possible cardiovascular risk factor, but potential benefit of supplementation must be weighed against the current absence of definitive outcomes studies.