Therapeutic, III.

V itamin D deficiency is a common problem with implications for human health.1 A large body of epidemiological evidence links vitamin D deficiency with a higher risk of cardiovascular disorders, including hypertension. 2,3A meta-analysis of observational studies found that every 16-ng/mL decrease in vitamin D was associated with a 16% higher risk of hypertension. 4 A meta-analysis of population genetic studies suggested that polymorphisms related to Background-A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited. Methods and Results-A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels ≤25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D 3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fiftyfive participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, −0.8 versus −1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, −0.05, P=0.34). Results were consistent across prespecified subgroups. Disruption of these receptors in animals is associated with elevated blood pressure, which can be normalized with vitamin D administration. Conclusions-Vitamin 8 Clinical Perspective on p 262These observations raise the possibility that vitamin D supplementation could reduce blood pressure in humans. However, results of randomized, intervention trials have been conflicting, with some studies, but not others, suggesting a benefit. [9][10][11][12][13][14] In most of the trials, blood pressure was not the primary end point, nor was it measured with standardized protocols. These trials also typically randomized <150 participants and included a large proportion of individuals who were already on antihypertensive therapy. Importantly, very few nonwhite individuals have been included in prior studies, despite the high prevalence of both vitamin D deficiency and elevated bloo...