A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk

Adam D Gepner, Rekha Ramamurthy, Diane C Krueger, Claudia E Korcarz, Neil Binkley, James H Stein, Adam D Gepner, Rekha Ramamurthy, Diane C Krueger, Claudia E Korcarz, Neil Binkley, James H Stein

Abstract

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. -0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26). In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk.

Trial registration: ClinicalTrials.gov NCT00690417 NCT01049048.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. CONSORT 2010 Flow Diagram.
Figure 1. CONSORT 2010 Flow Diagram.
The first 34 subjects were part of a pilot study performed under NCT 00690417. The remainder of the subjects were performed under NCT 01049048.
Figure 2. Interactions Between the Effects of…
Figure 2. Interactions Between the Effects of Treatment Group and Baseline Vitamin D Status on Outcome Variables.
Abbreviations as in Table 1.

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