Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes

Abstract

There is a plausible physiological theory, supported by many observational studies, that vitamin D supplementation should be effective for improving cardiovascular end points, such as blood pressure (BP), large artery stiffness, atherosclerosis, endothelial function and clinical events. However, results from randomised controlled trials (RCTs) have been inconsistent. In this review, we evaluated the evidence regarding the effectiveness of vitamin D supplementation for cardiovascular surrogate and hard clinical end points. RCTs were assessed in terms of sample size, duration of supplementation, baseline vitamin D level inclusion criteria (i.e., absence of vitamin D deficiency), dosage of vitamin D and population under investigation. Forty-five RCTs were identified. Eight RCTs with BP and 6 RCTs with large artery stiffness as the end points were found to comply with guidelines for the optimal design of clinical trials evaluating nutrient effects. Only 2 of the RCTs with an optimal design were effective in decreasing BP with vitamin D supplementation, although these were of moderate sample size (<150) and very short duration (8 weeks for both), whilst no RCT was effective in reducing large artery stiffness. Similar results were observed for atherosclerotic and endothelial function markers as end points. Only 1 RCT reported cardiovascular events as an end point and found neither increased nor decreased incident cardiovascular events over 7 years of follow-up. In conclusion, results from published RCTs indicate that vitamin D supplementation is ineffective in improving cardiovascular health among various patient populations, including in the presence or absence of vitamin D deficiency.

Keywords: Blood pressure; Cardiovascular health; Large artery stiffness; Randomized controlled trials; Vitamin D supplementation.

Fig. 1

Longitudinal cohort and case-control studies on the association between vitamin D and incidence of cardiovascular events or cardiovascular mortality according to sample size and population characteristics. Blue bars indicate studies that reported significant associations between vitamin D and cardiovascular end points, and grey bars indicate studies that reported no significant associations. (Colours refer to the online version only.)

Fig. 2

Randomised controlled trials (RCTs) with vitamin D supplementation as the intervention according to sample size and the outcome in terms of effective or no effect on cardiovascular end points (reported either as primary or secondary outcomes). Each grey dotted circle represents a different cardiovascular end point, and the size of the circle is proportional to the number of RCTs for each end point. Blue circles indicate a significant improvement with vitamin D supplementation (effective RCTs), and grey circles indicate that RCTs had no significant effect on respective end points. Numbers above the circles represent the corresponding RCT reference number. bBP, brachial blood pressure; RHI, reactive hyperaemia index; FMD, flow-mediated dilation; DC, distensibility coefficient of the carotid artery; CIMT, carotid intimal medial thickness; AIx, augmentation index; crPWV, carotid-radial pulse wave velocity; cfPWV, carotid-femoral pulse wave velocity; baPWV, brachial-ankle pulse wave velocity; cBP, central blood pressure; BPV, visit-to-visit blood pressure variability. (Colours refer to the online version only.)

Fig. 3

Randomised controlled trials (RCTs) on the effect of vitamin D supplementation according to trial duration and estimated monthly dose on brachial blood pressure and carotid-femoral pulse wave velocity. Blue bars indicate effective RCTs (significant reduction in end points), and grey bars indicate RCTs that had no effect on end points. Black dotted horizontal lines indicate adequate dose to raise serum vitamin D levels above deficiency levels. Black dotted vertical line indicates RCT duration of 6 months. Monthly dose was calculated using the highest dose if there was more than 1 vitamin D supplementation group. IU, international units. * Vitamin D₂ supplementation. ^† Vitamin D plus calcium. ^‡ Single dose. ^§ Vitamin D/calcium-fortified milk. (Colours refer to the online version only.)