Effect of Vitamin D on Blood Pressure and Hypertension in the General Population

An Update Meta-Analysis of Cohort Studies and Randomized Controlled Trials

Dongdong Zhang, MD; Cheng Cheng, MD; Yan Wang, MD1; Hualei Sun, MD; Songcheng Yu, MD; Yuan Xue, MD; Yiming Liu, MD; Wenjie Li, MD, PhD; Xing Li, MD

Disclosures

Prev Chronic Dis. 2020;17(1):e03 

In This Article

Abstract and Introduction

Abstract

Background: The effect of vitamin D supplementation on blood pressure has been explored in previous meta-analyses, but whether the association is causal in the general population is still unknown. We evaluated the association comprehensively and quantitatively.

Methods: We searched PubMed and Embase for relevant cohort studies and randomized controlled trials (RCTs). We used a 2-step generalized least-squares method to assess the dose–response association of circulating 25-hydroxyvitamin D (25[OH]D) and hypertension and a fixed-effects model to pool the weighted mean differences (WMDs) and corresponding 95% confidence intervals (95% CIs) of blood pressure across RCTs.

Results: We identified 11 cohort studies and 27 RCTs, with 43,320 and 3,810 participants, respectively. The dose–response relationship between circulating 25(OH)D levels and hypertension risk was approximately L-shaped (P nonlinearity = .04), suggesting that the risk of hypertension increased substantially below 75 nmol/L as 25(OH)D decreased, but it remained significant over the range of 75–130 nmol/L. However, pooled results of RCTs showed that there was no significant reduction in systolic blood pressure (WMD, −0.00 mm Hg; 95% CI, −0.71 to 0.71) or diastolic blood pressure (WMD, 0.19 mm Hg; 95% CI, −0.29 to 0.67) after vitamin D intervention.

Conclusions: The results of this meta-analysis indicate that supplementation with vitamin D does not lower blood pressure in the general population. RCTs with long-term interventions and a sufficient number of participants who have low levels of vitamin D are needed to validate these findings.

Introduction

Emerging evidence suggests that vitamin D deficiency is a widespread global problem.[1] According to the Institute of Medicine (IOM), vitamin D deficiency is defined as circulating 25-hydroxyvitamin D (25[OH]D) level <50 nmol/L based on the optimal concentration for skeletal health.[2] Interest has increased concerning the potential health consequences of vitamin D deficiency, such as increased risk of cardiovascular diseases, cancers, and Alzheimer's disease.[3–5] Although observational data have demonstrated that poor vitamin D status is associated with increased risk of hypertension,[6–9] randomized controlled trials (RCTs) have provided little support for the beneficial effect of vitamin D supplementation on blood pressure.[10–13] Considering the potential residual confounding, inferring causality or reversibility of this relationship and reaching consensus from these findings is difficult.

Several meta-analyses of observational studies and RCTs have been published, but results are conflicting.[14–17] Golzarand et al evaluated 30 RCTs with 4,744 participants and concluded that vitamin D has a beneficial effect in subgroups of daily doses >800 IU/d, a duration less than 6 months, or older subjects.[14] Kunutsor et al suggested that supplementation with vitamin D significantly reduced diastolic blood pressure (DBP) by 1.31 mm Hg in participants with preexisting cardiometabolic conditions.[16] However, another meta-analysis performed by incorporating individual data supported that vitamin D supplementation is ineffective in lowering blood pressure.[15]

Taken together, it may be hypothesized that the increased blood pressure or risk of hypertension is partly explained by individuals' baseline vitamin D status, the sample size, the intervention dose, and the follow-up duration. Meanwhile, considering that pre-existing conditions such as diabetes, cardiovascular disease, and kidney disease may influence the physiologic mechanism of vitamin D on blood pressure, considerable variability may exist between individual patients and the general population. Therefore, restricting the participants to the general population may help to explore the true association hidden by the confounders. Analyzing the population as a whole rather than restricting analyses to certain population subgroups may help us to explore the true association hidden by confounders. In addition, results from at least 10 more studies including 1,716 participants have been published on this topic since the latest meta-analysis in 2015.[10–12,18–24]

We aimed to provide a comprehensive and quantitative meta-analysis from the published cohort studies and RCTs on the effect of vitamin D involving hypertension risk and blood pressure levels in the general population.

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