Modifiers of the Effects of Vitamin D Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis

The inconsistent findings concerning the effects of vitamin D supplementation on cardiometabolic risk factors and the large heterogeneity in the published literature call for further research to identify sources of heterogeneity and potential effect modifiers. We performed a meta-analysis of randomized controlled trials (RCTs) published until March 2024 that reported estimates for the effects of vitamin D supplementation on cardiometabolic factors and relevant baseline covariates of RCT participants. A total of 17 656 participants from 99 RCTs were analyzed, and weighted mean differences (95% confidence intervals (CI)) for the intervention status were derived using random-effects modeling. Overall, compared with the placebo, vitamin D supplementation (median dose: 3320 international unit (IU)·day⁻¹; range 40–120 000 IU·day⁻¹) had favorable effects on systolic blood pressure (SBP; −2.04 (95% CI, −3.50, −0.59) mmHg; 1 mmHg = 0.133 kPa), diastolic blood pressure (DBP; −3.00 (95% CI, −3.61, −2.39) mmHg), total cholesterol (TC; −0.12 (95% CI, −0.21, −0.03) mmol·L⁻¹), fasting blood glucose (FBG; −0.13 (95% CI, −0.20, −0.05) mmol·L⁻¹), hemoglobin A1C (A1C; −0.09% (95% CI, −0.13%, −0.05%)), and fasting blood insulin (FBI: −7.61 (95% CI, −11.93, −3.30) pmol·L⁻¹). The benefits of vitamin D were most evident in trials performed in non-Westerners, participants with baseline 25-hydroxyvitamin D (25[OH]D) lower than 15.0 ng·mL⁻¹, non-obese (body mass index (BMI) < 30 kg·m⁻²), and older (age ≥ 50 years). The findings of this study underscore the need for personalized vitamin D intervention strategies that comprehensively account for individual patient characteristics (such as ethnocultural background, age, BMI, and circulating 25[OH]D level), intervention dosage, and intervention duration to optimize cardiometabolic health outcomes.