Effects of vitamin D supplementation on inflammatory markers in heart failure: a systematic review and meta-analysis of randomized controlled trials

Seven randomized, parallel-group trials in heart failure patients; six adult RCTs and one infant study. Adults were predominantly >60 years old and >50% male in reported studies; HF diagnosed with varying severity (NYHA II–III and/or reduced ejection fraction). Total randomized participants across six trials with data for pooling = 1012; most designs were double-blind, with Schroten 2013 open-label with blinded endpoint and one trial with single-blind participants.

Vitamin D regimens across trials: Boxer 2014 – 50,000 IU vitamin D3 weekly + 800 mg calcium for 6 months; McKeag 2014 – 1,000 IU vitamin D3 + 400 IU vitamin D2 daily (with placebo control) for 12 months; Schleithoff 2006 – 2,000 IU vitamin D3 daily + 500 mg calcium for 9 months; Schroten 2013 – 2,000 IU vitamin D3 daily for 6 weeks; Shedeed 2012 – 1,000 IU vitamin D3 daily for 3 months; Witham 2010 – 100,000 IU vitamin D2 bolus every 3 months for 9 months; Witte 2005 – 400 IU vitamin D with 250 mg calcium daily for 9 months.

Vitamin D supplementation reduced follow-up TNF-alpha concentrations versus controls (SMD -0.21; 95% CI -0.41 to -0.01; p = 0.04; I2 = 0%). No significant differences in CRP, IL-6, or IL-10. The TNF-alpha reduction persisted in sensitivity analyses focusing on low-bias studies; no concurrent improvements in HF biomarkers or clinical outcomes (e.g., LVEF or natriuretic peptides) were observed. Conclusion: vitamin D may have a small, specific anti-inflammatory effect in heart failure and could be a helpful adjunct in vitamin D–deficient patients, but larger trials with deficient populations and longer-term clinical endpoints are needed.

Small sample sizes in most trials; heterogeneity in vitamin D form (D2 vs D3) and dosing with varying calcium co-supplementation; inclusion of an infant study; some trials at high risk of bias; inconsistent reporting of baseline and follow-up vitamin D status; potential seasonal effects; no consistent improvement in HF clinical endpoints; possible publication bias for some markers.