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

Systematic review and meta-analysis of randomized controlled trials in patients with heart failure. The included studies enrolled mostly older adults with varying heart failure severity, plus one infant trial, and compared vitamin D supplementation with placebo.

Oral vitamin D supplementation was tested across trials, using vitamin D3 in most studies and vitamin D2 in others, with daily doses from 400 IU to 2,000 IU, a weekly 50,000 IU regimen, or 100,000 IU bolus doses given quarterly. Intervention duration ranged from 6 weeks to 12 months; several arms also included calcium co-supplementation, and comparators were placebo-controlled.

Vitamin D showed a small but statistically significant anti-inflammatory signal in heart failure, driven by a reduction in TNF-α, but it did not improve CRP, IL-6, or IL-10. Pooled TNF-α across 5 RCTs (n=380) favored vitamin D (SMD -0.21, 95% CI -0.41 to -0.01; p=0.04; I2=0%), and the effect remained in a low-risk-of-bias sensitivity analysis (SMD -0.25, 95% CI -0.49 to -0.01; p=0.04). CRP (n=231; SMD -0.08, 95% CI -0.46 to 0.30; p=0.7), IL-10 (n=247; SMD 1.14, 95% CI -0.90 to 3.19; p=0.3), and IL-6 (n=154; SMD -2.00, 95% CI -5.65 to 1.65; p=0.3) were not significantly changed. Overall, the authors concluded vitamin D may have modest anti-inflammatory effects, but evidence is insufficient to support vitamin D alone for improving inflammation or heart failure outcomes.

Evidence was based on a small number of trials with limited pooled sample sizes for each biomarker, and results were heterogeneous for IL-10 and IL-6. Trial designs varied by vitamin D form, dose, duration, calcium co-supplementation, baseline vitamin D status, and population characteristics, including one infant study that influenced sensitivity analyses. Long-term clinical heart failure outcomes and detailed adverse event reporting were not provided in the extracted text.