Table 1.

Vitamin D Supplementation and Cardiovascular Outcomes: Summary of RCTs

Trial / Study	VITAL Manson et al., [30]	ViDA Scragg et al., [31]	D-Health Thompson et al., [32]	Barbarawi et al. Meta-Analysis [33]
Population & Key Characteristics	N = 25,871; men ≥ 50, women ≥ 55; generally healthy U.S. adults without prior CVD or cancer	N = 5,110; community-dwelling adults aged 50–84 years, New Zealand	N = 21,315; adults aged 60–84 years, Australia	N = 83,291 (pooled from 21 RCTs); diverse populations including general community and selected risk groups
Inclusion/Exclusion Summary	Excluded: prior CVD, cancer, renal failure, hypercalcemia, other major illnesses	Excluded: current treatment for CVD, renal impairment (creatinine > 150 µmol/L), hypercalcemia, recent supplementation	Excluded: current high-dose vitamin D use (> 500 IU/day), hypercalcemia, renal failure, sarcoidosis	Inclusion: RCTs reporting CVD outcomes with vitamin D vs. placebo; no restriction by baseline deficiency status
Intervention (Dose & Regimen)	Cholecalciferol 2,000 IU/day (and/or omega-3 fatty acids); placebo-controlled	Cholecalciferol 100,000 IU/month (oral bolus); placebo-controlled	Cholecalciferol 60,000 IU/month (oral bolus); placebo-controlled	Various: daily (400–5000 IU), weekly, or monthly bolus regimens
Baseline 25(OH)D Status	Mean ~ 30 ng/mL (majority sufficient)	Mean ~ 27 ng/mL (27% <20 ng/mL)	Mean ~ 24 ng/mL (10% <20 ng/mL)	Variable across trials; not selected for deficiency in most
Primary Cardiovascular Endpoint	MACE (composite of MI, stroke, CV death)	CVD events (MI, stroke, CV death, heart failure, revascularization)	MACE (composite of MI, stroke, CV death)	MACE (composite, as defined by each trial); also MI, stroke, CV mortality, all-cause mortality
Key Cardiovascular Findings	HR 0.97 (95% CI, 0.85–1.12); p = 0.66	HR 1.02 (95% CI, 0.87–1.20); p = 0.81	HR 0.91 (95% CI, 0.81–1.01); p = 0.08	RR for MACE: 1.00 (95% CI, 0.95–1.06); p = 0.85
Comments	No selection for deficiency; null primary outcome. Subgroup analysis suggested possible benefit in those with normal BMI	Monthly bolus regimen; null primary outcome. Secondary analysis showed improved pulse wave velocity in deficient participants (p = 0.03)	Signal for reduced MI in prespecified analysis (HR 0.81, 0.67–0.98). Monthly bolus design may limit generalizability to daily dosing	Largest meta-analysis to date. Consistent null findings across all prespecified subgroups (by dose, baseline 25(OH)D, intervention duration, and study quality)

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; BMI, body mass index; CI, confidence interval; CV, cardiovascular; CVD, cardiovascular disease; HR, hazard ratio; MACE, major adverse cardiovascular events; MI, myocardial infarction; RR, risk ratio

Note: All trials primarily enrolled participants from the general community without pre-selection for vitamin D deficiency. The consistent neutral findings across these large-scale studies do not support the routine use of vitamin D supplementation for cardiovascular protection in the general population