Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease.
Level 2 - randomized trial
Individual randomized, placebo-controlled trial
PubMed 30415629 · doi:10.1056/NEJMoa1809944
What was done
A nationwide, randomized, placebo-controlled trial with a 2-by-2 factorial design evaluated vitamin D3 (cholecalciferol, 2000 IU/day) and marine n-3 fatty acids (1 g/day) for the prevention of cancer and cardiovascular disease in US men aged 50 or older and women aged 55 or older. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or cardiovascular death). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. Median follow-up was 5.3 years.
What was found
Among 25,871 randomized participants (including 5,106 Black participants), vitamin D supplementation did not reduce primary or secondary end points compared to placebo: - Invasive cancer: 793 cases in the vitamin D group vs 824 in placebo (HR 0.96; 95% CI, 0.88 to 1.06; P=0.47; 1,617 total cases). - Major cardiovascular events: 396 vs 409 (HR 0.97; 95% CI, 0.85 to 1.12; P=0.69; 805 total events). - Cancer death: HR 0.83 (95% CI, 0.67 to 1.02; 341 deaths). - Breast cancer: HR 1.02 (95% CI, 0.79 to 1.31). - Prostate cancer: HR 0.88 (95% CI, 0.72 to 1.07). - Colorectal cancer: HR 1.09 (95% CI, 0.73 to 1.62). - Myocardial infarction: HR 0.96 (95% CI, 0.78 to 1.19). - Stroke: HR 0.95 (95% CI, 0.76 to 1.20). - Cardiovascular death: HR 1.11 (95% CI, 0.88 to 1.40). - Expanded composite cardiovascular end point: HR 0.96 (95% CI, 0.86 to 1.08). - All-cause mortality: HR 0.99 (95% CI, 0.87 to 1.12; 978 deaths). - No excess risk of hypercalcemia or other adverse events was identified.
Why it matters
In a large, diverse cohort of older adults, routine supplementation with 2000 IU daily of vitamin D3 did not lower the incidence of invasive cancer or major cardiovascular events.
Limits
Only a single dose of vitamin D3 was tested. Baseline vitamin D levels and potential effects in deficient subgroups are not reported in the abstract. Follow-up of 5.3 years may be insufficient to assess cancers with long latency periods. The study was restricted to older adults (men ≥50, women ≥55).
Cited by
- supports The VITAL trial enrolled approximately 25,000 participants in a four-arm study design.