Table 4.

Summary of Evidence of the Effects of Vitamin Supplements on Cardiovascular Disease

Beta-carotene	Some cohort studies have linked low serum levels or low dietary intake of beta-carotene with higher CVD risk. RCTs of beta-carotene supplements document no benefit in the general population and increased risk of lung cancer in patients who were at high risk of lung cancer.162
Calcium	Calcium supplementation with vitamin D3 is recommended as a means to prevent osteoporosis, especially in women. A recent meta-analysis of RCTs suggests that calcium supplementation may increase the risk of myocardial infarction.84
Vitamin D	Emerging evidence from observational studies suggests that low serum vitamin D levels are associated with higher risk of CVD events. RCTs of vitamin D supplementation have not shown conclusive reductions in risk of CVD.163 Additional trials using higher doses of vitamin D supplementation are ongoing.
Vitamin E	Several prospective cohort studies have linked vitamin E consumption or supplementation with lower risk of CHD. RCTs have failed to show reductions in CVD events with supplemental vitamin E, and 2 meta-analyses suggest that high-dose vitamin E supplements may increase total mortality.162,164
Folic acid, vitamin B6, vitamin B12	Observational studies have associated low folate intake, low serum folate levels, and high homocysteine levels with higher risk of CVD outcomes. RCTs have confirmed that folic acid supplementation lowers blood homocysteine levels. Long-term RCTs have not documented benefits of folic acid with or without vitamin B6 and vitamin B12 on CVD outcomes. In some trials, supplemental folic acid was associated with increased risk of CVD.165
Fish oils	Multiple cohort studies have documented an inverse relationship between fish intake and subsequent CHD, in particular CHD death.39 A meta-analysis of larger and multiple smaller RCTs, largely in higher-risk populations, demonstrated a reduction in total mortality with fish oil supplementation.39 Four of 8 large RCTs among patients with and without preexisting CVD demonstrated reductions in CHD events; several of these trials had potentially relevant limitations.46
Multivitamins	Although some cohort studies have observed lower CVD risk with multivitamin supplements, 5 RCTs, rated to be of fair to poor quality, have not documented any clear CVD benefit of multivitamin use in mixed populations.166

CVD indicates cardiovascular disease; RCT, randomized controlled trial; and CHD, coronary heart disease.