The following are key points to remember about this meta-analysis of 179 randomized controlled trials published from January 2012 through October 2017:

1. The most common supplements—multivitamins, vitamin D, calcium, and vitamin C—demonstrated no statistically significant effect on any of 9 cardiovascular and mortality outcomes.
2. Folic acid (B₉) had a statistically significant effect in reduction of stroke (risk ratio [RR] 0.80, p = 0.003) and reduction in total cardiovascular disease (CVD) (RR 0.83, p = 0.002).
3. Extended-release niacin (B₃) at doses of 1-3 grams/day increased all-cause mortality in which statins were taken (RR 1.10, p = 0.05). The authors caution against long-term use of extended release niacin as an adjunct to statin therapy due to increased all-cause mortality.
4. Antioxidant combinations (>2 of vitamins A, C, and E, beta-carotene, selenium, and zinc) were associated with an increase in all-cause mortality (RR 1.06, p = 0.05). Studies containing selenium were excluded; the revised analysis showed an even greater increase in all-cause mortality (RR 1.09, p = 0.002).
5. No significant effect on CVD outcomes or all-cause mortality was detected for vitamins A, B₆, or E, beta-carotene, zinc, iron, magnesium, selenium, or multivitamins.
6. The China Stroke Primary Prevention Trial was the primary driver of stroke reduction with folic acid. Because the effect might be due to lack of folic acid fortification in China, the investigators recommend that proposals to study folic acid or B-vitamin complex supplementation for stroke or CVD reduction in regions such as North America, where folic acid fortification is required, should be preceded by large trials of these nutrients.
7. Supplements generally showed a notable lack of effect on CVD outcomes and all-cause mortality. Longer-term studies might demonstrate such effects.
8. Additional studies on multivitamins might be of benefit considering the small but non-significant benefit seen on all-cause mortality (RR 0.95, p = 0.12).
9. Study results confirm recommendations to adopt healthy dietary patterns that emphasize plant-based foods as a natural source of most vitamins and minerals.

Keywords: Dietary Supplements, Primary Prevention, Folic Acid, Selenium, Ascorbic Acid, beta Carotene, Vitamin A, Vitamin B 6, Vitamin B Complex, Niacin, Magnesium, Iron, Zinc, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Antioxidants, Calcium, Dietary, Vitamin D, China, Stroke

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