Supplementation of certain micronutrients benefited cardiometabolic health, but others did not, according to a systematic review and meta-analysis.

Specifically, supplementation with omega-3 fatty acids, folic acid and coenzyme Q10 conferred certain benefits, supplementation with vitamin C, vitamin D, vitamin E and selenium had no effect on CVD risk and supplementation with beta-carotene was harmful, researchers wrote in the Journal of the American College of Cardiology.

“For the first time, we developed a comprehensive, evidence-based integrative map to characterize and quantify micronutrient supplements’ potential effects on cardiometabolic outcomes,” Simin Liu, MD, MS, MPH, ScD, professor of epidemiology and medicine at Brown University, said in a press release. “Our study highlights the importance of micronutrient diversity and the balance of health benefits and risks.”

Liu and colleagues analyzed 884 randomized controlled trials evaluating 27 types of micronutrients. The analysis included 883,627 participants and covered 4,895,544 person-years.

Benefits vary

The following micronutrients were associated with moderate- to high-quality evidence for reducing CVD risk factors: omega-3 fatty acids, omega-6 fatty acids, L-arginine, L-citrulline, folic acid, vitamin D, magnesium, zinc, alpha-lipolic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein and quercetin, according to the researchers.

Supplementation with omega-3 fatty acids was linked with reduced risk for CVD mortality (RR = 0.93; 95% CI, 0.88-0.97), MI (RR = 0.85; 95% CI, 0.78-0.92) and CHD events (RR = 0.86; 95% CI, 0.8-0.93), while supplementation with folic acid reduced risk for stroke (RR = 0.84; 95% CI, 0.72-0.97) and supplementation with coenzyme Q10 reduced risk for all-cause mortality (RR = 0.68; 95% CI, 0.49-0.94), Liu and colleagues wrote.

There was no relationship between CVD or diabetes risk and supplementation with vitamin C, vitamin D, vitamin E and selenium, and supplementation with beta-carotene increased risk for all-cause mortality (RR = 1.1; 95% CI, 1.05-1.15), CVD mortality (RR = 1.12; 95% CI, 1.06-1.18) and stroke (RR = 1.09; 95% CI, 1.01-1.17), according to the researchers.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” Liu said in the release.

More than antioxidant properties

In a related editorial, Juan G. Gormaz, PhD, from the faculty of medicine at the University of Chile in Santiago, and Rodrigo Carrasco, MD, PhD, from the Chilean Society of Cardiology and Cardiovascular Surgery in Santiago, wrote that “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as omega-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The study supports the hypothesis that “only compounds able to have an impact on oxidative stress through more than one pathway and/or that have pleiotropic properties should have a significant clinical effect,” Gormaz and Carrasco wrote.