Micronutrient Supplementation to Reduce Cardiovascular Risk

Quick Takes

  • Supplementation of some but not all micronutrients may benefit cardiometabolic health outcomes in diverse populations.
  • n-3 fatty acid supplementation reduced CVD mortality, MI, and CHD events.
  • Vitamins C, D, and E were not associated with a lower risk for CVD or T2D.
  • Beta carotene supplementation was associated with a higher risk for all-cause mortality, CVD mortality, and stroke.
  • Whole-food diets to promote cardiometabolic health with personalized combinations of micronutrients should be validated for long-term efficacy in future clinical trials with diverse populations.

Study Questions:

Are micronutrients associated with cardiovascular disease (CVD) outcomes?


This systematic review and meta-analysis included randomized controlled intervention trials that examined antioxidant micronutrients associated with CVD risk factors and clinical events. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were used for this study, and the protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). References were identified by searching the PubMed, Web of Science, and Embase databases from inception until May 1, 2022. Studies were eligible if they used antioxidant micronutrients to improve CVD risk factors (i.e., blood pressure, lipids, glucose control, and type 2 diabetes risk) and/or events. CVD events included all-cause mortality, CVD mortality, myocardial infarction (MI), stroke, coronary heart disease (CHD), and arrhythmia.


A total of 884 randomized controlled trials (RCTs) evaluating 27 types of micronutrients were included. Participants totaled 883,527 or 4,895,544 person-years. Evidence was graded as moderate for the majority of studies. n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR], 0.92; 95% confidence interval [CI], 0.85-0.99), MI (RR, 0.86; 95% CI, 0.76-0.96), and CHD events (RR, 0.86; 95% CI, 0.80-0.93). Vitamins C, D, E, and selenium showed no effect on CVD or type 2 diabetes (T2D) risk. At the same time, beta carotene supplementation increased all-cause mortality (RR, 1.09; 95% CI, 1.00-1.20), CVD mortality events (RR, 1.14; 95% CI, 1.05-1.23), and stroke risk (RR, 1.17; 95% CI, 1.00-1.38). In addition, supplementation of n-6 fatty acid, L-arginine, L-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors.


The authors concluded that supplementing for some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations.


This large systematic review and meta-analysis examined a variety of RCTs with the supplementation of micronutrients. Not surprisingly, benefits but also risks were noted for some of the micronutrients. While CVD and diabetes benefits were observed for n-3 fatty acids, an increased risk for events was reported for supplementation of beta carotene. These data suggest the importance of rigorous RCTs to examine supplementation among diverse populations.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Statins, Diet

Keywords: Antioxidants, Arginine, Arrhythmias, Cardiac, beta Carotene, Blood Glucose, Blood Pressure, Cardiovascular Diseases, Coronary Disease, Curcumin, Diabetes Mellitus, Type 2, Dietary Supplements, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Folic Acid, Genistein, Magnesium, Melatonin, Metabolic Syndrome, Micronutrients, Myocardial Infarction, Primary Prevention, Quercetin, Risk Assessment, Risk Factors, Selenium, Stroke, Thioctic Acid, Vitamin E, Vitamin D, Zinc

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