“For the first time, we developed a comprehensive evidence-based map of all available intervention trials studying dietary supplements' potential effects on cardiometabolic risk factors and clinical outcomes,” said Dr. Simin Liu, MD, MS, MPH, ScD, professor of epidemiology and medicine at Brown University and a lead researcher on the study.
“Findings highlight the importance of micronutrient diversity, dosage and target populations that could benefit the most from supplements.”
The work – carried out by researchers from the China Agricultural University, Brown University and the Icahn School of Medicine at Mount Sinai – was funded by the U.S. Fulbright Program, the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund and the Beijing Municipal Natural Science Foundation.
A comprehensive mapping of micronutrients
Antioxidant micronutrients and their free radical deactivation powers have long been linked to cardiovascular disease or type-2 diabetes prevention, particularly when consumed in food as part of heart-healthy Mediterranean or Dietary Approach to Stop Hypertension (DASH) diets.
The analysis, however, points out that results from studies on the effects of antioxidants as supplements have been inconsistent and therefore “one reason why this approach hasn’t yet been widely adopted in preventative cardiology.”
“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” the researchers wrote.
As such, they set out to systematically map micronutrient supplements reported in all publicly available and accessible studies, along with their effects on cardiovascular risk factors and multiple cardiovascular diseases. A search of the PubMed, Web of Science and Embase databases up to May 1, 2022 produced a total of 884 randomized, controlled trials on micronutrients taken as dietary supplements. The pooled data sets included 883,627 participants (with a combined 4,895,544 person-years) and 27 types of micronutrients.
“We used an integrative framework to look at the totality, quality and consistency of the available evidence and systematically quantify sources of heterogeneities across studies and populations,” Liu explained.
The healthy, the ineffective and the risky
The analysis determined that supplementation with n-3 fatty acid, n-6 fatty acid, L-arginine, L-citrulline, folic acid, magnesium, zinc, a-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein and quercetin showed moderate- to high-quality evidence for reducing risk factors for cardiovascular disease.
Among these, “long-chain n-3 fatty acids were the most effective in reducing cardiovascular disease mortality, myocardial infarction and coronary heart disease events”, while “folic acid reduced the risk of stroke, and coenzyme Q10 decreased all-cause mortality events,” the researchers wrote.
In contrast, supplementation with vitamins C, D and E and selenium showed no effects on long-term cardiovascular disease events, and b-carotene increased all-cause mortality, cardiovascular disease mortality events and stroke risk.
The researchers call for further study including large, high-quality interventional trials to investigate the long-term effects of certain micronutrients on health, noting that strategies may require cultural adaptations for global application.
“This work will guide the future design of precision-based intervention trials to determine the clinical efficacy of multiple combinations of micronutrients on cardiometabolic health outcomes,” Liu added.
Source: Journal of the American College of Cardiology
“Micronutrient Supplementation to Reduce Cardiovascular Risk”
doi: 10.1016/j.jacc.2022.09.048
Authors: Peng An, et al.
