Popular vitamin or mineral supplements taken by millions of adults do not help prevent or treat cardiovascular disease (CVD), with the exception of folic acid, which appears to reduce the stroke risk, a comprehensive literature review concludes.
The findings reinforce current recommendations to adopt healthy diets that are heavy in plant-based foods from which these vitamins are derived naturally, the researchers say.
The study was published online May 28 in the Journal of the American College of Cardiology (JACC).
Vitamins and mineral supplements are widely used to improve overall health and longevity. In 2012, more than half of the US population (52%) was taking supplements, according to data from the National Health and Nutrition Examination Survey. Yet there is no consensus on whether individual vitamins or minerals or combination supplements are beneficial for CVD prevention and treatment, the authors write.
A team of researchers led by David Jenkins, MD, professor and Canada research chair in nutrition and metabolism, Department of Nutritional Sciences, University of Toronto, Ontario, did a systematic review and meta-analysis of 179 relevant randomized controlled trials (RCTs) on vitamin and mineral supplement use published from January 2012 to October 2017.
They found that none of the four most commonly used supplements — multivitamins, vitamin D, calcium, and vitamin C — had a significant effect on CVD outcomes or all-cause mortality.
Vitamin D, the most studied nutrient, with 43 RCTs, “convincingly” showed a lack of harm or benefit. The overall risk ratio (RR) was 0.99 (95% confidence interval [CI], 0.95 – 1.03; P = .58) for all-cause mortality, with no heterogeneity and high-quality evidence. Vitamin D supplementation also had no impact on total CVD (RR, 0.95; 95% CI, 0.86 – 1.05; P = .31).
The one exception seems to be the benefit of folic acid for stroke prevention. In two of seven RCTs, folic acid reduced the risk for stroke (RR, 0.80; 95% CI, 0.69 – 0.93; P = .003), with no heterogeneity and moderate-quality evidence. A meta-analysis of the seven studies also showed a similar benefit for folic acid driven by the China Stroke Primary Prevention Trial (CSPPT).
As reported previously by theheart.org | Medscape Cardiology, CSPPT, which included more than 20,000 adults with hypertension but without a history of myocardial infarction, showed that daily treatment of 10 mg of enalapril plus 0.8 mg of folic acid for 4.5 years reduced the risk for first stroke by 21% compared with taking enalapril alone.
A subanalysis of the CSPPT published May 7 in JACC showed that hypertensive adults with low platelet count who took the enalapril/folic acid combination saw a 73% risk reduction in first stroke when compared with enalapril alone.
“Whether these data are sufficient to change clinical practice in areas of the world where folic acid food fortification is already in place is still a matter for discussion,” Jenkins commented in a news release.
The team’s review also found that B-complex vitamins reduced the risk for stroke in 9 of 12 studies in the meta-analysis (RR, 0.90; 95% CI, 0.81 – 1.00; P = .04) with no heterogeneity and moderate-quality evidence.
Niacin and antioxidants appeared to increase the risk for all-cause mortality. Vitamins A, B6, and E and multivitamins, as well as β-carotene, zinc, iron, magnesium, and selenium, had no significant effect on CVD outcomes and all-cause mortality.
The researchers say a limitation of their analysis is not considering data from cohort studies, which are longer and more representative of the general population than are randomized clinical trials. Also, grouping many types of antioxidants may have been suboptimal because their mechanisms of action may also be very different.
Despite these and other limitations, the researchers say their review supports the 2014 US Preventive Services Task Force (USPSTF) recommendation stating that the current evidence is “insufficient to assess the balance of benefits and harms of single or paired nutrient supplements (except for β-carotene and vitamin E) [that were recommended against] for the prevention of cardiovascular disease and cancer.”
“In the absence of further studies, the current data on supplement use reinforce advice to focus on healthy dietary patterns, with an increased proportion of plant foods in which many of these required vitamins and minerals can be found,” the authors conclude.
In an audio commentary accompanying the publication, Valentin Fuster, MD, PhD, Mount Sinai Hospital, New York City, and editor-in chief of JACC, summed up the new paper with five points:
“First, since the 2013-2014 assessment and report of the USPSTF, the most notable finding has been the effect of folic acid in reducing stroke with significance driven by the 5-year, 20,000 Chinese CSPPT randomized controlled trial,” Fuster said.
Second, such reduction in stroke has also been supported by RCTs of vitamin B complex in which folic acid was a component, he said.
“Third, niacin or vitamin B3 may increase all-cause mortality, possibly related to its adverse effects on glycemic response,” Fuster said. “Fourth, antioxidant mixtures do not appear to benefit cardiovascular disease but may also increase all-cause mortality.
“And fifth, in the absence of further studies, the current data on supplement use reinforces advice to focus on healthy dietary patterns with an increased proportion of plant foods from which many of these required vitamins and minerals can be derived.”
He concluded with a “personal point” that can be taken from the study: “Unless we talk about the combination of vitamin B6, vitamin B12, and certainly the use of folic acid for the prevention of stroke, all the rest of the information about vitamins and minerals cannot convince us and justify their use, at least if we only focus on the cardiovascular system.”
The study was supported by the Canada Research Chair Endorsement, Loblaw Cos Ltd, and the Canadian Institutes for Health Research. A complete list of author disclosures appears with the original article.
J Am Coll Cardiol. Published online May 28, 2018. Abstract