Most commonly-used vitamin and mineral supplements do not prevent cardiovascular events or prolong life, with the exception of folic acid and B-complex vitamins, according to analysis of systematic reviews and meta-analyses.
Multivitamins, vitamin D, calcium, and vitamin C, along with less commonly-used selenium, all demonstrated no consistent benefit for the prevention of cardiovascular disease, heart attack, or stroke, or for delaying death from any cause, whether people were deficient or not, David Jenkins, MD, of the University of Toronto, and colleagues reported online in the Journal of the American College of Cardiology.
The only nutrients with a significant benefit were folic acid alone, which was associated with lower total cardiovascular disease (CVD) risk as well as fewer strokes, and B vitamins containing folic acid, B6, and B12, which was associated with reduced stroke risk.
Niacin (vitamin B3) given with statins and antioxidants were actually associated with an increased risk of all-cause mortality. This last finding was not entirely surprising, Jenkins told MedPage Today, given past concerns about the safety of beta-carotene.
Since the 2016 U.S. Preventive Services Task Force (USPSTF) report suggesting insufficient evidence to support supplements for prevention of CVD and cancer, evidence from the large China Stroke Primary Prevention Trial (CSPPT) identified a potential role of folic acid supplementation in reducing cardiovascular disease, particularly stroke. Inclusion of that trial in the meta-analysis of folic acid and CVD risk yielded a 22% reduction in CVD risk – with a number needed to treat to prevent one negative CVD outcome of 111, compared with 72 for statin use in the 2016 USPSTF report.
Jenkins and colleagues wrote that their findings confirm the USPSTF conclusions of insufficient evidence for most supplements for the prevention of cardiovascular disease. However, that report didn’t consider B vitamin complexes specifically.
It is now clear that B vitamin therapy prevents stroke, J. David Spence, MD, of the University of Western Ontario in London, Ontario, commented in an email to MedPage Today. “In the early studies of B vitamin therapy for stroke prevention, harm from cyanocobalamin among participants with impaired renal function obscured the benefit of B vitamins.”
“The CSPPT in over 20,000 participants showed a 25% reduction of stroke with folic acid in primary prevention, and greater reductions in higher-risk patients – i.e., 30% reduction of stroke among participants with LDL-C greater than 2 mmol/L, and 70% reduction of stroke among participants with low platelet counts and high levels of total homocysteine. Benefits were seen even among participants with renal impairment,” noted Spence.
“In jurisdictions [e.g., North America] where folate fortification is the norm, the main cause of elevated homocysteine is metabolic vitamin B12 deficiency, which is often missed. In those countries, it would be important to use methylcobalamin (not cyanocobalamin) to achieve the benefits observed with folic acid in the large Chinese study,” Spence concluded.
Researchers noted that supplements, once used to treat vitamin and mineral deficiencies, are now also used to address subclinical deficiencies and purportedly to promote overall health and longevity. Nevertheless, official recommendations focus on meeting requirements through diet — generally high in fruit and vegetables, low in saturated fat and trans fat — rather than through supplementation.
National Health and Nutrition Examination Survey data (1999 to 2012) on about 38,000 adults showed that in 2012, up to 52% of the population was taking supplements, including 31% taking multivitamins.
For the review, the group considered 179 randomized controlled trials on vitamin and mineral supplement use published between January 2012 and October 2017, in order to include data published before and after the USPSTF analyses.
Commenting on the lack of effect of commonly-used supplements, Jenkins told MedPage Today that “they look fairly innocuous – if there is a benefit, that may be shown in future research. And while we had learned from the Chinese study that folate was protective for stroke, it was interesting to see that supported by the B complex. We can measure people for deficiency in folate, B12, and B6. It’s possible that folate supplementation could be helpful if they are deficient and have a risk of stroke. Assessment is also useful in the elderly – I’m a great believer in making measurements and then treating.”
While the findings are reassuring, Jenkins cautioned that the CSPPT study was done in China, where food is not fortified with folic acid, in contrast to North America where many grain products are fortified: “Further research needs to be done in the North American population to assess the effects, not only on CVD, but more importantly, on all-cause mortality.”
Limitations of the review included the exclusion of data from cohort studies, which are longer and more representative of the general population than randomized clinical trials. Also, grouping many types of antioxidants may have been suboptimal, as their mechanisms of action may differ.
This work was supported by the Canada Research Chair Endorsement, Loblaw Cos., and the Canadian Institutes for Health Research (CIHR).
Jenkins and several co-authors reported multiple relationships with agricultural/food manufacturing industry.