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Providing perspectives on recent research into vitamins and nutritionals


Folic Acid Supplements Reduce Stroke Risk

By Michael McBurney

Skeptics don’t believe that vitamins are absorbed from pills. People are chastised for wasting money on dietary supplements. Researchers review results of randomized controlled trials (RCTs) and conclude that vitamin supplements don’t help prevent chronic disease. Experts step up and explain that decades of nutrition research shouldn’t be ignored. The problem is that understanding nutrient-disease relationships requires measuring nutritional status. Proof of this fact can be found in an RCT conducted in China. 

The China Stroke Primary Prevention Trial randomized 20,702 adults with hypertension (but no history of stroke or myocardial infarction) to one of 2 treatments:  a drug (enalpril) or enapril with 0.8 mg of folic acid. The important difference with this study was that the investigators measured folate levels in the majority of participants. Folate supplementation increased blood folate levels from 4.4 ng/mL (10.2 nmol/L) at baseline to 11.2 ng/mL (26.1 nmol/L). Differences in stroke occurrence rates between the two interventions were so great after 48 months that the study was terminated prematurely. Simply, folic acid supplementation saved lives. The risk of having a stroked was reduced 21% by using a folic acid supplement. The risk reduction was greatest in those with low baseline folate levels.  

When interviewed, the authors endorsed folic acid fortification and said, “We speculate that even in countries with folic acid fortification and widespread use of folic acid supplements such as the United States and Canada, there may still be room to further reduce stroke incidence using more targeted folic acid therapy”.  

In an accompanying editorial, Stampfer and Willett write, “These remarkable findings may represent an underestimate of the potential true effect of folic acid supplementation in this setting for several reasons.” The reasons are low adherence, mean folate levels in the control group increased 60% during the course of the trial, the trial was stopped prematurely before the full effect may have been measured, and there was a suggestion of increasing benefit in the treatment vs control group over time.

While other systematic reviews have reported modest benefits of folic acid supplementation in stroke prevention, today’s main citation demonstrates the importance of evaluating nutritional status when conducting nutrient supplementation studies. Without measuring serum folic acid, the investigators would not have known that mean folate levels increased 60% during the course of the trial.

In conclusion, today’s main citation provides proof that there is little value, if any, in evaluating the efficacy of vitamin, mineral and multivitamin supplements for the primary prevention of cardiovascular disease and cancer in the absence of nutritional status assessments.

Main Citation

Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Wang J, Yang X, Yang T, Xia C, Zhao G, Dong Q, Zhu D, Wang X, Ge J, Zhao L, Hu D, Liu L, Hou FF, for the CSPPT Investigators. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China. The CSPPT Randomized Clinical Trial. 2015 JAMA doi: 10.1001/jama.2015.2274

Other Citations

Stampfer M, Willett W. Folate supplements for stroke prevention: Targeted trial trumps the rest. 2015 JAMA doi: 10.1001/jama.2015.1961

Guallar E, Stranges S, Mulrow C, Appel LJ, Miller III, ER. Enough is enough: Stop wasting money on vitamin and mineral supplements. 2013 Ann Intern Med 159 (12):850-851. doi: 10.7326/0003-4819-159-12-201312170-00011

Yang H-T, Lee M, Hong K-S, Ovbiagele B, Saver JL. Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials. 2012 Eur J Int Med doi: 10.1016/j.ejim.2012.07.004

Fortmann SP, Burda BU, Senger CA, et al. Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force. 2013 Agency for Healthcare Research and Quality US, Rockville MD, Evidence Syntheses No 108