Multivitamins and Folic Acid Play a Role in the Primary Prevention of Stroke

Expert Opinion · May 27, 2015
Written by: Rebecca Gottesman MD, PhD

Two recent papers highlight the potential role of inexpensive treatments for primary prevention of stroke in the form of a multivitamin in the Japan Collaborative Cohort Study1 and folic acid supplementation in the China Stroke Primary Prevention Trial (CSPPT).2 Despite distinct methods and findings in these two studies, they further support the concept that medication choices may need to be personalized, where treatments may differ depending on an individual’s genotype, diet, or lifestyle.

The Japan Collaborative Cohort Study was an observational study of 72,180 Japanese adults without prior stroke or myocardial infarction, and the authors reported that use of a multivitamin was associated with a lower rate of stroke, although overall results did not reach significance. However, they did find that, among the subgroup of participants who had a diet low in fruits and vegetables, those who took a multivitamin had a significantly reduced rate of stroke (HR, 0.80). These results should be interpreted with caution given the possibility of a “healthy user” effect; individuals who take a daily multivitamin are more likely to take care of their health, be more physically active, and be more compliant with other medications.

In contrast, the CSPPT study was a randomized clinical trial of 20,702 hypertensive Chinese adults without prior stroke or myocardial infarction in which individuals were randomized to enalapril with folic acid vs enalapril alone. I was a coauthor on this paper. Randomization was performed within strata defined by MTHFR subgroup, and the results demonstrated that folic acid was associated with a significantly reduced risk of stroke (HR, 0.79). Prior studies of folic acid supplementation in secondary stroke prevention have failed to find a similar effect, but most were done in populations with adequate dietary levels of folate, both due to dietary supplementation (as is done in the United States) and due to MTHFR genotype. The TT genotype, which is associated with lower folate levels, is more common in China, and China does not have mandated folate supplementation, which means more residents are truly folate-deficient. These study results may indicate a potential role for folic acid supplementation either in areas of the world where dietary folic acid levels are low or for persons with the TT genotype who might be at higher risk for folate deficiency.

In combination, these studies emphasize that study of inexpensive, easily available treatments such as vitamin supplementation for stroke prevention might still have a role. A shift toward personalized medicine, as touted by President Obama in his recent initiative, might include decisions about vitamin or folic acid supplementation for stroke prevention depending on a person’s genotype or country of origin.

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