J Stroke.  2018 Jan;20(1):99-109. 10.5853/jos.2017.01522.

Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials

Affiliations
  • 1Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chiayi, Taiwan. menglee5126@gmail.com
  • 2Department of Neurology, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.
  • 3Stroke Center and Department of Neurology, Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • 4Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan.
  • 5Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.

Abstract

BACKGROUND AND PURPOSE
Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification.
METHODS
PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model.
RESULTS
The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05).
CONCLUSIONS
FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.

Keyword

Folic acid; Stroke; Prevention; Food, fortified; Meta-analysis

MeSH Terms

Folic Acid*
Food, Fortified
Humans
Outcome Assessment (Health Care)
Stroke*
Vitamin B 12
Folic Acid
Vitamin B 12
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