Page 77 - GTM-3-2

Global Translational Medicine

MINI-REVIEW
Folic acid supplementation for stroke

prevention: The devil is in the details

2
Kate C. Chiang 1 , Teja Kankanala , Priya Kankanala , Prisha Desai ,
2
2
and Ajay Gupta 2,3,4 *
1 School of Medicine, University College Dublin, Dublin, Ireland
2 Charak Foundation, California, United States of America
3 Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine, Orange,
California, United States of America
4 Department of Medical Education, School of Medicine, California University of Science and Medicine,
Colton, California, United States of America

Abstract

Cerebrovascular disease (CVD) is the second leading cause of death worldwide.
In addition to the traditional risk factors such as hypertension, diabetes, and
hyperlipidemia, nutritional folate deficiency may be an important risk factor for
CVD, especially in low-income countries. Folic acid supplementation has been
considered for stroke prevention, but trial results have been variable. Therefore,
in general, stroke patients do not receive folic acid supplementation routinely,
partly due to the lack of consensus regarding such necessity. To be metabolically
active, the synthetic folic acid, which is often taken as a supplement, needs
to be enzymatically converted to 5-methyltetrahydrofolate (5-MTHF) by the
endogenous enzyme methylenetetrahydrofolate reductase (MTHFR). 5-MTHF
*Corresponding author: promotes homocysteine catabolism while improving endothelial function and
Ajay Gupta
(ajayg1@hs.uci.edu) reducing superoxide generation. It has been shown that supplementation with
synthetic folic acid reduced the incidence of ischemic strokes in individuals with
Citation: Chiang KC, Kankanala T,
Kankanala P, Desai P, Gupta A. hypertension, but the efficacy of folic acid supplementation in primary prevention
Folic acid supplementation for of ischemic strokes was markedly reduced in the subset of hypertensive patients
stroke prevention: The devil is in with mutations in the MTHFR gene. Furthermore, supplementation with synthetic
the details. Global Transl Med.
2024;3(2):2509. folic acid may promote accumulation of unmetabolized free folic acid which may
doi: 10.36922/gtm.2509 increase risk of cancer, immune suppression, and cognitive impairment, especially
in patients with mutations in MTHFR. Since MTHFR genotyping is neither feasible
Received: December 22, 2023
Accepted: March 18, 2024 nor cost-effective in the vast population of patients at risk of ischemic stroke,
Published Online: June 19, 2024 supplementation with low-dose 5-MTHF merits examination in large well-designed
Copyright: © 2024 Author(s). clinical trials.
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution Keywords: Folic acid; Folate; Methylenetetrahydrofolate reductase; 5-methyltetrahydrofolate;
License, permitting distribution, Stroke; Cerebrovascular disease; Hypertension; Cardiovascular disease
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience
Publishing remains neutral with 1. Folic acid deficiency and cerebrovascular disease (CVD)
regard to jurisdictional claims in
published maps and institutional CVD is the leading cause of long-term disability and the second leading cause of death
1
affiliations. worldwide. Approximately 795,000 new or recurrent acute strokes secondary to CVD

Volume 3 Issue 2 (2024) 1 doi: 10.36922/gtm.2509