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Licensed Unlicensed Requires Authentication Published by De Gruyter December 12, 2012

Molecular mechanisms underlying the potentially adverse effects of folate

  • Kyle C. Strickland , Natalia I. Krupenko and Sergey A. Krupenko EMAIL logo


The importance of proper consumption of dietary folate for human health has been highlighted by an extensive number of publications over several decades. Fortification of grain products with folic acid was initiated with the specific intent to prevent neural tube defects, and the scope of this endeavor is unique in that its target population (women of the periconceptional period) is many times smaller than the population it affects (everyone who ingests fortified grain products). Folate fortification has been wildly successful in terms of its goal; since its inception, the incidence of neural tube defects has markedly decreased. In the wake of this public health triumph, it is important to catalog both the serendipitous benefits and potential side effects of folic acid supplementation. The vitamin is generally regarded as a harmless nutrient based on studies evaluating the safe upper limits of folate intake. In recent years, however, a concern has been raised with respect to a potential downside to folate supplementation; namely, its proposed ability to enhance proliferation of malignant tumors. The current review summarizes the available literature on the effects of folate supplementation and the molecular mechanisms by which high doses of folate may have negative consequences on human health, especially with regard to cancer.

Corresponding author: Sergey A. Krupenko, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA, Phone: +1 843 792–0845

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: This work was supported by the National Institutes of Heals grants DK54388 and CA095030 (to SAK). Kyle C. Strickland was supported by a Ruth L. Kirschstein National Research Service Award for Individual Predoctoral MD/PhD Fellows F30DK083215.

Employment or leadership: Medical University of South Carolina.

Honorarium: None declared.


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Received: 2012-8-30
Accepted: 2012-11-9
Published Online: 2012-12-12
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

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