Review
Version 1
Preserved in Portico This version is not peer-reviewed
The Hidden Dangers of Excess Folate, Uncovering the Molecular Mechanisms
Version 1
: Received: 29 September 2023 / Approved: 29 September 2023 / Online: 29 September 2023 (10:39:29 CEST)
A peer-reviewed article of this Preprint also exists.
Fardous, A.M.; Heydari, A.R. Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review. Nutrients 2023, 15, 4699. Fardous, A.M.; Heydari, A.R. Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review. Nutrients 2023, 15, 4699.
Abstract
This review delves into the intricate relationship between folate (Vitamin B9) intake, especially its synthetic form, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, essential for DNA synthesis, repair, and methylation, concerns arise from its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis, disturbances in DNA methylation, and impacts on embryogenesis, pregnancy outcomes, neurodevelopment, and disease risk. Notably, these consequences stretch beyond the immediate effects, potentially influencing future generations through epigenetic reprogramming. We probe into the molecular mechanisms underlying these effects, including accumulation of unmetabolized folic acid, Vitamin B12 dependent mechanisms, altered one carbon metabolism, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, we emphasize differences in the effects and mechanisms mediated by folic acid compared to natural folate. Given the widespread folic acid supplementation, it is imperative to further research its optimal intake levels, and the molecular pathways impacted by its excessive intake, ensuring the health and well-being of the global population.
Keywords
Unmetabolized folic acid (UMFA); folic acid; one-carbon cycle; Methylation; epigenetic; carcinogenesis; aging; neurodevelopment; embryogenesis; folate
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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