Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Folic Acid*/adverse effects ; Folic Acid Deficiency*; Pregnancy ; Female ; Humans ; Dietary Supplements/adverse effects ; Vitamin B 12 ; DNA Methylation

This review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis; disruption 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. The molecular mechanisms underlying these effects were examined, including altered one-carbon metabolism, the accumulation of unmetabolized folic acid, vitamin-B12-dependent mechanisms, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, differences in the effects and mechanisms mediated by folic acid compared with natural folate are highlighted. 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.

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R01 CA121298 United States CA NCI NIH HHS; CA121298 United States NH NIH HHS

Keywords: aging; carcinogenesis; embryogenesis; epigenetic; folate; folic acid; methylation; neurodevelopment; one-carbon cycle; unmetabolized folic acid (UMFA)

935E97BOY8 (Folic Acid)
P6YC3EG204 (Vitamin B 12)

Date Created: 20231114 Date Completed: 20231115 Latest Revision: 20240210

20240210

PMC10648405

10.3390/nu15214699

37960352