Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review
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 me...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/21/4699 |
| _version_ | 1797631446348726272 |
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| author | Ali M. Fardous Ahmad R. Heydari |
| author_facet | Ali M. Fardous Ahmad R. Heydari |
| author_sort | Ali M. Fardous |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T11:23:44Z |
| format | Article |
| id | doaj.art-c8309a08c7234bc4a82e0891c4c92324 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T11:23:44Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-c8309a08c7234bc4a82e0891c4c923242023-11-10T15:10:05ZengMDPI AGNutrients2072-66432023-11-011521469910.3390/nu15214699Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative ReviewAli M. Fardous0Ahmad R. Heydari1Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USADepartment of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USAThis 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.https://www.mdpi.com/2072-6643/15/21/4699unmetabolized folic acid (UMFA)folic acidone-carbon cyclemethylationepigeneticcarcinogenesis |
| spellingShingle | Ali M. Fardous Ahmad R. Heydari Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review Nutrients unmetabolized folic acid (UMFA) folic acid one-carbon cycle methylation epigenetic carcinogenesis |
| title | Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review |
| title_full | Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review |
| title_fullStr | Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review |
| title_full_unstemmed | Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review |
| title_short | Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review |
| title_sort | uncovering the hidden dangers and molecular mechanisms of excess folate a narrative review |
| topic | unmetabolized folic acid (UMFA) folic acid one-carbon cycle methylation epigenetic carcinogenesis |
| url | https://www.mdpi.com/2072-6643/15/21/4699 |
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