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Abstract
Folate, also referred to as Vitamin B9, is a type of vitamin that dissolves in water and plays a central role in preserving the integrity of DNA molecules and gene expression through the construction of DNA and methylation. Folate cannot be synthesised in vivo and must be obtained from the diet, particularly fruits and green leafy vegetables. deficiency of folate increases the risk of DNA stability due to uracil misincorporation into the DNA backbone and chromosome breaks, it can lead to the accumulation of deoxyuridine monophosphate (dUMP) which impairs the pathway of dTMP synthesis. in addition, it reduces the availability of methyl donors which causes impaired methylation patterns. Finally, it can generate oxidative stress leading to mtDNA damage and eventually to genomic instability. Different studies and measurement methods have produced varying evidence on the connection between folate and DNA stability, So we encourage to increase in folic acid intake for at-risk groups, but more rigorous human studies are needed before scientifically based public health recommendations about dietary requirements can be made.
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References
- . A. Randomized, P. Controlled, and C. Trial, "Protective effect of folic acid on oxidative DNA damage," Medicine (Baltimore), vol. 94, no. 45, pp. 1–10, 2015, doi: 10.1097/MD.0000000000001872.
- . M. Fenech, "Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity," Mutat. Res., vol. 733, pp. 21–33, 2012.
- . C. E. Clare, A. H. Brassington, W. Y. Kwong, et al., "One-carbon metabolism: linking nutritional biochemistry to epigenetic pro-programming of long-term development," Annu. Rev. Anim. Biosci., vol. 7, pp. 263–287, 2019, doi: 10.1146/annurev-animal-020518-115206.
- . J. W. Crott, S. T. Mashiyama, B. N. Ames, et al., "The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro," Cancer Epidemiol. Biomarkers Prev., vol. 10, pp. 1089–1096, 2001.
- . X. Wu, W. Xu, T. Zhou, et al., "The role of genetic polymorphisms as related to one-carbon metabolism, vitamin B6, and gene-nutrient interactions in maintaining genomic stability and cell viability in Chinese breast cancer patients," Int. J. Mol. Sci., vol. 17, no. 1003, pp. 1–10, 2016.
- . C. F. Bull, G. Mayrhofer, N. J. O’Callaghan, et al., "Folate deficiency induces dysfunctional long and short telomeres; both states are associated with hypomethylation and DNA damage in human WIL2-NS cells," Cancer Prev. Res. (Phila), vol. 7, pp. 128–138, 2014.
- . L. Donnellan, et al., "Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal," Mutagenesis, vol. 37, no. 1, pp. 24–33, 2022, doi: 10.1093/mutage/geab036.
- . S. S. Gropper and J. L. Smith, Advanced Nutrition and Human Metabolism, 6th ed., Belmont, CA: Wadsworth, 2013, pp. 344–353. [Online]. Available: https://www.cengage.co.uk/books/9781133104056/.
- . National Institutes of Health, "Folate: Dietary Supplement Fact Sheet," [Online]. Available: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/. [Accessed: Jun. 6, 2018].
- . R. Pieroth, et al., "Folate and its impact on cancer risk," Curr. Nutr. Rep., vol. 7, pp. 70–84, 2018.
- . C. Galeone, V. Edefonti, M. Parpinel, R. Talamini, and A. F. Olshan, "Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the ENHANCE Consortium," Cancer Epidemiol. Biomarkers Prev., vol. 136, no. 4, pp. 904–914, 2016.
- . X. Wang, J. Yu, and J. Wang, "Neural tube defects and folate deficiency: Is DNA repair defective?," Int. J. Mol. Sci., vol. 24, no. 3, pp. 2220, 2023.
- . L. H. Allen, "Causes of vitamin B12 and folate deficiency," Food Nutr. Bull., vol. 29, no. 2, suppl. 1, pp. S20–S34, 2008.
- . L. B. Bailey, P. J. Stover, H. McNulty, et al., "Biomarkers of nutrition for development—folate review," J. Nutr., vol. 145, no. 7, pp. 1636S–1680S, 2015.
- . S. C. Liew, "Folic acid and diseases—supplement it or not?," Rev. Assoc. Med. Bras., vol. 62, no. 1, pp. 90–100, 2016.
- . Y. Lin, et al., "Quantitation of in vivo human folate metabolism," Am. J. Clin. Nutr., vol. 80, no. 3, pp. 680–691, 2004.
- . A. M. Molloy, et al., "Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development," Food Nutr. Bull., vol. 29, no. 2, suppl. 1, pp. S101–S111, 2008.
- . Institute of Medicine, Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, Washington, DC: National Academy Press, 2000.
- . L. H. Allen, "Causes of vitamin B12 and folate deficiency," Food Nutr. Bull., vol. 29, no. 2, suppl. 1, pp. S20–S34, 2008.
- . C. H. Halsted, et al., "Metabolic interactions of alcohol and folate," J. Nutr., vol. 132, no. 8, pp. 2367S–2372S, 2002.
- . J. A. Villanueva, A. M. Devlin, and C. H. Halsted, "Reduced folate carrier: tissue distribution and effects of chronic ethanol intake in the micropig," Alcohol Clin. Exp. Res., vol. 25, pp. 415–420, 2001.
- . H. Tilg and A. M. Diehl, "Cytokines in alcoholic and nonalcoholic steatohepatitis," N. Engl. J. Med., vol. 343, no. 20, pp. 1467–1476, 2000.
- . D. J. McKillop, K. Pentieva, D. Daly, J. M. McPartlin, J. Hughes, J. J. Strain, J. M. Scott, and H. McNulty, "The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet," Br. J. Nutr., vol. 88, pp. 681–688, 2002.
- . J. Dang, "Folate retention in selected processed legumes," Food Chem., vol. 68, pp. 295–298, 2000.
- . R. Green and A. Datta Mitra, "Megaloblastic anemias: nutritional and other causes," Med. Clin. North Am., vol. 101, no. 2, pp. 297–317, 2017.
- . S. J. Duthie, et al., "Impact of folate deficiency on DNA stability," J. Nutr., vol. 132, no. 8, pp. 2444S–2449S, 2002.
- . I. Mellon and G. N. Champe, "Products of DNA mismatch repair genes mutS and mutL are required for transcription-coupled nucleotide-excision repair of the lactose operon in Escherichia coli," Proc. Natl. Acad. Sci. USA, vol. 93, pp. 1292–1297, 1996.
- . J. B. Mason and T. Levesque, "Folate: effects on carcinogenesis and the potential for cancer chemoprevention," Oncology, vol. 10, pp. 1727–1743, 1996.
- . M. Cravo, P. Fidalgo, A. D. Pereira, et al., "DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation," Eur. J. Cancer Prev., vol. 3, pp. 473–479, 1994.
- . G. A. Paspatis and D. G. Karamanolis, "Folate supplementation and adenomatous colonic polyps," Dis. Colon Rectum, vol. 37, pp. 1340–1341, 1994.
- . B. Libbus, L. Borman, C. H. Ventrone, et al., "Nutritional folate-deficiency in Chinese hamster ovary cells," Cancer Genet. Cytogenet., vol. 46, pp. 231–242, 1990.
- . R. Branda and F. Blickensderfer, "Folate deficiency increases genetic damage caused by alkylating agents and irradiation in Chinese hamster ovary cells," Cancer Res., vol. 53, pp. 5401–5408, 1993.
- . Y. I. Kim, I. P. Pogribny, A. G. Basnakian, et al., "Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumour suppressor gene," Am. J. Clin. Nutr., vol. 65, pp. 46–52, 1997.
- . B. Shane and E. L. R. Stokstad, "Vitamin B12-folate interrelationships," Annu. Rev. Nutr., vol. 5, pp. 115–141, 1985.
- . B. C. Blount, M. M. Mack, C. M. Wehr, et al., "Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage," Proc. Natl. Acad. Sci. USA, vol. 94, pp. 3290–3295, 1997.
- . L. Y. Tomita, "Folate and cancer: is there any association?," J. Inborn Errors Metab. Screening, vol. 4, pp. e160016, 2019, doi: 10.1177/2326409816678180.
- . A. Melse-Boonstra, C. E. West, M. B. Katan, F. J. Kok, and P. Verhoef, "Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults," Am. J. Clin. Nutr., vol. 79, pp. 424–429, 2004.
- . N. Craig, S. Johnson, K. Komachi, et al., "Basic genetic mechanisms," in Molecular Biology of the Cell, B. Alberts, D. Bray, J. Lewis, et al., Eds., New York and London: Garland Publishing, 1994, pp. 223–290.
References
. A. Randomized, P. Controlled, and C. Trial, "Protective effect of folic acid on oxidative DNA damage," Medicine (Baltimore), vol. 94, no. 45, pp. 1–10, 2015, doi: 10.1097/MD.0000000000001872.
. M. Fenech, "Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity," Mutat. Res., vol. 733, pp. 21–33, 2012.
. C. E. Clare, A. H. Brassington, W. Y. Kwong, et al., "One-carbon metabolism: linking nutritional biochemistry to epigenetic pro-programming of long-term development," Annu. Rev. Anim. Biosci., vol. 7, pp. 263–287, 2019, doi: 10.1146/annurev-animal-020518-115206.
. J. W. Crott, S. T. Mashiyama, B. N. Ames, et al., "The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro," Cancer Epidemiol. Biomarkers Prev., vol. 10, pp. 1089–1096, 2001.
. X. Wu, W. Xu, T. Zhou, et al., "The role of genetic polymorphisms as related to one-carbon metabolism, vitamin B6, and gene-nutrient interactions in maintaining genomic stability and cell viability in Chinese breast cancer patients," Int. J. Mol. Sci., vol. 17, no. 1003, pp. 1–10, 2016.
. C. F. Bull, G. Mayrhofer, N. J. O’Callaghan, et al., "Folate deficiency induces dysfunctional long and short telomeres; both states are associated with hypomethylation and DNA damage in human WIL2-NS cells," Cancer Prev. Res. (Phila), vol. 7, pp. 128–138, 2014.
. L. Donnellan, et al., "Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal," Mutagenesis, vol. 37, no. 1, pp. 24–33, 2022, doi: 10.1093/mutage/geab036.
. S. S. Gropper and J. L. Smith, Advanced Nutrition and Human Metabolism, 6th ed., Belmont, CA: Wadsworth, 2013, pp. 344–353. [Online]. Available: https://www.cengage.co.uk/books/9781133104056/.
. National Institutes of Health, "Folate: Dietary Supplement Fact Sheet," [Online]. Available: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/. [Accessed: Jun. 6, 2018].
. R. Pieroth, et al., "Folate and its impact on cancer risk," Curr. Nutr. Rep., vol. 7, pp. 70–84, 2018.
. C. Galeone, V. Edefonti, M. Parpinel, R. Talamini, and A. F. Olshan, "Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the ENHANCE Consortium," Cancer Epidemiol. Biomarkers Prev., vol. 136, no. 4, pp. 904–914, 2016.
. X. Wang, J. Yu, and J. Wang, "Neural tube defects and folate deficiency: Is DNA repair defective?," Int. J. Mol. Sci., vol. 24, no. 3, pp. 2220, 2023.
. L. H. Allen, "Causes of vitamin B12 and folate deficiency," Food Nutr. Bull., vol. 29, no. 2, suppl. 1, pp. S20–S34, 2008.
. L. B. Bailey, P. J. Stover, H. McNulty, et al., "Biomarkers of nutrition for development—folate review," J. Nutr., vol. 145, no. 7, pp. 1636S–1680S, 2015.
. S. C. Liew, "Folic acid and diseases—supplement it or not?," Rev. Assoc. Med. Bras., vol. 62, no. 1, pp. 90–100, 2016.
. Y. Lin, et al., "Quantitation of in vivo human folate metabolism," Am. J. Clin. Nutr., vol. 80, no. 3, pp. 680–691, 2004.
. A. M. Molloy, et al., "Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development," Food Nutr. Bull., vol. 29, no. 2, suppl. 1, pp. S101–S111, 2008.
. Institute of Medicine, Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, Washington, DC: National Academy Press, 2000.
. L. H. Allen, "Causes of vitamin B12 and folate deficiency," Food Nutr. Bull., vol. 29, no. 2, suppl. 1, pp. S20–S34, 2008.
. C. H. Halsted, et al., "Metabolic interactions of alcohol and folate," J. Nutr., vol. 132, no. 8, pp. 2367S–2372S, 2002.
. J. A. Villanueva, A. M. Devlin, and C. H. Halsted, "Reduced folate carrier: tissue distribution and effects of chronic ethanol intake in the micropig," Alcohol Clin. Exp. Res., vol. 25, pp. 415–420, 2001.
. H. Tilg and A. M. Diehl, "Cytokines in alcoholic and nonalcoholic steatohepatitis," N. Engl. J. Med., vol. 343, no. 20, pp. 1467–1476, 2000.
. D. J. McKillop, K. Pentieva, D. Daly, J. M. McPartlin, J. Hughes, J. J. Strain, J. M. Scott, and H. McNulty, "The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet," Br. J. Nutr., vol. 88, pp. 681–688, 2002.
. J. Dang, "Folate retention in selected processed legumes," Food Chem., vol. 68, pp. 295–298, 2000.
. R. Green and A. Datta Mitra, "Megaloblastic anemias: nutritional and other causes," Med. Clin. North Am., vol. 101, no. 2, pp. 297–317, 2017.
. S. J. Duthie, et al., "Impact of folate deficiency on DNA stability," J. Nutr., vol. 132, no. 8, pp. 2444S–2449S, 2002.
. I. Mellon and G. N. Champe, "Products of DNA mismatch repair genes mutS and mutL are required for transcription-coupled nucleotide-excision repair of the lactose operon in Escherichia coli," Proc. Natl. Acad. Sci. USA, vol. 93, pp. 1292–1297, 1996.
. J. B. Mason and T. Levesque, "Folate: effects on carcinogenesis and the potential for cancer chemoprevention," Oncology, vol. 10, pp. 1727–1743, 1996.
. M. Cravo, P. Fidalgo, A. D. Pereira, et al., "DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation," Eur. J. Cancer Prev., vol. 3, pp. 473–479, 1994.
. G. A. Paspatis and D. G. Karamanolis, "Folate supplementation and adenomatous colonic polyps," Dis. Colon Rectum, vol. 37, pp. 1340–1341, 1994.
. B. Libbus, L. Borman, C. H. Ventrone, et al., "Nutritional folate-deficiency in Chinese hamster ovary cells," Cancer Genet. Cytogenet., vol. 46, pp. 231–242, 1990.
. R. Branda and F. Blickensderfer, "Folate deficiency increases genetic damage caused by alkylating agents and irradiation in Chinese hamster ovary cells," Cancer Res., vol. 53, pp. 5401–5408, 1993.
. Y. I. Kim, I. P. Pogribny, A. G. Basnakian, et al., "Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumour suppressor gene," Am. J. Clin. Nutr., vol. 65, pp. 46–52, 1997.
. B. Shane and E. L. R. Stokstad, "Vitamin B12-folate interrelationships," Annu. Rev. Nutr., vol. 5, pp. 115–141, 1985.
. B. C. Blount, M. M. Mack, C. M. Wehr, et al., "Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage," Proc. Natl. Acad. Sci. USA, vol. 94, pp. 3290–3295, 1997.
. L. Y. Tomita, "Folate and cancer: is there any association?," J. Inborn Errors Metab. Screening, vol. 4, pp. e160016, 2019, doi: 10.1177/2326409816678180.
. A. Melse-Boonstra, C. E. West, M. B. Katan, F. J. Kok, and P. Verhoef, "Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults," Am. J. Clin. Nutr., vol. 79, pp. 424–429, 2004.
. N. Craig, S. Johnson, K. Komachi, et al., "Basic genetic mechanisms," in Molecular Biology of the Cell, B. Alberts, D. Bray, J. Lewis, et al., Eds., New York and London: Garland Publishing, 1994, pp. 223–290.