Stover PJ. Physiology of folate and vitamin B12 in health and disease. Nutr Rev 2004;62:S3–12; discussion S3. [Crossref]
Benedek TG. Methotrexate: from its introduction to non-oncologic therapeutics to anti-TNF-alpha. Clin Exp Rheumatol 2010;28:S3–8.
Herrmann W, Obeid R. The mandatory fortification of staple foods with folic acid: a current controversy in Germany. Dtsch Arztebl Int 2011;108:249–54.
Obeid R, Herrmann W. The emerging role of unmetabolized folic acid in human diseases: myth or reality? Curr Drug Metab 2012 Jun 29. [Epub ahead of print]. [Crossref]
CDC Grand Rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR Morb Mortal Wkly Rep 2010;59:980–4.
Bukowski R, Malone FD, Porter FT, Nyberg DA, Comstock CH, Hankins GD, et al. Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study. PLoS Med 2009;6:e1000061. [Crossref]
Carr DF, Whiteley G, Alfirevic A, Pirmohamed M. Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review. Pharmacogenomics J 2009;9:291–305. [PubMed] [Crossref]
Bailey SW, Ayling JE. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proc Natl Acad Sci USA 2009;106:15424–9. [Crossref]
Suh JR, Herbig AK, Stover PJ. New perspectives on folate catabolism. Annu Rev Nutr 2001;21:255–82. [Crossref]
Sanderson P, McNulty H, Mastroiacovo P, McDowell IF, Melse-Boonstra A, Finglas PM, et al. Folate bioavailability: UK Food Standards Agency workshop report. Br J Nutr 2003;90:473–9. [Crossref]
Morris MS, Jacques PF, Rosenberg IH, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr 2010;91:1733–44. [Crossref]
Bailey RL, Mills JL, Yetley EA, Gahche JJ, Pfeiffer CM, Dwyer JT, et al. Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged > or =60 y in the United States. Am J Clin Nutr 2010;92:383–9. [Crossref]
Obeid R, Kasoha M, Kirsch SH, Munz W, Herrmann W. Concentrations of unmetabolized folic acid and primary folate forms in pregnant women at delivery and in umbilical cord blood. Am J Clin Nutr 2010;92:1416–22. [Crossref]
Obeid R, Kirsch SH, Kasoha M, Eckert R, Herrmann W. Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults. Metab Clin Exp 2011;60:673–80.
Boilson A, Staines A, Kelleher CC, Daly L, Shirley I, Shrivastava A, et al. Unmetabolized folic acid prevalence is widespread in the older Irish population despite the lack of a mandatory fortification program. Am J Clin Nutr 2012;96:613–21. [Crossref]
Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008;87:517–33.
Mason JB. Unraveling the complex relationship between folate and cancer risk. Biofactors 2011;37:253–60. [Crossref]
Ulrich CM, Potter JD. Folate and cancer – timing is everything. J Am Med Assoc 2007;297:2408–9.
Lucock M, Yates Z. Folic acid fortification: a double-edged sword. Curr Opin Clin Nutr Metab Care 2009;12:555–64. [Crossref]
Elmore CL, Wu X, Leclerc D, Watson ED, Bottiglieri T, Krupenko NI, et al. Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol Genet Metab 2007;91:85–97. [Crossref]
Sittig LJ, Herzing LB, Xie H, Batra KK, Shukla PK, Redei EE. Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory. Genes Brain Behav 2012;11:193–200. [Crossref]
Morris MC, Evans DA, Bienias JL, Tangney CC, Hebert LE, Scherr PA, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641–5. [Crossref]
Leeming RJ, Lucock M. Autism: is there a folate connection? J Inherit Metab Dis 2009;32:400–2. [Crossref]
Zhou YH, Tang JY, Wu MJ, Lu J, Wei X, Qin YY, et al. Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis. PloS one 2011;6:e25142. [Crossref]
Clarke R, Halsey J, Bennett D, Lewington S. Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials. J Inherit Metab Dis 2011;34:83–91. [Crossref]
Heseker HB, Mason JB, Selhub J, Rosenberg IH, Jacques PF. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid. Br J Nutr 2009;102:173–80. [Crossref]
Marean A, Graf A, Zhang Y, Niswander L. Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival. Hum Mol Genet 2011;20:3678–83. [Crossref]
Butterworth CE Jr., Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989;50:353–8.
Oleinik NV, Krupenko NI, Reuland SN, Krupenko SA. Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation. Biochem Pharmacol 2006;72:256–66. [Crossref]
Sauer J, Mason JB, Choi SW. Too much folate: a risk factor for cancer and cardiovascular disease? Curr Opin Clin Nutr Metab Care 2009;12:30–6. [Crossref]
Matthews RG, Daubner SC. Modulation of methylenetetrahydrofolate reductase activity by S-adenosylmethionine and by dihydrofolate and its polyglutamate analogues. Adv Enzyme Regul 1982;20:123–31. [Crossref]
Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006;136:189–94.
Hirsch S, Miranda D, Fuentes C, Leiva L, Barrera G, Montoya M, et al. Effect of supraphysiological concentration of serum folate on natural killer cell activity in healthy subjects. e-SPAN J 2012;7:e125–8.
Farber S, Cutler EC, Hawkins JW, Harrison JH, Peirce EC 2nd, Lenz GG. The action of pteroylglutamic conjugates on man. Science 1947;106:619–21. [Crossref]
Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr 2000;130:129–32.
Rock CL, Lampe JW, Patterson RE. Nutrition, genetics, and risks of cancer. Annu Rev Public Health 2000;21:47–64. [Crossref]
Mason JB. Folate status: effects on carcinogenesis. In: Bailey LB, editor. Folate in health and disease. New York: Marcel Dekker Inc., 1995:361–78.
Goldman ID, Chattopadhyay S, Zhao R, Moran R. The antifolates: evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. Curr Opin Investig Drugs 2010;11:1409–23.
Ly A, Lee H, Chen J, Sie KK, Renlund R, Medline A, et al. Effect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring. Cancer Res 2011;71: 988–97. [Crossref]
McKay JA, Williams EA, Mathers JC. Gender-specific modulation of tumorigenesis by folic acid supply in the Apc mouse during early neonatal life. Br J Nutr 2008;99:550–8.
Ebbing M, Bonaa KH, Nygard O, Arnesen E, Ueland PM, Nordrehaug JE, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. J Am Med Assoc 2009;302:2119–26. [Crossref]
Figueiredo JC, Grau MV, Haile RW, Sandler RS, Summers RW, Bresalier RS, et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst 2009;101:432–5. [Crossref]
Larsson SC, Giovannucci E, Wolk A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 2006;131:1271–83. [Crossref]
Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. J Am Med Assoc 2007;297:2351–9.
Kim YI. Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 2008;17:2220–5. [Crossref]
Kawakita D, Matsuo K, Sato F, Oze I, Hosono S, Ito H, et al. Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma. Ann Oncol 2012;23:186–92. [Crossref]
Ibiebele TI, Hughes MC, Pandeya N, Zhao Z, Montgomery G, Hayward N, et al. High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr 2011;141:274–83. [Crossref]
Welzel TM, Katki HA, Sakoda LC, Evans AA, London WT, Chen G, et al. Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort. Cancer Epidemiol Biomarkers Prev 2007;16:1279–82. [Crossref]
French AE, Grant R, Weitzman S, Ray JG, Vermeulen MJ, Sung L, et al. Folic acid food fortification is associated with a decline in neuroblastoma. Clin Pharmacol Therapeut 2003;74:288–94. [Crossref]
Vargas AJ, Thompson PA. Diet and nutrient factors in colorectal cancer risk. Nutr Clin Pract 2012;27:613–23. [Crossref]
Kotsopoulos J, Kim YI, Narod SA. Folate and breast cancer: what about high-risk women? Cancer Causes Control 2012;23:1405–20. [Crossref]
Donkena KV, Karnes RJ, Young CY. Vitamins and prostate cancer risk. Molecules 2010;15:1762–83. [Crossref]
Roswall N. Folate and lung cancer risk. Lung Cancer 2010;67:380–1. [Crossref]
Ulrich CM. Folate and cancer prevention: a closer look at a complex picture. Am J Clin Nutr 2007;86:271–3.
Ulrich CM, Neuhouser M, Liu AY, Boynton A, Gregory JF 3rd, Shane B, et al. Mathematical modeling of folate metabolism: predicted effects of genetic polymorphisms on mechanisms and biomarkers relevant to carcinogenesis. Cancer Epidemiol Biomarkers Prev 2008;17:1822–31. [Crossref]
Han SS, Sue LY, Berndt SI, Selhub J, Burdette LA, Rosenberg PS, et al. Associations between genes in the one-carbon metabolism pathway and advanced colorectal adenoma risk in individuals with low folate intake. Cancer Epidemiol Biomarkers Prev 2012;21:417–27. [Crossref]
Liu AY, Scherer D, Poole E, Potter JD, Curtin K, Makar K, et al. Gene-diet-interactions in folate-mediated one-carbon metabolism modify colon cancer risk. Mol Nutr Food Res 2012 Sep 7. [Epub ahead of print].
Jhaveri MS, Wagner C, Trepel JB. Impact of extracellular folate levels on global gene expression. Mol Pharmacol 2001;60:1288–95.
Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci USA 1997;94:3290–5. [Crossref]
Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci 2002;22:1752–62.
Duthie SJ, Hawdon A. DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J 1998;12:1491–7.
Duthie SJ. Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 1999;55:578–92. [Crossref]
Bistulfi G, Foster BA, Karasik E, Gillard B, Miecznikowski J, Dhiman VK, et al. Dietary folate deficiency blocks prostate cancer progression in the TRAMP model. Cancer Prev Res (Phila) 2011;4:1825–34. [Crossref]
Khanna D, Park GS, Paulus HE, Simpson KM, Elashoff D, Cohen SB, et al. Reduction of the efficacy of methotrexate by the use of folic acid: post hoc analysis from two randomized controlled studies. Arthritis Rheum 2005;52:3030–8. [Crossref]
Carter JY, Loolpapit MP, Lema OE, Tome JL, Nagelkerke NJ, Watkins WM. Reduction of the efficacy of antifolate antimalarial therapy by folic acid supplementation. Am J Trop Med Hyg 2005;73:166–70.
van Eijk AM, Ouma PO, Williamson J, Ter Kuile FO, Parise M, Otieno K, et al. Plasma folate level and high-dose folate supplementation predict sulfadoxine-pyrimethamine treatment failure in pregnant women in Western kenya who have uncomplicated malaria. J Infect Dis 2008; 198:1550–3.
Salim A, Tan E, Ilchyshyn A, Berth-Jones J. Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial. Br J Dermatol 2006;154:1169–74. [Crossref]
Greenhalgh J, McLeod C, Bagust A, Boland A, Fleeman N, Dundar Y, et al. Pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer. Health Technol Assess 2010;14:33–9.
Tisman G, Garcia A. Control of prostate cancer associated with withdrawal of a supplement containing folic acid, L-methyltetrahydrofolate and vitamin B12: a case report. J Med Case Reports 2011;5:413. [Crossref]
Crott JW, Choi SW, Ordovas JM, Ditelberg JS, Mason JB. Effects of dietary folate and aging on gene expression in the colonic mucosa of rats: implications for carcinogenesis. Carcinogenesis 2004;25:69–76.
Crott JW, Liu Z, Keyes MK, Choi SW, Jang H, Moyer MP, et al. Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines. J Nutr Biochem 2008;19:328–35. [Crossref]
Lewis CM, Smith AK, Kamen BA. Receptor-mediated folate uptake is positively regulated by disruption of the actin cytoskeleton. Cancer Res 1998;58:2952–6.
Oser M, Condeelis J. The cofilin activity cycle in lamellipodia and invadopodia. J Cell Biochem 2009;108:1252–62. [Crossref]
Bernstein BW, Bamburg JR. ADF/cofilin: a functional node in cell biology. Trends Cell Biol 2010;20:187–95. [Crossref]
Zhu H, Cabrera RM, Wlodarczyk BJ, Bozinov D, Wang D, Schwartz RJ, et al. Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity. BMC Dev Biol 2007;7:128.
Chanson A, Sayd T, Rock E, Chambon C, Sante-Lhoutellier V, Potier de Courcy G, et al. Proteomic analysis reveals changes in the liver protein pattern of rats exposed to dietary folate deficiency. J Nutr 2005;135:2524–9.
Oleinik NV, Krupenko NI, Krupenko SA. ALDH1L1 inhibits cell motility via dephosphorylation of cofilin by PP1 and PP2A. Oncogene 2010;29:6233–44. [Crossref]
Winter-Vann AM, Kamen BA, Bergo MO, Young SG, Melnyk S, James SJ, et al. Targeting Ras signaling through inhibition of carboxyl methylation: an unexpected property of methotrexate. Proc Natl Acad Sci USA 2003;100:6529–34. [Crossref]
Bjorklund NK, Gordon R. A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton. Int J Dev Biol 2006;50:135–41. [Crossref]
Gao Y, Sztul E. A novel interaction of the Golgi complex with the vimentin intermediate filament cytoskeleton. J Cell Biol 2001;152:877–94. [Crossref]
Fox JT, Stover PJ. Folate-mediated one-carbon metabolism. Vitam Horm 2008;79:1–44.
Tibbetts AS, Appling DR. Compartmentalization of Mammalian folate-mediated one-carbon metabolism. Ann Rev Nutr 2010;30:57–81. [Crossref]
Kelemen LE. The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander? Int J Cancer 2006;119:243–50. [Crossref]
Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR. Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta 2002;1587:164–73.
Gao L, Chalupsky K, Stefani E, Cai H. Mechanistic insights into folic acid-dependent vascular protection: dihydrofolate reductase (DHFR)-mediated reduction in oxidant stress in endothelial cells and angiotensin II-infused mice: a novel HPLC-based fluorescent assay for DHFR activity. J Mol Cell Cardiol 2009;47:752–60.
Liu J, Schmitz JC, Lin X, Tai N, Yan W, Farrell M, et al. Thymidylate synthase as a translational regulator of cellular gene expression. Biochim Biophys Acta 2002;1587:174–82.
Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, et al. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 2012;336:1040–4. [Crossref]
Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 2012;148:259–72. [Crossref]
Krupenko SA. FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism. Chem Biol Interact 2009;178:84–93. [Crossref]
Oleinik NV, Krupenko NI, Krupenko SA. Epigenetic silencing of ALDH1L1, a metabolic regulator of cellular proliferation, in cancers. Genes Cancer 2011;2:130–9. [Crossref]
Oleinik NV, Krupenko NI, Priest DG, Krupenko SA. Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression. Biochem J 2005;391:503–11.
Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene 2007;26:7222–30.
Ghose S, Oleinik NV, Krupenko NI, Krupenko SA. 10-formyltetrahydrofolate dehydrogenase-induced c-Jun-NH2-kinase pathways diverge at the c-Jun-NH2-kinase substrate level in cells with different p53 status. Mol Cancer Res 2009;7:99–107.
Luka Z, Mudd SH, Wagner C. Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. J Biol Chem 2009;284:22507–11. [Crossref]
Tseng TL, Shih YP, Huang YC, Wang CK, Chen PH, Chang JG, et al. Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Cancer Res 2003;63:647–54.
Huang YC, Lee CM, Chen M, Chung MY, Chang YH, Huang WJ, et al. Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer. Clin Cancer Res 2007;13:1412–20. [Crossref]
Martinez-Chantar ML, Vazquez-Chantada M, Ariz U, Martinez N, Varela M, Luka Z, et al. Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 2008;47:1191–9.