skip page navigationOregon State University

Micronutrient Information Center

References: Folate


1. Food and Nutrition Board, Institute of Medicine. Folate. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press; 1998:196-305.  (National Academy Press)

2. Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000;130(2):129-132.  (PubMed)

3.  Bailey LB, Gregory JF, 3rd. Folate metabolism and requirements. J Nutr. 1999;129(4):779-782.  (PubMed)

4.  Desmoulin SK, Hou Z, Gangjee A, Matherly LH. The human proton-coupled folate transporter: Biology and therapeutic applications to cancer. Cancer Biol Ther. 2012;13(14):1355-1373.  (PubMed)

5.  Solanky N, Requena Jimenez A, D'Souza SW, Sibley CP, Glazier JD. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta. 2010;31(2):134-143.  (PubMed)

6.  Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol. 1999;10(5):417-428.  (PubMed)

7.  Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr. 2001;73(3):613-621.  (PubMed)

8.  Jacques PF, Kalmbach R, Bagley PJ, et al. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr. 2002;132(2):283-288.  (PubMed)

9.  McNulty H, Dowey le RC, Strain JJ, et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation. 2006;113(1):74-80.  (PubMed)

10.  Verlinde PH, Oey I, Hendrickx ME, Van Loey AM, Temme EH. L-ascorbic acid improves the serum folate response to an oral dose of [6S]-5-methyltetrahydrofolic acid in healthy men. Eur J Clin Nutr. 2008;62(10):1224-1230.  (PubMed)

11.  Lucock M, Yates Z, Boyd L, et al. Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status. Eur J Nutr. 2013;52(2):569-582.  (PubMed)

12.  Halsted CH, Villanueva JA, Devlin AM, Chandler CJ. Metabolic interactions of alcohol and folate. J Nutr. 2002;132(8 Suppl):2367S-2372S.  (PubMed)

13.  Pfeiffer CM, Sternberg MR, Schleicher RL, Rybak ME. Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of U.S. adults. J Nutr. 2013;143(6):957S-965S.  (PubMed)

14.  Stark KD, Pawlosky RJ, Sokol RJ, Hannigan JH, Salem N, Jr. Maternal smoking is associated with decreased 5-methyltetrahydrofolate in cord plasma. Am J Clin Nutr. 2007;85(3):796-802.  (PubMed)

15.  Hutson JR, Stade B, Lehotay DC, Collier CP, Kapur BM. Folic acid transport to the human fetus is decreased in pregnancies with chronic alcohol exposure. PLoS One. 2012;7(5):e38057.  (PubMed)

16.  Herbert V. Folic acid. In: Shils M, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999:433-446.

17.  Stabler SP. Clinical folate deficiency. In: Bailey LB, ed. Folate in Health and Disease. 2nd edition ed. Boca Raton, FL: CRC press, Taylor & Francis Group; 2010:409-428.

18.  Bailey LB. Dietary reference intakes for folate: the debut of dietary folate equivalents. Nutr Rev. 1998;56(10):294-299.  (PubMed)

19. Bailey LB, Gregory JF, 3rd. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr. 1999;129(5):919-922.  (PubMed)

20.  Wilcken B, Bamforth F, Li Z, et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 2003;40(8):619-625.  (PubMed)

21.  Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol. 1999;6(4):359-365.  (PubMed)

22.  Molloy AM, Daly S, Mills JL, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet. 1997;349(9065):1591-1593.  (PubMed)

23.  Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost. 1997;78(1):523-526.  (PubMed)

24. Kauwell GP, Wilsky CE, Cerda JJ, et al. Methylenetetrahydrofolate reductase mutation (677C-->T) negatively influences plasma homocysteine response to marginal folate intake in elderly women. Metabolism. 2000;49(11):1440-1443.  (PubMed)

25.  Shane B. Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.

26.  Eskes TK. Open or closed? A world of difference: a history of homocysteine research. Nutr Rev. 1998;56(8):236-244.  (PubMed)

27.  Czeizel AE, Dudas I, Vereczkey A, Banhidy F. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients. 2013;5(11):4760-4775.  (PubMed)

28.  MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338(8760):131-137.  (PubMed)

29.  Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327(26):1832-1835.  (PubMed)

30.  Talaulikar VS, Arulkumaran S. Folic acid in obstetric practice: a review. Obstet Gynecol Surv. 2011;66(4):240-247.  (PubMed)

31.  American College of Obstetricians and Gynecologists (ACOG). Neural tube defects. Washington, DC. 2003.  Available at: http://www.guideline.gov/content.aspx?id=3994. Accessed 12/19/14.

32.  McNulty B, Pentieva K, Marshall B, et al. Women's compliance with current folic acid recommendations and achievement of optimal vitamin status for preventing neural tube defects. Hum Reprod. 2011;26(6):1530-1536.  (PubMed)

33.  Nilsen RM, Vollset SE, Gjessing HK, et al. Patterns and predictors of folic acid supplement use among pregnant women: the Norwegian Mother and Child Cohort Study. Am J Clin Nutr. 2006;84(5):1134-1141.  (PubMed)

34.  Ray JG, Singh G, Burrows RF. Evidence for suboptimal use of periconceptional folic acid supplements globally. BJOG. 2004;111(5):399-408.  (PubMed)

35.  Quinlivan EP, Gregory JF, 3rd. Effect of food fortification on folic acid intake in the United States. Am J Clin Nutr. 2003;77(1):221-225.  (PubMed)

36.  National Birth Defects Prevention Network. Neural Tube Defect Ascertainment Project. Available at: http://www.nbdpn.org/ntd_folic_acid_information.php. Accessed 12/16/14.

37.  Copp AJ, Stanier P, Greene ND. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol. 2013;12(8):799-810.  (PubMed)

38.  Yan L, Zhao L, Long Y, et al. Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies. PLoS One. 2012;7(10):e41689.  (PubMed)

39.  De Marco P, Calevo MG, Moroni A, et al. Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population. J Hum Genet. 2002;47(6):319-324.  (PubMed)

40.  van der Put NM, Gabreels F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998;62(5):1044-1051.  (PubMed)

41.  De Marco P, Calevo MG, Moroni A, et al. Reduced folate carrier polymorphism (80A-->G) and neural tube defects. Eur J Hum Genet. 2003;11(3):245-252.  (PubMed)

42.  O'Leary VB, Mills JL, Parle-McDermott A, et al. Screening for new MTHFR polymorphisms and NTD risk. Am J Med Genet A. 2005;138A(2):99-106.  (PubMed)

43.  Christensen B, Arbour L, Tran P, et al. Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet. 1999;84(2):151-157.  (PubMed)

44.  Relton CL, Wilding CS, Pearce MS, et al. Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population. J Med Genet. 2004;41(4):256-260.  (PubMed)

45.  Brody LC, Conley M, Cox C, et al. A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. Am J Hum Genet. 2002;71(5):1207-1215.  (PubMed)

46.  van der Put NM, van den Heuvel LP, Steegers-Theunissen RP, et al. Decreased methylene tetrahydrofolate reductase activity due to the 677C-->T mutation in families with spina bifida offspring. J Mol Med (Berl). 1996;74(11):691-694.  (PubMed)

47.  Wilson A, Platt R, Wu Q, et al. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab. 1999;67(4):317-323.  (PubMed)

48.  Gilboa SM, Salemi JL, Nembhard WN, Fixler DE, Correa A. Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006. Circulation. 2010;122(22):2254-2263.  (PubMed)

49.  van Beynum IM, Kapusta L, Bakker MK, den Heijer M, Blom HJ, de Walle HE. Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands. Eur Heart J. 2010;31(4):464-471.  (PubMed)

50.  Yin M, Dong L, Zheng J, Zhang H, Liu J, Xu Z. Meta analysis of the association between MTHFR C677T polymorphism and the risk of congenital heart defects. Ann Hum Genet. 2012;76(1):9-16.  (PubMed)

51.  Wang W, Wang Y, Gong F, Zhu W, Fu S. MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies. PLoS One. 2013;8(3):e58041.  (PubMed)

52.  Badovinac RL, Werler MM, Williams PL, Kelsey KT, Hayes C. Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis. Birth Defects Res A Clin Mol Teratol. 2007;79(1):8-15.  (PubMed)

53.  Wilcox AJ, Lie RT, Solvoll K, et al. Folic acid supplements and risk of facial clefts: national population based case-control study. BMJ. 2007;334(7591):464.  (PubMed)

54.  Boyles AL, Wilcox AJ, Taylor JA, et al. Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts. Am J Med Genet A. 2008;146A(4):440-449.  (PubMed)

55.  Boyles AL, Wilcox AJ, Taylor JA, et al. Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study. Genet Epidemiol. 2009;33(3):247-255.  (PubMed)

56.  Luo YL, Cheng YL, Ye P, Wang W, Gao XH, Chen Q. Association between MTHFR polymorphisms and orofacial clefts risk: a meta-analysis. Birth Defects Res A Clin Mol Teratol. 2012;94(4):237-244.  (PubMed)

57.  Wilcox AJ. On the importance--and the unimportance--of birthweight. Int J Epidemiol. 2001;30(6):1233-1241.  (PubMed)

58.  Fekete K, Berti C, Trovato M, et al. Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation. Nutr J. 2012;11:75.  (PubMed)

59.  Baker PN, Wheeler SJ, Sanders TA, et al. A prospective study of micronutrient status in adolescent pregnancy. Am J Clin Nutr. 2009;89(4):1114-1124.  (PubMed)

60.  Lee HA, Park EA, Cho SJ, et al. Mendelian randomization analysis of the effect of maternal homocysteine during pregnancy, as represented by maternal MTHFR C677T genotype, on birth weight. J Epidemiol. 2013;23(5):371-375.  (PubMed)

61.  Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr. 2000;71(5 Suppl):1295S-1303S.  (PubMed)

62.  Vollset SE, Refsum H, Irgens LM, et al. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr. 2000;71(4):962-968.  (PubMed)

63.  Wang XM, Wu HY, Qiu XJ. Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and risk of preeclampsia: an updated meta-analysis based on 51 studies. Arch Med Res. 2013;44(3):159-168.  (PubMed)

64.  Wen SW, Champagne J, Rennicks White R, et al. Effect of folic acid supplementation in pregnancy on preeclampsia: the folic acid clinical trial study. J Pregnancy. 2013;2013:294312.  (PubMed)

65.  Lassi ZS, Salam RA, Haider BA, Bhutta ZA. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev. 2013;3:CD006896.  (PubMed)

66.  Schmidt RJ, Tancredi DJ, Ozonoff S, et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr. 2012;96(1):80-89.  (PubMed)

67.  Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(5):1272-1281.  (PubMed)

68.  Brown SB, Reeves KW, Bertone-Johnson ER. Maternal folate exposure in pregnancy and childhood asthma and allergy: a systematic review. Nutr Rev. 2014;72(1):55-64.  (PubMed)

69.  Ding R, Lin S, Chen D. The association of cystathionine beta synthase (CBS) T833C polymorphism and the risk of stroke: a meta-analysis. J Neurol Sci. 2012;312(1-2):26-30.  (PubMed)

70.  Seshadri N, Robinson K. Homocysteine, B vitamins, and coronary artery disease. Med Clin North Am. 2000;84(1):215-237.  (PubMed)

71.  Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325(7374):1202.  (PubMed)

72.  Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288(16):2015-2022.  (PubMed)

73.  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(1):83-91.  (PubMed)

74.  Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. Clin Nutr. 2012;31(4):448-454.  (PubMed)

75.  Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT. Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study. Circulation. 2001;103(22):2674-2680.  (PubMed)

76.  Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr. 1996;126(4 Suppl):1276S-1280S.  (PubMed)

77.  Rader JI. Folic acid fortification, folate status and plasma homocysteine. J Nutr. 2002;132(8 Suppl):2466S-2470S.  (PubMed)

78.  Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr. 2005;82(4):806-812.  (PubMed)

79.  Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation. 1999;99(1):178-182.  (PubMed)

80.  van Meurs JB, Pare G, Schwartz SM, et al. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. Am J Clin Nutr. 2013;98(3):668-676.  (PubMed)

81.  Holmes MV, Newcombe P, Hubacek JA, et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet. 2011;378(9791):584-594.  (PubMed)

82.  Clarke R, Bennett DA, Parish S, et al. Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias. PLoS Med. 2012;9(2):e1001177.  (PubMed)

83.  Ji Y, Tan S, Xu Y, et al. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: A meta-analysis. Neurology. 2013;81(15):1298-1307.  (PubMed)

84.  Zhang C, Chi FL, Xie TH, Zhou YH. Effect of B-vitamin supplementation on stroke: a meta-analysis of randomized controlled trials. PLoS One. 2013;8(11):e81577.  (PubMed)

85.  Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. J Am Coll Cardiol. 2011;57(12):1404-1423.  (PubMed)

86.  Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007;369(9576):1876-1882.  (PubMed)

87.  Yang Q, Botto LD, Erickson JD, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006;113(10):1335-1343.  (PubMed)

88.  Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115(4):459-467.  (PubMed)

89.  Qin X, Xu M, Zhang Y, et al. Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;222(2):307-313.  (PubMed)

90.  de Bree A, van Mierlo LA, Draijer R. Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2007;86(3):610-617.  (PubMed)

91.  McNeil CJ, Beattie JH, Gordon MJ, Pirie LP, Duthie SJ. Nutritional B vitamin deficiency disrupts lipid metabolism causing accumulation of proatherogenic lipoproteins in the aorta adventitia of ApoE null mice. Mol Nutr Food Res. 2012;56(7):1122-1130.  (PubMed)

92.  Blount BC, Mack MM, Wehr CM, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997;94(7):3290-3295.  (PubMed)

93.  Narayanan S, McConnell J, Little J, et al. Associations between two common variants C677T and A1298C in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo. Cancer Epidemiol Biomarkers Prev. 2004;13(9):1436-1443.  (PubMed)

94.  Rahman L, Voeller D, Rahman M, et al. Thymidylate synthase as an oncogene: a novel role for an essential DNA synthesis enzyme. Cancer Cell. 2004;5(4):341-351.  (PubMed)

95.  Hubner RA, Liu JF, Sellick GS, Logan RF, Houlston RS, Muir KR. Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma. Br J Cancer. 2007;97(10):1449-1456.  (PubMed)

96.  Desmoulin SK, Wang L, Polin L, et al. Functional loss of the reduced folate carrier enhances the antitumor activities of novel antifolates with selective uptake by the proton-coupled folate transporter. Mol Pharmacol. 2012;82(4):591-600.  (PubMed)

97.  Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr. 2012;3(1):21-38.  (PubMed)

98.  Butrum RR, Clifford CK, Lanza E. NCI dietary guidelines: rationale. Am J Clin Nutr. 1988;48(3 Suppl):888-895.  (PubMed)

99.  Crider KS, Bailey LB, Berry RJ. Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients. 2011;3(3):370-384.  (PubMed)

100.  Qin X, Cui Y, Shen L, et al. Folic acid supplementation and cancer risk: A meta-analysis of randomized controlled trials. Int J Cancer. 2013;133(5):1033-1041.  (PubMed)

101.  Vollset SE, Clarke R, Lewington S, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet. 2013;381(9871):1029-1036.  (PubMed)

102.  Kim DH, Smith-Warner SA, Spiegelman D, et al. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control. 2010;21(11):1919-1930.  (PubMed)

103.  Gibson TM, Weinstein SJ, Pfeiffer RM, et al. Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States. Am J Clin Nutr. 2011;94(4):1053-1062.  (PubMed)

104.  Stevens VL, McCullough ML, Sun J, Jacobs EJ, Campbell PT, Gapstur SM. High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer. Gastroenterology. 2011;141(1):98-105, 105 e101.  (PubMed)

105.  Zschabitz S, Cheng TY, Neuhouser ML, et al. B vitamin intakes and incidence of colorectal cancer: results from the Women's Health Initiative Observational Study cohort. Am J Clin Nutr. 2013;97(2):332-343.  (PubMed)

106.  Keum N, Giovannucci EL. Folic acid fortification and colorectal cancer risk. Am J Prev Med. 2014;46(3 Suppl 1):S65-72.  (PubMed)

107.  Kennedy DA, Stern SJ, Moretti M, et al. Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis. Cancer Epidemiol. 2011;35(1):2-10.  (PubMed)

108.  Kim YI. Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut. 2006;55(10):1387-1389.  (PubMed)

109.  Paspatis GA, Kalafatis E, Oros L, Xourgias V, Koutsioumpa P, Karamanolis DG. Folate status and adenomatous colonic polyps. A colonoscopically controlled study. Dis Colon Rectum. 1995;38(1):64-67; discussion 67-68.  (PubMed)

110.  Jaszewski R, Misra S, Tobi M, et al. Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial. World J Gastroenterol. 2008;14(28):4492-4498.  (PubMed)

111.  Wu K, Platz EA, Willett WC, et al. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma. Am J Clin Nutr. 2009;90(6):1623-1631.  (PubMed)

112.  Logan RF, Grainge MJ, Shepherd VC, Armitage NC, Muir KR. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology. 2008;134(1):29-38.  (PubMed)

113.  Figueiredo JC, Mott LA, Giovannucci E, et al. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int J Cancer. 2011;129(1):192-203.  (PubMed)

114.  Kennedy DA, Stern SJ, Matok I, et al. Folate intake, MTHFR polymorphisms, and the risk of colorectal cancer: a systematic review and meta-analysis. J Cancer Epidemiol. 2012;2012:952508.  (PubMed)

115.  Ding W, Zhou DL, Jiang X, Lu LS. Methionine synthase A2756G polymorphism and risk of colorectal adenoma and cancer: evidence based on 27 studies. PLoS One. 2013;8(4):e60508.  (PubMed)

116.  Nan H, Lee JE, Rimm EB, Fuchs CS, Giovannucci EL, Cho E. Prospective study of alcohol consumption and the risk of colorectal cancer before and after folic acid fortification in the United States. Ann Epidemiol. 2013;23(9):558-563.  (PubMed)

117.  Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M. Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev. 1999;8(6):513-518.  (PubMed)

118.  Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res. 1997;57(6):1098-1102.  (PubMed)

119.  Larsson SC, Giovannucci E, Wolk A. Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst. 2007;99(1):64-76.  (PubMed)

120.  Liu M, Cui LH, Ma AG, Li N, Piao JM. Lack of effects of dietary folate intake on risk of breast cancer: an updated meta-analysis of prospective studies. Asian Pac J Cancer Prev. 2014;15(5):2323-2328.  (PubMed)

121.  Brooks PJ, Zakhari S. Moderate alcohol consumption and breast cancer in women: from epidemiology to mechanisms and interventions. Alcohol Clin Exp Res. 2013;37(1):23-30.  (PubMed)

122.  Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst. 2000;92(3):266-269.  (PubMed)

123.  Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001;12(4):420-428.  (PubMed)

124.  Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281(17):1632-1637.  (PubMed)

125.  Tjonneland A, Christensen J, Olsen A, et al. Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2007;18(4):361-373.  (PubMed)

126.  Bassett JK, Baglietto L, Hodge AM, et al. Dietary intake of B vitamins and methionine and breast cancer risk. Cancer Causes Control. 2013;24(8):1555-1563.  (PubMed)

127.  Wang J, Wang B, Bi J, Di J. The association between two polymorphisms in the TYMS gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2011;128(1):203-209.  (PubMed)

128.  Weiner AS, Boyarskikh UA, Voronina EN, et al. Polymorphisms in the folate-metabolizing genes MTR, MTRR, and CBS and breast cancer risk. Cancer Epidemiol. 2012;36(2):e95-e100.  (PubMed)

129.  Linabery AM, Johnson KJ, Ross JA. Childhood cancer incidence trends in association with US folic acid fortification (1986-2008). Pediatrics. 2012;129(6):1125-1133.  (PubMed)

130.  Milne E, Royle JA, Miller M, et al. Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring. Int J Cancer. 2010;126(11):2690-2699.  (PubMed)

131.  Yan J, Yin M, Dreyer ZE, et al. A meta-analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children. Pediatr Blood Cancer. 2012;58(4):513-518.  (PubMed)

132.  Alzheimer's Association. 2013 Alzheimer's Disease Fact and Figures. Alzheimer's & Dementia. 9(2). Available at: http://www.alz.org/downloads/facts_figures_2013.pdf. Accessed 9/9/13.

133.  Hughes TF, Andel R, Small BJ, et al. Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins. Am J Geriatr Psychiatry. 2010;18(5):413-420.  (PubMed)

134.  Weir DG, Scott JM. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull. 1999;55(3):669-682.  (PubMed)

135.  Faux NG, Ellis KA, Porter L, et al. Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study. J Alzheimers Dis. 2011;27(4):909-922.  (PubMed)

136.  Van Dam F, Van Gool WA. Hyperhomocysteinemia and Alzheimer's disease: A systematic review. Arch Gerontol Geriatr. 2009;48(3):425-430.  (PubMed)

137. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol. 2005;62(4):641-645.  (PubMed)

138.  Morris MC, Evans DA, Schneider JA, Tangney CC, Bienias JL, Aggarwal NT. Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease. J Alzheimers Dis. 2006;9(4):435-443.  (PubMed)

139.  Wald DS, Kasturiratne A, Simmonds M. Serum homocysteine and dementia: meta-analysis of eight cohort studies including 8669 participants. Alzheimers Dement. 2011;7(4):412-417.  (PubMed)

140.  Ho RC, Cheung MW, Fu E, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Am J Geriatr Psychiatry. 2011;19(7):607-617.  (PubMed)

141.  Nilforooshan R, Broadbent D, Weaving G, et al. Homocysteine in Alzheimer's disease: role of dietary folate, vitamin B6 and B12. Int J Geriatr Psychiatry. 2011;26(8):876-877.  (PubMed)

142.  Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med. 2010;123(6):522-527 e522.  (PubMed)

143.  Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012;29(1):133-149.  (PubMed)

144.  Nachum-Biala Y, Troen AM. B-vitamins for neuroprotection: narrowing the evidence gap. Biofactors. 2012;38(2):145-150.  (PubMed)

145.  Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244.  (PubMed)

146.  Douaud G, Refsum H, de Jager CA, et al. Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013;110(23):9523-9528.  (PubMed)

147.  Watkins D, Rosenblatt DS. Update and new concepts in vitamin responsive disorders of folate transport and metabolism. J Inherit Metab Dis. 2012;35(4):665-670.  (PubMed)

148.  Zhao R, Min SH, Qiu A, et al. The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood. 2007;110(4):1147-1152.  (PubMed)

149.  Borzutzky A, Crompton B, Bergmann AK, et al. Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter. Clin Immunol. 2009;133(3):287-294.  (PubMed)

150.  Sofer Y, Harel L, Sharkia M, Amir J, Schoenfeld T, Straussberg R. Neurological manifestations of folate transport defect: case report and review of the literature. J Child Neurol. 2007;22(6):783-786.  (PubMed)

151.  Diop-Bove N, Kronn D, Goldman ID. Hereditary folate malabsorption. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, eds. GeneReviews™ [Internet]. Seattle, WA: University of Washington, Seattle; 2008.  (PubMed)

152.  Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2013;18(3):369-381.  (PubMed)

153.  Grapp M, Just IA, Linnankivi T, et al. Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency. Brain. 2012;135(Pt 7):2022-2031.  (PubMed)

154.  Ramaekers VT, Blau N, Sequeira JM, Nassogne MC, Quadros EV. Folate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neurological deficits. Neuropediatrics. 2007;38(6):276-281.  (PubMed)

155.  Ramaekers VT, Hausler M, Opladen T, Heimann G, Blau N. Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics. 2002;33(6):301-308.  (PubMed)

156.  Banka S, Blom HJ, Walter J, et al. Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency. Am J Hum Genet. 2011;88(2):216-225.  (PubMed)

157.  Cario H, Smith DE, Blom H, et al. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet. 2011;88(2):226-231.  (PubMed)

158.  Pfeiffer CM, Hughes JP, Lacher DA, et al. Estimation of trends in serum and RBC folate in the U.S. population from pre- to postfortification using assay-adjusted data from the NHANES 1988-2010. J Nutr. 2012;142(5):886-893.  (PubMed)

159.  Folate. In: Hendler SS, Rorvik, D.R., ed. PDR for Nutritional Supplements. 2nd ed. Montvale: Physicians' Desk Reference Inc.; 2008.

160.  Wiesinger H, Eydeler U, Richard F, et al. Bioequivalence evaluation of a folate-supplemented oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium versus ethinylestradiol/drospirenone and levomefolate calcium alone. Clin Drug Investig. 2012;32(10):673-684.  (PubMed)

161.  Tinker SC, Cogswell ME, Devine O, Berry RJ. Folic acid intake among U.S. women aged 15-44 years, National Health and Nutrition Examination Survey, 2003-2006. Am J Prev Med. 2010;38(5):534-542.  (PubMed)

162.  Kelly P, McPartlin J, Goggins M, Weir DG, Scott JM. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr. 1997;65(6):1790-1795.  (PubMed)

163.  Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. 2007;85(1):193-200.  (PubMed)

164.  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(6):1733-1744.  (PubMed)

165.  Troen AM, Mitchell B, Sorensen B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. 2006;136(1):189-194.  (PubMed)

166.  Tam C, O'Connor D, Koren G. Circulating unmetabolized folic acid: relationship to folate status and effect of supplementation. Obstet Gynecol Int. 2012;2012:485179.  (PubMed)

167.  Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res. 2001;47(1-2):27-35.  (PubMed)

168.  Wilson SM, Bivins BN, Russell KA, Bailey LB. Oral contraceptive use: impact on folate, vitamin B(6), and vitamin B(1)(2) status. Nutr Rev. 2011;69(10):572-583.  (PubMed)