Vitamin B9 (Folic Acid)
Description and function
Folic acid is a water-soluble B complex vitamin that functions as a co-enzyme involved in the metabolism of amino acids and in the synthesis of nucleic acid (DNA and RNA). It plays a particularly important role in cell division and in the development of rapidly growing tissues; for instance, it is involved in the renewal of red blood cells, in the development of immune cells, in the healing of injured tissues, in the development of the foetus and in child growth. Because of this important role in the development of rapidly growing tissues, folic acid requirements are particularly increased during infancy, pregnancy and lactation.
Folic acid also plays a role in the synthesis of neurotransmitters in the brain and in the regulation of the level of homocysteine. High levels of homocysteine are associated with the formation of atheromatous plaques and, as a consequence, with an increased risk for stroke, heart disease, and cognitive diseases like Alzheimer's disease.
Deficiency
Deficiencies of folic acid during pregnancy are associated with an increased incidence of foetal malformations, especially neural tube defects (e.g., anencephaly and spina bifida), and cleft lip/cleft palate.
Folic acid deficiency has also been associated with higher homocysteine levels and, as mentioned previously, an increased risk for stroke, heart disease, and cognitive diseases like Alzheimer's disease.
Other signs of folic acid deficiencies include megaloblastic anemia (a type of anaemia that is reversible with supplementation), glossitis (redness and inflammation of the tongue), tiredness, weakness, peripheral neuropathy, irritability, forgetfulness and diarrhoea.
Note: Because of the importance of folic acid in the development of the foetus, special recommendations have been developed for pregnant women and women of childbearing age.
Key Messages On Folate For Women Of Childbearing Age (from Health Canada)
- Eating according to Canada's Food Guide and taking a daily multivitamin that has 400 mcg (0.4 mg) of folic acid will help you prepare for a healthy pregnancy. Doing this can also reduce the risk to your baby of developing a neural tube defect (NTD).
- Make sure your supplement contains vitamin B12.
- Because many pregnancies are unplanned, all women who could become pregnant should take a daily multivitamin containing 400 mcg (0.4 mg) of folic acid. At a minimum, start taking your supplement 3 months before you get pregnant. Continue taking this supplement throughout your pregnancy to help meet your need for folic acid and other nutrients like iron.
- If you have had a pregnancy affected by a NTD or have a family history of this problem, you should see your doctor. You may need to take a higher dose of folic acid.
- If you have diabetes, obesity or epilepsy, you may be at higher risk of having a baby with a NTD. See your doctor before planning a pregnancy.
- Do not take more than the 1 daily dose of a multivitamin. Do not increase your dose of folic acid beyond 1000 mcg (1 mg) per day without talking to a doctor first.
- Do not take more than the 1 daily dose of a multivitamin. Do not increase your dose of folic acid beyond 1000 mcg (1 mg) per day without talking to a doctor first.
Sources
The best food sources are green leafy vegetables, legumes, nuts, seeds, liver, yeast, and fortified cereals. As indicated above, because of its importance during pregnancy, folic acid supplement of 400 mcg per day is recommended for all women of childbearing age.
Toxicity
Folic acid is usually considered safe, although it may precipitate neuropathy in patients with pernicious anaemia (Vitamin B12 deficiency). It may also lead to convulsions in patients taking anticonvulsant because of its antagonizing effect on this type of medication. Folic acid may also interfere with other medications such as antibiotics, methotrexate, oestrogen and some other.
Consult with your health care provider if you are taking medication and want to take supplements of folic acid. Although some authorities have identified a likely safe total intake of folic acid for adults from supplements of 1000 mcg per day, it is highly advisable to consult your health care provider before taking more than 400 mcg / day of folic acid.
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Additional sources of information
Scientific references
Books
Folic acid, vitamin B-12, and vitamin B-6. Shane B. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.
Folic acid. Herbert V. In: Shils M, Olson JA, Shike M, Ross AC, eds. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:433-446.
PDR for Nutritional Supplements. Hendler SS, Rorvik DR, eds. Montvale: Medical Economics Company, Inc; 2001.
Food and Nutrition Board, Institute of Medicine. Folic Acid. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press; 1998:193-305. (National Academy Press)
Scientific articles
A prospective study of folate intake and the risk of breast cancer. Zhang S, Hunter DJ, Hankinson SE, et al. JAMA. 1999;281(17):1632-1637.
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A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. JAMA. 1995;274(13):1049-1057.
[Abstract]
Alcohol, low-methionine--low-folate diets, and risk of colon cancer in men.Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Willett WC. J Natl Cancer Inst. 1995;87(4):265-273.
[Abstract]
Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Morris MC, Evans DA, Bienias JL, et al. Arch Neurol. 2005;62(4):641-645.
[Abstract]
Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease. Morris MC, Evans DA, Schneider JA, Tangney CC, Bienias JL, Aggarwal NT. J Alzheimers Dis. 2006;9(4):435-443.
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Dietary folate consumption and breast cancer risk. Rohan TE, Jain MG, Howe GR, Miller AB. J Natl Cancer Inst. 2000;92(3):266-269.
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Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Sellers TA, Kushi LH, Cerhan JR, et al. Epidemiology. 2001;12(4):420-428.
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Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Terry P, Jain M, Miller AB, Howe GR, Rohan TE. Int J Cancer. 2002;97(6):864-867.
[Abstract]
Dietary reference intakes for folate: the debut of dietary folate equivalents. Bailey LB. Nutr Rev. 1998;56(10):294-299.
[Abstract]
Does a high folate intake increase the risk of breast cancer? Kim YI. Nutr Rev. 2006;64(10 Pt 1):468-475.
[Abstract]
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.
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Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Cravo ML, Pinto AG, Chaves P, et al. Clin Nutr. 1998;17(2):45-49.
[Abstract]
Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. Bazzano LA, Reynolds K, Holder KN, He J. JAMA. 2006;296(22):2720-2726.
[Abstract]
Effects of B-vitamins on plasma homocysteine concentrations and on risk of cardiovascular disease and dementia. Clarke R, Lewington S, Sherliker P, Armitage J. Curr Opin Clin Nutr Metab Care. 2007;10(1):32-39.
[Abstract]
Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Kim YI, Baik HW, Fawaz K, et al. Am J Gastroenterol. 2001;96(1):184-195.
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Folate and carcinogenesis: an integrated scheme. Choi SW, Mason JB. J Nutr. 2000;130(2):129-132.
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Folate intake and colorectal cancer risk: a meta-analytical approach. Sanjoaquin MA, Allen N, Couto E, Roddam AW, Key TJ. Int J Cancer. 2005;113(5):825-828.
[Abstract]
Folate metabolism and requirements. Bailey LB, Gregory JF, 3rd. J Nutr. 1999;129(4):779-782.
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Folate status, vascular disease and cognition in elderly Canadians. Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Age Ageing. 1998;27(4):485-491.
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Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Cole BF, Baron JA, Sandler RS, et al. JAMA. 2007;297(21):2351-2359.
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Folic acid: influence on the outcome of pregnancy. Scholl TO, Johnson WG. Am J Clin Nutr. 2000;71(5 Suppl):1295S-1303S.
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Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Malinow MR, Bostom AG, Krauss RM. Circulation. 1999;99(1):178-182.
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Homocysteine and atherosclerosis. Gerhard GT, Duell PB. Curr Opin Lipidol. 1999;10(5):417-428.
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Homocysteine, B vitamins, and coronary artery disease. Seshadri N, Robinson K. Med Clin North Am. 2000;84(1):215-237.
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Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study. Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT. Circulation. 2001;103(22):2674-2680.
[Abstract]
Methylenetetrahydrofolate reductase mutation (677C-->T) negatively influences plasma homocysteine response to marginal folate intake in elderly women. Kauwell GP, Wilsky CE, Cerda JJ, et al. Metabolism. 2000;49(11):1440-1443.
[Abstract]
Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Ma J, Stampfer MJ, Giovannucci E, et al. Cancer Res. 1997;57(6):1098-1102.
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Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M. Cancer Epidemiol Biomarkers Prev. 1999;8(6):513-518.
[Abstract]
Microvascular disease and dementia in the elderly: are they related to hyperhomocysteinemia? Weir DG, Molloy AM. Am J Clin Nutr. 2000;71(4):859-860.
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Neural tube defect rates before and after food fortification with folic acid. Mills JL, Signore C. Birth Defects Res A Clin Mol Teratol. 2004;70(11):844-845.
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Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Su LJ, Arab L. Ann Epidemiol. 2001;11(1):65-72.
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Open or closed? A world of difference: a history of homocysteine research. Eskes TK. Nutr Rev. 1998;56(8):236-244.
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Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. Seshadri S, Beiser A, Selhub J, et al. N Engl J Med. 2002;346(7):476-483.
[Abstract]
Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. Bailey LB, Gregory JF, 3rd. J Nutr. 1999;129(5):919-922.
[Abstract]
Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Arch Neurol. 2007;64(1):86-92.
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Response of red blood cell folate to intervention: implications for folate recommendations for the prevention of neural tube defects. McNulty H, Cuskelly GJ, Ward M. Am J Clin Nutr. 2000;71(5 Suppl):1308S-1311S.
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Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Snowdon DA, Tully CL, Smith CD, Riley KP, Markesbery WR. Am J Clin Nutr. 2000;71(4):993-998.
[Abstract]
Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000. MMWR Morb Mortal Wkly Rep. 2004;53(17):362-365.
[Abstract]
Vitamin B(12) and folate in relation to the development of Alzheimer's disease. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Neurology. 2001;56(9):1188-1194.
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