Folate

Folate

Folate

For Patients & Caregivers

Folate is used to prevent certain types of anemia and birth defects. It may also reduce the risk of certain cancers.

Folate is a vitamin of the vitamin B complex. The main food sources of folate include fortified breakfast cereals and breads, liver, Brussels sprouts, potatoes, spinach, chickpeas and brewer’s yeast. It is also available in supplemental form as folic acid. Folate deficiency can result in the reduction of essential cell division and can lead to anemia. The vitamin has been shown to reduce the risk of neural tube defects and is vital for pregnant women.

Higher levels of folate have been shown to reduce the risk for breast cancer, pancreatic cancer and colon cancer.

  • To treat Alzheimer’s disease
    Studies have linked low folate levels with Alzheimer’s disease. Research also shows a possible link between the intake of folate and decreased risk of Alzheimer’s.
  • To prevent cancer
    Clinical studies have shown that higher levels of folate reduce the risk for breast, pancreatic and colon cancers. Folic acid supplementation does not appear to affect the risk of prostate cancer.
  • To prevent heart disease
  • Low folic acid levels have been linked to higher homocysteine levels, a risk factor for death caused by diseases of the heart and blood vessels. However, further studies are needed to understand this association.
  • To treat chronic fatigue syndrome
    Folic acid was ineffective in treating chronic fatigue syndrome.
  • To prevent neural tube birth defects
    Studies have shown a significant decrease in the risk of neural tube (tissue in the embryo that develops into the brain and the spinal cord) defects as a result of increased dietary folate.
  • You are taking Anticonvulsants (Concurrent use of folic acid may antagonize the effects of certain anticonvulsants).
  • You are taking Colestyramine, Sulfasalazine and Salicylazosulfapyridine (May reduce the absorption of folic acid).
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For Healthcare Professionals

Pteroylglutamic acid

Folate and folic acid are water-soluble vitamins of the vitamin B complex. Folate is naturally available in green leafy vegetables, whereas folic acid is the synthetic supplemental form and has higher bioavailability than folate (1).

Folate is essential during pregnancy and has been shown to reduce the risk of neural tube defects (10). Data also suggest a nearly 50% reduction in risk of medulloblastoma in children born to women who took folic acid supplements during pregnancy (11). Folate supplementation may benefit women with polycystic ovary syndrome (PCOS) (42). High folate intake was also found to reduce chromosomal aberrations in sperm of healthy men (12).

In other studies, folic acid has been shown effective in decreasing levels of homocysteine, a risk factor for cardiovascular disease mortality (13) (14) (15), and reducing blood pressure in smokers (5) (16). However, trials on the risk of stroke yielded mix results (17) (18) (19) (20). Folic acid supplementation was ineffective in the treatment of chronic fatigue syndrome (21). Due to its antagonistic effects, folic acid can reduce the side effects of methotrexate when used for rheumatoid arthritis (22) (23). However, it may decrease the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia (24) and psoriasis (25). Folic acid supplementation improved cognitive function in older adults (26) and response to cholinesterase inhibitors in patients with putative Alzheimer’s disease (27). In individuals chronically exposed to arsenic, folic acid supplementation lowers blood arsenic concentrations by facilitating urinary excretion (28).

Low levels of folate in the blood are associated with certain forms of cancer (9), whereas higher levels of dietary folate have been shown to reduce the risk of breast (2), pancreatic (3) and colon cancers (4) (5) (6) (32) (35). However, folic acid supplementation does not seem to affect the risk of prostate cancer (7) or colorectal adenoma in patients with a history colorectal adenoma without carcinoma (8). A combination of folic acid, and vitamins B6 and B12 had no effect on overall of invasive cancer or breast cancer (33). Recent data, however, suggest higher cancer incidence and mortality in patients with ischemic heart disease following supplementation with vitamin B12 and folic acid (34).

In children aged 0 — 4 years, folic acid-fortification was associated with a reduction in the incidence of Wilms tumor and primitive neuroectodermal tumors (PNET), but not other childhood cancers (36).
Findings of a meta analysis indicate that folic acid supplementation does not have a significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer, or hematological malignancy, but reduces the risk of melanoma (37).

Main sources include fortified breakfast cereals and breads, liver, Brussels sprouts, potatoes, spinach, chickpeas, and brewer’s yeast.

  • Alzheimer’s disease
  • Cancer prevention
  • Cardiovascular disease
  • Chronic fatigue syndrome
  • Neural tube birth defect prevention
Folic acid plays important roles in DNA synthesis, and as a methyl donor in several metabolic and nervous system biochemical processes. The amino acid serine reacts with tetrahydrofolate, resulting in 5,10- methylenetetrahydrofolate, the derivative involved in DNA synthesis. A methyl group is donated to cobalamin (B12) by 5-methyltetrahydrofolate, forming methylcobalamin. Methylcobalamin, in turn, donates a methyl group to the amino acid metabolite homocysteine, and converts it to methionine.  Methionine is the precursor of the methyl donor, S-adenosyl-methionine (SAMe), which plays a major role in several biochemical pathways  (41). Clinical studies indicate that folic acid supplementation improves endothelial function in patients with coronary atherosclerosis (31) and in smokers (16). In addition, both oral and intravenous folate administration resulted in comparable homocysteine-lowering effects (13).

Folic acid supplementation has been shown to reduce the risk of colon cancer (32); and dietary folate intake was more strongly associated with reduced breast cancer risk in women who also consumed high levels of folate cofactors (methionine, vitamin B12, and vitamin B6) (2).

  • Anticonvulsants: Concurrent use of folic acid may antagonize the effects of certain anticonvulsants (29).
  • Colestyramine, Sulfasalazine and Salicylazosulfapyridine: May reduce the absorption of folic acid (1).

  1. Gregory JF, III. Case study: folate bioavailability. J Nutr 2001;131:1376S-82S.

  2. Shrubsole MJ, Jin F, Dai Q, Shu XO, Potter JD, Hebert JR et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 2001;61:7136-41.

  3. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, Taylor PR, Virtamo J, Albanes D. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 2001;153:680-7.

  4. Fuchs CS, Willett WC, Colditz GA, Hunter DJ, Stampfer MJ, Speizer FE et al. The influence of folate and multivitamin use on the familial risk of colon cancer in women. Cancer Epidemiol Biomarkers Prev 2002;11:227-34.

  5. Van Guelpen B, Hultdin J, Johansson I, et al. Low folate levels may protect against colorectal cancer. Gut 2006;55(10):1461-6.

  6. Stevens VL, et al. Folate nutrition and prostate cancer incidence in a large cohort of US men. Am J Epidemiology 2006; 163(11):989-996.

  7. Cole BF, Baron JA, Sandler RS. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007 ;297(21):2351-9.

  8. Berry RJ, Li Z, Erickson D, et al. Prevention of neural-tube defects with folic acid in China. N Engl J Med 1999;341(20):1485-1490.

  9. Young SS, Eskenazi B, Marchetti FM, et al. The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod. 2008;23(5):1014-22. Epub 2008 Mar 19.

  10. Ducloux D, Aboubakr A, Motte G, Toubin G, Fournier V, Chalopin JM et al. Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12. Nephrol.Dial.Transplant. 2002;17:865-70.

  11. Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch.Intern.Med 2001;161:695-700.

  12. Mangoni AA, Sherwood RA, Swift CG, Jackson SH. Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Intern Med 2002;252:497-503.

  13. Al-Delaimy Wael K, et al. Folate intake and risk of stroke among women. Stroke. 2004 Jun;35(6):1259-63.

  14. Larsson SC, Mannisto S, Virtanen MJ, et al. Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers. Am J Epidemiol. 2008;167(8):954-61. Epub 2008 Feb 12.

  15. Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch.Intern.Med 1989;149:2501-3.

  16. Griffith SM, Fisher J, Clarke S, Montgomery B, Jones PW, Saklatvala J et al. Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term? Rheumatology.(Oxford) 2000;39:1102-9.

  17. Shiroky JB. The use of folates concomitantly with low-dose pulse methotrexate. Rheum.Dis.Clin North Am 1997;23:969-80.

  18. Connelly PJ, Prentice NP, Cousland G, Bonham J. A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer’s disease. Int J Geriatr Psychiatry 2008;23(2):155-60.

  19. Gamble MV, Liu X, Slavkovich V, et al. Folic acid supplementation lowers blood arsenic. Am J Clin Nutr. 2007;86(4):1202-9.

  20. Froscher W, Maier V, Laage M, Wolfersdorf M, Straub R, Rothmeier J et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol. 1995;18:165-82.

  21. Mason P. Dietary Supplements. London: Pharmaceutical Press; 2001.

  22. Title LM, Cummings PM, Giddens K, Genest JJ, Jr., Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll.Cardiol. 2000;36:758-65.

  23. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Annals of Internal Medicine 1998;129:517-24.

  24. Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA. 2008 Nov 5;300(17):2012-21.

  25. Ebbing M, Bonaa KH, Nygard O, et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA. 2009;302(19):2119-2126.

  26. Stevens VL, McCullough ML, Sun J, et al. High Levels of Folate From Supplements and Fortification Are Not Associated With Increased Risk of Colorectal Cancer. Gastroenterology. 2011 Jul;141(1):98-105, 105.e1.

  27. Linabery AM, Johnson KJ, Ross JA. Childhood cancer incidence trends in association with US folic acid fortification (1986-2008). Pediatrics. 2012 Jun;129(6):1125-33.

  28. 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 Sep 1;133(5):1033-41.

  29. Zettner A, Boss GR, Seegmiller JE. A long-term study of the absorption of large oral doses of folic acid. Ann Clin Lab Sci. 1981;11:516-524.

  30. Gregory JF 3d, Bhandari SD, Bailey LB, et al. Relative bioavailability of deuterium-labeled monoglutamyl tetrahydrofolates and folic acid in human subjects. Am J Clin Nutr. 1992;55:1147- 1153.

  31. Folic Acid. Alternative Medicine Review. 2005;10(3): 222-229.

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