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Folic acid


What is it?

Folic acid is a water-soluble B vitamin. Since 1998, it has been added to cold cereals, flour, breads, pasta, bakery items, cookies, and crackers, as required by federal law. Foods that are naturally high in folic acid include leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, fruits (such as bananas, melons, and lemons) beans, yeast, mushrooms, meat (such as beef liver and kidney), orange juice, and tomato juice.

Folic acid is used for preventing and treating low blood levels of folic acid (folic acid deficiency), as well as its complications, including “tired blood” (anemia) and the inability of the bowel to absorb nutrients properly. Folic acid is also used for other conditions commonly associated with folic acid deficiency, including ulcerative colitis, liver disease, alcoholism, and kidney dialysis.

Women who are pregnant or might become pregnant take folic acid to prevent miscarriage and “neural tube defects,” birth defects such as spina bifida that occur when the fetus’s spine and back don’t close during development.

Some people use folic acid to prevent colon cancer or cervical cancer. It is also used to prevent heart disease and stroke, as well as to reduce blood levels of a chemical called homocysteine. High homocysteine levels might be a risk for heart disease.

Folic acid is used for memory loss, Alzheimer’s disease, age-related hearing loss, preventing the eye disease age-related macular degeneration (AMD), reducing signs of aging, weak bones (osteoporosis), jumpy legs (restless leg syndrome), sleep problems, depression, nerve pain, muscle pain, AIDS, a skin disease called vitiligo, and an inherited disease called Fragile-X syndrome. It is also used for reducing harmful side effects of treatment with the medications lometrexol and methotrexate.

Some people apply folic acid directly to the gum for treating gum infections.

Folic acid is often used in combination with other B vitamins.

How effective is it?

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.

The effectiveness ratings for FOLIC ACID are as follows:

Effective for...

  • Treating and preventing folic acid deficiency.

Likely effective for...

  • Lowering homocysteine levels in people with kidney disease. About 85% of people with serious kidney disease have high levels of homocysteine. High levels of homocysteine have been linked to heart disease and stroke. Taking folic acid lowers homocysteine levels in people with serious kidney disease.
  • Lowering homocysteine levels (“hyperhomocysteinemia”) in people with high amounts of homocysteine in their blood. High levels of homocysteine have been linked to heart disease and stroke.
  • Reducing harmful effects of a medicine called methotrexate, which is sometimes used to treat rheumatoid arthritis and psoriasis. Taking folic acid seems to reduce nausea and vomiting, which are possible side effects of methotrexate treatment.
  • Decreasing the risk of certain birth defects (neural tube defects) when taken by pregnant women.

Possibly effective for...

  • Reducing the risk of getting colorectal cancer. Getting more folic acid from the diet and supplements seems to lower the chances of developing colon cancer, but does not seem to help people who already have colon cancer.
  • Reducing the risk of breast cancer. The benefit is greater when women get extra vitamin B12 and vitamin B6 in their diet in addition to folic acid.
  • Depression, when used with conventional antidepressant medicines. Limited research suggests that folic acid alone won’t help with depression.
  • Treating a skin disease called vitiligo.
  • Gum problems due to a drug called phenytoin when applied to the gums.
  • Treating gum disease during pregnancy, when used in mouthwash.
  • Reducing the risk of pancreatic cancer.
  • Macular degeneration. Some research shows that taking folic acid with other vitamins including vitamin B6 and vitamin B12 might help prevent getting the eye disease called age-related macular degeneration.

Possibly ineffective for...

  • Reducing the risk of heart attack, stroke, and other related conditions in people with coronary heart disease.
  • Reducing the possibility of another stroke.
  • Reducing harmful effects of a medicine called lometrexol.
  • Chronic fatigue syndrome.

Likely ineffective for...

  • Treating an inherited disease called Fragile-X syndrome.

Insufficient evidence to rate effectiveness for...

  • Preventing re-blockage of blood vessels after angioplasty, a procedure to open a closed blood vessel. Taking folic acid plus vitamin B6 and vitamin B12 might actually interfere with healing in cases where a device (stent) is inserted in the blood vessel to keep it open.
  • Alzheimer’s disease. Limited evidence suggests that elderly people who get more folic acid than the recommended dietary allowance (RDA) appear to have a lower risk of developing Alzheimer’s disease than people who get less folic acid.
  • Memory and thinking skills in older people. There is conflicting evidence about the role of folic acid in age-related decline in memory and thinking skills.
  • Preventing cervical cancer. There is some evidence that increasing folic acid intake from dietary and supplement sources, along with thiamine, riboflavin, and vitamin B12, might help to prevent cervical cancer.
  • Male infertility. Some research suggests that taking folic acid plus zinc sulfate daily can increase sperm count in men with low sperm counts.
  • Lung cancer. There does not appear to be a relationship between low levels of folic acid and lung cancer.
  • Restless leg syndrome. Taking folic acid seems to reduce symptoms. Researchers are studying whether folic acid deficiency causes restless leg syndrome.
  • Cancer due to a disease called ulcerative colitis. Taking folic acid might help to keep people with ulcerative colitis from getting cancer.
  • Liver disease.
  • Alcoholism.
  • Age-related hearing loss.
  • Sickle cell disease.
  • Weak bones (osteoporosis).
  • Other conditions.
More evidence is needed to rate folic acid for these uses.

How does it work?

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Folic acid is needed for the proper development of the human body. It is involved in producing the genetic material called DNA and in numerous other bodily functions.

Are there safety concerns?

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Folic acid is LIKELY SAFE for most people. Most adults do not experience any side effects when consuming the recommended amount each day, which is 400 mcg.

High doses of folic acid might cause abdominal cramps, diarrhea, rash, sleep disorders, irritability, confusion, nausea, stomach upset, behavior changes, skin reactions, seizures, gas, excitability, and other side effects.

There is some concern that taking too much folic acid for a long period of time might cause serious side effects. Some research suggests that taking folic acid in doses of 800-1200 mcg might increase the risk of heart attack in people who have heart problems. Other research suggests that taking these high doses might also increase the risk of cancer such as lung or prostate cancer.

Don't take more than 400 mcg per day unless directed by your healthcare provider.

Are there interactions with medications?

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Moderate

Be cautious with this combination.

5-Fluorouracil
There is some concern that taking large amounts of folic acid with 5-fluorouracil might increase some side effects of 5-fluorouracil, especially stomach problems. Talk with your healthcare provider before taking folic acid.

Capecitabine (Xeloda)
There is some concern that taking large amounts of folic acid might increase the side effects of capecitabine, especially stomach problems like diarrhea and vomiting. Talk with your healthcare provider before taking folic acid.

Fosphenytoin (Cerebyx)
Fosphenytoin (Cerebyx) is used for seizures. The body breaks down fosphenytoin (Cerebyx) to get rid of it. Folic acid can increase how quickly the body breaks down fosphenytoin (Cerebyx). Taking folic acid along with fosphenytoin (Cerebyx) might decrease the effectiveness of fosphenytoin (Cerebyx) for preventing seizures.

Methotrexate (MTX, Rheumatrex)
Methotrexate (MTX, Rheumatrex) works by decreasing the effects of folic acid in the body's cells. Taking folic acid pills along with methotrexate might decrease the effectiveness of methotrexate (MTX, Rheumatrex).

Phenobarbital (Luminal)
Phenobarbital (Luminal) is used for seizures. Taking folic acid can decrease how well phenobarbital (Luminal) works for preventing seizures.

Phenytoin (Dilantin)
The body breaks down phenytoin (Dilantin) to get rid of it. Folic acid might increase how quickly the body breaks down phenytoin (Dilantin). Taking folic acid and taking phenytoin (Dilantin) might decrease the effectiveness of phenytoin (Dilantin) and increase the possibility of seizures.

Primidone (Mysoline)
Primidone (Mysoline) is used for seizures. Folic acid might cause seizures in some people. Taking folic acid along with primidone (Mysoline) might decrease how well primidone works for preventing seizures.

Pyrimethamine (Daraprim)
Pyrimethamine (Daraprim) is used to treat parasite infections. Folic acid might decrease the effectiveness of pyrimethamine (Daraprim) for treating parasite infections.

Are there interactions with herbs and supplements?

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Green tea
There is some concern that green tea might keep folic acid from working the way it should in the body. This might lead to a condition that is similar to folic acid deficiency.

Are there interactions with foods?

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Food
Taking folic acid with food reduces its absorption slightly, but probably not enough to be important.

Zinc
Researchers don't agree on whether or not folic acid interferes with zinc absorption. But for people who get enough zinc in their diet, the effect of folic acid probably isn't important.

What dose is used?

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The following doses have been studied in scientific research:

BY MOUTH:
  • For folic acid deficiency: the typical dose is 250-1000 mcg (micrograms) per day.
  • For preventing neural tube defects: at least 400 mcg of folic acid per day from supplements or fortified food should be taken by women capable of becoming pregnant and continued through the first month of pregnancy. Women with a history of previous pregnancy complicated by such neural tube defects usually take 4 mg per day beginning one month before and continuing for three months after conception.
  • For reducing colon cancer risk: 400 mcg per day.
  • For treating high levels of homocysteine in the blood:
    • 0.5-5 mg (milligrams)/day has been used, although 0.8-1 mg/day is appears to be more effective.
    • In people with end-stage renal disease, high homocysteine levels may be more difficult to treat, and doses of 0.8-15 mg/day have been used. Other dosage plans such as 2.5-5 mg 3 times weekly have also been used. Doses higher than 15 mg daily do not seem to be more effective.
  • For improving the response to medications for depression: 200-500 mcg daily has been used.
  • For vitiligo: 5 mg is typically taken twice daily.
  • For reduction of toxicity associated with methotrexate therapy for rheumatoid arthritis (RA) or psoriasis: 1 mg/day is probably enough, but up to 5 mg/day may be used.
  • For preventing macular degeneration: folic acid 2.5 mg, vitamin B12 (cyanocobalamin) 1000 mcg, and vitamin B6 (pyridoxine) 50 mg daily.
The adequate intakes (AI) for infants are 65 mcg for infants 0-6 months and 80 mcg for infants 7-12 months of age. The recommended dietary allowances (RDAs) for folate in DFE, including both food folate and folic acid from fortified foods and supplements are: Children 1-3 years, 150 mcg; Children 4-8 years, 200 mcg; Children 9-13 years, 300 mcg; Adults over 13 years, 400 mcg; Pregnant women 600 mcg; and breast-feeding women, 500 mcg. The tolerable upper intake levels (UL) of folate are 300 mcg for children 1-3 years of age, 400 mcg for children 4-8 years, 600 mcg for children 9-13 years, 800 mcg for adolescents 14-18 years, and 1000 mcg for everyone over 18 years of age.

Other names

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5'-methyltetrahydrofolate, 5'-MTHF, Acide Folique, Acide Ptéroylglutamique, Acide Ptéroylmonoglutamique, Acido Folico, B Complex Vitamin, Complexe de Vitamines B, Complexe Vitaminique B, Dihydrofolate, Folacin, Folacine, Folate, Folinic Acid, L-methylfolate, Methylfolate, Méthylfolate, Pteroylglutamic Acid, Pteroylmonoglutamic Acid, Pteroylpolyglutamate, Tetrahydrofolate, Tétrahydrofolate, Vitamin B9, Vitamine B9.

Methodology

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To learn more about how this article was written, please see the Natural Medicines Comprehensive Database methodology.methodology (http://www.nlm.nih.gov/medlineplus/druginfo/natural/methodology.html).

References

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To see all references for the Folic acid page, please go to http://www.nlm.nih.gov/medlineplus/druginfo/natural/1017.html.

  1. Willems FF, Boers GH, Blom HJ, et al. Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol 2004;141:825-30.
  2. Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to calcium L-methylfolate. EFSA J 2004;135:1-20. Available at: http://www.efsa.europa.eu/en/scdocs/doc/135.pdf. (Accessed 18 March 10).
  3. L-methylfolate. Pharmacist's Letter / Prescriber's Letter 2010;26:260311.
  4. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009;302:2119-26.
  5. Bedford Laboratories. Leucovorin calcium [package insert]. Bedford, OH. September 2008. Available at: http://www.bedfordlabs.com/BedfordLabsWeb/products/inserts/LCV-P02.pdf.
  6. Clippe C, Freyer G, Milano G, Trillet-Lenoir V. Lethal toxicity of capecitabine due to abusive folic acid prescription. Clin Oncol (R Coll Radiol) 2003;15:299-300.
  7. Figueiredo JC, Grau MV, Haile RW, et al. Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J Natl Cancer Inst 2009;101:432-5.
  8. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64.
  9. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369:208-16.
  10. Luchsinger JA, Tang MX, Miller J, et al. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 2007;64:86-92.
  1. Durga J, Verhoef P, Anteunis LJC, et al. Effects of folic acid supplementation on hearing in older adults. Ann Intern Med 2007;146:1-9.
  2. Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, et al. The antifolate activity of tea catechins. Cancer Res 2005;65:2059-64.
  3. Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women. Arch Intern Med 2009;169:335-41.
  4. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354:2764-72.
  5. Van Guelpen B, Hultdin J, Johansson I, et al. Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake. Stroke 2005;36:1426-31.
  6. Bonaa KH, Njolstad I, Ueland PM, et al. NORVIT: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Enlg J Med 2006;354:1578-88.
  7. Corrada M, Kawas C. Reduced risk of Alzheimer's disease with high folate Intake: The Baltimore Longitudinal Study of Aging. Alzheimers Dement 2005;1:11-18.
  8. 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;62:641-5.
  9. Oakley GP, Mandel JS. Folic acid fortification remains an urgent health priority. Br Med J 2004;329:1376.
  10. Charles D, Ness AR, Campbell D, et al. Taking folate in pregnancy and risk of maternal breast cancer. Br Med J 2004;329:1375-6.
  11. Herrmann H. Prevention of cardiovascular events after percutaneous coronary intervention. N Engl J Med 2004;350:2708-10.
  12. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81.
  13. Hanley DF. The challenge of stroke prevention. JAMA 2004;291:621-2.
  14. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-75.
  15. van Oort FV, Melse-Boonstra A, Brouwer IA, et al. Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am J Clin Nutr 2003;77:1318-23.
  16. Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, et al. Secondary prevention with folic acid: effects on clinical outcomes. J Am Coll Cardiol 2003;41:2105-13.
  17. Hernandez BY, McDuffie K, Wilkens LR, et al. Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control 2003;14:859-70.
  18. Godfrey PS, Toone BK, Carney MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990;336:392-5.
  19. Passeri M, Cucinotta D, Abate G, et al. Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano) 1993;5:63-71.
  20. Coppen A, Swade C, Jones SA, et al. Depression and tetrahydrobiopterin: the folate connection. J Affect Disord 1989;16:103-7.
  21. Taylor MJ, Carney S, Geddes J, Goodwin G. Folate for depressive disorders. Cochrane Database Syst Rev 2003;:CD003390.
  22. Tolmunen T, Voutilainen S, Hintikka J, et al. Dietary folate and depressive symptoms are associated in middle-aged Finnish men. J Nutr 2003;133:3233-6.
  23. Morris MS, Fava M, Jacques PF, et al. Depression and folate status in the US Population. Psychother Psychosom 2003;72:80-7.
  24. Tiemeier H, van Tuijl HR, Hofman A, et al. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry 2002;159:2099-101.
  25. Alpert M, Silva RR, Pouget ER. Prediction of treatment response in geriatric depression from baseline folate level: interaction with an SSRI or a tricyclic antidepressant. J Clin Psychopharmacol 2003;23:309-13.
  26. Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000;69:228-32.
  27. van der Griend R, Haas FJ, Biesma DH, et al. Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives. Atherosclerosis 1999;143:177-83.
  28. Eros E, Geher P, Gomor B, Czeizel AE. Epileptogenic activity of folic acid after drug induces SLE (folic acid and epilepsy). Eur J Obstet Gynecol Reprod Biol 1998;80:75-78.
  29. Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anaemia. Public Health Nutr 2000;3:125-50.
  30. Badner NH, Freeman D, Spence JD. Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increases. Anesth Analg 2001;93:1507-10.
  31. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.
  32. Keating JN, Wada L, Stokstad ELR, King JC. Folic acid: effect on zinc absorption in humans and in the rat. Am J Clin Nutr 1987;46:835-9.
  33. Schroder H, Clausen N, Ostergard E, Pressler T. Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia. Ped Hematol Oncol 1986;3:241-7.
  34. Endresen GK, Husby G. Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposal for guidelines. Scand J Rheumatol 2001;30:129-34.
  35. Griffith SM, Fisher J, Clarke S, 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.
  36. Dierkes J, Domrose U, Ambrosch A, et al. Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease. Clin Nephrol 1999;51:108-15.
  37. Bostom AG, Shemin D, Gohh RY, et al. Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients. Kidney Int 2001;59:s246-s252.
  38. Dierkes J, Domrose U, Bosselmann P, et al. Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease. J Renal Nutr 2001;11:67-72.
  39. Bostom A, Shemin D, Gohh R, et al. Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients. Transplantation 2000;69:2128-31.
  40. Sunder-Plassmann G, Fodinger M, Buchmayer H, et al. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna Multicenter Study. J Am Soc Nephrol 2000;11:1106-16.
  41. Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention. The Swiss Heart Study: A randomized controlled trial. JAMA 2002;288:973-9.
  42. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57.
  43. den Heijer M, Brouwer IA, Bos GMJ, et al. Vitamin supplementation reduces blood homocysteine levels. A controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol 1998;18:356-61.
  44. Sunder-Plassmann G, Winkelmayer WC, Fodinger M. Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease. Expert Opin Investig Drugs 2000;9:2637-51.
  45. Keebler ME, De Souza C, Fonesca V. Diagnosis and treatment of hyperhomocysteinemia. Curr Atheroscler Rep 2001;3:54-63.
  46. Selhub J, Jacques PF, Bostom AG, et al. Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. Publ Health Rev 2000;28:117-45.
  47. van der Griend R, Biesma DH, Haas FJLM, et al. The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations. J Int Med 2000;248:223-9.
  48. Clarke R, Armitage J. Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost 2000;26:341-8.
  49. Bostom AG, Selhub J, Jacques PF, Rosenberg IH. Power shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour. Ann Int Med 2001;135:133-7.
  50. Holven KB, Holm T, Aukrust P, et al. Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects. Am J Med 2001;110:536-42.
  51. Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000;72:324-32.
  52. Bronstrup A, Hages M, Prinz-Langenohl R, Pietrzik K. Effects of folic acid and combinations of folic acid and vitamin B12 on plasma homocysteine concentrations in healthy young women. Am J Clin Nutr 1998;68:1104-10.
  53. Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ 1998;316:894-8.
  54. Nunn PP, Allistone JC. Resistance to trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. Implication of folinic acid. Chest 1984;86:149-50.
  55. Bygbjerg IC, Lund JT, Hording M. Effect of folic and folinic acid on cytopenia occurring during cotrimoxazole treatment of Pneumocystis carinii pneumonia. Scand J Infect Dis 1988;20:685-6.
  56. Halsted CH, McIntyre PA. Intestinal malabsorption caused by aminosalicylic acid therapy. Arch Int Med 1972;130;935-9.
  57. Evans DI, Attock B. Folate deficiency in pulmonary tuberculosis: relationship to treatment and to serum vitamin A and beta carotene. Tubercle 1971;52:288-94.
  58. Line DH, Seitanidis B, Morgan JO, Hoffbrand AV. The effects of chemotherapy on iron, folate, and vitamin B12 metabolism in tuberculosis. Q J Med 1971;40:331-40.
  59. Koutts J, Van der Weyden MB, Cooper M. Effect of trimethoprim on folate metabolism in human bone marrow. Aust NZ J Med 1973;3:245-50.
  60. Kauwell GPA, Baily LB, Gregory JF, et al. Zinc status is not adversely affected by folic acid supplementation and zinc intake does not impair folate utilization in human subjects. J Nutr 1995;125:66-72.
  61. Fuller NJ, Bates CJ, Evans PH, Lucas A. High folate intakes related to zinc status in preterm infants. Eur J Pediatr 1992;151:51-3.
  62. Butterworth CE, Hatch K, Cole P, et al. Zinc concentration in plasma and erythrocytes of subjects receiving folic acid supplementation. Am J Clin Nutr 1988;47:484-6.
  63. Kakar F, Henderson MM. Potential toxic side effects of folic acid (letter). J Natl Cancer Inst 1985;74:263.
  64. Milne DB, Canfield WK, Mahalko JR, Sandstead HH. Effect of oral folic acid supplements on zinc, copper, and iron absorption and excretion. Am J Clin Nutr 1984;39:535-9.
  65. Thompson JB, Hess DR, Poley JR, et al. Intestinal malabsorption induced by paraminosalicylic acid (abstract). Gastroenterology 1970;58:1001.
  66. Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis 1994;170:912-7.
  67. Stock C. Trimethoprim-sulfamethoxazole and folinic acid (letter). Ann Intern Med 1985;102:277.
  68. Hollander H. Leukopenia, trimethoprim-sulfamethoxazole, and folinic acid (letter). Ann Intern Med 1985;102:138.
  69. Kinzie BJ, Taylor JW. Trimethoprim and folic acid (letter). Ann Int Med 1984;101:565.
  70. Naderer O, Nafziger AN, Bertino JS. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions. Antimicrob Agents Chemother 1997;41:2466-70.
  71. Kobrinsky NL, Ramsay NKC. Acute megaloblastic anemia induced by high-dose trimethoprim-sulfamethoxazole. Ann Int Med 1981;94:780-1.
  72. Pelliniemi TT, Kasanen A, Sundquist H. Lack of haematological side effects during prophylactic use of trimethoprim over four years. Curr Ther Res 1983;34:436-40.
  73. Van Delden C, Hirschel B. Folinic acid supplements to pyrimethamine-sulfadiazine for Toxoplasma encephalitis are associated with better outcome (letter). J Infect Dis 1996;173:1294-5.
  74. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Gastroenterology 1989;97:255-9.
  75. Drake S, Lampasona V, Nicks HL, Schwarzmann SW. Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia. Clin Pharm 1985;4:507-16.
  76. Longstreth GF, Green R. Folate status in patients receiving maintenance doses of sulfasalazine. Arch Int Med 1983;143:902-4.
  77. Prouse PJ, Shawe D, Gumpel JM. Macrocytic anemia in patients treated with sulfasalazine for rheumatoid arthritis. BMJ 1986;293:1407.
  78. Corcino J, Waxman S, Herbert V. Mechanism of triamterene-induced megaloblastosis. Ann Intern Med 1970;73:419-24.
  79. Russell RM, Dutta SK, Oaks EV, et al. Impairment of folic acid absorption by oral pancreatic extracts. Dig Dis Sci 1980;25:369-73.
  80. Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception 1991;44:277-88.
  81. Barone C, Bartoloni C, Ghirlanda G, Gentiloni N. Megaloblastic anemia due to folic acid deficiency after oral contraceptives. Haematologica 1979;64:190-5.
  82. Shojania AM. Oral contraceptives: effect on folate and vitamin B12 metabolism. Can Med Assoc J 1982;126:244-7.
  83. Check WA. Folate for oral contraceptive users may reduce cervical cancer risk. J Am Med Assoc 1980;244:633-4.
  84. Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Cochrane Review). Cochrane Database Syst Rev 2000;2:CD000951.
  85. Berchtold P, Dahlqvist A, Gustafson A, Asp NG. Effects of a biguanide (metformin) on vitamin B12 and folic acid absorption and intestinal enzyme activities. Scand J Gastroenterol 1971;6:751-4.
  86. Aarsand AK, Carlsen SM. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. J Int Med 1998;244:169-74.
  87. Buysschaert M, Wallemacq PE, Dramais AS, Hermans MP. Hyperhomocysteinemia in type 2 diabetes. Diabetes Care 2000;23:1816-22.
  88. Russell RM, Krasinski SD, Samloff IM, et al. Folic acid malabsorption in atrophic gastritis: possible compensation by bacterial folate synthesis. Gastroenterology 1986;91:1476-82.
  89. Klipstein FA, Berlinger FG, Reed LJ. Folate deficiency associated with drug therapy for tuberculosis. Blood 1967;29:697-712.
  90. Frequin ST, Wevers RA, Braam M, et al. Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone. J Neurol 1993;240:305-8.
  91. Baggott JE, Morgan SL, Ha T, et al. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J 1992;282:197-202.
  92. Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid and aspirin. Blood 1971;38:405-16.
  93. Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-81.
  94. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
  95. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96.
  96. Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 1998;32:802-17.
  97. Dansky LV, Rosenblatt DS, Andermann E. Mechanisms of teratogenesis: folic acid and antiepileptic therapy. Neurology 1992;42:32-42.
  98. Hiilesmaa VK, Teramo K, Granstrom ML, Bardy AH. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J 1983;287:577-9.
  99. Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. New Engl J Med 1981;305:1513-7.
  100. Butterworth CE, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr 1982;35:73-82.
  101. Lawrence VA, Loewenstein JE, Eichner ER. Aspirin and folate binding: in vivo and in vitro studies of serum binding and urine excretion of endogenous folate. J Lab Clin Med 1984;103:944-8.
  102. Wong WY, Merkus HM, Thomas CM, et al. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril 2002;77:491-8.
  103. Botez MI, Peyronnard J, Berube L, Labrecque R. Relapsing neuropathy, cerebral atrophy and folate deficiency. Appl Neurophysiol 1979;42:171-83.
  104. Botez MI, Cadotte M, Beaulieu R, et al. Neurologic disorders responsive to folic acid therapy. Can Med Assoc J 1976;115:217-23.
  105. Smith AD. Homocysteine, B vitamins, and cognitive deficit in the elderly. Am J Clin Nutr 2002;75:785-6.
  106. Duthie SJ, Whalley LJ, Collins AR, et al. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002;75:908-13.
  107. Huang RF, Ho Y, Lin H, et al. Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells. J Nutr 1999;129:25-31.
  108. Shrubsole MJ, Jin F, Dai Q, et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 2001;61:7136-41.
  109. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 2001;153:680-7.
  110. Fuchs CS, Willett WC, Colditz GA, 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.
  111. Su LJ, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 2001;11:65-72.
  112. van der Dijs FP, Fokkema MR, Dijck-Brouwer DA, et al. Optimization of folic acid, vitamin B12, and vitamin B6 supplements in pediatric patients with sickle cell disease. Am J Hematol 2002;69:239-46.
  113. Thambyrajah J, Landray MJ, McGlynn FJ, et al. Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure? Circulation 2000;102:871-5.
  114. Stulc T, Melenovsky V, Grauova B, et al. Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy. Nutrition 2001;17:721-3.
  115. Stehouwer CD. Clinical relevance of hyperhomocysteinaemia in atherothrombotic disease. Drugs and Aging 2000;16:251-60.
  116. Mayer O, Simon J, Rosolova H, et al. The effects of folate supplementation on some coagulation parameter and oxidative status surrogates. Eur J Clin Pharmacol 2002;58:1-5.
  117. Bazzano LA, He J, Ogden LG, et al. Dietary intake of folate and risk of stroke in US men and women: NHANES I epidemiolgic follow-up study. Stroke 2002;33:1183-8.
  118. Loscalzo J. Folate and nitrate-induced endothelial dysfunction. A simple treatment for a complex pathobiology. Circulation 2001;104:1086-8.
  119. Gori T, Burstein JM, Ahmed S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance. Circulation 2001:104;1119-23.
  120. Pullin CH, Ashfield-Watt PA, Burr ML, et al. Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype. J Am Coll Cardiol 2001;38:1799-805.
  121. Woo KS, Chook P, Chan LL, et al. Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation. Am J Med 2002;112:535-9.
  122. Thambyrajah J, Landray MJ, Jones HJ, et al. A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease. J Am Coll Cardiol 2001;37:1858-63.
  123. Voutilainen S, Rissanen TH, Virtanen J, et al. Low dietary folate intake is associated with an excess incidence of acute coronary events. Circulation 2001;103:2674-80.
  124. Loria CM, Ingram DD, Feldman JJ, et al. Serum folate and cardiovascular disease mortality among US men and women. Arch Intern Med 2000;160:3258-62.
  125. Mangoni AA, Jackson SH. Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med 2002;112:556-65.
  126. Koebnick C, Heins UA, Hoffman I, et al. Folate status during pregnancy in women is improved by long-term high vegetable intake compared with the average western diet. J Nutr 2001;131:733-9.
  127. Nallamothu BK, Fendrick M, Rubenfire M, et al. Potential clinical and economic effects of homocyst(e)ine lowering. Arch Intern Med 2000;160:3406-12.
  128. Wald DS, Bishop L, Wald NJ, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med 2001;161:695-700.
  129. Vos E. Multivitamin supplements are effective and inexpensive agents to lower homocysteine levels. Arch Intern Med 2001;161:774-5.
  130. McKay DL, Perrone G, Rasmussen H, et al. Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. J Nutr 2000;130:3090-6.
  131. de Bree A, Verschuren WM, Blom HJ, Kromhout D. Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y. Am J Clin Nutr 2001;73:1027-33.
  132. Murua AL, Quintana I, Janson J, et al. Plasmatic homocysteine response to vitamin supplementation in elderly people. Thromb Res 2000;100:495-500.
  133. Rasmussen LB, Ovesen L, Bulow I, et al. Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women. Am J Clin Nutr 2000;72:1156-63.
  134. Fohr IP, Prinz-Langenohl R, Bronstrup A, et al. 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr 2002;75:275-82.
  135. Gregory JF. Case study: folate bioavailability. J Nutr 2001;131:1376S-1382S.
  136. Checkoway H, Powers K, Smith-Weller T, et al. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002;155:732-8.
  137. Sunder-Plassmann G, Fodinger M, Buchmayer H, et al. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study. J Am Soc Nephrol 2000;11:1106-16.
  138. Antony AC. Megaloblastic Anemias. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone 2000: 451-79.
  139. Russell RM, Golner BB, Krasinski SD, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med 1988;112:458-63.
  140. Schnyder G, Roffi M, Pin R, et al. Decreased rate of coronary stenosis after lowering of plasma homocysteine levels. N Engl J Med 2001;345:1593-600.
  141. Beaulieu AJ, Gohh RY, Han H, et al. Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients. Arterioscler Thromb Vasc Biol 1999;19:2918-21.
  142. Green TJ, Houghton LA, Donovan U, et al. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc 1998;98:49-55.
  143. Grace E, Emans SJ, Drum DE. Hematologic abnormalities in adolescents who take oral contraceptive pills. J Pediatrics 1982;101:771-4.
  144. Title LM, Cummings PM, Giddens K, et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758-65.
  145. Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med 1989;149:2501-3.
  146. Manns B, Hyndman E, Burgess E, et al. Oral vitamin B and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia. Kidney Int 2001;59:1103-9.
  147. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78.
  148. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002. Available at: www.nap.edu/books/0309072794/html/.
  149. Tremblay R, Bonnardeaux A, Geadah D, et al. Hyperhomocystinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins. Kidney Int 2000;58:851-8.
  150. Riddell LJ, Chisholm A, Williams S, Mann JI. Dietary strategies for lowering homocysteine concentrations. Am J Clin Nutr 2000;71:1448-54.
  151. Kauwell GP, Lippert BL, Wilsky CE, et al. Folate status of elderly women following moderate folate depletion responds only to a higher folate intake. J Nutr 2000;130:1584-90.
  152. Lashner BA. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J Cancer Res Clin Oncol 1993;119:549-54.
  153. Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn's disease. Correlation with disease activity. Dig Dis Sci 1993;38:1614-8.
  154. Nardini M, De Stefano R, Iannuccelli M, et al. Treatment of depression with L-5-hydroxytryptophan combined with chlorimipramine, a double-blind study. Int J Clin Pharmacol Res 1983;3:239-50.
  155. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline . Washington, DC: National Academy Press, 2000. Available at: http://books.nap.edu/books/0309065542/html/.
  156. Suitor CW, Bailey LB. Food folate vs synthetic folic acid: a comparison. J Am Diet Assoc 1999;99:285.
  157. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100:88-94.
  158. Fava M, Borus JS, Alpert JE, et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997;154:426-8.
  159. Ortega RM, Manas LR, Andres P, et al. Functional and psychic deterioration in elderly people may be aggravated by folate deficiency. J Nutr 1996;126:1992-9.
  160. Nelen WL, Blom HJ, Steegers EA, et al. Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obstet Gynecol 2000;95:519-24.
  161. Usui M, Matsuoka H, Miyazaki H, et al. Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clin Sci (Colch) 1999;96:235-9
  162. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000;71:993-8.
  163. Jacobson W, Saich T, Borysiewicz, LK, et al. Serum folate and chronic fatigue syndrome. Neurol 1993;43:2645-7.
  164. Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 2000;5:93-108.
  165. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52.
  166. Zimmerman J. Drug interactions in intestinal transport of folic acid and methotrexate. Further evidence for the heterogeneity of folate transport in the human small intestine. Biochem Pharmacol 1992;44:1839-42.
  167. Longsreth GF, Newcomer AD, Westbrook PR. Para-aminosalicylic acid-induced malabsorption. Am J Dig Dis 1972;17:731-4.
  168. Amer College of Rheumatology ad hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31.
  169. Joosten E, Pelemans W. Megaloblastic anaemia in an elderly patient treated with triamterene. Neth J Med 1991;38:209-11.
  170. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55.
  171. Glaxo-Wellcome, Inc. Daraprim package insert. Research Triangle Park, NC; August 1996.
  172. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  173. Taliani U, Camellini A, Bernardi P, et al. A clinical case of severe megaloblastic anemia during treatment with primidone. Acta Biomed Ateneo Parmense 1989;60:245-8.
  174. Grieco A, Caputo S, Bertoli A, et al. Megaloblastic anemia due to sulphasalazine responding to drug withdrawal alone. Postgrad Med J 1986;62:307-8.
  175. Logan EC, Williamson LM, Ryrie DR. Sulphasalazine associated pancytopenia may be caused by acute folate deficiency. Gut 1986;27:868-72.
  176. Krogh-Jensen M, Ekelund S, Svendsen L. Folate and homocysteine status and haemolysis in patients treated with sulphasalazine for arthritis. Scand J Clin Lab Invest 1996;56:421-9.
  177. Prasad AS, Lei KY, Moghissi KS, et al. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12 and folic acid. Am J Obstet Gynecol 1976;125:1063-9.
  178. Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34:1172-4.
  179. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-6.
  180. Leeb BF, Witzmann G, Ogris E, et al. Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients. Clin Exp Rheumatol 1995;13:459-63.
  181. Carpentier JL, Bury J, Luyckx A, et al. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187-90.
  182. Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med 1998;104:422-30.
  183. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9.
  184. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20.
  185. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6.
  186. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35.
  187. Kahn SB, Fein SA, Brodsky I. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 1968;9:550-60.
  188. Tonstad S, Silverstein M, Aksnes L, Ose L. Low dose colestipol in adolescents with familial hypercholesterolemia. Arch Dis Child 1996;74:157-60.
  189. Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4:423-40.
  190. West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut 1975;16:93-8.
  191. Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5.
  192. Gorbach SL. Bengt E. Gustafsson memorial lecture. Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30.
  193. Traccis S, Monaco F, Sechi GP, et al. Long-term therapy with carbamazepine: Effects on nerve conduction velocity. Eur Neurol 1983;22:410-6.
  194. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scan 1984;69:226-31.
  195. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82.
  196. Kishi T, Fujita N, Eguchi T, et al. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci 1997;145:109-12.
  197. Garabedian-Ruffalo SM, Ruffalo RL. Drug and nutrient interactions. Am Fam Physician 1986;33:165-74.
  198. Bostom AG, Garber C. Endpoints for homocysteine-lowering trials. Lancet 2000;355:511-2.
  199. Vermeulen EG, Stehouwer CD, Twisk JW, et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet 2000;355:517-22.
  200. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Dis 2000;60:121-31.
  201. US Food and Drug Administration, Center for Food Safety, and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Letter regarding dietary supplement health claim for folic acid with respect to neural tube defects. 2000. Available at: http://www.fda.gov/Food/LabelingNutrition/LabelClaims/ QualifiedHealthClaims/ucm073058.htm.
  202. Bostom AG, Shemin D, Bagley P, et al. Controlled comparison of L-5-Methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients. Circulation 2000;101:2829-32.
  203. Voutilainen S, Lakka TA, Porkkala-Sarataho E, et al. Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Clin Nutr 2000;54:424-8.
  204. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-27.
  205. Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
  206. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24.
  207. Ortiz Z, Shea B, Suarez-Almazor ME, et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol 1998;25:36-43.
  208. Morgan SL, Baggott JE, Vaughn WH, et al. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1990;33:9-18.
  209. Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41.
  210. Muggia FM, Synold TW, Newman EM, et al. Failure of pretreatment with intravenous folic acid to alter the cumulative hematologic toxicity of lometrexol. J Natl Cancer Inst 1996;88:1495-6.
  211. Brown WT, Cohen IL, Fisch GS, et al. High dose folic acid treatment of fragile (X) males. Am J Med Genet 1986;23:263-71.
  212. Hagerman RJ, Jackson AW, Levitas A, et al. Oral folic acid versus placebo in the treatment of males with the fragile X syndrome. Am J Med Genet 1986;23:241-62.
  213. Rosenblatt DS, Duschenes EA, Hellstrom FV, et al. Folic acid blinded trial in identical twins with fragile X syndrome. Am J Hum Genet 1985;37:543-52.
  214. Gillberg C, Wahlstrom J, Johansson R, et al. Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX). Dev Med Child Neurol 1986;28:624-7.
  215. Fisch GS, Cohen IL, Gross AC, et al. Folic acid treatment of fragile X males: a further study. Am J Med Genet 1988;30:393-9.
  216. Strom CM, Brusca RM, Pizzi WJ. Double-blind, placebo-controlled crossover study of folinic acid Leucovorin for the treatment of fragile X syndrome. Am J Med Genet 1992;44:676-82.
  217. Montes LF, Diaz ML, Lajous J, et al. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42.
  218. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol 1997;77:460-2.
  219. Pack AR, Thomson ME. Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. J Clin Periodontol 1980;7:402-14.
  220. Drew HJ, Vogel RI, Molofsky W, et al. Effect of folate on phenytoin hyperplasia. J Clin Periodontol 1987;14:350-6.
  221. Brown RS, Di Stanislao PT, Beaver WT, et al. The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study. Oral Surg Oral Med Oral Pathol 1991;70:565-8.
  222. Brattstrom LE, Israelsson B, Jeppsson JO, et al. Folic acid-an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988;48:215-21.
  223. Woodside JV, Yarnell JW, McMaster D, et al. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial. Am J Clin Nutr 1998;67:858-66.
  224. Landgren F, Israelsson B, Lindgren A, et al. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995;237:381-8.
  225. Brouwer IA, van Dusseldorp M, Thomas CM, et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 1999;69:99-104.
  226. Freudenheim JL, Graham S, Marshall JR, et al. Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 1991;20:368-74.
  227. Slattery ML, Schaffer D, Edwards SL, et al. Are dietary factors involved in DNA methylation associated with colon cancer? Nutr Cancer 1997;28:52-62.
  228. Baron JA, Sandler RS, Haile RW, et al. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst 1998;90:57-62.
  229. Tseng M, Murray SC, Kupper LL, Sandler RS. Micronutrients and the risk of colorectal adenomas. Am J Epidemiol 1996;144:1005-14.
  230. La Vecchia C, Braga C, Negri E et al. Intake of selected micronutrients and risk of colorectal cancer. Int J Cancer 1997;73:525-30.
  231. Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997;112:29-32.
  232. Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57:1098-102.
  233. Christensen B, Landaas S, Stensvold I, et al. Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction. Atherosclerosis 1999;147:317-26.
  234. Morrow LE, Grimsley EW. Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J 1999;92:866-70.
  235. Bostom AG, Gohh RY, Beaulieu AJ, et al. Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial. Ann Intern Med 1997;127:1089-92.
  236. Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-9.
  237. Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996.
  238. Woo KS, Chook P, Lolin YI, et al. Folic acid improves arterial endothelial function in adults with hyperhomocysteinemia. J Am Coll Cardiol 1999;34:2002-6.
  239. Carlsen SM, Folling I, Grill V, et al. Metformin increases total homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-7.
  240. McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
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