Uses of this Supplement
Cancer, Colorectal
Cancer, Lung
Rheumatoid Arthritis
  Supplements with Similar Uses
View List by Use
  Drugs that Interact
Tetracycline-containing Medications
  Drugs that Deplete this Substance
View List
  Supplements with Similar Side Effects
View List by Side Effect
  Learn More About
Look Up > Supplements > Vitamin B9 (Folic Acid)
Vitamin B9 (Folic Acid)
Dietary Sources
Commercial Preparations
Therapeutic Uses
Dosage Ranges and Duration of Administration
Side Effects/Toxicology


Folic acid functions with vitamin B12 in many genetic, metabolic, and nervous system processes. Folic acid helps protect against heart disease, birth defects, osteoporosis, and certain cancers. It is vital to DNA and RNA synthesis, and therefore is critical to cell division, maintenance of the genetic code, regulation of cell division, and transfer of inherited characteristics. As many as 15% of people may have a genetic mutation causing higher homocysteine levels. This results in an increased risk for heart disease, and, in women, increased risk of having children with neural tube defects. Folic acid is essential to protein metabolism, notably for its role in reducing homocysteine levels by converting it to methionine.

The Framingham Heart Study (1998) found that folic acid supplementation reduced homocysteine levels by about 25%. In 1998, researchers at the Harvard School of Public Health published data from the Nurses Health Study showing that intake of folic acid and vitamin B6 well above the current RDA reduced the risk of congestive heart disease (CHD) by about 30%. The study tracked 80,082 women over a 14-year period.

Deficiency of folic acid has been linked to several birth defects, including the neural tube defect spina bifida. Up to half of neural tube defects are believed to be preventable if women of childbearing age supplement their diet with folic acid. Adequate intake of folic acid should begin several weeks before and continue through at least the first four weeks of pregnancy. Women who have previously had a child with neural tube defect can reduce the risk of recurrence by about 70% through supplementation with up to 4 mg folic acid per day. Studies suggest that the levels of folic acid necessary to prevent neural tube defects are more easily derived from fortified foods and supplements than from natural food sources alone.

Increased homocysteine concentrations in the blood may also play a role in osteoporosis by interfering with collagen cross-linking, leading to a defective bone matrix. Folic acid helps produce neurotransmitters such as serotonin and dopamine. These regulate brain functions including mood, sleep, and appetite. Correcting folic acid deficiency has reversed mental or psychological symptoms in some, particularly in the elderly. Folic acid exerts a mild antidepressant effect. Supplementation optimizes the effect of the drug Prozac.

At particular risk for folate deficiency are the elderly, alcoholics, psychiatric patients, people taking certain medications, and women taking contraceptive pills. Folic acid is required for the formation of healthy red and white blood cells. Folic acid deficiency causes macrocytic anemia in which the red blood cells are fewer in number, larger in size, and contain less oxygen-carrying hemoglobin than normal cells. Folic acid deficiency may play a role in cancer development, particularly cancers of the cervix, lung, and colon, possibly through its action in DNA synthesis. In a study published in 1996, researchers examined the relationship between folate status and colorectal cancer in male smokers involved in the alpha-tocopherol beta-carotene (ATBC) study. Those with diets higher in folic acid had significantly reduced risk of colon cancer. Low blood levels of folic acid may increase the risk of cervical dysplasia. Low folic acid intake may also contribute to rheumatoid arthritis, constipation, cataracts, headaches, and infertility.

Dietary Sources
  • Liver
  • Lentils
  • Rice germ
  • Brewer's yeast
  • Soy flour
  • Black-eyed peas
  • Navy beans
  • Kidney beans
  • Peanuts
  • Spinach
  • Turnip greens
  • Lima beans
  • Whole wheat
  • Asparagus

Food processing (e.g., boiling, heating) can destroy folic acid. Food stored at room temperature for long periods can also lose its folic acid content.

As of January 1998, commercial grain products have been fortified with 140 mcg of folic acid per 100 g of grain product. This will result in an average increase in folic acid intake of 100 mcg per day.


Folic acid occurs in food in its unactivated form (folate).

B9 supplements are available as both folic acid and folinic acid (5-methyl-tetra-hydrofolate). While folic acid is the more stable compound, folinic acid is the most efficient at raising body stores.

Commercial Preparations

Folic acid is widely available in multivitamin and B-complex preparations. Standard over-the-counter preparations include 400 mcg and 800 mcg tablets. Prescription folic acid is available in 1 mg tablets in packages of 30, 100, 1,000, and UD 100, as injections of 5 mg/ml in 10 vials. Folinic acid is available as 5 mg, 15 mg and 25 mg tablets in 30s, 100s, and UD 50s. Injections (3 mg/ml) are available.

Therapeutic Uses
  • Supplementation indicated for women of childbearing age to prevent neural tube birth defects
  • Protects against heart disease and stroke
  • Protects against osteoporosis
  • Indicated for prevention and treatment of cervical dysplasia
  • Helps prevent cervical, lung, and colon cancer
  • May relieve depression
  • Indicated for mental or psychiatric symptoms in elderly
  • May improve acne
  • Supplementation indicated for individuals with AIDS
  • Indicated, with B12, for macrocytic anemia
  • Aids in the formation of healthy red blood cells, preventing macrocytic anemia
  • Indicated for candidiasis
  • Helps prevent and treat rheumatoid arthritis
  • May aid constipation
  • Adjunctive therapy of cataracts
  • May relieve headaches
  • Part of therapy for treatment of infertility
  • May decrease risk of stroke
  • Used in treatment of sickle-cell anemia

Dosage Ranges and Duration of Administration

The RDA for folic acid follows.

  • Infants under 6 months: 25 mcg
  • 6 to 12 months: 35 mcg
  • Children 1 to 3 years: 50 mcg
  • Children 4 to 6 years: 75 mcg
  • Children 7 to 10 years: 100 mcg
  • Male and female 11 to 14: 150 mcg
  • Males 15+: 400 mcg
  • Females 15+: 400 mcg
  • Pregnant females: 400 mcg
  • Lactating females: 280 mcg
  • Tolerable upper intake: 1,000 mcg/day

Side Effects/Toxicology

Folic acid toxicity is rare. High doses (>15 mg) can cause gastrointestinal disturbances, sleep problems, and allergic skin reactions.


Folic acid supplementation can mask vitamin B12 deficiency. Vitamin B12 deficiency can lead to irreversible neurological damage. Therefore, folic acid supplementation should always include vitamin B12.

High dosage folic acid supplementation should be used with extreme caution in those with epilepsy. It may increase seizure activity.


In a randomized, double-blind, placebo-controlled study, folic acid supplementation (27.5 mg/week for 53 weeks) in 79 patients with rheumatoid arthritis countered the adverse effects of methotrexate without compromising therapeutic efficacy (Morgan et al. 1994).


In one study, the bioavailability of tetracycline hydrochloride was reduced significantly by concomitant administration of vitamin B complex to healthy subjects (Omray 1981). Patients should be cautioned to take vitamin B complex supplements at different times from tetracycline.


Bendich A, Deckelbaum R, eds. Prevention Nutrition: The Comprehensive Guide for Health Professionals. Totowa, NJ: Humana Press; 1997.

Bronstrup A, Hages M, Prniz-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;68:1104-1110.

Cancers, Nutrition and Food. Washington, DC: World Cancer Research Fund/American Institute for Cancer Research; 1997.

Drug Facts and Comparisons 1999. Facts and Comparisons; 1998.

Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing. 1998;27:485-491.

Giles WH, Kittner SJ, Croft JB, Anda RF, Casper ML, Ford ES. Serum folate and risk for coronary heart disease: Results from a cohort of US adults. Ann Epidemiol. 1998;8:490-496.

Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part II: Improvement with folic acid. Ann Pharmacother. 1998;32:947-961.

Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998;338:1009-1015.

Morgan S, Baggott J, Vaughn W, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. Ann Intern Med. 1994;121:833-841.

Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long-term, low-dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol. 1998;25:441-446.

Murray MT. Encyclopedia of Nutritional Supplements. Rocklin, Calif: Prima Health; 1996.

Omray A. Evaluation of pharmacokinetic parameters of tetracylcine hydrochloride upon oral administration with vitamin C and vitamin B complex. Hindustan Antibiot Bull. 1981;23(VI):33-37.

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.

Reavley N. Vitamins etc. Melbourne, Australia: Bookman Press; 1998.

Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998;279:359-364.

Ringer D, ed. Physicians' Guide to Nutriaceuticals. St. Joseph, Mich: Nutritional Data Resources; 1998.

Watkins ML. Efficacy of folic acid prophylaxis for the prevention of neural tube defects. Ment Retard Dev Disab Res Rev. 1998;4:282-290.

Wolf PA. Prevention of stroke. Lancet. 1998;352 (suppl III):15-18.

Copyright © 2000 Integrative Medicine Communications

This publication contains information relating to general principles of medical care that should not in any event be construed as specific instructions for individual patients. The publisher does not accept any responsibility for the accuracy of the information or the consequences arising from the application, use, or misuse of any of the information contained herein, including any injury and/or damage to any person or property as a matter of product liability, negligence, or otherwise. No warranty, expressed or implied, is made in regard to the contents of this material. No claims or endorsements are made for any drugs or compounds currently marketed or in investigative use. The reader is advised to check product information (including package inserts) for changes and new information regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.