Vitamins >> Vitamin B9 (Folic acid) Safety

Toxicity

No adverse effects have been associated with the consumption of excess folate from foods.  Concerns regarding safety are limited to synthetic folic acid intake. Deficiency of vitamin B₁₂, though often undiagnosed, may affect a significant number of people, especially older adults (see Vitamin B₁₂).  One symptom of vitamin B₁₂ deficiency is megaloblastic anemia, which is indistinguishable from that associated with folate deficiency.  Large doses of folic acid given to an individual with an undiagnosed vitamin B₁₂ deficiency could correct megaloblastic anemia without correcting the underlying vitamin B₁₂ deficiency, leaving the individual at risk of developing irreversible neurologic damage. Most cases of this sort of neurologic progression in vitamin B₁₂ deficiency have been seen at doses of folic acid of 5,000 mcg (5 mg) and above. In order to be very sure of preventing irreversible neurological damage in B₁₂ deficient individuals, the Food and Nutrition Board of the Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1,000 mcg (1 mg daily).  The board also noted that vitamin B₁₂ deficiency is very rare in women in their childbearing years, making the consumption of folic acid at or above 1000 mcg/day unlikely to cause problems, although there is limited data on the effects of large doses.

*Source of intake should be from food and formula only.

Drug interactions

When taken in very large therapeutic dosages, for example in the treatment of severe arthritis, nosteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen may interfere with the metabolism of folate.  Routine low dose use of NSAIDs has not been found to adversely affect folate status.  The anticonvulsant, phenytoin, has been shown to inhibit the intestinal absorption of folate, and several studies have associated decreased folate status with long-term use of the anti-convulsants, phenytoin, phenobarbital, and primidone.  However, few studies controlled for differences in folate intake between anticonvulsant users and nonusers. Taking folic acid at the same time as the cholesterol-lowering agents, cholestyramine and colestipol, may decrease the absorption of folic acid. Methotrexate is a folic acid antagonist used to treat a number of diseases, including rheumatoid arthritis and psoriasis.  Some of the side effects of methotrexate are similar to those of severe folate deficiency, and increased dietary folate or supplemental folic acid may decrease side effects without reducing the efficacy of methotrexate.  A number of other medications have been shown to have antifolate activity, including trimethoprim (an antibiotic), pyrimethanine (an antimalarial), triamterene (a blood pressure medication), and sulfasalazine (a treatment for ulcerative colitis).  Early studies of oral contraceptives (birth control pills) containing high doses of estrogen indicated an adverse effect on folate status, which has not been supported by more recent studies on low dose oral contraceptives, in which dietary folate was controlled.

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