Safety Issues

How safe is folic acid?

Folic acid has few safety concerns associated with it. Like vitamin C, it is water soluble and excess is excreted in the urine, which helps to limit its toxicity. Nevertheless, recommended doses should not be exceeded unnecessarily.

The primary concern for the general population is that folic acid may affect undiagnosed vitamin B12 deficiency. As a result, a tolerable upper intake level (UL) of 1 mg daily has been set for folic acid obtained from either supplements or fortified foods. ⁵² A prescription is necessary for folic acid supplements in excess of 1 mg per daily dose to ensure physician assessment of the vitamin B12 status of the individual.

Folic acid may interfere with the metabolism of medications, including anticonvulsants, antineoplastic agents that interfere with folic acid metabolism, oral contraceptives and others.

How do I identify patients who mayhave vitamin B12 deficiency?

Clinical symptoms of vitamin B12 deficiency include tiredness, easy fatiguability, chronic malaise, sore tongue, ataxic gait, particularly in the dark, and numbness of the fingers. Patients with signs of red crack tongue, peripheral neuropathy, ataxia, pallor and other signs of anemia should be investigated for B12 deficiency.

One of the concerns of recommending daily folic acid supplementation, in particular dosages exceeding 1.0 mg/ day, is the potential for an undetected vitamin B12 deficiency. Folic acid can mask B12 deficiency by correcting the megaloblastic anemia changes normally identifiable on routine hematologic panels, but it does not prevent the neurological complications of B12 deficiency. There is the added concern that high doses of folic acid may precipitate or exacerbate B12 deficiency neurological symptoms.

A prudent physician needs to keep in mind the possibility of a vitamin B12 deficiency. Routine dietary interviews can help detect vegetarians and those excluding fresh fruits and vegetables and liver from their diets. A greater level of suspicion is needed to identify individuals with occult pernicious anemia, celiac sprue and related disorders. Inflammatory bowel disease, diabetes mellitus and gastrocolonic bypass treatment for obesity are examples of disorders for which patients are at risk of B12 deficiency.

All women given high dose folic acid (i. e. > 1.0 mg/ day) need to be evaluated for possible vitamin B12 deficiency. Women taking folic acid supplements at < 1.0 mg/ day without multivitamins that include B12 who are vegetarians, have underlying health concerns limiting absorption of micronutrients, or have related concerns should be assessed for B12 deficiency.

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