folic acid (generic name)
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SafetyDISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.
Avoid folic acid supplements if hypersensitive or allergic to any of the product ingredients.
Side Effects and Warnings
An intravenous loading dose of folic acid, vitamin B6, and vitamin B12 followed by oral administration of folic acid plus vitamin B6 and vitamin B12, taken daily after coronary stenting, might actually increase restenosis rates. Due to the potential for harm, this combination of vitamins should not be recommended for patients receiving coronary stents.
Erythema, urticaria, skin flushing, rash, and itching have been reported.
Nausea, bloating, flatulence, cramps, bitter taste, and diarrhea have been reported.
The color of urine may become more intense.
Folic acid may mask the symptoms of pernicious, aplastic, or normocytic anemias caused by vitamin B12 deficiency and may lead to neurological damage.
Irritability, excitability, general malaise, altered sleep patterns, vivid dreaming, overactivity, confusion, impaired judgment, increased seizure frequency, and psychotic behavior have been reported. Very high doses can cause significant central nervous system (CNS) side effects. Supplemental folic acid might increase seizures in people with seizure disorders, particularly in very high doses.
Anaphylaxis and bronchospasm have also been reported.
Pregnancy and Breastfeeding
Pregnancy: It is recommended that all women capable of becoming pregnant consume folate in order to reduce the risk of the fetus developing a neural tube defect. Folic acid supplementation in higher than recommended doses is categorized as FDA Pregnancy Category C.
Breastfeeding: Folic acid is present in the breast milk and is likely safe to use during breastfeeding under the supervision of a qualified healthcare provider.
Interactions with Drugs
Excessive use of alcohol increases the requirement for folic acid.
Aminosalicylic acid can reduce dietary folate absorption, worsening the folate deficiency often seen with active tuberculosis, or preventing its reversal during treatment. Megaloblastic anemia occurs rarely and usually when there are other contributing factors, such as concurrent vitamin B12 malabsorption. Patients being treated for tuberculosis may be advised to take folic acid supplements if their dietary folate intake is low.
Chronic use of large doses of antacids can reduce folic acid absorption, but this is likely only significant if dietary folate intake is very low. Maintenance of the recommended daily intake of folic acid in the diet is recommended.
Antibiotic therapy can disrupt the normal gastrointestinal (GI) flora, interfering with the absorption of folic acid. Folate supplements are not considered necessary.
Aspirin may decrease serum folate levels, especially with chronic large doses. It is suggested that folate is just being redistributed in the body rather than an actual folate deficiency; therefore folate supplementation is not considered necessary.
Carbamazepine (Tegretol®) can reduce serum folate levels, but megaloblastic anemia has not been reported. Pregnant women taking carbamazepine may be especially at risk from reduced folate levels.
Cholestyramine reduces folic acid absorption. It can lower serum and red blood cell folate levels in children taking large doses for several months. Maintenance of dietary folate intake is recommended.
Colestipol (Colestid®) can interfere with absorption of folic acid, and reduced serum folate levels may occur. Maintenance of dietary folate intake is recommended.
Cycloserine can reduce serum folate levels, and rare cases of megaloblastic anemia have occurred. Maintenance of dietary folate intake is recommended.
Limited data suggests that diuretics ("water pills") may increase excretion of folic acid. Reduced red blood cell folate levels, possibly contributing to increased homocysteine levels, a risk factor for cardiovascular disease, were found in one group of people taking diuretics for six months or longer. The need for folic acid supplementation during diuretic therapy requires further study before a firm recommendation can be made. Currently, maintenance of dietary folate intake is recommended.
Reduced serum and red blood cell folate levels can occur in some women taking conjugated estrogens (Premarin®), but this is unlikely in women with adequate dietary folate intake. Supplements are recommended only for those women with inadequate dietary intake or other conditions that contribute to folate deficiency, and for those diagnosed with, or at increased risk for, cervical dysplasia (due to family history for example).
Folic acid absorption from the small intestine is optimal at pH 5.5 to 6. The increased pH associated with the use of H2 blockers (such as cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®), and ranitidine (Zantac®)) may therefore reduce folic acid absorption, but this is probably only significant if dietary folate intake is very low. Another class of prescription drugs that may affect folic acid absorption is proton pump inhibitors (PPIs). These are used for reflux disease and ulcers and include esomeprazole (Nexium®), lansoprazole (Prevacid®), omeprazole (Prilosec®), pantoprazole (Protonix®), and rabeprazole (Aciphex®). Maintenance of dietary folate intake is recommended.
Reduced vitamin B12 and, to a lesser extent, folate levels occur in some people with diabetes and can contribute to hyperhomocysteinemia, which adds to their already increased risk of cardiovascular disease. The reduced folate levels seen in diabetics have been linked to metformin use in some cases, possibly as a result of reduced folic acid absorption. Symptomatic folate deficiency is unlikely to occur with metformin, but people with diabetes may need folic acid supplements to reduce hyperhomocysteinemia. Diabetes should be treated by a qualified healthcare provider.
Methotrexate is a folate antagonist that prevents the conversion of folic acid to its active form, and lowers plasma and red blood cell folate levels. Folic acid supplements reduce side effects without reducing the efficacy of methotrexate in treating rheumatoid arthritis or psoriasis. Patients being treated with methotrexate for cancer should avoid folic acid supplements, unless recommended by their oncologist. Folic acid could interfere with the anticancer effects of methotrexate.
Chronic cigarette smoking is associated with diminished folate status.
Folate-dependent enzymes have been inhibited in laboratory experiments by certain NSAIDs (ibuprofen (Advil®, Motrin®, Nuprin®), naproxen (Anaprox®, Aleve®), indomethacin (Indocin®), and sulindac (Clinoril®). Clinical significance is unknown.
Reduced folate levels can occur in some people taking pancreatic extracts (such as Pancrease®, Cotazym®, Viokase®, Creon®, Ultrase®) possibly due to reduced absorption. Folate levels should be checked in patients taking pancreatic enzymes for prolonged periods.
Pentamidine is a prescription drug used to treat Pneumocystis carinii pneumonia (PCP). Decreased serum folate levels and megaloblastic bone marrow changes can occur rarely with prolonged intravenous pentamidine (Pentacarinat®, Pentam 300®) therapy. Most patients are unlikely to need folic acid supplements.
Phenobarbital (Luminal®) and primidone (Mysoline®) can reduce serum folate levels, occasionally leading to megaloblastic anemia (usually in people with low dietary folate intake), and possibly contributing to neurological side effects, mental changes, and cerebral atrophy. Pregnant women taking phenobarbital or primidone may be especially at risk from reduced folate levels. Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital or primidone and worsening seizure control. Folic acid may increase metabolism of phenobarbital. Seizure activity should be monitored closely.
Pyrimethamine (Daraprim®) is a folate antagonist that prevents conversion of folic acid to its active form. Patients taking pyrimethamine should avoid folic acid supplements since they can antagonize the therapeutic effects against Toxoplasmosis and Pneumocystis carinii pneumonia. Patients taking lower doses of pyrimethamine for prolonged periods should maintain the recommended dietary folate intake and monitored for folate deficiency. Folic acid does not antagonize the effects of pyrimethamine in the treatment of malaria. Folinic acid may be used as an alternative to folic acid when indicated. Pyrimethamine also reduces serum folate levels.
One study found that administration of folic acid to pregnant women might not interfere with the protective effect of sulfadoxine/pyrimethamine combination when used for intermittent preventative treatment of malaria.
Sulfasalazine inhibits absorption and metabolism of folic acid. Patients on chronic sulfasalazine therapy may be advised to increase their dietary folate intake, and to take a supplement if they have any other condition, which could also contribute to deficiency.
Triamterene (Dyrenium®) is a folate antagonist that prevents conversion of folic acid to its active form, and also reduces folate absorption. Reduced serum and red blood cell folate levels have occurred, and occasional cases of megaloblastic anemia, usually in people with other conditions contributing to folate deficiency. Patients on chronic triamterene therapy should to maintain the recommended dietary folate intake, or take a supplement if advised by their physician.
There is a general belief that folic/folinic acid supplements do not interfere with the therapeutic effects of trimethoprim. However, this view has been challenged, and failure of trimethoprim therapy has occurred rarely when folinic acid is given concurrently.
Interactions with Herbs and Dietary Supplements
Reduced serum and red blood cell folate levels can occur in some women taking conjugated estrogens (Premarin®) or birth control pills, but this is unlikely in women with adequate dietary folate intake. Theoretically this interaction may occur with estrogenic herbs and supplements as well.
Taking folic acid along with vitamin B12 may increase the risk of vitamin B12 deficiency. Caution is advised when taking both of these vitamins together.
Normal supplemental doses of folic acid are unlikely to have an adverse effect on zinc balance in people with adequate dietary zinc intake. The data on the effects of supplemental folic acid on dietary zinc absorption are conflicting.