Topic Contents

Folic Acid

Uses

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

This supplement has been used in connection with the following health conditions:

Used for	Why
3 Stars Abnormal Pap Smear 10 mg daily under medical supervision	Large amounts of folic acid have been shown to improve the abnormal Pap smears of some women who are taking birth control pills. Large amounts of folic acid —10 mg per day—have been shown to improve the abnormal Pap smears of women who are taking birth control pills.¹ Folic acid does not improve the Pap smears of women who are not taking oral contraceptives.² ^{, 3} High blood levels of folate (the food form of folic acid) have been linked to protection against the development of cervical dysplasia but these higher levels may only be a marker for eating more fruit and vegetables.⁴ ^{, 5}
3 Stars Birth Defects At least 400 mcg daily	Supplementing with folic acid before and during the early weeks of pregnancy dramatically reduces the risk of neural tube defects. Several studies and clinical trials have shown that 50% or more of NTDs can be prevented if women consume a folic acid -containing supplement before and during the early weeks of pregnancy.⁶ ^{, 7} The United States Department of Public Health, the Centers for Disease Control and Prevention (CDC), and the March of Dimes recommend that all women who are capable of becoming pregnant supplement with 400 mcg folic acid daily. Daily supplementation prior to pregnancy is necessary because most pregnancies in the United States are unplanned⁸ and the protective effect of folic acid occurs in the first four weeks of fetal development,⁹ before most women know they are pregnant. For women who have had a previous NTD-affected pregnancy, the CDC recommends daily supplementation with 4,000 mcg per day of folic acid. In a preliminary study, this amount of supplemental folic acid before and during early pregnancy resulted in a 71% reduction in the recurrence rate of NTDs.¹⁰
3 Stars Depression and Folic Acid Deficiency See a doctor for evaluation	Taking folic acid can help correct deficiencies associated with depression. A deficiency of the B vitamin folic acid can also disturb mood. A large percentage of depressed people have low folic acid levels.¹¹ Folic acid supplements appear to improve the effects of lithium in treating manic-depressives.¹² Depressed alcoholics report feeling better with large amounts of a modified form of folic acid.¹³ Anyone suffering from chronic depression should be evaluated for possible folic acid deficiency by a doctor. Those with abnormally low levels of folic acid are sometimes given short-term, high amounts of folic acid (10 mg per day).
3 Stars High Homocysteine (Vitamin B12, Vitamin B6) 400 to 1,000 mcg of folic acid daily, 10 to 50 mg of vitamin B6 daily, and 50 to 300 mcg of vitamin B12 daily	Vitamin B6, folic acid, and vitamin B12 all play a role in converting homocysteine to other substances within the body and have consistently lowered homocysteine levels in trials. Vitamin B6 , folic acid , and vitamin B12 all play a role in converting homocysteine to other substances within the body. By so doing, they consistently lower homocysteine levels in research trials,¹⁴ ^{, 15} ^{, 16} a finding that is now well accepted. Several studies have used (and some doctors recommend) 400–1,000 mcg of folic acid per day, 10–50 mg of vitamin B6 per day, and 50–300 mcg of vitamin B12 per day. Of these three vitamins, folic acid supplementation lowers homocysteine levels the most for the average person.¹⁷ ^{, 18} It also effectively lowers homocysteine in people on kidney dialysis.¹⁹ In 1996, the FDA required that all enriched flour, rice, pasta, cornmeal, and other grain products contain 140 mcg of folic acid per 3½ ounces.²⁰ This level of fortification has led to a measurable decrease in homocysteine levels.²¹ However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,²² suggesting that the FDA-mandated supplementation is inadequate to optimally protect people against high homocysteine levels. Therefore, people wishing to lower their homocysteine levels should continue to take folic acid supplements despite the FDA-mandated fortification program.
3 Stars Pregnancy and Postpartum Support 800 mcg daily, beginning before pregnancy	Supplementing with folic acid protects against the formation of birth defects, such as spina bifida. It also may lead to few infections for mothers and higher birth weight for babies. Most doctors, many other healthcare professionals, and the March of Dimes recommend that all women of childbearing age supplement with 400 mcg per day of folic acid . Such supplementation could protect against the formation of neural tube defects (such as spina bifida) during the time between conception and when pregnancy is discovered. The requirement for the B vitamin folic acid doubles during pregnancy, to 800 mcg per day from all sources.²³ Deficiencies of folic acid during pregnancy have been linked to low birth weight²⁴ and to an increased incidence of neural tube defects (e.g., spina bifida) in infants. In one study, women who were at high risk of giving birth to babies with neural tube defects were able to lower their risk by 72% by taking folic acid supplements prior to and during pregnancy.²⁵ Several preliminary studies have shown that a deficiency of folate in the blood may increase the risk of stunted growth of the fetus.²⁶ ^{, 27} ^{, 28} ^{, 29} ^{, 30} ^{, 31} ^{, 32} ^{, 33} This does not prove, however, that folic acid supplementation results in higher birth weights. Although some trials have found that folic acid and iron , when taken together, have improved birth weights,³⁴ ^{, 35} ^{, 36} ^{, 37} other trials have found supplementation with these nutrients to be ineffective.³⁸ ^{, 39} ^{, 40} The relationship between folate status and the risk of miscarriage is also somewhat unclear. In some studies, women who have had habitual miscarriages were found to have elevated levels of homocysteine (a marker of folate deficiency).⁴¹ ^{, 42} ^{, 43} ^{, 44} In a preliminary study, 22 women with recurrent miscarriages who had elevated levels of homocysteine were treated with 15 mg per day of folic acid and 750 mg per day of vitamin B6 , prior to and throughout their next pregnancy. This treatment reduced homocysteine levels to normal and was associated with 20 successful pregnancies.⁴⁵ It is not known whether supplementing with these vitamins would help prevent miscarriages in women with normal homocysteine levels. As the amounts of folic acid and vitamin B6 used in this study were extremely large and potentially toxic, this treatment should be used only with the supervision of a doctor. In other studies, however, folate levels did not correlate with the incidence of habitual miscarriages.⁴⁶ ^{, 47} ^{, 48} Preliminary⁴⁹ and double-blind⁵⁰ evidence has shown that women who use a multivitamin-mineral formula containing folic acid beginning three months before becoming pregnant and continuing through the first three months of pregnancy have a significantly lower risk of having babies with neural tube defects (e.g., spina bifida) and other congenital defects. In addition to achieving significant protection against birth defects, women who take folic acid supplements during pregnancy have been reported to have fewer infections, and to give birth to babies with higher birth weights and better Apgar scores. ⁵¹ (An Apgar score is an evaluation of the well-being of a newborn, based on his or her color, crying, muscle tone, and other signs.) However, if a woman waits until after discovering her pregnancy to begin taking folic acid supplements, it will probably be too late to prevent a neural tube defect.
3 Stars Schizophrenia and Folic Acid Deficiency If deficient: 10 to 20 mg a day under medical supervision	People with schizophrenia may have a tendency to be deficient in folic acid and they may see improvements when given supplements. People with schizophrenia may have a greater tendency to be deficient in folic acid than the general population,⁵² and they may show improvement when given supplements. A preliminary trial found that, among schizophrenic patients with folic acid deficiency, those given folic acid supplements had more improvement, and shorter hospital stays than those not given supplements.⁵³ In a double-blind trial, a very high amount of folic acid (15 mg daily) was given to schizophrenic patients being treated with psychiatric medications who had low or borderline folic acid levels. The patients receiving the folic acid supplements had significant improvement, which became more significant over the six-month course of the trial.⁵⁴ The symptoms of folic acid deficiency can be similar to those of schizophrenia, and two cases of wrong “schizophrenia” diagnoses have been reported.⁵⁵ ^{, 56} In one of these cases, an initial supplement of 20 mg daily of folic acid and a maintenance supplemental intake of 10 mg daily, led to resolution of symptoms.⁵⁷
2 Stars Age-Related Cognitive Decline 800 mcg per day	Folic acid has been shown to slow the rate of cognitive decline in people with high homocysteine levels. In a double-blind trial, elderly people with high homocysteine levels received 800 mcg of folic acid per day or a placebo for three years. Compared with placebo, folic acid supplementation significantly slowed the rate of decline of memory and of other measures of cognitive function.⁵⁸ Supplementation with homocysteine-lowering B vitamins (folic acid, vitamin B12, and vitamin B6) also slowed the rate of brain atrophy in elderly people who had mild cognitive impairment and high homocysteine levels.⁵⁹ Preliminary evidence suggests that B vitamins may not slow cognitive decline in people with normal homocysteine levels.
2 Stars Atherosclerosis Consult a qualified healthcare practitioner	Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research. Taking folic acid may help lower homocysteine levels. Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research,⁶⁰ ^{, 61} though uncertainty remains about whether elevated homocysteine actually causes heart disease.⁶² ^{, 63} Although some reports have found associations between homocysteine levels and dietary factors, such as coffee and protein intakes,⁶⁴ evidence linking specific foods to homocysteine remains preliminary. Higher blood levels of vitamin B6 , vitamin B12 , and folic acid are associated with low levels of homocysteine⁶⁵ and supplementing with these vitamins lowers homocysteine levels.⁶⁶ ^{, 67} While several trials have consistently shown that B6, B12, and folic acid lower homocysteine, the amounts used vary from study to study. Many doctors recommend 50 mg of vitamin B6, 100–300 mcg of vitamin B12, and 500–800 mcg of folic acid. Even researchers finding only inconsistent links between homocysteine and heart disease have acknowledged that a B vitamin might offer protection against heart disease independent of the homocysteine-lowering effect.⁶⁸ In one trial, people with normal homocysteine levels had demonstrable reversal of atherosclerosis when supplementing B vitamins (2.5 mg folic acid, 25 mg vitamin B6, and 250 mcg of vitamin B12 per day).⁶⁹ Similar results were seen in another study.⁷⁰ In another study, supplementing with 5 mg per day of folic acid for 18 months reversed atherosclerosis in the carotid artery (an artery that supplies the brain) in people who had one or more risk factors for cardiovascular disease.⁷¹ For the few cases in which vitamin B6, vitamin B12, and folic acid fail to normalize homocysteine, adding 6 grams per day of betaine (trimethylglycine) may be effective.⁷² Of these four supplements, folic acid appears to be the most important.⁷³ Attempts to lower homocysteine by simply changing the diet rather than by using vitamin supplements have not been successful.⁷⁴
2 Stars Breast Cancer 400 mcg daily	For women who drink alcohol, folic acid may reduce breast cancer risk by reversing the damaging effect alcohol has on DNA. Among women who drink alcohol, those who consume relatively high amounts of folate from their diet have been reported to be at reduced risk of breast cancer, compared with women who drink alcohol but consumed less folate, according to a preliminary study.⁷⁵ In a similar report, consumption of folic acid-containing supplements was associated with a lower risk of breast cancer in women who drank alcohol, compared with women who drank alcohol but did not take such supplements.⁷⁶ The damaging effect alcohol has on DNA—the material responsible for normal replication of cells—is partially reversed by folic acid. Therefore, a potential association between both dietary folate and folic acid supplements and protection against breast cancer in women who drink alcohol is consistent with our understanding of the biochemical effects of these substances. A combined intake from food and supplements of at least 600 mcg per day was associated with a 43% reduced risk of breast cancer in women who consumed 1.5 drinks per day or more, compared with women who drank the same amount but did not take folic acid-containing supplements.⁷⁷ No research has yet explored the effect of folic acid supplementation in people who have already been diagnosed with cancer. Cancer patients taking the chemotherapy drug methotrexate must not take folic acid supplements without the direction of their oncologist.
2 Stars Celiac Disease Consult a qualified healthcare practitioner	The malabsorption that occurs in celiac disease can lead to multiple nutritional deficiencies. Supplementing with folic acid may correct a deficiency. The malabsorption that occurs in celiac disease can lead to multiple nutritional deficiencies. The most common nutritional problems in people with celiac disease include deficiencies of essential fatty acids, iron , vitamin D , vitamin K , calcium , magnesium , and folic acid .⁷⁸ Zinc malabsorption also occurs frequently in celiac disease⁷⁹ and may result in zinc deficiency, even in people who are otherwise in remission.⁸⁰ People with newly diagnosed celiac disease should be assessed for nutritional deficiencies by a doctor. Celiac patients who have not yet completely recovered should supplement with a high-potency multivitamin-mineral . Some patients may require even higher amounts of some of these vitamins and minerals—an issue that should be discussed with their healthcare practitioner. Evidence of a nutrient deficiency in a celiac patient is a clear indication for supplementation with that nutrient. After commencement of a gluten-free diet, overall nutritional status gradually improves. However, deficiencies of some nutrients may persist, even in people who are strictly avoiding gluten. For example, magnesium deficiency was found in 8 of 23 adults with celiac disease who had been following a gluten-free diet and were symptom-free. When these adults were supplemented with magnesium for two years, their bone mineral density increased significantly.⁸¹
2 Stars Celiac Disease (Vitamin B6, Vitamin B12) 3 mg vitamin B6, 0.8 mg folic acid, and 0.5 mg vitamin B12	Daily supplementation with a combination of vitamin B6 (3 mg), folic acid (0.8 mg), and vitamin B12 (0.5 mg) have been shown to help relieve depression in people with celiac disease. In one trial, 11 people with celiac disease suffered from persistent depression despite being on a gluten-free diet for more than two years. However, after supplementation with vitamin B6 (80 mg per day) for six months, the depression disappeared.⁸² Daily supplementation with a combination of vitamin B6 (3 mg), folic acid (0.8 mg), and vitamin B12 (0.5 mg) for 6 months also improved psychological well-being in people with long-standing celiac disease who had poor psychological well-being despite being on a strict gluten-free diet.⁸³
2 Stars Colon Cancer 400 mcg daily	Folic acid appears to be effective against colon cancer, especially in people with ulcerative colitis, people who drink alcohol, and people in remission from colon cancer. People with ulcerative colitis (UC) are at increased risk for colon cancer. Many patients with this disease take the drug sulfasalazine , which depletes folic acid.⁸⁴ In a preliminary report, patients with long-standing UC who took folic acid supplements (at least 400 mcg per day) had a 62% lower incidence of colon cancer or precancerous changes in the colon, compared with those who did not supplement with folic acid.⁸⁵ Although this difference was not statistically significant, the researchers recommended that people who take sulfasalazine should supplement with folic acid to potentially reduce the risk of colon cancer.⁸⁶ As dietary folate increases, the risks of precancerous polyps in the colon⁸⁷ and colon cancer itself decrease, according to some,⁸⁸ but not all, reports.⁸⁹ In one study, women who had taken folic acid supplements had a statistically significant 75% reduction in the risk of colon cancer, compared with women not taking folic acid supplements, but only when they had been supplementing with folic acid for more than 15 years.⁹⁰ In another report, the association between dietary folate and protection from precancerous polyps grew much stronger when use of folic acid supplements was considered (as opposed to studying only folate intake from food).⁹¹ However, one double-blind study found that supplementing with 1 mg of folic acid per day for three to eight years did not prevent recurrences of precancerous polyps in people who had already had at least one polyp.⁹² The protection from colon cancer associated with high intake of folate has been reported to occur more in consumers of alcohol than in nondrinkers.⁹³ This finding fits well with evidence that folate reverses damage to DNA caused by alcohol consumption.⁹⁴ Damaged DNA can lead to abnormal cellular replication—a step toward cancer. Some nutritionally oriented doctors recommend folic acid supplementation for prevention of recurrences in patients who formerly had colon cancer but are now in complete remission. However, no research has yet explored the effect of folic acid supplementation in people who have already been diagnosed with cancer. Cancer patients taking the chemotherapy drug methotrexate must not take folic acid supplements without the direction of their oncologist.
2 Stars Halitosis and Gum Disease Use 5 ml twice per day of a 0.1% solution	Folic acid is often recommended by doctors to help prevent and treat periodontitis and has been shown to reduce the severity of gingivitis when taken as a mouthwash. Nutritional supplements recommended by some doctors for prevention and treatment of periodontitis include vitamin C (people with periodontitis are often found to be deficient),⁹⁵ vitamin E , selenium , zinc, coenzyme Q10 , and folic acid .⁹⁶ Folic acid has also been shown to reduce the severity of gingivitis when taken as a mouthwash.⁹⁷
2 Stars Heart Attack 500 to 800 mcg daily	Taking folic acid may reduce blood levels of homocysteine. High homocysteine levels have been linked to an increased heart attack risk. High blood levels of the amino acid homocysteine have been linked to an increased risk of heart attack in most,⁹⁸ ^{, 99} ^{, 100} ^{, 101} though not all,¹⁰² ^{, 103} studies. A blood test screening for levels of homocysteine, followed by supplementation with 400 mcg of folic acid and 500 mcg of vitamin B12 per day could prevent a significant number of heart attacks, according to one analysis.¹⁰⁴ Folic acid ¹⁰⁵ ^{, 106} and vitamins B6 and B12 are known to lower homocysteine.¹⁰⁷ There is a clear association between low blood levels of folate and increased risk of heart attacks in men.¹⁰⁸ Based on the available research, some doctors recommend 50 mg of vitamin B6, 100–300 mcg of vitamin B12, and 500–800 mcg of folic acid per day for people at high risk of heart attack.
2 Stars Intermittent Claudication (Alpha-Linolenic Acid, Fish Oil, Oleic Acid, Vitamin B6, Vitamin E) 200 mg of EPA and 130 mg of DHA daily, plus small amounts of vitamin B6, folic acid, vitamin E, oleic acid, and alpha-linolenic acid	In one study, men with intermittent claudication who drank a milk product fortified with fish oil, vitamin B6, folic acid, vitamin E, oleic acid, and alpha-linolenic acid could walk further without pain than those who drank regular milk. Men with intermittent claudication consumed a fortified milk product or regular milk daily for one year. The fortified product provided daily 130 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid (EPA and DHA, two fatty acids in fish oil ), small amounts of supplemental vitamin E , folic acid , and vitamin B6 , and additional amounts of oleic acid and alpha-linolenic acid. Compared with regular milk, the fortified milk product significantly increased the distance the participants could walk before the onset of pain .¹⁰⁹
2 Stars Macular Degeneration (Vitamin B6, Vitamin B12) 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12	In a double-blind study of female health professionals who had cardiovascular disease or risk factors, daily supplementation with folic acid, vitamin B6, and vitamin B12 significantly decreased age-related macular degeneration. In a double-blind study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 7.3 years significantly decreased the incidence of age-related macular degeneration.¹¹⁰
2 Stars Migraine Headache (For a subset of people ) 5 mg per day	Taking folic acid may improve migraines in people with high homocysteine levels and a certain genetic characteristic. In a preliminary trial, supplementation with 5 mg of folic acid per day for six months completely eliminated recurrent migraine attacks in 10 of 16 children and reduced the number of attacks by 50 to 75% in the other six children. The children selected to be in this study had elevated homocysteine levels (which can be reduced by folic acid supplementation), as well as a certain genetic characteristic known as a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene.¹¹¹ Further research is needed to determine whether folic acid supplementation would be beneficial for migraine patients who do not have these specific characteristics.
2 Stars Osteoporosis and High Homocysteine 5 mg with 1,500 mcg of vitamin B12 daily	Homocystinuria, a condition associated with high homocysteine levels, frequently causes osteoporosis. By lowering homocysteine levels, folic acid may help prevent osteoporosis. Folic acid , vitamin B6 , and vitamin B12 are known to reduce blood levels of the amino acid homocysteine, and homocystinuria, a condition associated with high homocysteine levels, frequently causes osteoporosis. Therefore, some researchers have suggested that these vitamins might help prevent osteoporosis by lowering homocysteine levels.¹¹² In a double-blind study of people who had suffered a stroke and had high homocysteine levels, daily supplementation with 5 mg of folic acid and 1,500 mcg of vitamin B12 for two years reduced the incidence of fractures by 78%, compared with a placebo.¹¹³ The reduction in fracture risk appeared to be due to an improvement in bone quality, rather than to a change in bone mineral density. However, supplementation with these vitamins did not reduce fracture risk in people who had only mildly elevated homocysteine levels and relatively high pretreatment folic acid levels.¹¹⁴ For the purpose of lowering homocysteine, amounts of folic acid and vitamins B6 and B12 found in high-potency B-complex supplements and multivitamins should be adequate.
2 Stars Preeclampsia 5 mg daily	Supplementing with folic acid and vitamin B6 may lower homocysteine levels. Elevated homocysteine damages the lining of blood vessels and can lead to the preeclamptic symptoms. Women with preeclampsia have been shown to have elevated blood levels of homocysteine .¹¹⁵ ^{, 116} ^{, 117} ^{, 118} Research indicates elevated homocysteine occurs prior to the onset of preeclampsia.¹¹⁹ Elevated homocysteine damages the lining of blood vessels,¹²⁰ ^{, 121} ^{, 122} ^{, 123} ^{, 124} ^{, 125} ^{, 126} which can lead to the preeclamptic signs of elevated blood pressure , swelling, and protein in the urine.¹²⁷ In one preliminary trial, women with a previous pregnancy complicated by preeclampsia and high homocysteine supplemented with 5 mg of folic acid and 250 mg of vitamin B6 per day, successfully lowering homocysteine levels.¹²⁸ In another trial studying the effect of vitamin B6 on preeclampsia incidence, supplementation with 5 mg of vitamin B6 twice per day significantly reduced the incidence of preeclampsia. Women in that study were not, however, evaluated for homocysteine levels.¹²⁹ In fact, no studies have yet determined whether lowering elevated homocysteine reduces the incidence or severity of preeclampsia. Nevertheless, despite a lack of proof that elevated homocysteine levels cause preeclampsia, many doctors believe that pregnant women with elevated homocysteine should attempt to reduce those levels to normal.
2 Stars Schizophrenia and High Homocysteine (Vitamin B12, Vitamin B6) Take folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (400 mcg) daily	People with schizophrenia who have high homocysteine levels may improve symptoms by supplementing with folic acid, vitamin B6, and vitamin B12. In another double-blind study, daily supplementation with folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (400 mcg) for three months improved symptoms of schizophrenia compared with a placebo.¹³⁰ All of the participants in this study had elevated blood levels of homocysteine, which can be decreased by taking these three B vitamins. Based on this study, it would seem reasonable to measure homocysteine levels in people with schizophrenia and, if they are elevated, to supplement with folic acid, vitamin B6, and vitamin B12.
2 Stars Sickle Cell Anemia and High Homocysteine Consult a qualified healthcare practitioner	In one trial, patients with sickle cell anemia who were given folic acid plus aged garlic extract, vitamin C, and vitamin E saw significant improvement and less painful crises. In a preliminary trial, 20 patients with sickle cell anemia were given either 1 mg of folic acid per day or folic acid plus 6 grams of aged garlic extract, 6 grams of vitamin C, and 1,200 mg of vitamin E per day for six months.¹³¹ Patients taking the combination had a significant improvement in their hematocrit (an index of anemia) and less painful crises than those taking just folic acid. Preliminary research has found that patients with sickle cell anemia are more likely to have elevated blood levels of homocysteine compared to healthy people.¹³² ^{, 133} Elevated homocysteine is recognized as a risk factor for cardiovascular disease .¹³⁴ In particular, high levels of homocysteine in sickle cell anemia patients have been associated with a higher incidence of stroke .¹³⁵ Deficiencies of vitamin B6 , vitamin B12, and folic acid occur more frequently in people with sickle cell anemia than in others¹³⁶ ^{, 137} ^{, 138} and are a cause of high homocysteine levels.¹³⁹ A controlled trial found homocysteine levels were reduced 53% in children with sickle cell anemia receiving a 2–4 mg supplement of folic acid per day, depending on age, but vitamin B6 or B12 had no effect on homocysteine levels.¹⁴⁰ A double-blind trial of children with sickle cell anemia found that children given 5 mg of folic acid per day had less painful swelling of the hands and feet compared with those receiving placebo, but blood abnormalities and impaired growth rate associated with sickle cell anemia were not improved.¹⁴¹ In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily.¹⁴² Anyone taking this amount of folic acid should have vitamin B12 status assessed by a healthcare professional.
2 Stars Skin Ulcers Consult a qualified healthcare practitioner	Large amounts of folic acid given both orally and by injection could promote healing of chronic skin ulcers due to poor circulation. An older preliminary report suggested that large amounts of folic acid given both orally and by injection could promote healing of chronic skin ulcers due to poor circulation.¹⁴³ No controlled research has further investigated this claim.
2 Stars Thalassemia If deficient: 250 to 1,000 mcg daily	Some studies have found people with thalassemia to be frequently deficient in folic acid, taking folic acid supplements may help. Test tube studies have shown that propionyl-L-carnitine (a form of L-carnitine ) protects red blood cells of people with thalassemia against free radical damage.¹⁴⁴ In a preliminary study, children with beta thalassemia major who took 100 mg of L-carnitine per 2.2 pounds of body weight per day for three months had a significantly decreased need for blood transfusions.¹⁴⁵ Some studies have found people with thalassemia to be frequently deficient in folic acid , vitamin B12 ,¹⁴⁶ and zinc .¹⁴⁷ ^{, 148} Researchers have reported improved growth rates in zinc-deficient thalassemic children who were given zinc supplements of 22.5 to 90 mg per day, depending on age.¹⁴⁹ ^{, 150} Magnesium has been reported to be low in thalassemia patients in some,¹⁵¹ ^{, 152} but not all,¹⁵³ studies. A small, preliminary study reported that oral supplements of magnesium, 7.2 mg per 2.2 pounds of body weight per day, improved some red blood cell abnormalities in thalassemia patients.¹⁵⁴
2 Stars Ulcerative Colitis Consult a qualified healthcare practitioner	People with ulcerative colitis may be at a higher risk of colon cancer, supplementing with folic acid may reduce the risk. UC is linked to an increased risk of colon cancer . Studies have found that people with UC who take folic acid supplements or who have high blood levels of folic acid have a reduced risk of colon cancer compared with people who have UC and do not take folic acid supplements.¹⁵⁵ ^{, 156} ^{, 157} Although these associations do not prove that folic acid was responsible for the reduction in risk, this vitamin has been shown to prevent experimentally induced colon cancer in animals.¹⁵⁸ Moreover, low blood folic acid levels have been found in more than half of all people with UC.¹⁵⁹ People with UC who are taking the drug sulfasalazine , which inhibits the absorption of folic acid,¹⁶⁰ are at a particularly high risk of developing folic acid deficiency. Folic acid supplementation may therefore be important for many people with UC. Since taking folic acid may mask a vitamin B12 deficiency, however, people with UC who wish to take folic acid over the long term should have their vitamin B12 status assessed by a physician. Alcohol consumption is known to promote folic acid deficiency and has also been linked to an increased risk of colon cancer.¹⁶¹ People with UC should, therefore, keep alcohol intake to a minimum.
2 Stars Vitiligo Refer to label instructions	Studies have shown folic acid to be effective at skin repigmentation in people with vitiligo. A clinical report describes the use of vitamin supplements in the treatment of vitiligo.¹⁶² Folic acid and/or vitamin B12 and vitamin C levels were abnormally low in most of the 15 people studied. Supplementation with large amounts of folic acid (1–10 mg per day), along with vitamin C (1 gram per day) and intramuscular vitamin B12 injections (1,000 mcg every two weeks), produced marked repigmentation in eight people. These improvements became apparent after three months, but complete repigmentation required one to two years of continuous supplementation. In another study of people with vitiligo, oral supplementation with folic acid (10 mg per day) and vitamin B12 (2,000 mcg per day), combined with sun exposure, resulted in some repigmentation after three to six months in about half of the participants.¹⁶³ This combined regimen was more effective than either vitamin supplementation or sun exposure alone.
1 Star Age-Related Cognitive Decline (Vitamin B6, Vitamin B12) Refer to label instructions	In a study of women with cardiovascular disease or related risk factors, supplementing daily with folic acid, vitamin B6, and vitamin B12 appeared to prevent age-related cognitive decline in those with low dietary intake. In a study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 5.4 years had no effect on cognitive function. However, supplementation appeared to prevent age-related cognitive decline in the 30% of women who had low dietary intake of B vitamins.¹⁶⁴
1 Star Alzheimer’s Disease Refer to label instructions	Some researchers feel Alzheimer’s disease may be related to folic acid deficiency. Some researchers have found an association between Alzheimer’s disease and deficiencies of vitamin B12 and folic acid ;¹⁶⁵ ^{, 166} however, other researchers consider such deficiencies to be of only minor importance.¹⁶⁷ In a study of elderly Canadians, those with low blood levels of folate were more likely to have dementia of all types, including Alzheimer’s disease, than those with higher levels of folate.¹⁶⁸ Little is known about whether supplementation with either vitamin would significantly help people with this disease. Nonetheless, it makes sense for people with Alzheimer’s disease to be medically tested for vitamin B12 and folate deficiencies and to be treated if they are deficient.
1 Star Bipolar Disorder Refer to label instructions	Folic acid deficiency is associated with both mania and depression. Getting enough folic acid helps the body manufacture serotonin and other neurotransmitters. Both folic acid and vitamin B12 are used in the body to manufacture serotonin and other neurotransmitters. It is well known that deficiency of either nutrient is associated with depression.¹⁶⁹ ^{, 170} There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.¹⁷¹ Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.¹⁷² ^{, 173} ^{, 174} Some studies have found that people who take lithium long term, and who also have high blood levels of folic acid, respond better to lithium.¹⁷⁵ ^{, 176} Not all studies have confirmed these findings, however.¹⁷⁷ A double-blind study of patients receiving lithium therapy showed that the addition of 200 mcg of folic acid per day resulted in clinical improvement, whereas placebo did not.¹⁷⁸
1 Star Crohn’s Disease Refer to label instructions	Folic acid is needed to repair intestinal cells damaged by Crohn’s disease. Supplementation may offset some of the deficiency caused by Crohn’s-related malabsorption. Crohn’s disease often leads to malabsorption . As a result, deficiencies of many nutrients are common. For this reason, it makes sense for people with Crohn’s disease to take a high potency multivitamin-mineral supplement. In particular, deficiencies in zinc , folic acid , vitamin B12 , vitamin D , and iron have been reported.¹⁷⁹ ^{, 180} ^{, 181} Zinc, folic acid, and vitamin B12 are all needed to repair intestinal cells damaged by Crohn’s disease. Some doctors recommend 25 to 50 mg of zinc (balanced with 2 to 4 mg of copper), 800 mcg of folic acid, and 800 mcg of vitamin B12. Iron status should be evaluated by a doctor before considering supplementation.
1 Star Dermatitis Herpetiformis Refer to label instructions	Supplementing with folic acid can counteract the nutrient deficiency that often occurs as a result of malabsorption. People with DH frequently have mild malabsorption (difficulty absorbing certain nutrients) associated with low stomach acid (hypochlorhydria) and inflammation of the stomach lining (atrophic gastritis).¹⁸⁵ Mild malabsorption may result in anemia ¹⁸⁶ and nutritional deficiencies of iron , folic acid ,¹⁸⁷ ^{, 188} vitamin B12 ,¹⁸⁹ ^{, 190} and zinc .¹⁹¹ ^{, 192} ^{, 193} More severe malabsorption may result in loss of bone mass.¹⁹⁴ Additional subtle deficiencies of vitamins and minerals are possible, but have not been investigated. Therefore, some doctors recommend people with DH have their nutritional status checked regularly with laboratory studies. These doctors may also recommend multivitamin-mineral supplements and, to correct the low stomach acid, supplemental betaine HCl (a source of hydrochloric acid).
1 Star Diarrhea Refer to label instructions	Folic acid can help repair intestinal lining damage caused by acute diarrhea. Acute diarrhea can damage the lining of the intestine. Folic acid can help repair this damage. In one preliminary trial, supplementing with very large amounts of folic acid (5 mg three times per day for several days) shortened the duration of acute infectious diarrhea by 42%.¹⁹⁵ However, a double-blind trial failed to show any positive effect with the same level of folic acid.¹⁹⁶ Therefore, evidence that high levels of folic acid supplementation will help people with infectious diarrhea remains weak.
1 Star Down’s Syndrome Refer to label instructions	People with Down’s syndrome may be deficient in folic acid and may benefit from supplementation. The red blood cells of people with Down’s syndrome are unusual in ways that suggest either vitamin B12 or folic acid deficiency.¹⁹⁷ ^{, 198} ^{, 199} However, folic acid levels have been found to be normal in each of these studies, and only one study has found lower levels of vitamin B12 in Down’s syndrome as compared with healthy individuals.²⁰⁰ Intervention trials using either vitamin B12 or folic acid have not been done.
1 Star Epilepsy Refer to label instructions	Folic acid may help reduce epileptic seizure frequency, people taking anticonvulsant medications should talk to their doctor before deciding whether to use folic acid. Folic acid supplementation (5 mg per day) was reported to reduce epileptic seizure frequency, though the effect was not significantly better than with placebo.²⁰¹ Folic acid supplementation of as little as 800 mcg per day has also been reported to interfere with the action of anticonvulsant medications, resulting in an increase in the frequency and/or severity of seizures;²⁰² ^{, 203} ^{, 204} ^{, 205} this effect occurs only in a small number of cases.²⁰⁶ ^{, 207} People taking anticonvulsant medications should consult with the prescribing physician before deciding whether to use folic acid.
1 Star HIV and AIDS Support Refer to label instructions	Low folic acid levels are also common in HIV-positive people, supplementing may help correct a deficiency. In HIV-positive people with B-vitamin deficiency, the use of B-complex vitamin supplements appears to delay progression to and death from AIDS.²⁰⁸ Thiamine ( vitamin B1 ) deficiency has been identified in nearly one-quarter of people with AIDS.²⁰⁹ It has been suggested that a thiamine deficiency may contribute to some of the neurological abnormalities that are associated with AIDS. Vitamin B6 deficiency was found in more than one-third of HIV-positive men; vitamin B6 deficiency was associated with decreased immune function in this group.²¹⁰ In a population study of HIV-positive people, intake of vitamin B6 at more than twice the recommended dietary allowance (RDA is 2 mg per day for men and 1.6 mg per day for women) was associated with improved survival.²¹¹ Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.²¹²
1 Star Lung Cancer Refer to label instructions	Together, folic acid and vitamin B12 help cells replicate normally. In one trial, smokers with precancerous lung changes who were given folic acid and vitamin B12 saw a significant reversal of their condition. Folic acid and vitamin B12 work together in the body to help cells replicate normally. In a double-blind trial, smokers with precancerous changes in the lungs were given a placebo or the combination of 10,000 mcg of folic acid and 500 mcg of vitamin B12 per day for four months.²¹³ A significant reversal of precancerous changes occurred in those given vitamin supplements compared with those given the placebo.²¹⁴ No trials have investigated whether either vitamin given alone or the combination of both vitamins would help to treat people who already have lung cancer.
1 Star Peripheral Vascular Disease Refer to label instructions	As with other vascular diseases, people with thromboangiitis obliterans are more likely to have low levels of folic acid. Supplementing with folic acid may help correct a deficiency. As with other vascular diseases, people with TAO are more likely to have high levels of homocysteine and low levels of folic acid .²¹⁵ However, no research has tested folic acid as prevention or treatment for this disease.
1 Star Psoriasis Only for people who are not taking prescription drugs such as methotrexate that interfere with folic acid metabolism	High amounts of folic acid have been shown to improve psoriasis. Folic acid antagonist drugs have been used to treat psoriasis. In one preliminary report, extremely high amounts of folic acid (20 mg taken four times per day), combined with an unspecified amount of vitamin C , led to significant improvement within three to six months in people with psoriasis who had not been taking folic acid antagonists;those who had previously taken these drugs saw a worsening of their condition.²¹⁶
1 Star Restless Legs Syndrome Refer to label instructions	People with familial restless leg syndrome appear to have an unusually high requirement for folic acid. Supplementing with folic acid may help relieve uncomfortable sensations. In some people with RLS, the condition may be genetic. People with familial RLS appear to have inherited an unusually high requirement for folic acid . Although not all people with RLS suffer from uncomfortable sensations, folate-deficient people with this condition always do.²¹⁷ In one report, 45 people were identified to be from families with folic acid-responsive RLS. The amount of folic acid required to relieve their symptoms was extremely large, ranging from 5,000 to 30,000 mcg per day.²¹⁸ Such amounts should only be taken under the supervision of a healthcare professional.
1 Star Seborrheic Dermatitis Refer to label instructions	Supplementing with folic acid has been shown to improve adult seborrheic dermatitis. One physician reported that injections of B-complex vitamins were useful in the treatment of seborrheic dermatitis in infants.²²⁴ A preliminary trial found that 10 mg per day of folic acid was helpful in 17 of 20 cases of adult seborrheic dermatitis.²²⁵ However, this study also found that oral folic acid did not benefit infants with cradle cap. A preliminary study found that topical application of vitamin B6 ointment (containing 10 mg B6 per gram of ointment) to affected areas improved adult seborrheic dermatitis.²²⁶ However, oral vitamin B6 (up to 300 mg per day) was ineffective. Injections of vitamin B12 were reported to improve in 86% of adults with seborrheic dermatitis in a preliminary trial.²²⁷ Oral administration of vitamin B12 for seborrheic dermatitis has not been studied.
1 Star Stroke and High Homocysteine Refer to label instructions	Elevated blood levels of homocysteine have been linked to stroke risk in most studies. Supplementing with folic acid may lower homocysteine levels and reduce stroke risk. Elevated blood levels of homocysteine , a toxic amino acid byproduct, have been linked to risk of stroke in most studies.²²⁸ ^{, 229} ^{, 230} Supplementation with folic acid , vitamin B6 , and vitamin B12 generally lowers homocysteine levels in humans.²³¹ ^{, 232} ^{, 233} In a pooled analysis (meta-analysis) of eight randomized trials, folic acid supplementation in varying amounts (usually 0.5 mg to 5 mg per day) reduced stroke risk by 18%.²³⁴
1 Star Thromboangiitis Obliterans Refer to label instructions	As with other vascular diseases, people with thromboangiitis obliterans are more likely to have low levels of folic acid. Supplementing with folic acid may help correct a deficiency. As with other vascular diseases, people with TAO are more likely to have high levels of homocysteine and low levels of folic acid .²³⁵ However, no research has tested folic acid as prevention or treatment for this disease.

How It Works

How to Use It

Many doctors recommend that all women who are or who could become pregnant take 400 mcg per day in order to reduce the risk of birth defects . Some doctors also extend this recommendation to other people in an attempt to reduce the risk of heart disease by lowering homocysteine levels. Since the FDA mandated addition of folic acid to grain products, the average intake of folic acid from food has increased in the United States by about 100 mcg per day. However, studies have found that this amount of folic acid is inadequate to maintain normal folate levels in a significant percentage of the groups assessed.²³⁶ It now appears that, for pregnant women, supplementing with at least 300 mcg (and optimally 400 mcg) of folic acid per day is sufficient to prevent a folate deficiency, even if dietary intake is low.

Where to Find It

Beans, leafy green vegetables, citrus fruits, beets, wheat germ, and meat are good sources of folic acid.

Possible Deficiencies

Many people consume less than the recommended amount of folic acid. Scientists have found that people with heart disease commonly have elevated blood levels of homocysteine , a laboratory test abnormality often controllable with folic acid supplements. This suggests that many people in Western societies have a mild folic acid deficiency. In fact, it has been suggested that increasing folic acid intake could prevent an estimated 13,500 deaths from cardiovascular diseases each year.²³⁷

Folic acid deficiency has also been common in alcoholics , people living at poverty level, those with malabsorption disorders or liver disease (e.g., cirrhosis ), and women taking the birth control pill. Recently, elderly people with hearing loss have been reported to be much more likely to be folic acid deficient than healthy elderly people.²³⁸ A variety of prescription drugs including cimetidine , antacids, some anticancer drugs, triamterene , sulfasalazine , and anticonvulsants interfere with folic acid.

Deficiency of folic acid can be precipitated by situations wherein the body requires greater than normal amounts of the vitamin, such as pregnancy , infancy, leukemia, exfoliative dermatitis, and diseases that cause the destruction of blood cells.²³⁹

The relationship between folic acid and prevention of neural tube defects is partly thought to result from the high incidence of folate deficiency in many societies. To protect against neural tube defects, the U.S. Food and Drug Administration has mandated that some grain products provide supplemental folic acid at a level expected to increase the dietary intake by an average of 100 mcg per day per person. As a result of folic acid added to the food supply, fewer Americans will be depleted compared with the past. In 1999, scientific evidence began to demonstrate that the folic acid added to the U.S. food supply was having positive effects, including a partial lowering of homocysteine levels.²⁴⁰ In the same year, however, a report from the North Carolina Birth Defects Monitoring Program suggested the current level of folic acid fortification has not reduced the incidence of neural-tube defects.²⁴¹ Many doctors and the Centers for Disease Control in Atlanta²⁴² believe that optimal levels of folic acid intake may still be higher than the amount now being added to food by several hundred micrograms per day. A low blood level of folate has also been associated with an increased risk of miscarriage.²⁴³

People with kidney failure have an increased risk of folic acid deficiency.²⁴⁴ Recipients of kidney transplants often have elevated homocysteine levels, which may respond to supplementation with folic acid.²⁴⁵ The usual recommended amount of 400 mcg per day may not be enough for these people, however. Larger amounts (up to 2.4 mg per day) may produce a better outcome, according to one double-blind trial.²⁴⁶

Folate deficiency is more prevalent among elderly African American women than among elderly white women.²⁴⁷

Best Form to Take

Folic acid naturally found in food is much less available to the body compared with synthetic folic acid found both in supplements and added to grain products in the United States. Women with a recent history of giving birth to babies with neural tube defects participated in a study to determine which form of folic acid is best absorbed—dietary folic acid or folic acid from supplements.²⁴⁸ They received either orange juice containing 400 mcg of folic acid per day or a supplement containing the same amount. Overall, the supplement folic acid was better absorbed than the folic acid from orange juice.

Interactions

Interactions with Supplements, Foods, & Other Compounds

Folic acid is needed by the body to utilize vitamin B12. Proteolytic enzymes inhibit folic acid absorption.²⁴⁹ People taking proteolytic enzymes are advised to supplement with folic acid.

Interactions with Medicines

Certain medicines interact with this supplement.

What Are Drug Interactions

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

Acetazolamide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁵⁰ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Aluminum Hydroxide

Folic acid is needed by the body to utilize vitamin B12 . Antacids,²⁵¹ including aluminum hydroxide, inhibit folic acid absorption. People taking antacids are advised to supplement with folic acid.
Amiloride

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁵² Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.
Amiloride-Hydrochlorothiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁵³ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.
Aspirin

Increased loss of folic acid in urine has been reported in rheumatoid arthritis patients.²⁵⁴ Reduced blood levels of the vitamin have also been reported in people with arthritis who take aspirin.²⁵⁵ Some doctors recommend for people with arthritis who regularly take aspirin to supplement 400 mcg of folic acid per day—an amount frequently found in multivitamins .

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Azathioprine

People receiving dialysis for kidney failure often have low blood levels of folic acid. However, folic acid blood levels should return to normal following kidney transplant. A preliminary study of people taking azathioprine to prevent organ rejection revealed that blood levels of folic acid remained well below those of individuals not taking the drug. The highest blood folic acid level was observed in an individual who had not taken azathioprine for two years.²⁵⁶ Controlled studies are needed to determine whether people taking azathioprine should supplement with folic acid.
Bendroflumethiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁵⁷ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Bumetanide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁵⁸ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Chlorothiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁵⁹ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Chlorthalidone

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁶⁰ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Cholestyramine

Bile acid sequestrants may prevent absorption of folic acid and the fat-soluble vitamins A , D , E , and K .²⁶¹ ^{, 262} Other medications and vitamin supplements should be taken one hour before or four to six hours after bile acid sequestrants for optimal absorption.²⁶³ Animal studies suggest calcium and zinc may also be depleted by taking cholestyramine.²⁶⁴
Colesevelam

A review of literature suggests that women who use OCs may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.²⁶⁵ ^{, 266} ^{, 267} OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .²⁶⁸ ^{, 269} ^{, 270} OCs may interfere with manganese absorption.²⁷¹ The clinical importance of these actions remains unclear.
Colestipol

Bile acid sequestrants, including colestipol, may prevent absorption of folic acid and the fat-soluble vitamins A , D , E , K .²⁷² ^{, 273} People taking colestipol should consult with their doctor about vitamin malabsorption and supplementation. People should take other drugs and vitamin supplements one hour before or four to six hours after colestipol to improve absorption.²⁷⁴

Animal studies suggest calcium and zinc may be depleted by taking cholestyramine, another bile acid sequestrant. ²⁷⁵ Whether these same interactions would occur with colestipol is not known.
Cycloserine

Cycloserine may interfere with calcium and magnesium absorption.²⁷⁶ The clinical significance of these interactions is unclear.

Cycloserine may interfere with the absorption and/or activity of folic acid, vitamin B6, and vitamin B12.²⁷⁷ ^{, 278} The clinical importance of this interaction is unclear.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Desogestrel-Ethinyl Estradiol

Oral contraceptive (OC) use can cause folic acid depletion.²⁸¹ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁸² Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Dichlorphenamide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.²⁸³ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Ethinyl Estradiol and Levonorgestrel

Oral contraceptive (OC) use can cause folic acid depletion.²⁸⁴ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁸⁵ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Ethinyl Estradiol and Norethindrone

Oral contraceptive (OC) use can cause folic acid depletion.²⁸⁸ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁸⁹ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Ethinyl Estradiol and Norgestimate

Oral contraceptive (OC) use can cause folic acid depletion.²⁹² In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁹³ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Ethinyl Estradiol and Norgestrel

Oral contraceptive (OC) use can cause folic acid depletion.²⁹⁶ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁹⁷ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Furosemide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁰² Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Hydrochlorothiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁰³ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Hydroflumethiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁰⁴ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Indapamide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁰⁵ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Indomethacin

Indomethacin has been reported to decrease absorption of folic acid and vitamin C .³⁰⁶ Under certain circumstances, indomethacin may interfere with the actions of vitamin C.³⁰⁷ Calcium and phosphate levels may also be reduced with indomethacin therapy.³⁰⁸ It remains unclear whether people taking this drug need to supplement any of these nutrients.
Isoniazid

Isoniazid may interfere with the activity of other nutrients, including vitamin B3 (niacin) , vitamin B12 , vitamin D , and vitamin E , folic acid , calcium , and magnesium .³⁰⁹ ^{, 310} Supplementation with vitamin B6 is thought to help prevent isoniazid-induced niacin deficiency; however, small amounts of vitamin B6 (e.g. 10 mg per day) appear to be inadequate in some cases.³¹¹ People should consider using a daily multivitamin-mineral supplement during isoniazid therapy.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Lansoprazole

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including lansoprazole, inhibit folic acid absorption.³¹² People taking antacids are advised to supplement with folic acid.
Levonorgestrel

Oral contraceptive (OC) use can cause folic acid depletion.³¹⁵ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³¹⁶ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Levonorgestrel-Ethinyl Estrad

Oral contraceptive (OC) use can cause folic acid depletion.³¹⁷ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³¹⁸ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Magnesium Hydroxide

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including magnesium hydroxide, inhibit folic acid absorption.³²⁵ People taking antacids are advised to supplement with folic acid.
Mestranol and Norethindrone

Oral contraceptive (OC) use can cause folic acid depletion.³²⁶ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³²⁷ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Metformin

Metformin therapy has been shown to deplete vitamin B12,³²⁸ and sometimes, but not always,³²⁹ folic acid as well.³³⁰ This depletion occurs through the interruption of a calcium-dependent mechanism. Supplementation with calcium has reversed this effect in a clinical trial.³³¹ People taking metformin should supplement vitamin B12 and folic acid or ask their doctor to monitor folic acid and vitamin B12 levels.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Methazolamide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³³² Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Methyclothiazide

Diuretics, including thiazide diuretics, cause increased loss of sodium in the urine. By removing sodium from the body, diuretics also cause water to leave the body. This reduction of body water is the purpose of taking diuretics. Therefore, there is usually no reason to replace lost sodium, although strict limitation of salt intake in combination with the actions of diuretics can sometimes cause excessive sodium depletion. On the other hand, people who restrict sodium intake, and in the process reduce blood pressure, may need to have their dose of diuretics lowered.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Metolazone

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.² Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Neomycin

Neomycin can decrease absorption or increase elimination of many nutrients, including calcium , carbohydrates, beta-carotene , fats, folic acid , iron , magnesium , potassium , sodium, and vitamin A , vitamin B12 , vitamin D , and vitamin K .³³³ ^{, 334} Surgery preparation with oral neomycin is unlikely to lead to deficiencies. It makes sense for people taking neomycin for more than a few days to also take a multivitamin-mineral supplement.
Norgestimate-Ethinyl Estradiol

Oral contraceptive (OC) use can cause folic acid depletion.³³⁵ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³³⁶ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Omeprazole

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including omeprazole, inhibit folic acid absorption.³³⁹ People taking antacids are advised to supplement with folic acid.
Polythiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁴⁰ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Ranitidine

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including ranitidine, inhibit folic acid absorption.³⁴¹ People taking antacids are advised to supplement with folic acid.
Salsalate

Salsalate and aspirin produce anti-inflammatory effects after they are converted in the body to salicylic acid. Studies have shown that aspirin can reduce the amount of folic acid in the blood,³⁴² though it is not known whether this change is significant. Controlled studies are needed to determine whether people taking salsalate are at risk for folic acid deficiency.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Sodium Bicarbonate

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including sodium bicarbonate, inhibit folic acid absorption.³⁴³ People taking antacids are advised to supplement with folic acid.
Spironolactone

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁴⁴ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Folic acid is also an important cause of elevated homocysteine levels. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.
Spironolacton-Hydrochlorothiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁴⁵ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.
Sulfamethoxazole

Sulfonamides, including sulfamethoxazole, can interfere with the activity of folic acid, vitamin B6, and vitamin K.³⁴⁶ This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

Note: Since sulfamethoxazole is often prescribed in combination with trimethoprim (for example, in Bactrim or Septra), it may be easy to associate this interaction with trimethoprim. However, this interaction is not known to occur with trimethoprim alone.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Sulfasalazine

Sulfasalazine decreases the absorption of folic acid.³⁴⁷ Biochemical evidence of depletion of folic acid has been reported in people taking this drug,³⁴⁸ although available evidence remains mixed.³⁴⁹ ^{, 350}

Folic acid is needed for the normal healthy replication of cells. Perhaps as a result, there is evidence that folic acid can reverse precancerous changes in humans.³⁵¹ Ulcerative colitis, a disease commonly treated with sulfasalazine, is associated with an increased risk of colon cancer . Folate deficiency has also been linked to an increased risk for colon cancer.³⁵² It is plausible that some of the increased risk for colon cancer in people with ulcerative colitis may be related to folate depletion caused by sulfasalazine.

Folic acid supplementation may help protect against colon cancer.³⁵³ One study found that people who have ulcerative colitis and who supplement with folic acid have a 55% lower risk of getting colon cancer, compared with ulcerative colitis patients who do not supplement with folic acid (although this dramatic association with protection did not quite reach statistical significance).³⁵⁴ Researchers at the University of Chicago Medical Center reported a 62% lower risk of colon cancer in folic acid supplementers.³⁵⁵ They suggested that the link between folic acid supplementation and protection from colon cancer may well be due to overcoming the folic acid deficiency induced by sulfasalazine.

Many doctors believe that it is important for all people taking sulfasalazine to supplement with folic acid. Folic acid in the amount of 800 mcg can be found in many multivitamins and B-complex vitamins . People wishing to supplement with more—typically 1,000 mcg per day—should consult their doctor.
Tetracycline

Tetracycline can interfere with the activity of folic acid , potassium , and vitamin B2 , vitamin B6 , vitamin B12 , vitamin C , and vitamin K .³⁵⁶ This is generally not a problem when taking tetracycline for two weeks or less. People taking tetracycline for longer than two weeks should ask their doctor about vitamin and mineral supplementation. Taking 500 mg vitamin C simultaneously with tetracycline was shown to increase blood levels of tetracycline in one study.³⁵⁷ The importance of this interaction is unknown.

Taking large amounts of niacinamide, a form of vitamin B3 , can suppress inflammation in the body. According to numerous preliminary reports, niacinamide, given in combination with tetracycline or minocycline , may be effective against bullous pemphigoid, a benign, autoimmune blistering disease of the skin.³⁵⁸ ^{, 359} ^{, 360} ^{, 361} ^{, 362} ^{, 363} ^{, 364} Preliminary evidence also suggests a similar beneficial interaction may exist between tetracycline and niacinamide in the treatment of dermatitis herpetiformis .³⁶⁵ ^{, 366}
Torsemide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁶⁷ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Triamterene-Hydrochlorothiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁶⁸ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.
Trichlormethiazide

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.³⁶⁹ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Trimethoprim/ Sulfamethoxazole

Sulfonamides, including sulfamethoxazole , can interfere with the activity of folic acid and vitamin B6.³⁷⁰ This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

TMP/SMX has, on rare occasions, been associated with anemia due to folic acid deficiency.³⁷¹ This effect may be due to trimethoprim.³⁷² TMP/SMX should be used with caution in patients with folic acid deficiency, for which a blood test is available. Folic acid replacement does not interfere with the antibacterial activity of TMP/SMX.³⁷³ People with AIDS -related pneumonia given TMP/SMX had a worse survival rate when folinic acid, an activated form of folic acid, was added.³⁷⁴

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Reduce Side Effects

Desogestrel-Ethinyl Estradiol

Oral contraceptive (OC) use can cause folic acid depletion.²⁷⁹ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁸⁰ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Ethinyl Estradiol and Levonorgestrel

Oral contraceptive (OC) use can cause folic acid depletion.²⁸⁶ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁸⁷ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Ethinyl Estradiol and Norethindrone

Oral contraceptive (OC) use can cause folic acid depletion.²⁹⁰ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁹¹ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Ethinyl Estradiol and Norgestrel

Oral contraceptive (OC) use can cause folic acid depletion.²⁹⁴ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.²⁹⁵ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Fenofibrate

Increased blood levels of homocysteine are associated with increased risk of atherosclerosis and heart disease . One study revealed that fenofibrate dramatically increases blood homocysteine levels, though blood levels of vitamins were not reduced.²⁹⁸ In one study, supplementation with 10 mg per day of folic acid prevented the increase in homocysteine levels resulting from fenofibrate therapy.²⁹⁹ Further research is needed to determine whether supplemental vitamin B6 and vitamin B12, which are also capable of lowering homocysteine levels, might lower fenofibrate-induced elevations in homocysteine levels.
Levonorgestrel

Oral contraceptive (OC) use can cause folic acid depletion.³¹³ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³¹⁴ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Levonorgestrel-Ethinyl Estrad

Oral contraceptive (OC) use can cause folic acid depletion.³¹⁹ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³²⁰ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.
Norgestimate-Ethinyl Estradiol

Oral contraceptive (OC) use can cause folic acid depletion.³³⁷ In a double-blind trial of OC users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.³³⁸ Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.

Support Medicine

Fluoxetine

Low blood levels of folic acid have been correlated to poor response to fluoxetine.³⁰⁰ Furthermore, the addition of folic acid to fluoxetine appears to enhance the effectiveness of the drug. A double-blind trial found that depressed women receiving 500 mcg of folic acid per day in addition to fluoxetine experienced significant improvement in their symptoms, as well as fewer side effects, compared with women receiving only fluoxetine.³⁰¹ Similar results were not observed in men; however, men appear to have a higher requirement for folic acid than do women, so a higher intake may be necessary.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Lithium

Some studies have found that people taking lithium long term who have high blood levels of folic acid respond better to lithium.³²¹ ^{, 322} Not all studies have confirmed these findings, however.³²³

A double-blind study was conducted combining 200 mcg folic acid per day with lithium therapy.³²⁴ Even though the volunteers in this study were doing well on lithium alone before the study, addition of folic acid further improved their condition, whereas placebo did not. There is no evidence that folic acid reduces side effects of lithium. Based on the available evidence, it is suggested people taking lithium also take at least 200 mcg of folic acid per day.

Reduces Effectiveness

none

Potential Negative Interaction

none

Explanation Required

Carbamazepine

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.³⁷⁵ ^{, 376} ^{, 377} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.³⁷⁸

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.³⁷⁹ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.³⁸⁰ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.³⁸¹

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.³⁸² In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.³⁸³

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.³⁸⁴ ^{, 385} ^{, 386} ^{, 387} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.³⁸⁸ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Erythromycin

Erythromycin may interfere with the absorption and/or activity of calcium , folic acid , magnesium , vitamin B6 and vitamin B12 ,³⁸⁹ which may cause problems, especially with long-term erythromycin treatment. Until more is known, it makes sense for people taking erythromycin for longer than two weeks to supplement with a daily multivitamin-multimineral .
Famotidine

Some evidence indicates that other vitamins and minerals, such as folic acid ³⁹⁰ and copper ,³⁹¹ require the presence of stomach acid for optimal absorption. Long-term use of H-2 blockers may therefore promote a deficiency of these nutrients. Individuals requiring long-term use of H-2 blockers may therefore benefit from a multiple vitamin/mineral supplement .
Felbamate

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.³⁹² ^{, 393} ^{, 394} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.³⁹⁵

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.³⁹⁶ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.³⁹⁷ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.³⁹⁸

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.³⁹⁹ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴⁰⁰

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴⁰¹ ^{, 402} ^{, 403} ^{, 404} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴⁰⁵ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Gabapentin

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁴⁰⁶ ^{, 407} ^{, 408} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis .

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁴⁰⁹ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁴¹⁰ Other practitioners suggest that 1mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁴¹¹

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁴¹² In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴¹³

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴¹⁴ ^{, 415} ^{, 416} ^{, 417} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴¹⁸ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Levetiracetam

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁴¹⁹ ^{, 420} ^{, 421} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.⁴²²

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁴²³ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁴²⁴ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁴²⁵

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁴²⁶ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴²⁷

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴²⁸ ^{, 429} ^{, 430} ^{, 431} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴³² Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Medroxyprogesterone

In a one-year study of predominantly malnourished women in India and Thailand, medroxyprogesterone used for contraception was associated with increased blood levels of vitamin A and folic acid.⁴³³ The clinical meaning of these changes remains unclear.
Methotrexate

In cancer treatment, methotrexate works by blocking activation of folic acid. Folic acid-containing supplements may interfere with methotrexate therapy in people with cancer.⁴³⁴ Methotrexate therapy can lead to folic acid deficiency. People using methotrexate for cancer treatment should ask their prescribing doctor before using any folic acid-containing supplements. There is no concern about folic acid supplementation for people with cancer using chemotherapy drugs other than methotrexate.

Until recently, it was believed that methotrexate helped people with rheumatoid arthritis also by interfering with folic acid metabolism. However, this is not necessarily so, as some studies have shown that folic acid supplementation in amounts ranging from 5–50 mg per week did not alter the efficacy of methotrexate in the treatment of rheumatoid arthritis.⁴³⁵ ^{, 436} ^{, 437} Many doctors now believe that people with rheumatoid arthritis taking methotrexate should supplement large amounts of folic acid. In separate double-blind trials, 5 mg per week of folic acid and 2.5–5 mg per week of folinic acid (an activated form of folic acid) have substantially reduced side effects of methotrexate without interfering with the therapeutic action in rheumatoid patients.⁴³⁸ ^{, 439} Folic or folinic acid was taken at a different time from methotrexate and sometimes only five days per week. Daily (as opposed to weekly) supplementation with folic acid (5 mg per day for 13 days) was found to reduce blood levels of methotrexate;⁴⁴⁰ however, the researchers in this study suggest that the reduction in blood methotrexate levels by folic acid does not necessarily mean that the folic acid is interfering with the therapeutic action of the drug. It is possible that the lower blood levels of methotrexate are simply an indication that the drug is being taken up more rapidly by the cells as a result of folic acid supplementation. In most of the studies cited here, folic acid supplementation was begun 24 hours after the administration of methotrexate. Because of the uncertainty regarding this interaction, persons taking methotrexate for rheumatoid arthritis who are considering supplementation with folic acid should first consult with their doctor.

People who are prescribed methotrexate to treat severe psoriasis experience fewer side effects if they also supplement high amounts (5 mg per day) of folic acid.⁴⁴¹ As is the case with methotrexate and rheumatoid arthritis, supplementing folic acid did not interfere with the activity of methotrexate. Such high levels of folic acid should not be taken without clinical supervision.
Nizatidine

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including nizatidine, inhibit folic acid absorption.⁴⁴² People taking antacids are advised to supplement with folic acid.

There is some evidence that other vitamins and minerals, such as folic acid ⁴⁴³ and copper ,⁴⁴⁴ require the presence of stomach acid for optimal absorption. Long-term use of H-2 blockers may therefore promote a deficiency of these nutrients. Individuals requiring long-term use of H-2 blockers may therefore benefit from a multiple vitamin/mineral supplement.
Oxcarbazepine

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁴⁴⁵ ^{, 446} ^{, 447} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.⁴⁴⁸

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁴⁴⁹ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁴⁵⁰ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁴⁵¹

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁴⁵² In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴⁵³

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴⁵⁴ ^{, 455} ^{, 456} ^{, 457} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴⁵⁸ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Phenobarbital

Long-term treatment with phenobarbital results in dramatic reductions in folic acid blood levels, though the clinical significance of this effect is unclear.⁴⁵⁹ Nevertheless, some healthcare practitioners might recommend supplemental folic acid to individuals taking phenobarbital.

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁴⁶⁰ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁴⁶¹ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁴⁶²

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁴⁶³ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴⁶⁴

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴⁶⁵ ^{, 466} ^{, 467} ^{, 468} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴⁶⁹ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Phenytoin

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁴⁷⁰ ^{, 471} ^{, 472} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.⁴⁷³

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁴⁷⁴ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁴⁷⁵ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁴⁷⁶

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁴⁷⁷ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴⁷⁸

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴⁷⁹ ^{, 480} ^{, 481} ^{, 482} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴⁸³ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Piroxicam

Piroxicam may prevent inflammation by blocking the activity of enzymes that depend on folic acid.⁴⁸⁴ However, other studies show that people taking NSAIDs such as aspirin have lower than normal levels of folic acid in their red blood cells.⁴⁸⁵ Further research is needed to determine whether supplemental folic acid prevents a deficiency of the vitamin or indirectly reduces the beneficial effects of piroxicam.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Primidone

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁴⁸⁶ ^{, 487} ^{, 488} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.⁴⁸⁹

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁴⁹⁰ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁴⁹¹ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁴⁹²

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁴⁹³ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁴⁹⁴

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁴⁹⁵ ^{, 496} ^{, 497} ^{, 498} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁴⁹⁹ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Sulindac

Sulindac blocks the activity of enzymes that depend on folic acid⁵⁰⁰ and may, like aspirin, reduce the amount of folic acid in red blood cells.⁵⁰¹ Further research is needed to determine whether supplementing folic acid changes the effects of sulindac therapy or prevents a deficiency of this vitamin in the body.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Topiramate

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁵⁰² ^{, 503} ^{, 504} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis . Carbamazepine alone has also been shown to reduce blood levels of folic acid.⁵⁰⁵

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁵⁰⁶ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁵⁰⁷ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁵⁰⁸

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁵⁰⁹ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁵¹⁰

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁵¹¹ ^{, 512} ^{, 513} ^{, 514} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁵¹⁵ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Triamterene

Triamterene is a weak folic acid antagonist that has been associated with folic acid-deficiency anemia in people already at risk for folic acid deficiency.⁵¹⁶ However, people treated long term with triamterene, without additional risk for folic acid deficiency, were found to have normal folic acid levels and no signs of folic acid deficiency.⁵¹⁷ The use of multivitamin supplements containing folic acid appears to diminish the occurrence of birth defects associated with triamterene. According to one study,⁵¹⁸ pregnant women who took folic acid–containing multivitamin supplements in addition to their prescription drugs had fewer babies with heart defects and deformities of the upper lip and mouth.

One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.⁵¹⁹ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.
Trimethoprim

The use of multivitamin supplements containing folic acid diminishes the occurrence of birth defects associated with trimethoprim. According to one study,⁵²⁰ pregnant women who took folic acid–containing multivitamin supplements in addition to their prescription drugs had fewer babies with heart defects and deformities of the upper lip and mouth.

The combination drug trimethoprim/sulfamethoxazole (TMP/SMX) has been rarely associated with folic acid-deficiency anemia.⁵²¹ This action may be due to trimethoprim-induced folic acid depletion.⁵²² Trimethoprim and TMP/SMX should be used with caution in patients with folic acid deficiency, for which blood tests are available. Folic acid replacement does not interfere with the antibacterial activity of trimethoprim⁵²³ or TMP/SMX.⁵²⁴
Valproate

Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.⁵²⁵ ^{, 526} ^{, 527} Homocysteine, a potential marker for folic acid deficiency, is a compound used experimentally to induce seizures and is associated with atherosclerosis .

One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects , such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk.⁵²⁸ Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects.⁵²⁹ Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.⁵³⁰

One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.⁵³¹ In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.⁵³²

Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures.⁵³³ ^{, 534} ^{, 535} ^{, 536} However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures.⁵³⁷ Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.

The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist.

Side Effects

With the exception of rare cases of allergic reactions,⁵³⁸ folic acid is not generally associated with side effects,⁵³⁹ although there have been rare case reports of allergic reactions to the vitamin.⁵⁴⁰ Folic acid supplementation can interfere with the laboratory diagnosis of vitamin B12 deficiency, possibly allowing the deficiency to progress undetected to the point of irreversible nerve damage.⁵⁴¹ Although vitamin B12 deficiency is uncommon, no one should supplement with 1,000 mcg or more of folic acid without consulting a doctor.

In a double-blind trial, people with diabetes who also had with kidney disease received a daily placebo or 2.5 mg of folic acid, 1 mg of vitamin B12, and 25 mg of vitamin B6 for three years. Compared with the placebo, vitamin supplementation accelerated the decline in kidney function and increased the incidence of cardiovascular events (such as heart attacks) and heart disease-related deaths.⁵⁴² Based on this study, diabetics with kidney disease should not take these vitamins without a doctor's supervision.

Vitamin B12 deficiencies often occur without anemia (even in people who do not take folic acid supplements). Some doctors do not know that the absence of anemia does not rule out a B12 deficiency. If this confusion delays diagnosis of a vitamin B12 deficiency, the patient could be injured, sometimes permanently. This problem is rare and should not happen with doctors knowledgeable in this area using correct testing procedures.

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470. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scand 1984;69:226–31.

471. Apeland T, Mansoor MA, Strandjord RE, Kristensen O. Homocysteine concentrations and methionine loading in patients on antiepileptic drugs. Acta Neurol Scand 2000;101:217–23.

472. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–50.

473. Apeland T, Mansoor MA, Strandjord RE, et al. Folate, homocysteine and methionine loading in patients on carbamazepine. Acta Neurol Scand 2001;103:294–9.

474. Biale Y, Lewenthal H. Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs. Eur J Obstet Gynecol Reprod Biol 1984;18:211–6.

475. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs 1999;57:535–44 [review].

476. Hiilesmaa VK, Teramo K, Granstrom JL, et al. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J (Clin Res Ed) 1983;287:577–9.

477. Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol 1981;19:57–60.

478. Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid-responsive neonatal seizures. J Child Neurol 1999;14:529–32.

479. Guidolin L, Vignoli A, Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5:301–3.

480. Lewis DP, Van Dyke DC, Willhite LA. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726–35 [review].

481. Berg MJ, Rivey MP, Vern BA, et al. Phenytoin and folic acid: individualized drug-drug interaction. Ther Drug Monit 1983;5:395–9.

482. Reynolds EH. Effects of folic acid on the mental state and fit frequency of drug treated epileptic patients. Lancet 1967;1:1086.

483. 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;80:75–8.

484. 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.

485. Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid, and aspirin. Blood 1971;38:405–16.

486. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scand 1984;69:226–31.

487. Apeland T, Mansoor MA, Strandjord RE, Kristensen O. Homocysteine concentrations and methionine loading in patients on antiepileptic drugs. Acta Neurol Scand 2000;101:217–23.

488. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–50.

489. Apeland T, Mansoor MA, Strandjord RE, et al. Folate, homocysteine and methionine loading in patients on carbamazepine. Acta Neurol Scand 2001;103:294–9.

490. Biale Y, Lewenthal H. Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs. Eur J Obstet Gynecol Reprod Biol 1984;18:211–6.

491. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs 1999;57:535–44 [review].

492. Hiilesmaa VK, Teramo K, Granstrom JL, et al. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J (Clin Res Ed) 1983;287:577–9.

493. Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol 1981;19:57–60.

494. Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid-responsive neonatal seizures. J Child Neurol 1999;14:529–32.

495. Guidolin L, Vignoli A, Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5:301–3.

496. Lewis DP, Van Dyke DC, Willhite LA. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726–35 [review].

497. Berg MJ, Rivey MP, Vern BA, et al. Phenytoin and folic acid: individualized drug-drug interaction. Ther Drug Monit 1983;5:395–9.

498. Reynolds EH. Effects of folic acid on the mental state and fit frequency of drug treated epileptic patients. Lancet 1967;1:1086.

499. 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;80:75–8.

500. 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.

501. Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid, and aspirin. Blood 1971;38:405–16.

502. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scand 1984;69:226–31.

503. Apeland T, Mansoor MA, Strandjord RE, Kristensen O. Homocysteine concentrations and methionine loading in patients on antiepileptic drugs. Acta Neurol Scand 2000;101:217–23.

504. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–50.

505. Apeland T, Mansoor MA, Strandjord RE, et al. Folate, homocysteine and methionine loading in patients on carbamazepine. Acta Neurol Scand 2001;103:294–9.

506. Biale Y, Lewenthal H. Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs. Eur J Obstet Gynecol Reprod Biol 1984;18:211–6.

507. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs 1999;57:535–44 [review].

508. Hiilesmaa VK, Teramo K, Granstrom JL, et al. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J (Clin Res Ed) 1983;287:577–9.

509. Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol 1981;19:57–60.

510. Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid-responsive neonatal seizures. J Child Neurol 1999;14:529–32.

511. Guidolin L, Vignoli A, Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5:301–3.

512. Lewis DP, Van Dyke DC, Willhite LA. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726–35 [review].

513. Berg MJ, Rivey MP, Vern BA, et al. Phenytoin and folic acid: individualized drug-drug interaction. Ther Drug Monit 1983;5:395–9.

514. Reynolds EH. Effects of folic acid on the mental state and fit frequency of drug treated epileptic patients. Lancet 1967;1:1086.

515. 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;80:75–8.

516. Jackson EK. Diuretics. In Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York: McGraw Hill, 1996, 706.

517. Mason JB, Zimmerman J, Otradovec CL, et al. Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency. J Lab Clin Med 1991;117:365–9.

518. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608–14.

519. 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.

520. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. New Engl J Med 2000;343:1608–14.

521. Sahai J. Urinary tract infections. In Applied Therapeutics: The Clinical Use of Drugs, 6th ed. Vancouver, WA: Applied Therapeutics, 1995, 63–6.

522. Kahn SB, Fein SA, Brodsky I. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 1968;9:550–60.

523. Threlkeld DS, ed. Systemic Anti-Infectives, Miscellaneous Anti-Infectives, Trimethoprim. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Aug 1992, 408–a.

524. Sahai J. Urinary tract infections. In Applied Therapeutics: The Clinical Use of Drugs, 6th ed. Vancouver, WA: Applied Therapeutics, 1995, 63–6.

525. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scand 1984;69:226–31.

526. Apeland T, Mansoor MA, Strandjord RE, Kristensen O. Homocysteine concentrations and methionine loading in patients on antiepileptic drugs. Acta Neurol Scand 2000;101:217–23.

527. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–50.

528. Biale Y, Lewenthal H. Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs. Eur J Obstet Gynecol Reprod Biol 1984;18:211–6.

529. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs 1999;57:535–44 [review].

530. Hiilesmaa VK, Teramo K, Granstrom JL, et al. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J (Clin Res Ed) 1983;287:577–9.

531. Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol 1981;19:57–60.

532. Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid-responsive neonatal seizures. J Child Neurol 1999;14:529–32.

533. Guidolin L, Vignoli A, Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5:301–3.

534. Lewis DP, Van Dyke DC, Willhite LA. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726–35 [review].

535. Berg MJ, Rivey MP, Vern BA, et al. Phenytoin and folic acid: individualized drug-drug interaction. Ther Drug Monit 1983;5:395–9.

536. Reynolds EH. Effects of folic acid on the mental state and fit frequency of drug treated epileptic patients. Lancet 1967;1:1086.

537. 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;80:75–8.

538. Smith J, Empson M, Wall C. Recurrent anaphylaxis to synthetic folic acid. Lancet 2007;370:652.

539. Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989;50:353–8.

540. Valdivieso R, Cevallos F, Caballero MT, Quirce S. Chronic urticaria caused by folic acid. Ann Allergy Asthma Immunol 2009;103:81–2.

541. Wald NJ, Bower C. Folic acid, pernicious anaemia, and prevention of neural tube defects. Lancet 1994;343:307.

542. House AA, Eliasziw M, Cattran DC, et al. Effect of B-vitamin therapy on progression of diabetic nephropathy. A randomized controlled trial. JAMA 2010;303:1603–9.

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Last Review: 11-07-2012

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2013.

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Topic Contents

Folic Acid

Uses

This supplement has been used in connection with the following health conditions:

How It Works

How to Use It

Where to Find It

Possible Deficiencies

Best Form to Take

Interactions

Interactions with Supplements, Foods, & Other Compounds

Interactions with Medicines

Replenish Depleted Nutrients

Reduce Side Effects

Support Medicine

Reduces Effectiveness

Potential Negative Interaction

Explanation Required

Side Effects

Side Effects

Related Information

References