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    Folic Acid

    Folic Acid

    Uses

    What Are Star Ratings?

    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
    Gingivitis (Folic Acid Rinse)
    5 ml of a 0.1% solution used as a mouth rinse twice per day
    Rinsing with a folic acid solution may help reduce inflammation and bleeding.

    A 0.1% solution of folic acid used as a mouth rinse (5 ml taken twice a day for 30 to 60 days) has reduced gum inflammation and bleeding in people with gingivitis in double-blind trials.14 , 15 The folic acid solution is rinsed in the mouth for one to five minutes and then spit out. Folic acid was also found to be effective when taken in capsule or tablet form (4 mg per day),16 though in another trial studying pregnant women with gingivitis, only the mouthwash-and not folic acid in pill form-was effective.17 However, this may have been due to the body's increased requirement for folic acid during pregnancy.

    Phenytoin (Dilantin) therapy causes gum disease (gingival hyperplasia) in some people. A regular program of dental care has been reported to limit or prevent gum disease in people taking phenytoin.18 , 19 , 20 Double-blind research has shown that a daily oral rinse with a liquid folic acid preparation inhibited phenytoin-induced gum disease more than either folic acid in pill form or placebo.21

    3 Stars
    High Homocysteine (Vitamin B6, Vitamin B12)
    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.
    dd
    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.22 Deficiencies of folic acid during pregnancy have been linked to low birth weight23 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.24 Several preliminary studies have shown that a deficiency of folate in the blood may increase the risk of stunted growth of the fetus.25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 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,33 , 34 , 35 , 36 other trials have found supplementation with these nutrients to be ineffective.37 , 38 , 39

    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).40 , 41 , 42 , 43 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.44 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.45 , 46 , 47

    Preliminary48 and double-blind49 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. 50 (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,51 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.52 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.53 The symptoms of folic acid deficiency can be similar to those of schizophrenia, and two cases of wrong "schizophrenia" diagnoses have been reported.54 , 55 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.56
    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.57 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.58 Preliminary evidence suggests that B vitamins may not slow cognitive decline in people with normal homocysteine levels.

    2 Stars
    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.59

     

    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

    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.78 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.79
    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 .80 Zinc malabsorption also occurs frequently in celiac disease81 and may result in zinc deficiency, even in people who are otherwise in remission.82 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.83

    2 Stars
    Colon Cancer
    400 mcg daily
    Folic acid appears to be effective against colon cancer, especially in people with ulcerative colitis, and people who drink alcohol.

    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.

    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 B6, Vitamin B12)
    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
    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 ;164 , 165 however, other researchers consider such deficiencies to be of only minor importance.166 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.167 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.168 , 169 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.170 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.171 , 172 , 173 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.174 , 175 Not all studies have confirmed these findings, however.176 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.177

    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.178 , 179 , 180 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).184 Mild malabsorption may result in anemia 185 and nutritional deficiencies of iron , folic acid ,186 , 187 vitamin B12 ,188 , 189 and zinc .190 , 191 , 192 More severe malabsorption may result in loss of bone mass.193 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).

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    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%.194 However, a double-blind trial failed to show any positive effect with the same level of folic acid.195 Therefore, evidence that high levels of folic acid supplementation will help people with infectious diarrhea remains weak.

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    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.196 , 197 , 198 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.199 Intervention trials using either vitamin B12 or folic acid have not been done.

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    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.200 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;201 , 202 , 203 , 204 this effect occurs only in a small number of cases.205 , 206 People taking anticonvulsant medications should consult with the prescribing physician before deciding whether to use folic acid.

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    Gingivitis (Folic Acid Oral)
    Refer to label instructions
    In pill form, folic acid may improve gingivitis symptoms, although one study found the mouth rinse form to be more effective.

    A 0.1% solution of folic acid used as a mouth rinse (5 ml taken twice a day for 30 to 60 days) has reduced gum inflammation and bleeding in people with gingivitis in double-blind trials.207 , 208 The folic acid solution is rinsed in the mouth for one to five minutes and then spit out. Folic acid was also found to be effective when taken in capsule or tablet form (4 mg per day),209 though in another trial studying pregnant women with gingivitis, only the mouthwash-and not folic acid in pill form-was effective.210 However, this may have been due to the body's increased requirement for folic acid during pregnancy.

    Phenytoin (Dilantin) therapy causes gum disease (gingival hyperplasia) in some people. A regular program of dental care has been reported to limit or prevent gum disease in people taking phenytoin.211 , 212 , 213 Double-blind research has shown that a daily oral rinse with a liquid folic acid preparation inhibited phenytoin-induced gum disease more than either folic acid in pill form or placebo.214

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    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.215 Thiamine ( vitamin B1 ) deficiency has been identified in nearly one-quarter of people with AIDS.216 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.217 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.218 Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.219

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    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.220 A significant reversal of precancerous changes occurred in those given vitamin supplements compared with those given the placebo.221 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.

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    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 .222 However, no research has tested folic acid as prevention or treatment for this disease.

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    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.223

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    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.224 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.225 Such amounts should only be taken under the supervision of a healthcare professional.

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    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.231 A preliminary trial found that 10 mg per day of folic acid was helpful in 17 of 20 cases of adult seborrheic dermatitis.232 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.233 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.234 Oral administration of vitamin B12 for seborrheic dermatitis has not been studied.

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    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.235 , 236 , 237 Supplementation with folic acid , vitamin B6 , and vitamin B12 generally lowers homocysteine levels in humans.238 , 239 , 240 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%.241

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    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 .242 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.243 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.244

    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.245 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.246

    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.247 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.248 Many doctors and the Centers for Disease Control in Atlanta249 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.250

    People with kidney failure have an increased risk of folic acid deficiency.251 Recipients of kidney transplants often have elevated homocysteine levels, which may respond to supplementation with folic acid.252 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.253

    Folate deficiency is more prevalent among elderly African American women than among elderly white women.254

    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.255 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.256 People taking proteolytic enzymes are advised to supplement with folic acid.

    Interactions with Medicines

    Certain medicines interact with this supplement.

    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.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.
    • Aluminum Hydroxide

      Folic acid is needed by the body to utilize vitamin B12 . Antacids,258 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.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.

    • 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.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.

    • Aspirin

      Increased loss of folic acid in urine has been reported in rheumatoid arthritis patients.261 Reduced blood levels of the vitamin have also been reported in people with arthritis who take aspirin.262 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.263 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.264 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.265 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.266 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.267 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 .268 , 269 Other medications and vitamin supplements should be taken one hour before or four to six hours after bile acid sequestrants for optimal absorption.270 Animal studies suggest calcium and zinc may also be depleted by taking cholestyramine.271

    • Colesevelam

      A review of literature suggests that women who use OCs may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.272 , 273 , 274 OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .275 , 276 , 277 OCs may interfere with manganese absorption.278 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 .279 , 280 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.281

      Animal studies suggest calcium and zinc may be depleted by taking cholestyramine, another bile acid sequestrant. 282 Whether these same interactions would occur with colestipol is not known.

    • Cycloserine

      Cycloserine may interfere with calcium and magnesium absorption.283 The clinical significance of these interactions is unclear.

      Cycloserine may interfere with the absorption and/or activity of folic acid, vitamin B6, and vitamin B12.284 , 285 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 use can cause folic acid depletion.288 In a double-blind trial of oral contraceptive 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 oral contraceptives 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.290 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.291 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.292 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.295 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.296 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.299 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.300 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 use can cause folic acid depletion.303 In a double-blind trial of oral contraceptive users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.304 Women with cervical dysplasia diagnosed while they are taking oral contraceptives 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.309 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.310 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.311 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.312 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 .313 Under certain circumstances, indomethacin may interfere with the actions of vitamin C.314 Calcium and phosphate levels may also be reduced with indomethacin therapy.315 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 .316 , 317 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.318 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.319 People taking antacids are advised to supplement with folic acid.

    • Levonorgestrel

      Oral contraceptive (OC) use can cause folic acid depletion.322 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.323 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 use can cause folic acid depletion.324 In a double-blind trial of oral contraceptive users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.325 Women with cervical dysplasia diagnosed while they are taking oral contraceptives 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.332 People taking antacids are advised to supplement with folic acid.

    • Mestranol and Norethindrone

      Oral contraceptive use can cause folic acid depletion.333 In a double-blind trial of oral contraceptive users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.334 Women with cervical dysplasia diagnosed while they are taking oral contraceptives 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 B12,335 and sometimes, but not always,336 folic acid as well.337 This depletion occurs through the interruption of a calcium-dependent mechanism. Supplementation with calcium has reversed this effect in a clinical trial.338 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.339 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 .340 , 341 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 use can cause folic acid depletion.342 In a double-blind trial of oral contraceptive users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.343 Women with cervical dysplasia diagnosed while they are taking oral contraceptives 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.346 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.347 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.348 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,349 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.350 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.351 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.352 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.353 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.354 Biochemical evidence of depletion of folic acid has been reported in people taking this drug,355 although available evidence remains mixed.356 , 357

      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.358 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.359 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.360 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).361 Researchers at the University of Chicago Medical Center reported a 62% lower risk of colon cancer in folic acid supplementers.362 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 .363 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.364 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.365 , 366 , 367 , 368 , 369 , 370 , 371 Preliminary evidence also suggests a similar beneficial interaction may exist between tetracycline and niacinamide in the treatment of dermatitis herpetiformis .372 , 373

    • 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.374 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.375 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.376 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 B6.377 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.378 This effect may be due to trimethoprim.379 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.380 People with AIDS -related pneumonia given TMP/SMX had a worse survival rate when folinic acid, an activated form of folic acid, was added.381

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

    Reduce Side Effects

    • Desogestrel-Ethinyl Estradiol

      Oral contraceptive use can cause folic acid depletion.286 In a double-blind trial of oral contraceptive 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 oral contraceptives 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.293 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.294 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.297 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.298 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 use can cause folic acid depletion.301 In a double-blind trial of oral contraceptive users with cervical dysplasia , supplementation with very large amounts (10 mg per day) of folic acid improved cervical health.302 Women with cervical dysplasia diagnosed while they are taking oral contraceptives 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.305 In one study, supplementation with 10 mg per day of folic acid prevented the increase in homocysteine levels resulting from fenofibrate therapy.306 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.320 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.321 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 use can cause folic acid depletion.326 In a double-blind trial of oral contraceptives 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 oral contraceptives 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.344 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.345 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.307 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.308 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.328 , 329 Not all studies have confirmed these findings, however.330

      A double-blind study was conducted combining 200 mcg folic acid per day with lithium therapy.331 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.382 , 383 , 384 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.385

      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.386 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.387 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.388

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.389 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.390

      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.391 , 392 , 393 , 394 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.395 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 ,396 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 397 and copper ,398 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.399 , 400 , 401 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.402

      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.403 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.404 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.405

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.406 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.407

      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.408 , 409 , 410 , 411 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.412 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.413 , 414 , 415 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.416 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.417 Other practitioners suggest that 1mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.418

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.419 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.420

      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.421 , 422 , 423 , 424 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.425 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.426 , 427 , 428 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.429

      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.430 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.431 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.432

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.433 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.434

      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.435 , 436 , 437 , 438 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.439 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.440 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.441 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.442 , 443 , 444 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.445 , 446 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;447 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.448 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.449 People taking antacids are advised to supplement with folic acid.

      There is some evidence that other vitamins and minerals, such as folic acid 450 and copper ,451 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.452 , 453 , 454 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.455

      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.456 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.457 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.458

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.459 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.460

      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.461 , 462 , 463 , 464 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.465 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.466 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.467 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.468 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.469

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.470 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.471

      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.472 , 473 , 474 , 475 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.476 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.477 , 478 , 479 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.480

      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.481 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.482 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.483

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.484 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.485

      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.486 , 487 , 488 , 489 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.490 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.491 However, other studies show that people taking NSAIDs such as aspirin have lower than normal levels of folic acid in their red blood cells.492 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.493 , 494 , 495 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.496

      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.497 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.498 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.499

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.500 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.501

      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.502 , 503 , 504 , 505 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.506 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 acid507 and may, like aspirin, reduce the amount of folic acid in red blood cells.508 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.509 , 510 , 511 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.512

      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.513 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.514 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.515

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.516 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.517

      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.518 , 519 , 520 , 521 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.522 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.523 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.524 The use of multivitamin supplements containing folic acid appears to diminish the occurrence of birth defects associated with triamterene. According to one study,525 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.526 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,527 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.528 This action may be due to trimethoprim-induced folic acid depletion.529 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 trimethoprim530 or TMP/SMX.531

    • Valproate

      Several studies have shown that multiple anticonvulsant therapy reduces blood levels of folic acid and dramatically increases homocysteine levels.532 , 533 , 534 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.535 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.536 Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.537

      One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency.538 In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.539

      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.540 , 541 , 542 , 543 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.544 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

    Side Effects

    With the exception of rare cases of allergic reactions,545 folic acid is not generally associated with side effects,546 although there have been rare case reports of allergic reactions to the vitamin.547 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.548 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.549 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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