Topic Contents

Folic Acid

Uses

1.	Pregnancy and Postpartum Support
2.	Vitamin B-Complex
3.	Birth Defects Prevention

What Are "Star" Ratings?

a7_3star Reliable and relatively consistent scientific data showing a substantial health benefit.

a7_2star Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

a7_1star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

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.

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

Used for	Amount	Why
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.
Abnormal Pap Smear 10 mg daily under medical supervision 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} Learn More

Used for	Amount	Why
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.
Birth Defects At least 400 mcg daily 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 Learn More

Used for	Amount	Why
Depression and Folic Acid Deficiency	See a doctor for evaluation	Taking folic acid can help correct deficiencies associated with depression.
Depression and Folic Acid Deficiency See a doctor for evaluation 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).

Used for	Amount	Why
High Homocysteine (Vitamin B12, Vitamin B6)	400 to 1,000 mcg of folic acid daily, 10 to 50 mg of vitamin B6 daily, and 50 to 300 mcg of vitamin B12 daily	Vitamin B6, folic acid, and vitamin B12 all play a role in converting homocysteine to other substances within the body and have consistently lowered homocysteine levels in trials.
High Homocysteine 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. By so doing, they consistently lower homocysteine levels in research trials,¹⁴ ^{, 15} ^{, 16} a finding that is now well accepted. Several studies have used (and some doctors recommend) 400–1,000 mcg of folic acid per day, 10–50 mg of vitamin B6 per day, and 50–300 mcg of vitamin B12 per day. Of these three vitamins, folic acid supplementation lowers homocysteine levels the most for the average person.¹⁷ ^{, 18} It also effectively lowers homocysteine in people on kidney dialysis.¹⁹ In 1996, the FDA required that all enriched flour, rice, pasta, cornmeal, and other grain products contain 140 mcg of folic acid per 3½ ounces.²⁰ This level of fortification has led to a measurable decrease in homocysteine levels.²¹ However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,²² suggesting that the FDA-mandated supplementation is inadequate to optimally protect people against high homocysteine levels. Therefore, people wishing to lower their homocysteine levels should continue to take folic acid supplements despite the FDA-mandated fortification program. Learn More

Used for	Amount	Why
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.
Pregnancy and Postpartum Support 800 mcg daily, beginning before pregnancy Most doctors, many other healthcare professionals, and the March of Dimes recommend that all women of childbearing age supplement with 400 mcg per day of folic acid. Such supplementation could protect against the formation of neural tube defects (such as spina bifida) during the time between conception and when pregnancy is discovered. The requirement for the B vitamin folic acid doubles during pregnancy, to 800 mcg per day from all sources.²³ Deficiencies of folic acid during pregnancy have been linked to low birth weight²⁴ and to an increased incidence of neural tube defects (e.g., spina bifida) in infants. In one study, women who were at high risk of giving birth to babies with neural tube defects were able to lower their risk by 72% by taking folic acid supplements prior to and during pregnancy.²⁵ Several preliminary studies have shown that a deficiency of folate in the blood may increase the risk of stunted growth of the fetus.²⁶ ^{, 27} ^{, 28} ^{, 29} ^{, 30} ^{, 31} ^{, 32} ^{, 33} This does not prove, however, that folic acid supplementation results in higher birth weights. Although some trials have found that folic acid and iron, when taken together, have improved birth weights,³⁴ ^{, 35} ^{, 36} ^{, 37} other trials have found supplementation with these nutrients to be ineffective.³⁸ ^{, 39} ^{, 40} The relationship between folate status and the risk of miscarriage is also somewhat unclear. In some studies, women who have had habitual miscarriages were found to have elevated levels of homocysteine (a marker of folate deficiency).⁴¹ ^{, 42} ^{, 43} ^{, 44} In a preliminary study, 22 women with recurrent miscarriages who had elevated levels of homocysteine were treated with 15 mg per day of folic acid and 750 mg per day of vitamin B6, prior to and throughout their next pregnancy. This treatment reduced homocysteine levels to normal and was associated with 20 successful pregnancies.⁴⁵ It is not known whether supplementing with these vitamins would help prevent miscarriages in women with normal homocysteine levels. As the amounts of folic acid and vitamin B6 used in this study were extremely large and potentially toxic, this treatment should be used only with the supervision of a doctor. In other studies, however, folate levels did not correlate with the incidence of habitual miscarriages.⁴⁶ ^{, 47} ^{, 48} Preliminary⁴⁹ and double-blind⁵⁰ evidence has shown that women who use a multivitamin-mineral formula containing folic acid beginning three months before becoming pregnant and continuing through the first three months of pregnancy have a significantly lower risk of having babies with neural tube defects (e.g., spina bifida) and other congenital defects. In addition to achieving significant protection against birth defects, women who take folic acid supplements during pregnancy have been reported to have fewer infections, and to give birth to babies with higher birth weights and better Apgar scores. ⁵¹ (An Apgar score is an evaluation of the well-being of a newborn, based on his or her color, crying, muscle tone, and other signs.) However, if a woman waits until after discovering her pregnancy to begin taking folic acid supplements, it will probably be too late to prevent a neural tube defect. Learn More

Used for	Amount	Why
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.
Schizophrenia and Folic Acid Deficiency If deficient: 10 to 20 mg a day under medical supervision People with schizophrenia may have a greater tendency to be deficient in folic acid, than the general population⁵² and they may show improvement when given supplements. A preliminary trial found that, among schizophrenic patients with folic acid deficiency, those given folic acid supplements had more improvement, and shorter hospital stays than those not given supplements.⁵³ In a double-blind trial, a very high amount of folic acid (15 mg daily) was given to schizophrenic patients being treated with psychiatric medications who had low or borderline folic acid levels. The patients receiving the folic acid supplements had significant improvement, which became more significant over the six-month course of the trial.⁵⁴ The symptoms of folic acid deficiency can be similar to those of schizophrenia, and two cases of wrong “schizophrenia” diagnoses have been reported.⁵⁵ ^{, 56} In one of these cases, an initial supplement of 20 mg daily of folic acid and a maintenance supplemental intake of 10 mg daily, led to resolution of symptoms.⁵⁷ 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.⁵⁸ 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.

Used for	Amount	Why
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.
Age-Related Cognitive Decline 800 mcg per day 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.⁵⁹ Whether folic acid would slow cognitive decline in people with normal homocysteine levels is not known. Learn More

Used for	Amount	Why
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.
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,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 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.⁷¹ Of these four supplements, folic acid appears to be the most important.⁷² Attempts to lower homocysteine by simply changing the diet rather than by using vitamin supplements have not been successful.⁷³ Learn More

Used for	Amount	Why
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.
Breast Cancer 400 mcg daily 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.⁷⁴ 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.⁷⁵ 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.⁷⁶ No research has yet explored the effect of folic acid supplementation in people who have already been diagnosed with cancer. Cancer patients taking the chemotherapy drug methotrexate must not take folic acid supplements without the direction of their oncologist. Learn More

Used for	Amount	Why
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.
Celiac Disease 3 mg vitamin B6, 0.8 mg folic acid, and 0.5 mg vitamin B12 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.⁷⁷ 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.⁷⁸ Learn More

Used for	Amount	Why
Celiac Disease and Folic Acid Deficiency	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.
Celiac Disease and Folic Acid Deficiency Consult a qualified healthcare practitioner 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.⁷⁹ Zinc malabsorption also occurs frequently in celiac disease⁸⁰ and may result in zinc deficiency, even in people who are otherwise in remission.⁸¹ 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.⁸²

Used for	Amount	Why
Colon Cancer	400 mcg daily	Folic acid appears to be effective against colon cancer, especially in people with ulcerative colitis, people who drink alcohol, and people in remission from colon cancer.
Colon Cancer 400 mcg daily 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.⁸³ 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.⁸⁴ 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.⁸⁵ As dietary folate increases, the risks of precancerous polyps in the colon⁸⁶ and colon cancer itself decrease, according to some,⁸⁷ but not all, reports.⁸⁸ 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.⁸⁹ 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).⁹⁰ 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.⁹¹ The protection from colon cancer associated with high intake of folate has been reported to occur more in consumers of alcohol than in nondrinkers.⁹² This finding fits well with evidence that folate reverses damage to DNA caused by alcohol consumption.⁹³ Damaged DNA can lead to abnormal cellular replication—a step toward cancer. Some nutritionally oriented doctors recommend folic acid supplementation for prevention of recurrences in patients who formerly had colon cancer but are now in complete remission. However, no research has yet explored the effect of folic acid supplementation in people who have already been diagnosed with cancer. Cancer patients taking the chemotherapy drug methotrexate must not take folic acid supplements without the direction of their oncologist. Learn More

Used for	Amount	Why
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.
Halitosis and Gum Disease Use 5 ml twice per day of a 0.1% solution Nutritional supplements recommended by some doctors for prevention and treatment of periodontitis include vitamin C (people with periodontitis are often found to be deficient),⁹⁴ vitamin E, selenium, zinc, coenzyme Q10, and folic acid.⁹⁵ Folic acid has also been shown to reduce the severity of gingivitis when taken as a mouthwash.⁹⁶

Used for	Amount	Why
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.
Heart Attack 500 to 800 mcg daily High blood levels of the amino acid homocysteine have been linked to an increased risk of heart attack in most,⁹⁷ ^{, 98} ^{, 99} ^{, 100} though not all,¹⁰¹ ^{, 102} 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.¹⁰³ Folic acid¹⁰⁴ ^{, 105} and vitamins B6 and B12 are known to lower homocysteine.¹⁰⁶ There is a clear association between low blood levels of folate and increased risk of heart attacks in men.¹⁰⁷ 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. Learn More

Used for	Amount	Why
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.
Intermittent Claudication 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 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.¹⁰⁸ Learn More

Used for	Amount	Why
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.
Macular Degeneration 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 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.¹⁰⁹ Learn More

Used for	Amount	Why
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.
Migraine Headache 5 mg per day 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.¹¹⁰ Further research is needed to determine whether folic acid supplementation would be beneficial for migraine patients who do not have these specific characteristics. Learn More

Used for	Amount	Why
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.
Osteoporosis and High Homocysteine 5 mg with 1,500 mcg of vitamin B12 daily 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.¹¹¹ 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.¹¹² 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.¹¹³ 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.

Used for	Amount	Why
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.
Preeclampsia 5 mg daily Women with preeclampsia have been shown to have elevated blood levels of homocysteine.¹¹⁴ ^{, 115} ^{, 116} ^{, 117} Research indicates elevated homocysteine occurs prior to the onset of preeclampsia.¹¹⁸ Elevated homocysteine damages the lining of blood vessels,¹¹⁹ ^{, 120} ^{, 121} ^{, 122} ^{, 123} ^{, 124} ^{, 125} which can lead to the preeclamptic signs of elevated blood pressure, swelling, and protein in the urine.¹²⁶ 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.¹²⁷ 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.¹²⁸ 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. Learn More

Used for	Amount	Why
Schizophrenia and High Homocysteine (Vitamin B12, Vitamin B6)	Take folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (400 mcg) daily	People with schizophrenia who have high homocysteine levels may improve symptoms by supplementing with folic acid, vitamin B6, and vitamin B12.
Schizophrenia and High Homocysteine Take folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (400 mcg) daily People with schizophrenia may have a greater tendency to be deficient in folic acid, than the general population¹²⁹ 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.¹³⁰ 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.¹³¹ The symptoms of folic acid deficiency can be similar to those of schizophrenia, and two cases of wrong “schizophrenia” diagnoses have been reported.¹³² ^{, 133} 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.¹³⁴ 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.¹³⁵ 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.

Used for	Amount	Why
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.
Sickle Cell Anemia and High Homocysteine Consult a qualified healthcare practitioner 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.¹³⁶ 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.¹³⁷ ^{, 138} Elevated homocysteine is recognized as a risk factor for cardiovascular disease.¹³⁹ In particular, high levels of homocysteine in sickle cell anemia patients have been associated with a higher incidence of stroke.¹⁴⁰ Deficiencies of vitamin B6, vitamin B12, and folic acid occur more frequently in people with sickle cell anemia than in others¹⁴¹ ^{, 142} ^{, 143} and are a cause of high homocysteine levels.¹⁴⁴ 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.¹⁴⁵ 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.¹⁴⁶ In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily.¹⁴⁷ Anyone taking this amount of folic acid should have vitamin B12 status assessed by a healthcare professional.

Used for	Amount	Why
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.
Skin Ulcers Consult a qualified healthcare practitioner 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.¹⁴⁸ No controlled research has further investigated this claim. Learn More

Used for	Amount	Why
Thalassemia and Folic Acid Deficiency	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.
Thalassemia and Folic Acid Deficiency If deficient: 250 to 1,000 mcg daily 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.¹⁴⁹ 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.¹⁵⁰ Some studies have found people with thalassemia to be frequently deficient in folic acid, vitamin B12,¹⁵¹ and zinc.¹⁵² ^{, 153} 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.¹⁵⁴ ^{, 155} Magnesium has been reported to be low in thalassemia patients in some,¹⁵⁶ ^{, 157} but not all,¹⁵⁸ 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.¹⁵⁹

Used for	Amount	Why
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.
Ulcerative Colitis Consult a qualified healthcare practitioner 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.¹⁶⁰ ^{, 161} ^{, 162} 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.¹⁶³ Moreover, low blood folic acid levels have been found in more than half of all people with UC.¹⁶⁴ People with UC who are taking the drug sulfasalazine, which inhibits the absorption of folic acid,¹⁶⁵ 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.¹⁶⁶ People with UC should, therefore, keep alcohol intake to a minimum. Learn More

Used for	Amount	Why
Vitiligo	Refer to label instructions	Studies have shown folic acid to be effective at skin repigmentation in people with vitiligo.
Vitiligo A clinical report describes the use of vitamin supplements in the treatment of vitiligo.¹⁶⁷ 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.¹⁶⁸ This combined regimen was more effective than either vitamin supplementation or sun exposure alone. Learn More

Used for	Amount	Why
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.
Age-Related Cognitive Decline 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.¹⁶⁹ Learn More

Used for	Amount	Why
Alzheimer’s Disease	Refer to label instructions	Some researchers feel Alzheimer’s disease may be related to folic acid deficiency.
Alzheimer’s Disease Some researchers have found an association between Alzheimer’s disease and deficiencies of vitamin B12 and folic acid;¹⁷⁰ ^{, 171} however, other researchers consider such deficiencies to be of only minor importance.¹⁷² 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.¹⁷³ 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. Learn More

Used for	Amount	Why
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.
Bipolar Disorder 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.¹⁷⁴ ^{, 175} There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.¹⁷⁶ Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.¹⁷⁷ ^{, 178} ^{, 179} 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.¹⁸⁰ ^{, 181} Not all studies have confirmed these findings, however.¹⁸² 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.¹⁸³ Learn More

Used for	Amount	Why
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 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.¹⁸⁴ ^{, 185} ^{, 186} 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. Learn More

Used for	Amount	Why
Dermatitis Herpetiformis and Folic Acid Deficiency	Refer to label instructions	Supplementing with folic acid can counteract the nutrient deficiency that often occurs as a result of malabsorption.
Dermatitis Herpetiformis and Folic Acid Deficiency 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).¹⁸⁷ Mild malabsorption may result in anemia¹⁸⁸ and nutritional deficiencies of iron, folic acid,¹⁸⁹ ^{, 190} vitamin B12,¹⁹¹ ^{, 192} and zinc.¹⁹³ ^{, 194} ^{, 195} More severe malabsorption may result in loss of bone mass.¹⁹⁶ 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).

Used for	Amount	Why
Diarrhea	Refer to label instructions	Folic acid can help repair intestinal lining damage caused by acute diarrhea.
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%.¹⁹⁷ However, a double-blind trial failed to show any positive effect with the same level of folic acid.¹⁹⁸ Therefore, evidence that high levels of folic acid supplementation will help people with infectious diarrhea remains weak. Learn More

Used for	Amount	Why
Down’s Syndrome	Refer to label instructions	People with Down’s syndrome may be deficient in folic acid and may benefit from supplementation.
Down’s Syndrome The red blood cells of people with Down’s syndrome are unusual in ways that suggest either vitamin B12 or folic acid deficiency.¹⁹⁹ ^{, 200} ^{, 201} 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.²⁰² Intervention trials using either vitamin B12 or folic acid have not been done. Learn More

Used for	Amount	Why
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.
Epilepsy Folic acid supplementation (5 mg per day) was reported to reduce epileptic seizure frequency, though the effect was not significantly better than with placebo.²⁰³ 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;²⁰⁴ ^{, 205} ^{, 206} ^{, 207} this effect occurs only in a small number of cases.²⁰⁸ ^{, 209} People taking anticonvulsant medications should consult with the prescribing physician before deciding whether to use folic acid. Learn More

Used for	Amount	Why
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.
HIV and AIDS Support In HIV-positive people with B-vitamin deficiency, the use of B-complex vitamin supplements appears to delay progression to and death from AIDS.²¹⁰ Thiamine (vitamin B1) deficiency has been identified in nearly one-quarter of people with AIDS.²¹¹ 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.²¹² 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.²¹³ Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.²¹⁴ Learn More

Used for	Amount	Why
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.
Lung Cancer 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.²¹⁵ A significant reversal of precancerous changes occurred in those given vitamin supplements compared with those given the placebo.²¹⁶ 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. Learn More

Used for	Amount	Why
Peripheral Vascular Disease and 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.
Peripheral Vascular Disease and Thromboangiitis Obliterans As with other vascular diseases, people with TAO are more likely to have high levels of homocysteine and low levels of folic acid.²¹⁷ However, no research has tested folic acid as prevention or treatment for this disease.

Used for	Amount	Why
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.
Psoriasis Only for people who are not taking prescription drugs such as methotrexate that interfere with folic acid metabolism 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.²¹⁸ Learn More

Used for	Amount	Why
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.
Restless Legs Syndrome 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.²¹⁹ 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.²²⁰ Such amounts should only be taken under the supervision of a healthcare professional. Learn More

Used for	Amount	Why
Seborrheic Dermatitis	Refer to label instructions	Supplementing with folic acid has been shown to improve adult seborrheic dermatitis.
Seborrheic Dermatitis One physician reported that injections of B-complex vitamins were useful in the treatment of seborrheic dermatitis in infants.²²¹ A preliminary trial found that 10 mg per day of folic acid was helpful in 17 of 20 cases of adult seborrheic dermatitis.²²² 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.²²³ 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.²²⁴ Oral administration of vitamin B12 for seborrheic dermatitis has not been studied. Learn More

Used for	Amount	Why
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.
Stroke and High Homocysteine Elevated blood levels of homocysteine, a toxic amino acid byproduct, have been linked to risk of stroke in most studies.²²⁵ ^{, 226} ^{, 227} Supplementation with folic acid, vitamin B6, and vitamin B12 generally lowers homocysteine levels in humans.²²⁸ ^{, 229} ^{, 230} 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%.²³¹

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. 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.

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. 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.

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. 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. Many doctors and the Centers for Disease Control in Atlanta 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.

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

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

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

Interactions with Medicines

Certain medicines interact with this supplement.

	Some medicines may increase the need for this supplement.
	Some medicines interact with this supplement, so they should not be taken together.
	Some interactions between this supplement and certain medicines require more explanation. Click the link to see details.

Note: The following list only includes the generic or class name of a medicine. To find a specific brand name, use the Medicines Index.

	Acetazolamide
	Aluminum Hydroxide
	Amiloride
	Amiloride-Hydrochlorothiazide
	Aspirin
	Azathioprine
	Bendroflumethiazide
	Bumetanide
	Chlorothiazide
	Chlorthalidone
	Cholestyramine
	Colesevelam
	Colestipol
	Cycloserine
	Desogestrel-Ethinyl Estradiol
	Desogestrel-Ethinyl Estradiol
	Dichlorphenamide
	Ethinyl Estradiol and Levonorgestrel
	Ethinyl Estradiol and Levonorgestrel
	Ethinyl Estradiol and Norethindrone
	Ethinyl Estradiol and Norethindrone
	Ethinyl Estradiol and Norgestimate
	Ethinyl Estradiol and Norgestrel
	Ethinyl Estradiol and Norgestrel
	Fenofibrate
	Fluoxetine
	Furosemide
	Hydrochlorothiazide
	Hydroflumethiazide
	Indapamide
	Indomethacin
	Isoniazid
	Lansoprazole
	Levonorgestrel
	Levonorgestrel
	Levonorgestrel-Ethinyl Estrad
	Levonorgestrel-Ethinyl Estrad
	Lithium
	Magnesium Hydroxide
	Mestranol and Norethindrone
	Metformin
	Methazolamide
	Methotrexate
	Methyclothiazide
	Metolazone
	Neomycin
	Nitric Oxide Gas
	Norgestimate-Ethinyl Estradiol
	Norgestimate-Ethinyl Estradiol
	Omeprazole
	Polythiazide
	Ranitidine
	Salsalate
	Sodium Bicarbonate
	Spironolactone
	Spironolacton-Hydrochlorothiazide
	Sulfamethoxazole
	Sulfasalazine
	Tetracycline
	Torsemide
	Triamterene-Hydrochlorothiazide
	Trichlormethiazide
	Trimethoprim/ Sulfamethoxazole
	Methotrexate
	Methotrexate
	Carbamazepine
	Erythromycin
	Famotidine
	Felbamate
	Gabapentin
	Levetiracetam
	Medroxyprogesterone
	Nizatidine
	Oxcarbazepine
	Phenobarbital
	Phenytoin
	Piroxicam
	Primidone
	Sulindac
	Topiramate
	Triamterene
	Trimethoprim
	Valproate

Side Effects

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

References

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2. Zarcone R, Bellini P, Carfora E, et al. Folic acid and cervix dysplasia. Minerva Ginecol 1996;48:397–400.

3. Butterworth CE, Hatch KD, Soong S-J, et al. Oral folic acid supplementation for cervical dysplasia: A clinical intervention trial. Am J Obstet Gynecol 1992;166:803–9.

4. Butterworth CE Jr, Hatch KD, Macaluso M, et al. Folate deficiency and cervical dysplasia. JAMA 1992;267:528–33.

5. Piyathilake CJ, Macaluso M, Brill I, et al. Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia. Nutrition 2007;23:203–10.

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16. Ubbink JB, Vermaak WJH, ven der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927–33.

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22. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998;338:1009–15.

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28. Goldenberg RL, Tamura T, Cliver SP, et al. Serum folate and fetal growth retardation: a matter of compliance? Obstet Gynecol 1992;795 (Pt 1):719–22.

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30. Frelut ML, de Courcy GP, Christides JP, et al. Relationship between maternal folate status and foetal hypotrophy in a population with a good socio-economical level. Int J Vitam Nutr Res 1995;65:267–71.

31. Ek J. Plasma and red cell folate in mothers and infants in normal pregnancies. Relation to birth weight. Acta Obstet Gynecol Scand 1982;61:17–20.

32. Malinow MR, Rajkovic A, Duell PB, et al. The relationship between maternal and neonatal umbilical cord plasma homocyst(e)ine suggests a potential role for maternal homocyst(e)ine in fetal metabolism. Am J Obstet Gynecol 1998;178:228–33.

33. Burke G, Robinson K, Refsum H, et al. Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. N Engl J Med 1992;326:69–70 [letter].

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35. Rolschau J, Date J, Kristoffersen K. Folic acid supplement and intrauterine growth. Acta Obstet Gynecol Scand 1979;58:343–6.

36. Blot I, Papiernik E, Kaltwasser JP, et al. Influence of routine administration of folic acid and iron during pregnancy. Gynecol Obstet Invest 1981;12:294–304.

37. Baumslag N, Edelstein T, Metz J. Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Br Med J 1970;1:16–7.

38. Fleming AF, Martin JD, Hahnel R, Westlake AJ. Effects of iron and folic acid antenatal supplements on maternal haematology and fetal wellbeing. Med J Aust 1974;2:429–36.

39. Fletcher J, Gurr A, Fellingham FR, et al. The value of folic acid supplements in pregnancy. J Obstet Gynaecol Br Commonw 1971;78:781–5.

40. Giles PF, Harcourt AG, Whiteside MG. The effect of prescribing folic acid during pregnancy on birth-weight and duration of pregnancy. A double-blind trial. Med J Aust 1971;2:17–21.

41. Sutterlin M, Bussen S, Ruppert D, Steck T. Serum levels of folate and cobalamin in women with recurrent spontaneous abortion. Hum Reprod 1997;12:2292–6.

42. Wouters MG, Boers GH, Blom HJ, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993;60:820–5.

43. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet 1992;339:1122–3 [letter].

44. Quere I, Bellet H, Hoffet M, et al. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril 1998;69:152–4.

45. Quere I, Mercier E, Bellet H, et al. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001;75:823–5.

46. Pietrzik K, Prinz R, Reusch K, et al. Folate status and pregnancy outcome. Ann N Y Acad Sci 1992;669:371–3.

47. Neiger R, Wise C, Contag SA, et al. First trimester bleeding and pregnancy outcome in gravidas with normal and low folate levels. Am J Perinatol 1993;10:460–2.

48. Neela J, Raman L. The relationship between maternal nutritional status and spontaneous abortion. Natl Med J India 1997;10:15–6.

49. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal mulitivitamin use. Am J Epidemiol 2000;151:878–84.

50. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996;62:179–83.

51. Tamura T, Goldenberg R, Freeberg L, et al. Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. Am J Clin Nutr 1992:56;365–70.

52. Herran A, Garcia-Unzueta MT, Amado JA, et al. Folate levels in psychiatric outpatients. Psychiatry Clin Neurosci 1999;53:531–3.

53. Carney MW, Sheffield BF. Associations of subnormal serum folate and vitamin B12 values and effects of replacement therapy. J Nerv Ment Dis 1970;150:404–12.

54. Procter A. Enhancement of recovery from psychiatric illness by methylfolate. Br J Psychiatry 1991;159:271–2.

55. Freeman JM, Finkelstein JD, Mudd SH. Folate-responsive homocystinuria and “schizophrenia.” A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med 1975;292:491–6.

56. Folate-responsive homocystinuria and “schizophrenia.”Nutr Rev 1982;40:242–5.

57. Folate-responsive homocystinuria and “schizophrenia.”Nutr Rev 1982;40:242–5.

58. Levine J, Stahl Z, Sela BA, et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 2006;60:265–9.

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Last Review: 05-11-2011

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2011.

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Folic Acid

Topic Contents

Folic Acid

Uses

Related Topics

What Are "Star" Ratings?

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

Abnormal Pap Smear

Birth Defects

Depression and Folic Acid Deficiency

High Homocysteine

Pregnancy and Postpartum Support

Schizophrenia and Folic Acid Deficiency

Age-Related Cognitive Decline

Atherosclerosis

Breast Cancer

Celiac Disease

Celiac Disease and Folic Acid Deficiency

Colon Cancer

Halitosis and Gum Disease

Heart Attack

Intermittent Claudication

Macular Degeneration

Migraine Headache

Osteoporosis and High Homocysteine

Preeclampsia

Schizophrenia and High Homocysteine

Sickle Cell Anemia and High Homocysteine

Skin Ulcers

Thalassemia and Folic Acid Deficiency

Ulcerative Colitis

Vitiligo

Age-Related Cognitive Decline

Alzheimer’s Disease

Bipolar Disorder

Crohn’s Disease

Dermatitis Herpetiformis and Folic Acid Deficiency

Diarrhea

Down’s Syndrome

Epilepsy

HIV and AIDS Support

Lung Cancer

Peripheral Vascular Disease and Thromboangiitis Obliterans

Psoriasis

Restless Legs Syndrome

Seborrheic Dermatitis

Stroke and High Homocysteine

How It Works

How to Use It

Where to Find It

Possible Deficiencies

Best Form to Take

Interactions

Interactions with Supplements, Foods, & Other Compounds

Interactions with Medicines

Side Effects

Side Effects

References