Folic Acid: Health Benefits, Side Effects, Uses, Dose & Precautions

Other Name(s):

5'-methyltetrahydrofolate, 5'-MTHF, Acide Folique, Acide Ptéroylglutamique, Acide Ptéroylmonoglutamique, Acido Folico, B Complex Vitamin, Complexe de Vitamines B, Complexe Vitaminique B, Dihydrofolate, Folacin, Folacine, Folate, Folinic Acid, L-methylfolate, Methylfolate, Méthylfolate, Pteroylglutamic Acid, Pteroylmonoglutamic Acid, Pteroylpolyglutamate, Tetrahydrofolate, Tétrahydrofolate, Vitamin B9, Vitamine B9.

Overview
Uses
Side Effects
Precautions
Interactions
Dosing

Overview

Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food, and folic acid is the synthetic form of this vitamin. Since 1998, folic acid has been added to cold cereals, flour, breads, pasta, bakery items, cookies, and crackers, as required by federal law. Foods that are naturally high in folate include leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, fruits (such as bananas, melons, and lemons) beans, yeast, mushrooms, meat (such as beef liver and kidney), orange juice, and tomato juice.

Folic acid is used for preventing and treating low blood levels of folate (folate deficiency), as well as its complications, including "tired blood" (anemia) and the inability of the bowel to absorb nutrients properly. Folic acid is also used for other conditions commonly associated with folate deficiency, including ulcerative colitis, liver disease, alcoholism, and kidney dialysis.

Women who are pregnant or might become pregnant take folic acid to prevent miscarriage and "neural tube defects," birth defects such as spina bifida that occur when the fetus's spine and back do not close during development. Women also take folic acid before and during pregnancy to prevent other complications such as increased blood pressure during pregnancy and to improve the growth and development of the child.

Some people use folic acid to prevent various types of cancer, including colon cancer or cervical cancer, as well as to reduce nerve pain in people with high levels of blood sugar (diabetes). It is also used to prevent heart disease and stroke, as well as to reduce blood levels of a chemical called homocysteine. High homocysteine levels might be a risk for heart disease.

Folic acid is used for pimples on the skin, gum inflammation, memory loss, Alzheimer's disease, age-related hearing loss, preventing the eye disease age-related macular degeneration (AMD), reducing signs of aging, weak bones (osteoporosis), a disorder that causes a strong urge to move ones legs (restless legs syndrome; RLS), sleep problems, depression or feeling down, seizures, nerve pain, muscle or bone pain, AIDS, a skin disease called vitiligo, an inflammatory disease called gout, and an inherited disease called Fragile-X syndrome. It is also used for reducing harmful side effects of treatment with the medications nitroglycerin, lometrexol or methotrexate. Folic acid is used to help the body make sperm.

Some people apply folic acid directly to the gum for treating gum infections.

If it is difficult for the patient to take folic acid by mouth, it is sometimes given with a needle for preventing and treating low blood levels of folate (folate deficiency). Folic acid is also given with a needle for chronic fatigue syndrome, a condition with chronic fever, aches, and tiredness.

Folic acid is often used in combination with other B vitamins.

How does work?

Folate is needed for the proper development of the human body. It is involved in producing the genetic material called DNA and in numerous other bodily functions.

QUESTION

The first sign of pregnancy is most often: See Answer

Uses

Effective for...

Folate deficiency. Taking folic acid improves folate deficiency.

Likely Effective for...

Kidney disease. About 85% of people with serious kidney disease have high levels of homocysteine. High levels of homocysteine have been linked to heart disease and stroke. Taking folic acid lowers homocysteine levels in people with serious kidney disease. However, folic acid supplementation does not appear to reduce the risk of heart disease-related events.
High amounts of homocysteine in the blood (hyperhomocysteinemia). High levels of homocysteine have been linked to heart disease and stroke. Taking folic acid lowers homocysteine levels by 20% to 30% in people with normal to slightly elevated homocysteine levels. It is recommended that people with homocysteine levels greater than 11 micromoles/L supplement with folic acid and vitamin B12.
Reducing harmful effects of a medicine called methotrexate. Taking folic acid seems to reduce nausea and vomiting, which are possible side effects of methotrexate treatment.
Birth defects (neural tube defects). Consuming high amounts of folate in the diet and taking folic acid supplements during pregnancy reduces the risk of neural tube birth defects.

Possibly Effective for...

Age-related vision loss (age-related macular degeneration). Some research shows that taking folic acid with other vitamins including vitamin B6 and vitamin B12 reduces the risk of developing age-related vision loss.
Depression. Limited research suggests that taking folic acid along with antidepressants seems to improve symptoms in people with depression.
High blood pressure. Research suggests that taking folic acid daily for at least 6 weeks reduces blood pressure in people with high blood pressure. However, taking folic acid with blood pressure medication does not seem to lower blood pressure any more than taking just the medication alone.
Gum problems due to a drug called phenytoin. Applying folic acid to the gums seems to prevent gum problems caused by phenytoin. However, taking folic acid by mouth does not seem to improve symptoms of this condition.
Gum disease during pregnancy. Applying folic acid to the gums seems to improve gum disease during pregnancy.
A skin discoloration disorder called vitiligo. Taking folic acid by mouth seems to improve symptoms of vitiligo.

Possibly Ineffective for...

Preventing re-blockage of blood vessels after angioplasty. There is inconsistent evidence on the benefits of taking folic acid after a procedure to widen the blood vessels. However, taking folic acid plus vitamin B6 and vitamin B12 might actually interfere with healing in cases where a device (stent) is inserted in the blood vessel to keep it open.
Cancer of the white blood cells (acute lymphoblastic leukemia). Taking folate during pregnancy does not reduce the risk of childhood cancer of the white blood cells.
Iron deficiency. Taking folic acid with iron supplements is not more effective than taking the iron supplements without folic acid for treating and preventing iron deficiency and anemia caused by too little iron in the body.
Breast cancer. Consuming folate in the diet might lower the risk of developing breast cancer in women who also eat high amounts of methionine, vitamin B12 (cyanocobalamin), or vitamin B6 (pyridoxine), but research is not consistent. Other research suggests that taking folic acid supplements alone does not lower the risk of breast cancer.
Heart disease. Research suggests that taking folic acid alone or with vitamin B6 (pyridoxine) and vitamin B12 does not reduce the risk of death or heart disease-related events in people with heart disease.
Chronic fatigue syndrome. Daily injections of folic acid appear to have no effect on symptoms of chronic fatigue syndrome.
Memory and thinking skills in older people. Most evidence does not suggest that folic acid is beneficial for age-related decline in memory and thinking skills.
Diarrhea. Taking a specific nutritional supplement with added folic acid and possibly vitamin B12 does not seem to prevent diarrhea in children at risk of malnutrition. Taking this product may increase the risk of having diarrhea last more than a few days.
Fetal and early infant death. Taking folic acid during pregnancy does not seem to reduce the risk of having a baby die just before or after birth.
Toxicity from the drug lometrexol. Daily injections of folic acid appear to have no effect on symptoms of chronic fatigue syndrome.
Lower respiratory tract infections.Taking a specific nutritional supplement with added folic acid and possibly vitamin B12 does not seem to prevent infections in the lungs in children at risk of malnutrition.
Weak bones (osteoporosis). In elderly individuals with osteoporosis, taking folic acid with vitamin B12 and possibly vitamin B6 (pyridoxine) does not seem to prevent broken bones.
Premature infants. Taking folic acid during pregnancy does not seem to decrease the risk of having a premature baby.

Likely Ineffective for...

Growths in the large intestine and rectum (colorectal adenoma).Taking folic acid supplements does not seem to prevent growths in the large intestine or rectum.
Inherited disease called Fragile-X syndrome.Taking folic acid by mouth does not improve symptoms of fragile-X-syndrome.

Insufficient Evidence to Rate Effectiveness for...

Acne. Limited evidence suggests that taking a specific nutritional supplement, containing vitamin B3 (nicotinamide), a compound isolated from grains (azelaic acid), zinc, vitamin B6 (pyridoxine), copper, and folic acid (NicAzel, Elorac Inc., Vernon Hills, IL) appears to reduce inflammation associated with pimples on the face.
Alzheimer's disease. Limited evidence suggests that elderly people who consume more folic acid than the recommended dietary allowance (RDA) appear to have a lower risk of developing Alzheimer's disease than people who consume less folic acid.
Autism. Limited research suggests taking folic acid during pregnancy might reduce the risk of autism in the child.
Beta-thalassemia. Beta-thalassemia is a disorder of the blood that results in the production of less hemoglobin, the protein that carries oxygen in the blood. Patients with beta-thalassemia usually have bone and muscle pain and have less strength. In children with this disorder, limited research suggests taking folic acid by itself, or with L-carnitine a compound similar to an amino acid from protein, might reduce bone pain and help increase strength.
Bipolar disorder. Taking folic acid does not appear to improve the antidepressant effects of lithium in people with bipolar disorder. However, taking folate with the medication valproate improves the effects of valproate.
Cervical cancer. There is some evidence that increasing folic acid and folate intake from dietary and supplement sources, along with thiamine, riboflavin, and vitamin B12, might help to prevent cervical cancer.
Colon cancer, rectal cancer. Research suggests that taking folic acid or eating folate in the diet can reduce the risk of developing colon or rectal cancer. However, there is some research that does not suggest that taking folic acid or folate in the diet offers the same benefit. It is possible that folic acid may be more helpful for preventing colon cancer than rectal cancer or it may be more helpful for specific kinds of colon cancer.
Diabetes. Taking folic acid supplements does not seem to benefit people with diabetes.
Epilepsy. Taking folic acid does not reduce seizures in people with epilepsy.
Esophageal cancer. Research suggests that consuming more folate in the diet lowers the risk for developing esophageal cancer.
High amounts of homocysteine in the blood caused by the drug fenofibrate. Taking folic acid every other day might lower levels of homocysteine in the blood caused by the drug fenofibrate.
Stomach cancer. Research suggests that taking folic acid reduces the risk of developing some types of stomach cancer.
Gout. Early research suggests that folate might reduce the risk of gout.
Hearing loss. Low levels of folate in the blood seem to be related to the risk for sudden hearing loss in adults. Some evidence suggests that taking folic acid daily for 3 years slows the decline of hearing loss in older people who have low folate levels. It is not clear if folic acid supplementation reduces hearing loss in people with normal folate levels.
Low birth weight. Taking folic acid during pregnancy does not prevent some babies from being born at a low birth weight but it does seem to increase the overall average of birth weights. However, some early research suggests that taking folic acid before getting pregnant might reduce the risk of having a baby that is too small even when born full term. Although this risk is not reduced in mothers that start supplementation after the baby is conceived.
Male infertility. Some research suggests that taking folic acid plus zinc sulfate daily can increase sperm count in men with low sperm counts.
Lung cancer. There does not appear to be a relationship between low levels of folic acid and lung cancer in most people.
A type of skin cancer called melanoma. Limited research suggests that taking folic acid supplements might reduce the risk of melanoma (91312).
Helping medicines used for chest pain work longer. Some evidence suggests that taking folic acid does not help medications for chest pain (nitrates) work longer.
Cleft lip. Some research suggests that taking folic acid during pregnancy lowers the risk of left lip. However, other research shows no effect.
Pancreatic cancer. Eating more than 280 mcg of folate in the diet daily is linked to a lower risk of developing pancreatic cancer. However, other research suggests that folate intake is not linked to pancreatic cancer risk.
Nerve pain (peripheral neuropathy). There is conflicting evidence about the role of folic acid in nerve pain for people with diabetes (diabetic neuropathy). Some research suggests that taking folic acid with vitamin B6 (pyridoxine) and vitamin B12 improves some symptoms of nerve pain so that people feel happier. However, the nerves do not seem to function any better.
Cancer of the throat. Limited research suggests folic acid and folate from dietary and sources and supplements may protect against oropharyngeal cancer, a specific type of throat cancer.
Pre-eclampsia. Pre-eclampsia is marked by high blood pressure and protein in the urine during pregnancy. Limited research suggests taking folic acid supplements during pregnancy does not reduce the risk of pre-eclampsia.
Pregnancy-induced high blood pressure. Limited research suggests that taking folic acid during pregnancy does not reduce the risk of high blood pressure (gestational hypertension).
A disorder that causes a strong urge to move ones legs (restless legs syndrome; RLS). Taking folic acid seems to reduce symptoms of restless legs syndrome. Researchers are studying whether folic acid deficiency causes restless legs syndrome.
Schizophrenia. Taking a combination of folic acid and vitamin B12 may reduce some of the negative symptoms associated with schizophrenia, but only in some patients with a specific genetic make-up. In most people, folic acid does not help with these symptoms.
Sickle-cell disease. Taking folic acid might lower homocysteine levels. However, it is not known if this will benefit people with sickle-cell disease.
Stroke. Research suggests that people with high folate intake from the diet have a lower risk of stroke due to blood vessel ruptures (hemorrhagic stroke). However, intake of folate or folic acid from the diet does not seem to reduce the risk of stroke due to blood clots (ischemic stroke). Also, taking folic acid supplements does not seem to reduce the risk of stroke in people that live in areas where folic acid is added to some foods (folic acid fortification) but taking folic acid might reduce stroke risk in areas where foods are not fortified.
Cancer due to a disease called ulcerative colitis. Early research suggests that taking folic acid might prevent cancer in people with ulcerative colitis.
Alcoholism.
Liver disease.
Other conditions.

More evidence is needed to rate folic acid for these uses.

Side Effects

Folic acid is LIKELY SAFE for most people when taken by mouth or injected into the body. Most adults do not experience any side effects when used in doses less than 1 mg daily.

Folic acid is POSSIBLY UNSAFE when taken by mouth in large doses, long-term. High doses of folic acid might cause abdominal cramps, diarrhea, rash, sleep disorders, irritability, confusion, nausea, stomach upset, behavior changes, skin reactions, seizures, gas, excitability, and other side effects.

There is some concern that taking too much folic acid for a long period of time might cause serious side effects. Some research suggests that taking folic acid in doses of 800 mcg to 1.2 mg might increase the risk of heart attack in people who have heart problems. Other research suggests that taking these high doses might also increase the risk of cancer such as lung or prostate cancer.

Precautions

Pregnancy and breast-feeding: Folic acid is LIKELY SAFE when taken by mouth appropriately during pregnancy and breast-feeing. Taking 300-400 mcg of folic acid daily is commonly used during pregnancy to prevent birth defects.

Procedures to widen narrowed arteries (angioplasty): Using folic acid, vitamin B6, and vitamin B12 intravenously (by IV) or by mouth might worsen narrowed arteries. Folic acid should not be used by people recovering from this procedure.

Cancer: Early research suggests that taking 800 mcg to 1 mg of folic acid daily might increase the risk of cancer. Until more is known, people with a history of cancer should avoid high doses of folic acid.

Heart disease: Early research suggests that taking folic acid plus vitamin B6 might increase the risk for heart attack in people with a history of heart disease.

Malaria: Early research suggests that taking folic acid plus iron might increase the risk of death or need for treatment in hospital in areas of the world where malaria is common.

Anemia caused by vitamin B12 deficiency: Taking folic acid might mask anemia caused by vitamin B12 deficiency and delay appropriate treatment.

Seizure disorder: Taking folic acid supplements might make seizures worse in people with seizure disorders, particularly in high doses.

SLIDESHOW

16 Early Signs & Symptoms of Pregnancy: Could You Be Pregnant? See Slideshow

Interactions

5-FluorouracilInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

There is some concern that taking large amounts of folic acid with 5-fluorouracil might increase some side effects of 5-fluorouracil, especially stomach problems. Talk with your healthcare provider before taking folic acid.

Capecitabine (Xeloda)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

There is some concern that taking large amounts of folic acid might increase the side effects of capecitabine, especially stomach problems like diarrhea and vomiting. Talk with your healthcare provider before taking folic acid.

Fosphenytoin (Cerebyx)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Fosphenytoin (Cerebyx) is used for seizures. The body breaks down fosphenytoin (Cerebyx) to get rid of it. Folic acid can increase how quickly the body breaks down fosphenytoin (Cerebyx). Taking folic acid along with fosphenytoin (Cerebyx) might decrease the effectiveness of fosphenytoin (Cerebyx) for preventing seizures.

Methotrexate (MTX, Rheumatrex)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Methotrexate (MTX, Rheumatrex) works by decreasing the effects of folic acid in the body's cells. Taking folic acid pills along with methotrexate might decrease the effectiveness of methotrexate (MTX, Rheumatrex).

Phenobarbital (Luminal)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Phenobarbital (Luminal) is used for seizures. Taking folic acid can decrease how well phenobarbital (Luminal) works for preventing seizures.

Phenytoin (Dilantin)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

The body breaks down phenytoin (Dilantin) to get rid of it. Folic acid might increase how quickly the body breaks down phenytoin (Dilantin). Taking folic acid and taking phenytoin (Dilantin) might decrease the effectiveness of phenytoin (Dilantin) and increase the possibility of seizures.

Primidone (Mysoline)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Primidone (Mysoline) is used for seizures. Folic acid might cause seizures in some people. Taking folic acid along with primidone (Mysoline) might decrease how well primidone works for preventing seizures.

Pyrimethamine (Daraprim)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Pyrimethamine (Daraprim) is used to treat parasite infections. Folic acid might decrease the effectiveness of pyrimethamine (Daraprim) for treating parasite infections.

Dosing

The following doses have been studied in scientific research:

ADULTS

BY MOUTH:

For folic acid deficiency: the typical dose is 250 mcg (micrograms) to 1 mg (milligrams) per day.
For preventing neural tube defects: at least 400 mcg of folic acid per day from supplements or fortified food should be taken by women capable of becoming pregnant and continued through the first month of pregnancy. Women with a history of previous pregnancy complicated by such neural tube defects usually take 4 mg per day beginning one month before and continuing for three months after conception.
For reducing colon cancer risk: 400 mcg per day.
For treating high levels of homocysteine in the blood:

o 200 mcg to 15 mg/day has been used, although 800 mcg to 1 mg/day appears to be more effective.
In people with end-stage renal disease, high homocysteine levels may be more difficult to treat, and doses of 800 mcg to 40 mg/day have been used. Other dosage plans such as 2.5-5 mg 3 times weekly have also been used. Doses higher than 15 mg daily do not seem to be more effective.

For improving the response to medications for depression: 200-500 mcg daily has been used.
For vitiligo: 5 mg is typically taken twice daily.
For reduction of toxicity associated with methotrexate therapy for rheumatoid arthritis (RA) or psoriasis: 1 mg/day is probably enough, but up to 5 mg/day may be used.
For preventing macular degeneration: folic acid 2.5 mg, vitamin B12 (cyanocobalamin) 1000 mg, and vitamin B6 (pyridoxine) 50 mg daily.

APPLIED TO THE SKIN:

For gum problems in pregnancy: a mouthwash containing folic acid has been used twice daily for one minute.

GIVEN BY NEEDLE:

For homocysteine lowering in people with end-stage renal disease (ESRD): 10 mg post-hemodialysis three times per week has been given in the vein.

CHILDREN

BY MOUTH:

For gum problems due to a drug called phenytoin (6-15 years): folic acid 500 mcg daily has been used.

The adequate intakes (AI) for infants are 65 mcg for infants 0-6 months and 80 mcg for infants 7-12 months of age. The recommended dietary allowances (RDAs) for folate in DFE, including both food folate and folic acid from fortified foods and supplements are: Children 1-3 years, 150 mcg; Children 4-8 years, 200 mcg; Children 9-13 years, 300 mcg; Adults over 13 years, 400 mcg; Pregnant women 600 mcg; and breast-feeding women, 500 mcg. The tolerable upper intake levels (UL) of folate are 300 mcg for children 1-3 years of age, 400 mcg for children 4-8 years, 600 mcg for children 9-13 years, 800 mcg for adolescents 14-18 years, and 1 mg for everyone over 18 years of age.

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).

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Liem, A. H., van Boven, A. J., Veeger, N. J., Withagen, A. J., Robles de Medina, R. M., Tijssen, J. G., and van Veldhuisen, D. J. Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial. Int J Cardiol 2004;93(2-3):175-179. View abstract.

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Raman, G., Tatsioni, A., Chung, M., Rosenberg, I. H., Lau, J., Lichtenstein, A. H., and Balk, E. M. Heterogeneity and lack of good quality studies limit association between folate, vitamins B-6 and B-12, and cognitive function. J Nutr 2007;137(7):1789-1794. View abstract.

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