Folic Acid

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What is it?

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) and high blood levels of homocysteine (hyperhomocysteinemia). Women who are pregnant or might become pregnant take folic acid to prevent miscarriage and “neural tube defects.” These are serious birth defects such as spina bifida, when the fetal spine and back do not close in the womb. Folic acid is also used for many other conditions including depression, stroke, decline in memory and thinking skills in older people that is more than what is normal for their age, and many others.

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

It is effective?
Natural Medicines rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.

Effective for …

  • Folate deficiency. Taking folic acid improves folate deficiency.

Probably Effective for …

  • Kidney failure. About 85% of people with kidney failure 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 kidney failure. But it does not seem to reduce the risk of heart disease-related events.
  • High levels 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.
  • Toxicity caused by the drug methotrexate. Taking folic acid seems to reduce nausea and vomiting, which are possible side effects of methotrexate treatment.
  • Birth defects of the brain and spine (neural tube birth defects). Folic acid during pregnancy reduces the risk of neural tube birth defects. It is recommended that pregnant women get 600-800 mcg of folic acid per day from their diet or supplements starting 1 month before pregnancy and during pregnancy. Pregnant women with a history of neural tube birth defects are advised to get 4000 mcg of folic acid per day.

Possibly Effective for …

  • Decline in memory and thinking skills in older people that is more than what is normal for their age. Taking folic acid with or without other supplements may improve memory and thinking skills in older people with this condition. Folic acid seems to work best in people who have low levels of folate or high levels of homocysteine in the blood.
  • Depression. Limited research shows that taking folic acid along with antidepressants seems to improve symptoms in people with depression.
  • High blood pressure. Research shows that taking folic acid daily for at least 6 weeks reduces blood pressure in people with high blood pressure. But Taking folic acid with blood pressure medication does not seem to lower blood pressure more than taking only blood pressure medicine
  • Gum enlargement caused by the drug 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.
  • Stroke. Taking folic acid can reduce the risk of stroke by 10% to 25% in people who live in countries that don’t fortify grain products with folic acid. But folic acid doesn’t seem to prevent strokes in most people who live in countries that do fortify grain products with folic acid.
  • A skin disorder that causes white patches to develop on the skin (vitiligo). Taking folic acid by mouth seems to improve symptoms of vitiligo.

Possibly Ineffective for …

  • Low levels of healthy red blood cells (anemia) due to 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.
  • Decline in memory and thinking skills that occurs normally with age. Most research shows that taking folic acid does not prevent decline in memory and thinking skills in the elderly.
  • Cataracts. Research shows that taking folic acid with other vitamins including vitamin B6 and vitamin B12 does not prevent cataracts. In fact, it might increase the chance of needing to have cataracts removed.
  • Diarrhea. Taking a specific nutritional supplement with added folic acid and vitamin B12 does not seem to prevent diarrhea in children at risk of malnutrition. Taking this product may increase the risk of having diarrhea that lasts more than a few days.
  • Fall prevention. Taking folic acid with vitamin B-12 does not seem to prevent falls in older people who are also taking vitamin D.
  • Male infertility. Folic acid alone or with other ingredients does not seem to improve male fertility.
  • Death of an unborn or premature baby. Taking folic acid during pregnancy does not seem to reduce the risk of having a baby die just before or after birth.
  • Cancer of the white blood cells (leukemia). Taking folate during pregnancy does not reduce the risk of childhood cancer of the white blood cells.
  • Weak and brittle 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.
  • Physical performance in elderly adults. Taking folic acid with vitamin B-12 doesn’t seem to help older people walk better or have stronger hands.
  • A pregnancy complication marked by high blood pressure and protein in the urine (pre-eclampsia). High-dose folic acid does not reduce the risk of pre-eclampsia. But it isn’t clear if low-dose folic acid is beneficial.
  • Infection of the airways. 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.

Probably Ineffective for …

  • Non-cancerous 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.
  • An inherited condition marked by learning disabilities (fragile-X syndrome). Taking folic acid by mouth does not improve symptoms of fragile X syndrome.
  • Preterm birth. Taking folic acid during pregnancy does not decrease the risk of having a premature baby.

Insufficient Evidence to Make a Determination for …

  • Alzheimer disease. Some limited evidence has found that elderly people who consume more folic acid in the diet or from supplements appear to have a lower risk of developing Alzheimer 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.
  • A blood disorder that reduces levels of protein in the blood called hemoglobin (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.
  • Breast cancer. Consuming folate in the diet might lower the risk of developing breast cancer in some patients. It is unclear if folic acid supplements are beneficial.
  • Heart disease. Some research shows that taking folic acid doesn’t reduce the risk of death in people with heart disease. But it might reduce the risk of stroke in people with this condition.
  • Cancer of the cervix. 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 cancer of the cervix.
  • Child development. Some research shows that taking folic acid supplements during the last 22 weeks of pregnancy may improve the child’s mental function during childhood.
  • Long-term kidney disease (chronic kidney disease or CKD). Taking folic acid might help slow kidney function decline in people with CKD. But it is not beneficial when used along with vitamin B12 (cyanocobalamin). In fact, this combination might make kidney disease worse.
  • 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.
  • Heart problems at birth. Women who take folic acid or prenatal vitamins containing folic acid have a lower chance of giving birth to babies with heart problems.
  • Diseases, such as Alzheimer disease, that interfere with thinking (dementia). Some research shows that folic acid might help prevent or treat Alzheimer disease. But other early research shows that it might not be useful for treating other types of dementia.
  • Diabetes. Taking folic acid supplements does not seem to benefit people with diabetes.
  • Seizure disorder (epilepsy). Taking folic acid does not reduce seizures in people with epilepsy. But some early research suggests that folic acid might reduce seizures in children that are deficient in folic acid.
  • Cancer of the esophagus. Research suggests that consuming more folate in the diet lowers the risk for developing cancer of the esophagus.
  • 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.
  • Head and neck cancer. Getting more folic acid from the diet has been linked to a lower risk of head and neck cancer.
  • 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.
  • Toxicity caused by the drug lometrexol. Taking folic acid by mouth might reduce the harmful effects of the cancer drug lometrexol.
  • Infants born weighing less than 2500 grams (5 pounds, 8 ounces). Taking folic acid during pregnancy seems to increase the weight of infants at birth. Taking folic acid before getting pregnant or soon after might reduce the risk of having a baby that is too small at birth.
  • Lung cancer. There does not appear to be a relationship between low levels of folic acid and lung cancer in most people.
  • The most serious type of skin cancer (melanoma). Early research shows that taking folic acid might reduce the risk of melanoma.
  • Reduced benefit of nitrate therapy that happens when nitrates are used all day (nitrate tolerance). Some evidence suggests that taking folic acid does not help medications for chest pain (nitrates) work longer.
  • Cleft lip and cleft palate. Some research suggests that taking folic acid during pregnancy lowers the risk of cleft 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.
  • A type of throat cancer (pharyngeal cancer). Limited research suggests folic acid and folate from dietary and sources and supplements may protect against oropharyngeal cancer, a specific type of throat cancer.
  • High blood pressure during pregnancy. Limited research found that taking folic acid during pregnancy does not reduce the risk of high blood pressure.
  • 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.
  • Acne.
  • Alcoholism.
  • An eye disease that leads to vision loss in older adults (age-related macular degeneration or AMD).
  • A procedure to open a blocked or narrowed blood vessel (angioplasty).
  • Chronic fatigue syndrome (CFS).
  • Decline in memory and thinking skills that occurs normally with age.
  • Eczema (atopic dermatitis).
  • Nerve pain in people with diabetes (diabetic neuropathy).
  • Gum disease in women who are pregnant.
  • Nerve damage in the hands and feet (peripheral neuropathy).
  • A disorder that causes leg discomfort and an irresistible urge to move the legs (restless legs syndrome or RLS).
  • Other conditions.

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

How does it 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.

Is there concern for the safety of its use?
When taken by mouth: Folic acid is LIKELY SAFE for most people. Most adults do not experience any side effects when taking doses of less than 1 mg daily. A different form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF), is POSSIBLY SAFE for most people in doses up to 416 mcg daily.

Folic acid is POSSIBLY UNSAFE when taken by mouth in large doses, long-term. Although doses up to 5 mg daily have been safely used in some research, doses of folic acid greater than 1 mg daily 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 also 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 daily 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.

When given as a shot: Folic acid is LIKELY SAFE for most people when injected into the body. Most adults do not experience any side effects when used in doses less than 1 mg daily.

Special Precautions & Warnings:

Pregnancy and breast-feeding: Folic acid is LIKELY SAFE when taken by mouth appropriately while pregnant or breast-feeing. Taking 300-400 mcg of folic acid daily is commonly used during pregnancy to prevent birth defects. The maximum recommended amount of folic acid during pregnancy or breast-feeding is 800 mcg daily for parents under 18 years of age and 1000 mcg daily for parents over 18 years of age. A different form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF), is POSSIBLY SAFE in doses up to 416 mcg daily.

Children: Folic acid is LIKELY SAFE when taken by mouth in the recommended amounts for each age group. But children should avoid taking doses of folic acid above the daily upper limits, which are 300 mcg for children 1-3 years of age, 400 mcg for children 4-8 years of age, 600 mg for children 9-13 years of age, and 800 mcg for children 14-18 years of age. A different form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF), is POSSIBLY SAFE in children.

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.

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

Are there any drug interactions?

Fosphenytoin (Cerebyx)

Interaction Rating=Moderate Be cautious with this combination.

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.

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.

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.

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.

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

Pyrimethamine (Daraprim)

Interaction Rating=Moderate Be cautious with this combination.

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

Are there any interactions with herbs and supplements?
Green tea: There is some concern that green tea might keep folic acid from working the way it should in the body. This might lead to a condition that is similar to folic acid deficiency.
Vitamin B12: Folic acid, particularly in large doses, can hide vitamin B12 deficiency, and cause serious health effects. Be sure that your healthcare provider checks your vitamin B12 levels before you start taking folic acid.
Zinc: Folic acid might interferes with zinc absorption. But for people who get enough zinc in their diet, the effect of folic acid probably isn’t important.

Are there any interactions with food?
Food: Taking folic acid with food reduces its absorption slightly, but probably not enough to be important.

What dose is used?
The following doses have been studied in scientific research:

ADULTS

BY MOUTH:

  • General: The recommended dietary allowances (RDAs) for folate are provided as Dietary Folate Equivalents (DFE). This is because the folic acid found in supplements is absorbed better by the body than the folate found in food. 1 mcg DFE is the same as 1 mcg of folate in food. 1 mcg DFE is the same as 0.6 mcg of folic acid supplement. The RDAs for adults are 400 mcg DFE for men and women, 600 mcg DFE for pregnant women, and 500 mcg DFE for lactating women.
  • For folic acid deficiency: The typical dose is 250 mcg (micrograms) to 1 mg (milligrams) per day.
  • For preventing birth defects of the brain and spine (neural tube birth defects): Women capable of becoming pregnant should take 400 mcg of folic acid per day from fortified foods or supplements. Women who are pregnant are advised to take 600 mcg of folic acid per day from fortified foods or supplements. Women with a history of previous pregnancy complicated by neural tube defects usually take 4 mg per day beginning one month before and continuing for up to 3 months after conception.
  • For reducing colon cancer risk: 400 mcg per day.
  • For treating high amounts of homocysteine in the blood (hyperhomocysteinemia):
    • 200 mcg to 15 mg per day has been used, although daily doses of 800 mcg to 1 mg appear to be most 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 per day have been used. Other dosage plans such as 2.5-5 mg three times weekly have also been used. Doses higher than 15 mg daily do not seem to be more effective than lower doses.
  • For improving the response to medications for depression: 200-500 mcg daily has been used.
  • For a skin disorder that causes white patches to develop on the skin (vitiligo): 5 mg is typically taken twice daily.
  • For reduction of toxicity caused by the drug methotrexate: 1 mg per day is probably enough, but up to 5 mg per day may be used.
  • For stroke. 500 mcg to 40 mg of folic acid per day have been used. The greatest benefit seems to occur with folic acid doses of 800 mcg per day or lower.

GIVEN BY NEEDLE:

  • Kidney failure: 10 mg post-hemodialysis three times per week has been given in the vein.

CHILDREN

BY MOUTH:

  • General: The daily adequate intakes (AI) for infants are 65 mcg DFE for infants 0-6 months of age and 80 mcg DFE for infants 7-12 months of age. The recommended dietary allowances (RDAs) for folate in children are 150 mcg for children 1-3 years of age, 200 mcg DFE for children 4-8 years of age, 300 mcg DFE for children 9-13 years of age, and 400 mcg DFE for adolescents 14-18 years of age. For pregnant girls, the RDA is 600 mcg DFE. For lactating girls the RDA is 500 mcg DFE.
  • For gum enlargement caused by the drug phenytoin (6-15 years): Folic acid 500 mcg daily has been used.

By what other names is the product known?
5′-methyltetrahydrofolate, 5′-methyltetrahydrofolic acid, 5′-MTHF, Acide Folique, Acide Ptéroylglutamique, Acide Ptéroylmonoglutamique, Acido Folico, B Complex Vitamin, Complexe de Vitamines B, Complexe Vitaminique B, Dihydrofolate, Dihydrofolic Acid, Folacin, Folacine, Folate, Folinic Acid, L-methylfolate, Methylfolate, Méthylfolate, Methylfolic Acid, Pteroylglutamic Acid, Pteroylmonoglutamic Acid, Pteroylpolyglutamate, Tetrahydrofolate, Tétrahydrofolate, Vitamin B9, Vitamine B9.

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