Folic acid is a synthetic form of folate, also known as vitamin B9. Dietary supplements containing 5-MTHF, the form that's used by the body, are also available. Folate is a component of many foods, and supplementation is recommended as a treatment for health conditions that are linked to a folate deficiency. Its most common use is to promote the healthy development of the nervous system during pregnancy.
Folate was first identified in 1931 by scientist Lucy Wills who discovered that brewer's yeast, an extract high in folate, could reverse anemia during pregnancy. It was only in 1943 that scientists were able to isolate folate in its pure form, eventually synthesizing it in the lab as folic acid.
The synthesized vitamin served as the basis of the first cancer drug, aminopterin. Later, folic acid was found to prevent or treat other health conditions.
Neural Tube Defects
Folic acid is typically prescribed as a supplement during pregnancy to reduce the risk of neural tube defects. Neural tube defectsare birthdefectsof the brain, spine, or spinal cord. They develop during the first month of pregnancy, often before a woman even knows she is pregnant.
The two most commonneural tube defects are spina bifida (characterized by an undeveloped spine) and anencephaly (the absence of a major part of the brain, skull, and scalp).
Low levels of folate during pregnancy are associated with at least half of all neural tube defects. Taking 400 micrograms (mcg) of folic acid daily can reduce the risk of these defects by 50%, says the American Academy of Pediatrics.
Folic acid supplementation is considered the first-line defense against genetic birth defects like spina bifida and anencephaly.
Since 1998, folic acid has been added to cereals, baked goods, and other foods to further reduce the risk of neural tube defects. At least 80 countries have taken similar steps.
In addition to the prevention of neural tube defects, folic acid can be used to treat folate deficiency, often caused by ulcerative colitis, liver disease,alcoholism, andkidney dialysis.
- Folate deficiency can lead to a type of anemia known as megaloblastic anemia in which the bone marrow produces abnormal, immature red blood cells of unusually large size. Symptoms include extreme fatigue, heart palpitations, shortness of breath, open sores on the tongue, and changes in the color of the skin or hair.
- A deficiency of folate and other B vitamins can trigger a condition known as hyperhomocysteinemiain which there is too much of the amino acid homocysteine in the blood. This can occur in people with kidney disease or genetic disorders affecting the production of 5-MTHF. Chronic hyperhomocysteinemia is linked to an increased risk of cardiovascular disease, Alzheimer's disease, recurrent miscarriage, and bone fractures in the elderly.
Taking 250 mcg to 1,000 mcg of folic acid daily can usually help reverse folate deficiency.
Folic Acid and Inflammatory Bowel Disease (IBD)
Skin and Eye Disorders
Folic acid appears to be beneficial in the treatment of vitiligo, a chronic condition characterized by the loss of skin pigmentation. According to a two-year study from Sweden, the combination of folic acid and vitamin B12 appeared to completely stop the spread of vitiligo in 64% of the study participants.
The combination of folic acid and vitamin B12 also appears to slow the progression of macular degeneration, an aging-related eye disorder characterized by progressive vision loss, according to a 2016 study from Harvard University.
Compared to other supplements commonly used to treat macular degeneration, including thiamine (vitamin B1) and riboflavin (vitamin B2), high-dose folic acid proved most effective in slowing disease progression.
Folic acid is also believed by some to be effective in preventing stroke, treating high blood pressure, and alleviating symptoms of depression.
Limited benefits may include:
- While it is true that folic acid supplementation was shown to decrease the risk of stroke by 10-20% in poor developing countries, the same benefit was not seen in the developed world where fortification of food with folic acid is commonplace.
- The same applies to the relationship between hypertension (high blood pressure) and folic acid. While folic acid appears to reduce blood pressure slightly with ongoing use, it has no additive effect when used with traditional (and more effective) high blood pressure medications.
- Similarly, while depression is associated with low folate levels, the increased intake of folic acid has proven beneficial in some studies but not others, according to research from the Centers of Disease Control and Prevention.
There is no definitive evidence that it can treat Alzheimer's disease, bipolar depression, or chronic fatigue syndrome.
Potential Side Effects
Folic acid supplements are generally safe and well-toleratedwhen taken as prescribed. Doses over 1,000 mcg may cause side effects, including abdominal cramps, stomach upset, diarrhea, flatulence, taste disturbances, irritability, jitteriness, insomnia, nausea, and skin color changes.
Although rare, animal studies have shown that folic acid may cause behavior changes and seizures at very high doses.
Certain people may experience symptoms of a hypersensitive reaction, including rash, itchiness, and swelling. While rare, potentially life-threatening, whole-body reactions, called anaphylaxis, have been known to occur.
Call 911 or go to your nearest emergency room if you develop rash or hives, shortness of breath, wheezing, rapid heartbeat, dizziness, or the swelling of the face, throat, or tongue after taking a folic acid supplement.
Prostate Cancer Risk
Because they are nearly identical in molecular structure, folic acid and folate are considered by many to be the same thing. But they aren't.
What differentiates the two is how they are used by the body.
- Folate is converted in the digestive tract into the active form of vitamin B9, called 5-methyl-THF (5-MTHF).
- Folic acid needs to enter the bloodstream and be delivered to the liver and other tissues to be converted into 5-MTHF. It is a slow and inefficient process and one that can leave much of folic acid unmetabolized and freely circulating in the body.
About 30-40% of the population may have an MTHFR genetic defect impairing the conversion of folic acid to active folate.
While high levels of circulating folic acid won't cause harm to most people, there have been suggestions that high concentrations may increase the risk of prostate cancer.
In terms of prostate cancer risk, men who consistently take 1,000 mcg or more of folic acid appear to be at the greatest potential risk. On the flip side, men who get enough folate in their diet are at less risk.
Despite these shortcomings, folic acid is inexpensive, non-toxic, and unlikely to cause side effects unless taken in excess.
Folic acid can reduce the effectiveness of certain drugs, including:
- Anticonvulsants like Cerebryx (fosphenytoin), Dilantin (phenytoin), and Mysoline (primidone)
- Barbituates like Amytal (amobarbital), Butisol (butabarbital), and Luminal (phenobarbital)
- Methotrexate used to treat certain autoimmune disorders and cancer
- Daraprim (pyrimethamine) used to prevent malaria
Certain drugs can interfere with the absorption of folic acid, undermining its efficacy.
- Acid blockers, including antacids, H2 blockers, and proton pump inhibitors
- Azulfidine (sulfasalazine) use to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease
Separating drug and folic acid doses by two to four hours can often help prevent interactions, but it's best to talk with your healthcare provider and pharmacist for more specific advice.
Dosage and Preparation
Folic acid supplements are available over the counter in most drugstores, nutritional supplements stores, health food shops, and larger grocery stores. They can be found in capsule, tablet, soft gel cap, chewable tablet, and gummy forms.
Common doses range from 400 to 800 mcg in supplements for adults and 200 to 400 mcg in children’s multivitamins. Folic acid can be taken with food but is better absorbed on an empty stomach.
According to the Office of Dietary Supplements, only around 85% of folic acid will become available in the bloodstream if taken with food. When taken without food, nearly 100% of the folic acid will become bioavailable.
It is often recommended that you take a B-complex supplement rather than individual B vitamins. Doing so can lead to imbalances and/or mask symptoms of deficiency. Folic acid supplements, for example, can sometimes mask a potentially dangerous B12 deficiency.
5-MTHF is found in many high-quality supplements. Sold under the brand names MetafolinandDeplin, a 5-MTHF supplement may be appropriate for people with liver disease or genetic disorders that impede the conversion of folic acid.
Metafolin is available OTC and there are other 5-MTHF preparations in other supplements. Deplin is a prescription drug, that contains 15mg of 5-MTHF and is approved for the treatment of depression.
It is possible that taking 5-MTHF might not increase the risk of prostate cancer.
What to Look For
Vitamin supplements are not stringently regulated in the United States and can vary in quality from one brand to the next. To ensure quality and safety, choose supplements that have been tested and certified by an independent certifying body like the U.S. Pharmacopeia, ConsumerLab, or NSF International.
Which foods are highest in folic acid?
Generally speaking, you can get all of the folic acid you need from food, particularly now that cereals and other foods are fortified with the B vitamin. Even if you take a folic acid supplement, you can bolster your intake with the following real food options:
- Beef liver: 215 mcg per 3-ounce serving
- Spinach (cooked): 131 mcg per ½-cup serving
- Black-eyed peas: 105 mcg per ½-cup serving
- Asparagus: 89 mcg per four spears
- Brussel sprouts: 78 mcg per ½-cup serving
- Romaine lettuce: 64 mcg per one-cup serving
- Avocado: 58 mcg per ½-cup serving
- White rice (cooked): 54 mcg per ½-cup serving
- Broccoli: 52 mcg per ½-cup serving
- Mustard greens (cooked): 52 mcg per ½-cup serving