Folate

Folate (folic acid)

SOURCE: Office of Dietary Supplements. National Institutes of Health. Folate: Fact Sheet for Health Professionals. U.S. Department of Health and Human Services. Last modified March 2, 2018. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional (accessed April 4, 2018).

Selected food sources of folate and folic acid

SOURCE: U.S. Department of Agriculture (USDA) Agricultural Research Service, National Nutrient Database for Standard Reference, Release 24.

Folate is necessary to create new DNA (genetic material) and RNA when cells divide. It plays a critical role in developing healthy red blood cells. Folate also helps protect DNA from damage that may lead to diseases such as cancer. Along with vitamins B₆ and B₁₂, folate helps regulate the level of the amino acid homocysteine in the blood. Homocysteine regulation is related to cardiovascular health. In the fetus, folate is necessary for the proper development of the brain and spinal cord.

Folate is one of eight B-complex vitamins. Its function is closely intertwined with that of vitamins B₆ and B₁₂. Folate, from the Latin word folium, meaning leaf, was discovered in the late 1930s in yeast, and later found in spinach and other green leafy vegetables and in liver. Starting in 1998, the U.S. Food and Drug Administration (FDA) required certain foods, such as flour, corn meal, bread, cereal, rice, and pasta, to be fortified with a folic acid. In Canada and Chile, fortification of flour is mandatory.

Folate is essential for the normal development of the neural tube in the fetus. The neural tube develops into the brain and spinal cord. It closes between the third and fourth week after conception. Too little folate at this time can lead to serious malformations of the spine (spina bifida) and the brain (anencephaly). Because many women do not realize that they are pregnant so soon after conception, the United States has included folic acid in its fortified foods program. Adding folic acid to common foods made with grains has substantially reduced the number of babies born with neural tube defects in the United States.

The body also needs folate to produce healthy red blood cells. When not enough folate is present, the red blood cells do not divide and instead grow to be abnormally large. These malformed cells have a reduced ability to carry oxygen to other cells in the body, a condition known as megaloblastic anemia. Folate also aids in the production of other new cells. Adequate supplies of folate are especially important in fetuses and infants because they are growing rapidly, but, since the life span of a red blood cell is only about four months, both children and adults need a continuous supply of folate throughout life to create healthy new replacement blood cells.

Folate acts together with vitamin B₆ and vitamin B₁₂ to lower the level of homocysteine in the blood. Homocysteine is an amino acid that is naturally produced when the body breaks down protein. Moderate to high levels of homocysteine in the blood are potentially linked to an increased risk of cardiovascular disease (e.g., atherosclerosis, heart attack, stroke). The trio of folate, vitamin B₆, and vitamin B₁₂ lower homocysteine levels. However, it is not clear whether taking large doses of these vitamins, either alone or in combination, will prevent heart disease from developing in healthy individuals. The official position of the American Heart Association in 2012 stated, “We don't recommend widespread use of folic acid and B vitamin supplements to reduce the risk of heart disease and stroke. We advise a healthy, balanced diet that's rich in fruits and vegetables, whole grains, and fat-free or low-fat dairy products.”

Damage to DNA appears to contribute to the development of many different cancers. Because folate helps protect against DNA damage, researchers have looked at whether it can reduce the risk of developing cancer. Results are mixed, with benefits seen for some cancers but not for others. The American Cancer Society position in 2012 was as follows: “Low levels of folic acid in the blood have been linked with higher rates of colorectal cancer and some other types of cancer, as well as with certain birth defects. It is not clear whether consuming recommended (or higher) amounts of folic acid—from foods or in supplements—can lower cancer risk in some people. These issues are being studied. High doses of folic acid can interfere with the action of some chemotherapy drugs, such as methotrexate.”

Many clinical trials are underway to determine the safety and effectiveness of folate, both alone and in combination with other vitamins, in preventing cancer, cardiovascular disease, and dementias, such as Alzheimer's disease. Research is also underway on the effect of folate on schizophrenia and the feasibility of including folate in birth control pills. Individuals interested in participating in a clinical trial at no charge can find a list of open trials at http://www.clinicaltrials.gov .

People need a continuous supply of folate from their diet because of the role it plays in creating new blood cells. Because folate is water-soluble, little is stored in the body, and any excess is excreted in urine. Since the folic acid fortification program began in 1998, most healthy Americans get enough folate from their diet. The exception is pregnant women who should, under medical supervision, take a folic acid supplement (400 mcg for most women and higher doses for those who have already had a baby with a neural tube defect). Good natural sources of folate include beef liver, green leafy vegetables, and dried beans. Cooking animal products does not reduce the folate content much, but cooking vegetables can reduce the amount of folate by up to 40%, depending on the vegetable and the cooking method.

The following list gives the approximate folate content of some common foods:

The U.S. Institute of Medicine (IOM) of the National Academy of Sciences has developed values called Dietary Reference Intakes (DRIs) for vitamins and minerals. The DRIs consist of three sets of numbers. The recommended dietary allowance (RDA) defines the average daily amount of the nutrient needed to meet the health needs of 97%–98% of the population. The adequate intake (AI) is an estimate set when there is not enough information to determine an RDA. The tolerable upper intake level (UL) is the average maximum amount that can be taken daily without risking negative side effects. The DRIs are calculated for children, adult men, adult women, pregnant women, and breastfeeding women.

The IOM has not set RDAs for folate in children under one year old because of incomplete scientific information. Instead, it has set AI levels for this age group. RDAs and ULs for folate are measured in micrograms (mcg). Unlike the UL for many vitamins, the UL for folate refers only to folic acid that comes from fortified food or that is in folic acid dietary supplements, multivitamins, or B-complex vitamins. There is no UL for folate found in natural plant and animal foods. Dietary supplements containing more than 1,000 mcg (1 mg) of folic acid require a prescription. One mcg of folate from natural food sources is equal in biological activity in humans to 0.6 mcg of folic acid from supplements or fortified food.

The following are the daily RDAs and AIs and ULs for folic acid for healthy individuals:

Since many pregnancies are unplanned and unrecognized until after the critical period for brain and spinal cord formation, any woman who may become pregnant should be careful to include enough folate in her diet, and folic acid supplements should be taken before and in the first trimester of pregnancy.

Folic acid may mask vitamin B₁₂ deficiency. Folic acid supplements will reverse anemia symptoms, but they do not stop nerve damage caused by B₁₂ deficiency. Permanent nerve damage may result. People with suspected folate deficiency who begin taking folic acid supplements should also be evaluated for vitamin B₁₂ deficiency.

The following is a partial list of medications that may interfere with the ability of the body to absorb and use folate. Individuals taking these medications should check with their physician about the effects they may have on folate levels in the body:

No complications are expected when folate or folic acid is taken within recommended levels.

Most healthy people in the United States get enough folate in their diet because folate is added to many common foods, such as bread; however, this is not the case elsewhere. In Europe, low intakes are commonly reported, particularly in teenage girls and older people. Causes of folate deficiency include inadequate intake, impaired absorption (celiac disease, Crohn's disease, certain medications), inability of the body to use folate (enzyme deficiencies), increased folate needs (pregnancy, cancer), or increased loss or excretion (kidney dialysis, alcoholism). The elderly are the largest group at risk to develop folate deficiency.

The major symptom of folate deficiency in pregnant women is having a baby born with a brain or spinal cord abnormality. Other symptoms of folate deficiency include slow growth in infants and children; megaloblastic anemia; digestive problems, such as diarrhea; sore tongue; irritability; forgetfulness; and changes in mental state. These changes also have other causes and should be evaluated by a healthcare professional.

Complications of excess folic acid intake at levels above 1,000 mcg daily over an extended period can include seizures in individuals taking anticonvulsant medications and general irritability and restlessness in otherwise healthy individuals.

Parents need to be aware that infants and rapidly growing children are at higher risk for folate deficiency. Parents of children with digestive disorders or allergies to wheat products (e.g., celiac disease) should discuss the need for a folic acid supplement with their pediatrician.

See also Adult nutrition ; Alcohol consumption ; Cancer-fighting foods ; Celiac disease ; Crohn's disease ; Fad diets ; Nutrigenomics ; Vitamin B⁶ ; Vitamin B¹² ; Vitamins ; Whole grains .