In this article, we describe:
- the major purposes of this specific nutrient in the human body,
- its experimentally confirmed health uses,
- conventional ways to estimate nutrient status,
- nutrient’s toxicities and deficiencies,
- experimentally confirmed and approved levels of the nutrient intake for different demographics,
- dietary sources of the nutrient.
Folate is a water-soluble B vitamin that is naturally present in some foods. Folate is sometimes called “vitamin B9”. It is a generic term for naturally occurring food, dietary supplements and fortified foods folates including folic acid. Folic acid is the fully oxidized monoglutamate form of the vitamin that is used in fortified foods and most dietary supplements. Some dietary supplements also contain folate in the monoglutamyl form, 5-methyl-THF (also known as L-5- MTHF, 5-MTHF, L-methylfolate, and methylfolate).
Folate functions as a coenzyme in single-carbon transfers in the synthesis of nucleic acids (DNA and RNA), metabolism of amino acids, and in the synthesis of S-adenosyl-methionine, an important methyl donor. Another folate-dependent reaction, the methylation of deoxyuridylate to thymidylate in the formation of DNA, is required for proper cell division. An impairment of this reaction initiates a process that can lead to megaloblastic anemia, one of the hallmarks of folate deficiency.
B Complex vitamins are all water soluble and are not stored very well in the body. Thus, they are needed daily through diet or supplement to support their many functions. Deficiencies of one or more of the B vitamins may occur fairly easily, especially during times of fasting or dieting for weight loss or with diets that include substantial amounts of refined and processed food, sugar, or alcohol.
B complex vitamins are fairly easily digested from food or supplements and then absorbed into the blood, mainly from the small intestine. When the amount of Bs taken exceeds the body’s needs, the excess is easily excreted in the urine, giving it a dark yellow color.
Serum folate concentrations are sensitive to recent dietary intake and commonly used to assess folate status. A value above 3 ng/mL indicates adequacy. Erythrocyte folate concentrations provide a longer-term measure of folate intakes; a concentration above 140 ng/mL indicates adequate folate status.
Plasma homocysteine concentration is a commonly used functional indicator of folate status because homocysteine levels rise when the body cannot convert homocysteine to methionine due to a 5-MTHF deficiency. The most commonly used cutoff value for elevated homocysteine levels is 16 micromol/L, although slightly lower values of 12 to 14 micromol/L have also been used.
Isolated folate deficiency is uncommon and usually coexists with other nutrient deficiencies because of its strong association with poor diet, alcoholism, and malabsorptive disorders. Megaloblastic anemia is the primary clinical sign of folate or vitamin B12 deficiency.
Inadequate maternal folate status has been associated with low infant birth weight, preterm delivery, and fetal growth retardation.
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The following groups are among those most likely to be at risk of folate inadequacy: people with alcohol use disorder; women of childbearing age; pregnant women; people with malabsorptive disorders; people with the MTHFR polymorphism. Research had shown that inadequate folate status may exist for autism spectrum disorder; cancer (though data about dosage is controversial); cardiovascular disease and stroke; dementia, cognitive function, and Alzheimer’s disease; depression; preterm birth, congenital heart defects, and other congenital anomalies including Neural Tube Disorders.
Speaking about health benefits, it is worth mentioning that large amounts of folate can correct the megaloblastic anemia, but not the neurological damage, that can result from vitamin B12 deficiency. Some experts have therefore been concerned that high intakes of folate supplements might “mask” vitamin B12 deficiency until its neurological consequences become irreversible.
Concerns have been raised that high folic acid intakes might accelerate the progression of preneoplastic lesions, increasing the risk of colorectal and possibly other cancers in certain individuals. In addition, intakes of 1,000 mcg per day or more of folic acid from supplements during the periconception period have been associated with lower scores on several tests of cognitive development in children at ages 4–5 years than in children of mothers who took 400 mcg to 999 mcg.
Intakes of folic acid that exceed the body’s ability to reduce it to THF lead to unmetabolized folic acid in the body, which has been linked to reduced numbers and activity of natural killer cells, suggesting that it could affect the immune system. Unmetabolized folic acid might be related to cognitive impairment among older adults.
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Recommended Daily Allowances (RDAs) for Folate
Table below lists the current RDAs for folate as mcg of dietary folate equivalents (DFEs), to reflect the higher bioavailability of folic acid than that of food folate. At least 85% of folic acid is estimated to be bioavailable when taken with food, whereas only about 50% of folate naturally present in food is bioavailable.
- 1 mcg DFE = 1 mcg food folate
- 1 mcg DFE = 0.6 mcg folic acid from fortified foods or dietary supplements consumed with foods
- 1 mcg DFE = 0.5 mcg folic acid from dietary supplements taken on an empty stomach
|Birth to 6 months*||65 mcg DFE*||65 mcg DFE*|
|7–12 months*||80 mcg DFE*||80 mcg DFE*|
|1–3 years||150 mcg DFE||150 mcg DFE|
|4–8 years||200 mcg DFE||200 mcg DFE|
|9–13 years||300 mcg DFE||300 mcg DFE|
|14–18 years||400 mcg DFE||400 mcg DFE||600 mcg DFE||500 mcg DFE|
|19+ years||400 mcg DFE||400 mcg DFE||600 mcg DFE||500 mcg DFE|
* Adequate Intake (AI)
Food Sources of Folate
Folate is naturally present in a wide variety of foods, including vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, peas, seafood, eggs, dairy products, meat, poultry, and grains. Spinach, liver, asparagus, and brussels sprouts are among the foods with the highest folate levels.
In January 1998, the U.S. Food and Drug Administration (FDA) began requiring manufacturers to add 140 mcg folic acid/100 g to enriched breads, cereals, flours, cornmeals, pastas, rice, and other grain products to reduce the risk of neural tube defects (NTDs). Because cereals and grains are widely consumed in the United States, these products have become important contributors of folic acid to the American diet.
Since November 1, 1998, the Canadian government has also required the addition of 150 mcg folic acid/100 g to many grains, including enriched pasta, cornmeal, and white flour. Many other countries, including Costa Rica, Chile, and South Africa, have also established mandatory folic acid fortification programs.
Selected Food Sources of Folate and Folic Acid
|Braised beef liver, 3 ounces||215||54|
|Boiled spinach, ½ cup||131||33|
|Boiled black-eyed peas, ½ cup||105||26|
|Fortified breakfast cereals||100||25|
|Boiled asparagus, 4 spears||89||22|
|Boiled brussels sprouts, ½ cup||78||20|
|Shredded romaine lettuce, 1 cup||64||16|
|Raw avocado, sliced, ½ cup||59||15|
|Raw spinach, 1 cup||58||15|
|White rice, cooked, ½ cup||54||14|
|Cooked chopped broccoli, ½ cup||52||13|
|Boiled mustard greens, ½ cup||52||13|
|Boiled green peas, ½ cup||47||12|
|Canned kidney beans, ½ cup||46||12|
|Cooked spaghetti, ½ cup†||45||11|
|Wheat germ, 2 tablespoons||40||10|
|Canned tomato juice, ¾ cup||36||9|
|Dungeness crab, 3 ounces||36||9|
|Orange juice, ¾ cup||35||9|
|White bread, 1 slice†||32||8|
|Boiled turnip greens, ½ cup||32||8|
|Dry roasted peanuts, 1 ounce||27||7|
|Orange, 1 small||29||7|
|Raw papaya, cubed, ½ cup||27||7|
|Banana, 1 medium||24||6|
|Baker’s yeast, ¼ teaspoon||23||6|
|Hard-boiled egg, 1 large||22||6|
|Cantaloupe, cubed, ½ cup||17||4|
|Canned baked beans, ½ cup||15||4|
|Halibut fish, cooked, 3 ounces||12||3|
|Milk, 1% fat, 1 cup||12||3|
|Ground beef, cooked, 3 ounces||7||2|
|Roasted chicken breast, 3 ounces||3||1|
- *DV = Daily Value.
- The DV for folate used in the table above is 400 mcg for adults and children age 4 years and older. Manufacturers use the following conversion factors: 1 mcg DFE = 1 mcg naturally occurring folate = 0.6 mcg folic acid.
- Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.