Folic acid (also known as vitamin B9 or folacin) and folate (the naturally occurring form), as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B9. Folic acid is itself not biologically active, but its biological importance is due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver.
Vitamin B9 (folic acid and folate inclusive) is essential to numerous bodily functions ranging from nucleotide biosynthesis to the remethylation of homocysteine. The human body needs folate to synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in biological reactions involving folate.It is especially important during periods of rapid cell division and growth. Children and adults both require folic acid in order to produce healthy red blood cells and prevent anemia. Folate and folic acid derive their names from the Latin word folium (which means "leaf"). Leafy vegetables are a principal source, although, in Western diets, fortified cereals and bread may be a larger dietary source.
A lack of dietary folic acid leads to folate deficiency (FD). This can result in many health problems, the most notable one being neural tube defects in developing embryos. Low levels of folate can also lead to homocysteine accumulation as a result of the impairment of one-carbon metabolism mechanism methylation.DNA synthesis and repair are impaired and this could lead to cancer development.Supplementation in patients with ischaemic heart disease may, however, lead to increased rates of cancer and all-cause mortality.
Folate in foods and other sources
Certain foods are very high in folate:
* Leafy vegetables such as spinach, asparagus, turnip greens
* Legumes such as dried or fresh beans, peas and lentils
* Liver and liver products also contain high amounts of folate
* baker's yeast
* fortified grain products (pasta, cereal, bread); some breakfast cereals (ready-to-eat and others) are fortified with 25% to 100% of the recommended dietary allowance (RDA) for folic acid
* sunflower seeds
* certain fruits (orange juice, canned pineapple juice, cantaloupe, honeydew melon, grapefruit juice, banana, raspberry, grapefruit, strawberry) and vegetables (beets, corn, tomato juice, vegetable juice, broccoli, brussels sprouts, romaine lettuce, bok choy), beer.
A table of selected food sources of folate and folic acid can be found at the USDA National Nutrient Database for Standard Reference. Folic acid is added to grain products in many countries, and, in these countries, fortified products make up a significant source of the population's folic acid intake. Because of the difference in bioavailability between supplemented folic acid and the different forms of folate found in food, the dietary folate equivalent (DFE) system was established. 1 DFE is defined as 1 μg of dietary folate, or 0.6 μg of folic acid supplement. This is reduced to 0.5 μg of folic acid if the supplement is taken on an empty stomach.
Folic acid naturally found in food is susceptible to high heat and UV, and is soluble in water. It is heat-labile in acidic environments and may also be subject to oxidation.
The risk of toxicity from folic acid is low because folate is a water-soluble vitamin and is regularly removed from the body through urine.The Institute of Medicine has established a tolerable upper intake level (UL) for folate of 1 mg for adult men and women, and a UL of 800 µg for pregnant and lactating (breast-feeding) women less than 18 years of age. Supplemental folic acid should not exceed the UL to prevent folic acid from masking symptoms of vitamin B12 deficiency.
Research suggests high levels of folic acid can interfere with some antimalarial treatments.
A 10,000-patient study at Tufts University in 2007 concluded that excess folic acid worsens the effects of B12 deficiency and in fact may affect the absorption of B12.
A study at the University of Adelaide concluded that the intake of folic acid supplements during late pregnancy increases the risk of babies developing childhood asthma by 30%, although researchers emphasized that their finding did not contradict recommendations to supplement folic acid in first trimester, when no additional risk was found.
Folate deficiency may lead to glossitis, diarrhea, depression, confusion, anemia, and fetal neural tube defects and brain defects (during pregnancy). Folate deficiency is diagnosed by analyzing CBC and plasma vitamin B12 and folate levels. CBC may indicate megaloblastic anemia but this could also be a sign of vitamin B12 deficiency. A serum folate of 3 μg/L or lower indicates deficiency. Serum folate level reflects folate status but erythrocyte folate level better reflects tissue stores after intake. An erythrocyte folate level of 140 μg/L or lower indicates inadequate folate status. Increased homocysteine level suggests tissue folate deficiency but homocysteine is also affected by vitamin B12 and vitamin B6, renal function, and genetics. One way to differentiate between folate deficiency from vitamin B12 deficiency is by testing for methylmalonic acid levels. Normal MMA levels indicate folate deficiency and elevated MMA levels indicate vitamin B12 deficiency. Folate deficiency is treated with supplemental oral folate of 400 to 1000 μg per day. This treatment is very successful in replenishing tissues even if deficiency was caused by malabsorption. Patients with megaloblastic anemia need to be tested for vitamin B12 deficiency before folate treatment because if the patient has vitamin B12 deficiency, folate supplementation can remove the anemia but can also worsen neurologic problems. Morbidly obese patients with BMIs of greater than 50 are more likely to develop folate deficiency. Patients with celiac disease have a higher chance of developing folate deficiency. Cobalamin deficiency may lead to folate deficiency, which, in turn, increases homocysteine levels and finally may result in the development of cardiovascular disease or birth defects.