«Folate, distinct forms of which are known as folic acid, folacin, and vitamin B₉,^[7] is one of the B vitamins.^[4] It may be taken by mouth or by injection.^[4] The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.^[8] Folate in the form of folic acid is used to treat anemia caused by folic acid deficiency.^[4] Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby.^[4][9] Low levels in early pregnancy are believed to be the cause of more than half of babies born with NTDs.^[8] More than 80 countries use fortification of certain foods with folic acid as a measure to decrease the rate of NTDs.^[10] Long-term supplementation is also associated with small reductions in the risk of stroke and cardiovascular disease.^[11]

No common side effects are known.^[4] Concerns exist that large amounts of folic acid might hide vitamin B₁₂ deficiency. Folic acid is essential for the body to make DNA, RNA, and metabolise amino acids, which are required for cell division. Not consuming enough folate can lead to folate deficiency. This may result in a type of anemia in which low numbers of large red blood cell occur. Symptoms may include feeling tired, heart palpitations, shortness of breath, open sores on the tongue, and changes in the color of the skin or hair.^[8] Folate deficiency in children may develop within a month of poor dietary intake.^[12] In adults, normal total body folate is between 10 and 30 mg with blood levels of greater than 7 nmol/L (3 ng/mL).^[8]

Folate is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.^[13] The wholesale cost of supplements in the developing world is between US$0.001 and 0.005 per dose as of 2014.^[14] The term "folic" is from the Latin word folium (which means leaf) because it was found in dark-green leafy vegetables.^[15] Folate occur naturally in many foods.^[7][8]

"Folate" is the term used to name the many forms of the vitamin—namely folic acid and its congeners, including tetrahydrofolic acid (the activated form of the vitamin), methyltetrahydrofolate (the primary form found in the serum), methenyltetrahydrofolate, folinic acid, and folacin.^{[7][16][17][18]} Other name include vitamin B₉,^[1] vitamin B_c,^[2] vitamin M,^[3] and pteroyl-L-glutamate.

Folate is necessary for the production and maintenance of new cell, for DNA synthesis and RNA synthesis through methylation, and for preventing changes to DNA, thus for preventing cancer.^[19] It is especially important during periods of frequent cell division and growth, such as infancy and pregnancy. Folate deficiency hinders DNA synthesis and cell division, affecting hematopoietic cell and neoplasms the most because of their greater frequency of cell division. RNA transcription and subsequent protein synthesis are less affected by folate deficiency, as the mRNA can be recycled and used again (as opposed to DNA synthesis, where a new genomic copy must be created). Since folate deficiency limits cell division, erythropoiesis (production of red blood cell) is hindered. This lead to megaloblastic anemia, which is characterized by large, immature red blood cell. This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division, and produces abnormally large red cell called megaloblasts (and hypersegmented neutrophils) with abundant cytoplasm capable of RNA and protein synthesis, but with clumping and fragmentation of nuclear chromatin. Some of these large cell, although immature (reticulocytes), are released early from the marrow in an attempt to compensate for the anemia.^[20] Both adults and children need folate to make normal red and white blood cell and prevent anemia.^[21] Deficiency of folate in pregnant women has been implicated in NTDs; therefore, many developed countries have implemented mandatory folic acid fortification in cereals, etc. NTDs occur early in pregnancy (first month), therefore women must have abundant folate upon conception. Folate is required to make red blood cell and white blood cell and folate deficiency may lead to anemia, which causes fatigue, weakness, and inability to concentrate.^[22]

Folate intake during pregnancy has been linked to a lessened risk of neural tube defects (NTDs), and for this reason there is a recommendation that any woman planning to become pregnant consume a folate-containing dietary supplement before and during pregnancy.^[23] Compliance with this recommendation is not complete, and many women become pregnant without this being a planned pregnancy, or may not realize that they are pregnant until well into the first trimester, which is the critical period for reducing risk of NTDs. Countries have implemented either mandatory or voluntary food fortification of wheat flour and other grains, or else have no such program and depend on public health and healthcare practitioner advice to women of childbearing age. A meta-analysis of global birth prevalence of spina bifida showed that when mandatory fortification was compared to countries with voluntary fortification or no fortification program, there was a 30% reduction in live births with spina bifida.^[24] The United States Preventive Services Task Force recommends folic acid as the supplement or fortification ingredient, as forms of folate other than folic acid have not been studied.^[17]

A meta-analysis of folate supplementation during pregnancy reported a 28% lower risk of newborn congenital heart defect.^[25] Prenatal supplementation with folic acid did not appear to reduce the risk of preterm birth.^[26][27] One systematic review indicated no effect of folic acid on mortality, growth, body composition, respiratory, or cognitive outcomes of children from birth to 9 years old.^[28] There was no correlation between maternal folic acid supplementation and an increased risk for childhood asthma.^[29]

Folate is necessary for fertility in both men and women. It contributes to spermatogenesis. Therefore, receiving sufficient amounts through the diet is necessary to avoid low fertility.^[30] Also, polymorphisms in genes of enzymes involved in folate metabolism could be one reason for fertility complications in some women with unexplained infertility.^[31]

Taking folic acid over years reduced the risk of cardiovascular disease by 4%,^[11] where another study found it did not affect cardiovascular disease, even while reducing homocysteine levels.^[32] Several studies provided preliminary evidence that folate-rich diet were associated with reduced risk of cardiovascular diseases by lowering blood levels of homocysteine.^[7]

Long-term supplementation with folic acid reduced the risk of stroke by 10%, which may be due to the role folate plays in regulating homocysteine concentration.^[11] A meta-analysis indicated the risk of stroke appeared to be reduced only in some individuals, so a definite recommendation regarding supplementation beyond the current RDA has not been established.^[33] Asian populations had greater protection against stroke with folate supplementation than did European or North American subjects.^[11] Observed stroke reduction is consistent with the reduction in pulse pressure produced by folate supplementation of 5 mg per day, since hypertension is a key risk factor for stroke. Folic supplements are inexpensive and relatively safe to use, which is why people who have had stroke or who have hyperhomocysteinemia are encouraged to consume daily B vitamins including folic acid.^[34]

Studies on folic acid intake from food and folate supplementation with regards to cancer risk are based on the adequacy of chronic intake. Chronically insufficient intake of folic acid may increase the risk of colorectal, breast, ovarian, pancreas, brain, lung, cervica, and prostate cancer.^{[7][35][36][37][38]} Other studies showed that excessive dietary supplementation with folic acid may increase the risk of certain cancer, in particular prostate.^[39][40] A 2017 review found no relationship between taking folate supplements and cancer risk.^[41]

Folate is important for cell and tissues that divide rapidly.^[19] Cancer cell divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. The antifolate drug methotrexate is often used to treat cancer because it inhibits the production of the active form of THF from the inactive dihydrofolate (DHF). However, methotrexate can be toxic,^[42][43][44] producing side effects, such as inflammation in the digestive tract that make eating normally more difficult. Also, bone marrow depression (inducing leukopenia and thrombocytopenia) and acute kidney and liver failure have been reported.» (wikipedia)