Folic acid
IUPAC name	(S)-2-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)pentanedioic acid
Other names	N-[4(2-Amino-4-hydroxy pteridin-6-ylmethylamino) benzoyl]-L(+)-glutamic acid; pteroyl-L-glutamic acid; Vitamin B9; Vitamin M; Folacin
Identifiers
CAS number	[59-30-3]
RTECS number	LP5425000
SMILES	C1=CC(=CC=C1C(=O)NC (CCC(=O)O)C(=O)O) NCC2=CN=C3C(=N2) C(=O)N=C(N3)N
Properties
Molecular formula	C19H19N7O6
Molar mass	441. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to Registry of Toxic Effects of Chemical Substances ( RTECS) is a Database of Toxicity information compiled from the open scientific literature without reference A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Molar mass, symbol M, is the Mass of one mole of a substance ( Chemical element or Chemical compound) 403 g/mol
Appearance	yellow-orange crystalline powder
Melting point	250 °C (523 K), decomp.
Solubility in water	0. The melting point of a solid is the temperature range at which it changes state from solid to Liquid. Chemical decomposition or analysis is the separation of a Chemical compound into elements or smaller compounds Solubility is the characteristic Physical property referring to the ability of a given substance the Solute, to dissolve in a Solvent. Water is a common Chemical substance that is essential for the survival of all known forms of Life. 0016 mg/ml (25 °C)
Acidity (pKa)	1st: 2. 3, 2nd: 8. 3
Hazards
Main hazards	non-toxic, non-flammable
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Folic acid and folate (the anion form) are forms of the water-soluble Vitamin B₉. Occupational safety and health is a cross-disciplinary area concerned with protecting the Safety, Health and welfare of people engaged in In Chemistry, the standard state of a material is its state at 1 bar (100 Kilopascals exactly An ion is an Atom or Molecule which has lost or gained one or more Valence electrons giving it a positive or negative electrical charge The B vitamins are eight water-soluble Vitamins that play important roles in cell Metabolism. These occur naturally in food and can also be taken as supplements. Food is any substance usually composed primarily of Carbohydrates Fats water and/or Proteins that can be eaten or drunk by an Folate gets its name from the Latin word folium ("leaf").

Folate in foods and other sources

Leafy vegetables such as spinach, turnip greens, lettuces, dried beans and peas, fortified cereal products, sunflower seeds and certain other fruits and vegetables are rich sources of folate. Leaf vegetables, also called potherbs, greens, or leafy greens, are plant leaves eaten as a Vegetable, sometimes accompanied Spinach ( Spinacia oleracea) is a Flowering plant in the family of Amaranthaceae. For similar vegetables also called "turnip" see Turnip (disambiguation. Lettuce ( Lactuca sativa) is a Temperate annual or Biennial plant of the daisy family Asteraceae. Bean is a common name for large plant Seeds of several genera of the family Fabaceae (formerly Leguminosae used for human food or animal A pea (inaccurately called a '''sweet pea''' by food distubutors is most commonly the small spherical Seed or the seed-pod of the Legume Pisum The sunflower seed is the Fruit of the Sunflower ( Helianthus annuus) The term fruit has different meanings dependent on context and the term is not synonymous in Food preparation and Biology. The term " vegetable " generally means the edible parts of Plants The definition of the word is traditional rather than Scientific, however Some breakfast cereals (ready-to-eat and others) are fortified with 25% to 100% of the recommended dietary allowance (RDA) for folic acid. A breakfast cereal (often simply called cereal is a packaged food product made from Cereal intended to be consumed as part of a Breakfast. The Dietary Reference Intake (or DRI is a system of Nutrition recommendations from the Institute of Medicine (IOM of the US National Academy of Sciences A table of selected food sources of folate and folic acid can be found at the USDA National Nutrient Database for Standard Reference. Folate is also found in Vegemite, with an average serving (5gm) containing 100μg. Vegemite ( is a dark brown savoury food paste made from Yeast extract, used mainly as a spread on Sandwiches Toast and cracker biscuits Folate is also synthesized in bacteria.

History

A key observation by researcher Lucy Wills in 1931 led to the identification of folate as the nutrient needed to prevent anemia during pregnancy. Lucy Wills (1888-1964 Lucy Wills' key observations 70 years ago in Bombay (Mumbai Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Dr. Wills demonstrated that anemia could be reversed with brewer's yeast. Folate was identified as the corrective substance in brewer's yeast in the late 1930s and was extracted from spinach leaves in 1941. Spinach ( Spinacia oleracea) is a Flowering plant in the family of Amaranthaceae. It was first synthesized in 1946 by Yellapragada Subbarao. Yellapragada Subbarao ( January 12[[ 895]]- August 9 1948) remains in the views of many the most notable medical scientist to emerge from India

Biological roles of folate

• DNA and cell division

Folate is necessary for the production and maintenance of new cells. ^[1] This is especially important during periods of rapid cell division and growth such as infancy and pregnancy. Folate is needed to synthesize DNA bases (most notably thymine, but also purine bases) needed for DNA replication. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Purine ( 1) is a heterocyclic Aromatic Organic compound, consisting of a Pyrimidine ring fused to an Imidazole ring Thus folate deficiency hinders DNA synthesis and cell division, affecting most notably bone marrow and cancer, both of which participate in rapid cell division. RNA transcription, and subsequent protein synthesis, are less effected 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 cells (RBCs) is hindered and leads to megaloblastic anemia which is characterized by large immature RBCs. Erythropoiesis is the process by which Red blood cells (erythrocytes are produced Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Megaloblastic anemia is an Anemia (of macrocytic classification which results from inhibition of DNA synthesis in red blood cell production This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division and produces abnormally large cells (megaloblasts) with abundant cytoplasm capable of RNA and protein synthesis but with clumping and fragmentation of nuclear chromatin. Some of these large cells, although immature, are released early from the marrow in an attempt to compensate for the anemia caused by lack of RBCs. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative ^[2] Both adults and children need folate to make normal RBCs and prevent anemia. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative ^[3] Deficiency of folate in pregnant women has been implicated in neural tube defects and so many cereals sold in developed countries are enriched with folate to avoid such complications. A neural tube defect will occur in human Embryos if there is an interference with the closure of the Neural tube that occurs around the 28th day after Fertilization

• Biochemistry of DNA base and amino acid production

In the form of a series of tetrahydrofolate (THF) compounds, folate derivatives are substrates in a number of single-carbon-transfer reactions, and also are involved in the synthesis of dTMP (2'-deoxythymidine-5'-phosphate) from dUMP (2'-deoxyuridine-5'-phosphate). Tetrahydrofolic acid is a Folic acid derivative Metabolism Human synthesis It is produced from Dihydrofolic acid by Dihydrofolate Thymidine monophosphate, also known as 5'-thymidylic acid and abbreviated TMP, is a Nucleotide that is found in DNA. Deoxyuridine monophosphate is a Deoxynucleotide. It is an intermediate in the metabolism of Deoxyribonucleotides See also Uridine It is a substrate for an important reaction that involves vitamin B12 and it is necessary for the synthesis of DNA, required for all dividing cells.

The pathway leading to the formation of tetrahydrofolate (FH₄) begins when folate (F) is reduced to dihydrofolate (DHF) (FH₂), which is then reduced to THF. Tetrahydrofolic acid is a Folic acid derivative Metabolism Human synthesis It is produced from Dihydrofolic acid by Dihydrofolate Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Dihydrofolic acid is a Folic acid derivative acted upon by Dihydrofolate reductase to produce Tetrahydrofolic acid. Dihydrofolate reductase catalyses the last step. Dihydrofolate reductase, or DHFR, reduces Dihydrofolic acid to Tetrahydrofolic acid, using NADPH as Electron donor, which can be converted ^[4] Vitamin B₃ in the form of NADPH is a necessary cofactor for both steps of the synthesis. Nicotinamide adenine dinucleotide phosphate ( NADP+, in older notation triphosphopyridine nucleotide TPN) is used in anabolic reactions such as Lipid

Methylene-THF (CH₂FH₄) is formed from THF by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methylene is the chemical species R2C named after Methane, in which two of the carbon atom's valence electrons form no bonds Formaldehyde is a Chemical compound with the formula H2CO It is the simplest Aldehyde —an organic compound containing a terminal Carbonyl Serine (abbreviated as Ser or S) is an Organic compound with the formula H[[oxygen O]]2 CCH NH sub>2CH2OH Glycine (abbreviated as Gly or G) is the Organic compound with the formula NH2CH2COOH Methyl tetrahydrofolate (CH₃-THF) can be made from methylene-THF by reduction of the methylene group with NADPH. 5-Methyltetrahydrofolate, or 5-methyltetrahydrofolic acid is a methylated derivate of Tetrahydrofolate. If is important to note that Vitamin B₁₂ is the only acceptor of methyl-THF. There is also only one acceptor for methyl-B₁₂ which is homocysteine in a reaction catalyzed by homocysteine methyltransferase. This is important because a defect in homocysteine methyltransferase or a defeciency of B₁₂ can lead to a methyl-trap of THF and a subsequent deficiency. Thus, a deficiency in B₁₂ can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency. Another form of THF, formyl-THF or folinic acid) results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Folinic acid ( INN) or leucovorin ( USAN) generally administered as calcium folinate (or leucovorin calcium) is an Adjuvant Folinic acid ( INN) or leucovorin ( USAN) generally administered as calcium folinate (or leucovorin calcium) is an Adjuvant Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Finally, histidine can donate a single carbon to THF to form methenyl-THF.

In other words: F → DHF₂ → THF → CH_{2-THF Formyl-THF <--> Methynl-THF <--> Methylene-THF --> Methyl-THF}

Overview of drugs that interfere with folate reactions A number of drugs interfere with the biosynthesis of folic acid and THF. Among them are the dihydrofolate reductase inhibitors such as trimethoprim, pyrimethamine and methotrexate; the sulfonamides (competitive inhibitors of para-aminobenzoic acid in the reactions of dihydropteroate synthetase). Trimethoprim ( INN) (traɪˈmɛθəprɪm is a bacteriostatic Antibiotic mainly used in the Prophylaxis and treatment of Urinary tract infections Pyrimethamine ( Daraprim) is a Medication used for Protozoal infections There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide 4-Aminobenzoic acid (also known as para -aminobenzoic acid or PABA) is an Organic compound with the molecular formula C7H7NO2 Dihydropteroate synthetase is an enzyme classified under. It produces Dihydropteroate in Bacteria, but does not function in Humans.

• Recommended Daily Allowence (RDA)

The National Health and Nutrition Examination Survey (NHANES III 1988-91) and the Continuing Survey of Food Intakes by Individuals (1994-96 CSFII) indicated that most adults did not consume adequate folate. ^[5][6] However, the folic acid fortification program in the United States has increased folic acid content of commonly eaten foods such as cereals and grains, and as a result diets of most adults now provide recommended amounts of folate equivalents. A breakfast cereal (often simply called cereal is a packaged food product made from Cereal intended to be consumed as part of a Breakfast. ^[7]

Folate deficiency

Human reproduction

Folic acid is very important for all women who may become pregnant. Signs of Folic acid deficiency are often subtle Presentation Diarrhea, Loss of appetite, and Weight loss can occur Pregnancy ( Latin graviditas) is the carrying of one or more offspring known as a Fetus or Embryo, inside the Uterus of a Female Adequate folate intake during the periconceptional period, the time just before and just after a woman becomes pregnant, helps protect against a number of congenital malformations including neural tube defects. A neural tube defect will occur in human Embryos if there is an interference with the closure of the Neural tube that occurs around the 28th day after Fertilization ^[8] Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly). Spina bifida ( Latin: "split spine" is a developmental Birth defect involving the Neural tube: incomplete closure of the Embryonic neural Anencephaly is a Cephalic disorder that results from a Neural tube defect that occurs when the cephalic (head end of the neural tube fails to close usually between The risk of neural tube defects is significantly reduced when supplemental folic acid is consumed in addition to a healthy diet prior to and during the first month following conception. ^[9][10] Women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risk of some serious birth defects. The most notable birth defects that occur from folate deficiency are neural tube defects. In the developing vertebrate the neural tube is the Embryo 's precursor to the Central nervous system, which comprises the Brain and Spinal cord Taking 400 micrograms of synthetic folic acid daily from fortified foods and/or supplements has been suggested. The Recommended Dietary Allowance (RDA) for folate equivalents for pregnant women is 600-800 micrograms, twice the normal RDA of 400 micrograms for women who are not pregnant. ^[11]

Recent research has shown that it is also very important for men who are planning on fathering children, reducing birth defect risks. ^[12]

Folic acid supplements and masking of B₁₂ deficiency

There has been concern about the interaction between vitamin B₁₂ and folic acid. ^[13]Folic acid supplements can correct the anemia associated with vitamin B₁₂ deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B₁₂ deficiency. Permanent nerve damage could theoretically occur if vitamin B₁₂ deficiency is not treated. Therefore, intake of supplemental folic acid should not exceed 1000 micrograms (1000 mcg or 1 mg) per day to prevent folic acid from masking symptoms of vitamin B₁₂ deficiency. In fact, to date the evidence that such masking actually occurs is scarce, and there is no evidence that folic acid fortification in Canada or the US has increased the prevalence of vitamin B₁₂ deficiency or its consequences. ^[14]

However one recent study has demonstrated that high folic or folate levels when combined with low B₁₂ levels are associated with significant cognitive impairment among the elderly. ^[15] If the observed relationship for seniors between folic acid intake, B₁₂ levels, and cognitive impairment is replicated and confirmed, this is likely to re-open the debate on folic acid fortification in food, even though public health policies tend generally to support the developmental needs of infants and children over slight risks to other population groups.

In any case, it is important for older adults to be aware of the relationship between folic acid and vitamin B₁₂ because they are at greater risk of having a vitamin B₁₂ deficiency. If you are 50 years of age or older, ask your physician to check your B₁₂ status before you take a supplement that contains folic acid.

Health risk of too much folic acid

The risk of toxicity from folic acid is low. ^[16] 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. The Institute of Medicine (IOM is one of the United States National Academies, and is a not-for-profit non-governmental American organization chartered in 1970 as a part of the United Supplemental folic acid should not exceed the UL to prevent folic acid from masking symptoms of vitamin B₁₂ deficiency. ^[17]

Research suggests high levels of folic acid can interfere with some antimalarial treatments. Malaria is a vector -borne Infectious disease caused by Protozoan Parasites It is widespread in tropical and subtropical regions including ^[18]

A 10000-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. ^[19]

Some current issues and controversies about folate

Dietary fortification of folic acid

Since the discovery of the link between insufficient folic acid and neural tube defects (NTDs), governments and health organizations worldwide have made recommendations concerning folic acid supplementation for women intending to become pregnant. A neural tube defect will occur in human Embryos if there is an interference with the closure of the Neural tube that occurs around the 28th day after Fertilization Pregnancy ( Latin graviditas) is the carrying of one or more offspring known as a Fetus or Embryo, inside the Uterus of a Female For example, the United States Public Health Service (see External links) recommends an extra 0. Organization of the Public Health Service The Public Health Service Act placed the United States Public Health Service ( PHS) as the primary division 4 mg/day, which can be taken as a pill. However, many researchers believe that supplementation in this way can never work effectively enough since about half of all pregnancies in the U. S. are unplanned and not all women will comply with the recommendation.

This has led to the introduction in many countries of fortification, where folic acid is added to flour with the intention of everyone benefiting from the associated rise in blood folate levels. This is controversial, with issues having been raised concerning individual liberty, and the masking effect of folate fortification on pernicious anaemia (vitamin B₁₂ deficiency). Pernicious anemia (also known as Biermer's anemia, Addison's anemia, or Addison-Biermer anemia) is a form of Megaloblastic anemia due to However, almost all American countries now fortify their flour, along with a number of Middle Eastern countries and Indonesia. The Republic of Indonesia ( (Republik Indonesia is a Country in Southeast Asia. Mongolia and a number of ex-Soviet republics are amongst those having widespread voluntary fortification; about five more countries (including Morocco, the first African country) have agreed but not yet implemented fortification. Mongolia (mɒŋˈɡoʊliə, literally Mongol country/nation,) is a Landlocked Country in East The Union of Soviet Socialist Republics (USSR was a constitutionally Socialist state that existed in Eurasia from 1922 to 1991 Morocco (المغرب "al-Maghrib" officially the Kingdom of Morocco (المملكة المغربية is a country located in North Africa In the UK the Food Standards Agency has recommended fortification. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located The Food Standards Agency is a Non-ministerial government department of the Government of the United Kingdom. ^[20][21][22] To date, no EU country has yet mandated fortification. The European Union ( EU) is a political and economic union of twenty-seven member states, located primarily in ^[23] Australia is considering fortification, but a period for comments ending 2006-07-31 attracted strong opposition from industry as well as academia. For a topic outline on this subject see List of basic Australia topics. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 30 BC - Battle of Alexandria: Mark Antony achieves a minor victory over Octavian 's forces but most of his army subsequently ^[24]

Recent debate has emerged in the United Kingdom^[25] and Australia^[26] regarding the inclusion of folic acid in products such as bread and flour. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located For a topic outline on this subject see List of basic Australia topics. Bread is a Staple food prepared by Baking a Dough of Flour and Water. Flour is a powder made of Cereal grains It is the key ingredient of Bread, which is a staple food in many countries and therefore the availability

In the USA many grain products are fortified with folic acid.

In 1996, the United States Food and Drug Administration (FDA) published regulations requiring the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products. ^[27][28] This ruling took effect 1998-01-01, and was specifically targeted to reduce the risk of neural tube birth defects in newborns. Year 1998 ( MCMXCVIII) was a Common year starting on Thursday (link will display full 1998 Gregorian calendar) New Year See also New Year The Ancient Romans began their consular year on January 1st since 153 BC ^[29] There are concerns that the amount of folate added is insufficient[2]. Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9 In October 2006, the Australian press claimed that U. S. regulations requiring fortification of grain products were being interpreted as disallowing fortification in non-grain products, specifically Vegemite (an Australian yeast extract containing folate). Vegemite ( is a dark brown savoury food paste made from Yeast extract, used mainly as a spread on Sandwiches Toast and cracker biscuits Yeast extract is the common name for various forms of processed Yeast products that are used as food additives or flavourings The FDA later said the report was inaccurate, and no ban or other action was being taken against Vegemite. [3]

Since the folic acid fortification program took effect, fortified foods have become a major source of folic acid in the American diet. The Centers for Disease Control and Prevention in Atlanta, Georgia used data from 23 birth defect registries that cover about half of United States births and extrapolated their findings to the rest of the country. The Centers for Disease Control and Prevention (or CDC) is an agency of the United States Department of Health and Human Services based in unincorporated This data indicates that since the addition of folic acid in grain-based foods as mandated by the Food and Drug Administration, the rate of neural tube defects dropped by 25% in the United States. ^[30]

Although folic acid does reduce the risk of birth defects, it is only one part of the picture and should not be considered a cure. Even women taking daily folic acid supplements have been known to have children with neural tube defects.

Heart disease

Adequate concentrations of folate, vitamin B₁₂, or vitamin B₆ may decrease the circulating level of homocysteine, an amino acid normally found in blood. Homocysteine is a Chemical compound with the formula HSCH2CH2CH(NH2CO2H In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this There is evidence that an elevated homocysteine level is an independent risk factor for heart disease and stroke. ^[31] The evidence suggests that high levels of homocysteine may damage coronary arteries or make it easier for blood clotting cells called platelets to clump together and form a clot. ^[32] However, there is currently no evidence available to suggest that lowering homocysteine with vitamins will reduce risk of heart disease. Clinical intervention trials are needed to determine whether supplementation with folic acid, vitamin B₁₂ or vitamin B₆ can lower the risk of developing coronary heart disease. The NORVIT trial suggests that folic acid supplementation may do more harm than good. ^[33]

As of 2006, studies have shown that giving folic acid to reduce levels of homocysteine does not result in clinical benefit. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. One of these studies suggests that folic acid in combination with B₁₂ may even increase some cardiovascular risks. ^[34][35][36]

However a 2005 study found that 5 mg. of folate daily over a three-week period reduced pulse pressure by 4. 7 mmHg. compared with a placebo, and concluded that^[37]

Folic acid is a safe and effective supplement that targets large artery stiffness and may prevent isolated systolic hypertension.

Also, as a result of new research, "heart experts" at Johns Hopkins Medical Center reported in March 2008 ^[38] in favour of therapeutic folate, although they cautioned that it was premature for those at risk of heart attack to self-medicate. Johns Hopkins ( May 19, 1795, Anne Arundel County, Maryland &ndash December 24, 1873

Stroke

Folic acid appears to reduce the risk of stroke. A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain The reviews indicate only that in some individuals the risk of stroke appears to be reduced, but a definite recommendation regarding supplementation beyond the current recommended daily allowance has not been established for stroke prevention. ^[39] 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.

Cancer

The association between folate and cancer appears to be complex. ^[40] It has been suggested that folate may help prevent cancer, as it is involved in the synthesis, repair, and functioning of DNA, and a deficiency of folate may result in damage to DNA that may lead to cancer. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known ^[41] Some investigations have proposed that good levels of folic acid may be related to lower risk of esophagus, stomach and ovarian cancer, but benefices of folic acid against cancer may depend on when it is taken and on individual conditions. In addition folic acid may not be helpful, and could even be damaging, in people who already are suffering from cancer or from a precancerous condition. Conversely, it has been suggested that excess folate may promote tumor initiation. ^[42] Diets high in folate are associated with decreased risk of colorectal cancer; some studies show an association which is stronger for folate from foods alone than for folate from foods and supplements,^[43] while other studies find that folate from supplements is more effective due to greater bioavailability^[44] and a 2007 randomized clinical trial found that folate supplements did not reduce the risk of colorectal adenomas. Colorectal cancer, also called colon cancer or large bowel cancer, includes Cancerous growths in the colon, Rectum and An adenoma is a collection of growths (-oma of glandular origin ^[45] A 2006 prospective study of 81,922 Swedish adults found that diets high in folate from foods, but not from supplements, were associated with a reduced risk of pancreatic cancer. ^[46] Most epidemiologic studies suggest that diets high in folate are associated with decreased risk of breast cancer, but results are not uniformly consistent: one large cancer screening trial reported a potential harmful effect of high folate intake on breast cancer risk, suggesting that routine folate supplementation should not be recommended as a breast cancer preventive,^[47] but a 2007 Swedish prospective study found that a high folate intake was associated with a lower incidence of postmenopausal breast cancer. Breast cancer is a Cancer that starts in the cells of the Breast in women and men ^[48] It is very difficult to affirm how each nutrient or nutrient combination affects a person’s risk of cancer. People whose diets are rich in vegetables and low in animal fat and meat have lower risks for some of the most frequent types of cancer. Taking a variety of healthful foods, with most of them coming from plant sources, is a better solution than taking vitaminic supplements. So the authorities are not really sure if this will work for cancer or not, (or the age at which it is safe to start taking folate supplements) but hopefully this will all become clear in the light of research now underway.

Antifolates

Folate is important for cells and tissues that rapidly divide. ^[1] Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. The antifolate methotrexate is a drug often used to treat cancer because it inhibits the production of the active form of THF from the inactive dihydrofolate (DHF). Unfortunately, methotrexate can be toxic,^[49][50][51] producing side effects such as inflammation in the digestive tract that make it difficult to eat normally.

Folinic acid, under the drug name leucovorin, is a form of folate (formyl-THF) that can help "rescue" or reverse the toxic effects of methotrexate. Folinic acid ( INN) or leucovorin ( USAN) generally administered as calcium folinate (or leucovorin calcium) is an Adjuvant Folinic acid ( INN) or leucovorin ( USAN) generally administered as calcium folinate (or leucovorin calcium) is an Adjuvant ^[52] Folinic acid is not the same as folic acid. Folic acid supplements have little established role in cancer chemotherapy. ^[53][54] There have been cases of severe adverse effects of accidental substitution of folic acid for folinic acid in patients receiving methotrexate cancer chemotherapy. It is important for anyone receiving methotrexate to follow medical advice on the use of folic or folinic acid supplements. The supplement of folinic acid in patients undergoing methotrexate treatment is to give non rapidly dividing cells enough folate to maintain normal cell functions. The amount of folate given will be depleted by rapidly dividing cells (cancer) very fast and so will not negate the effects of methotrexate. Low dose methotrexate is used to treat a wide variety of non-cancerous diseases such as rheumatoid arthritis, lupus, scleroderma, psoriasis, asthma, sarcoidoisis, primary biliary cirrhosis, and inflammatory bowel disease. Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming Scleroderma is a chronic Autoimmune disease characterized by a hardening or Sclerosis in the Skin or other organs Psoriasis (səˈraɪəsɪs ( suh-RI-uh-sus) is a non-contagious disorder which affects the Skin and Joints It commonly causes red scaly Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are Sarcoidosis, also called sarcoid (from the Greek sarx, meaning "flesh" or Besnier-Boeck disease, is an immune system disorder characterized Primary biliary cirrhosis is an Autoimmune disease of the Liver marked by the slow progressive destruction of the small bile ducts ( Bile canaliculi) within In Medicine, inflammatory bowel disease ( IBD) is a group of inflammatory conditions of the large intestine and Small intestine ^[55] Low doses of methotrexate can deplete folate stores and cause side effects that are similar to folate deficiency. Both high folate diets and supplemental folic acid may help reduce the toxic side effects of low dose methotrexate without decreasing its effectiveness. ^[56][57] Anyone taking low dose methotrexate for the health problems listed above should consult with a physician about the need for a folic acid supplement. While the role in folate as a cancer treatment is well established its long term effectiveness is diminished by cellular response. In response to decreased THF the cell begins to transcribe more DHF reductase, the enzyme that reduces DHF to THF. Because methotrexate is a competitive inhibitor of DHF reductase increased concentrations of DHF reductase can overcome the drugs inhibition. Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the Enzyme prevents binding of the substrate and vice versa

Depression

Some evidence links low levels of folate with depression. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression ^[58] There is some limited evidence from randomised controlled trials that using folic acid in addition to antidepressant medication may have benefits. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression ^[59] Researchers at the University of York and Hull York Medical School have confirmed a link between depression and low levels of folate in a research study involving 15,315 . ^[60] However, the evidence is probably too limited at present for this to be a routine treatment recommendation.

Memory and mental agility

In a 3-year trial on 818 people over the age of 50, short-term memory, mental agility and verbal fluency were all found to be better among people who took 800 micrograms of folic acid daily—twice the current RDA—than those who took placebo. The study was reported in The Lancet on 19 January 2007. This article is about the journal For other uses of the term "lancet" see Lancet (disambiguation. Events 1419 - Hundred Years' War: Rouen surrenders to Henry V of England completing his reconquest of Normandy. ^[61]

Fertility

Folate is necessary for fertility in both men and women. Fertility is the natural capability of giving life As a measure "Fertility Rate" is the number of children born per couple person or population In men, it contributes to spermatogenesis. Spermatogenesis is the process by which male Spermatogonia develop into mature Spermatozoa. In women, on the other hand, it contributes to oocyte maturation, implantation, placentation, in addition to the general effects of folic acid and pregnancy. Oogenesis or rarely oögenesis is the creation of an Ovum (egg cell Implantation is an event that occurs early in pregnancy in which the Embryo adheres to the wall of Uterus. In biology placentation refers to the formation type and structure or arrangement of Placentas The function of placentation is to transfers nutrients from maternal tissue Therefore, it is necessary to receive sufficient amounts through the diet, in order to avoid subfertility. Female infertility|Male infertility Infertility primarily refers to the biological inability of a Man or a Woman to contribute to conception. ^[62]

Induction of acute renal failure

Folic acid is used in extremely high doses to induce Acute renal failure in murine models. Acute renal failure ( ARF) also known as acute kidney failure or acute kidney injury, is a rapid loss of Renal function due to damage to the The Old World rats and mice, part of the Subfamily Murinae in the family Muridae, comprise at least 519 species A model organism is a Species that is extensively studied to understand particular biological Phenomena, with the expectation that discoveries made It should be noted that the dose reported below represents about 120 years of the recommended daily intake [0. 4 mg for adults] in one application, an experiment irrelevant to human nutrition. The exact method through which folic acid induces kidney injury in such massive dose is unknown, however it is characterized by the appearance of folic acid crystals in renal tubules and acute tubular necrosis. A nephron (from Greek νεφρός (nephros meaning "kidney" is the basic structural and functional unit of the Kidney. Acute tubular necrosis or ( ATN) is a medical condition involving the death of tubular cells that form the Tubule that transports Urine to the Ureters This method of renal injury is also linked to increased expression of Tumor necrosis factor-alpha. Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic The dose of folic acid used to induce renal injury is usually around 250mg of folic acid per kg of body weight. The folic acid is usually administered in a vehicle of 0. 3mmol/L of sodium bicarbonate. Sodium bicarbonate or sodium hydrogen carbonate is the Chemical compound with the formula NaHCO3 ^[63]

Bibliography

• This article contains information from the public domain resource at http://www.cc.nih.gov/ccc/supplements/folate.html
• Herbert V. The public domain is a range of abstract materials &ndash commonly referred to as Intellectual property &ndash which are not owned or controlled by anyone (1999). Folic Acid. Shils M, Olson J, Shike M, Ross AC, (Eds. ). Nutrition in Health and Disease. Baltimore: Williams & Wilkins.
• Food and Nutrition Board, Institute of Medicine (1998). Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B₆, folate, vitamin B₁₂, pantothenic acid, biotin, and choline / a report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients. Washington, D. C. : National Academy Press. ISBN 0-309-06554-2.  
• Dietary Guidelines Advisory Committee, Agricultural Research Service, United States Department of Agriculture (USDA). Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2000. http://www.ars.usda.gov/dgac

References

External links

• Jane Higdon, "Folic Acid", Micronutrient Information Center, Linus Pauling Institute
• Health Canada article about folic acid
• US Public Health Service information page on folic acid
• BMJ Editorial – "Delaying folic acid fortification of flour"
• Folic Acid and Birth Defects Article from Journal of Postgraduate Medicine
• Folic Acid The Vitamin That Does Almost Everything-U. Oregon State University ( OSU) is a Coeducational public Research[[ university]] located in Corvallis, Oregon, United C Berkeley Wellness Letter April 2003
• BMC Pregnancy and Childbirth 2004: no vitamin B₁₂ problems in Canada after folic acid fortification
• The primary prevention of birth defects: Multivitamins or folic acid?
• Mills et al, Am J Clin Nutr 2003: no vitamin B₁₂ problems in the US after folic acid fortification
• Folic acid may help prevent throat cancer
• Folic acid may help treat bipolar disorder

Biochemistry links

• Folate biosynthesis (early stages)
• Folate biosynthesis (later stages)
• Folate coenzymes
• C₁ metabolism with folate
• Formylation, hydroxymethylation and methylation using folate
• IUPAC nomenclature of folate related compounds