Folic Acid

Plant Growth Regulators

Active substance -> EU Pesticides database: Not approved

Almost insoluble (NTP, 1992)

Slightly sol in methanol, less in ethanol and butanol; insol in acetone, chloroform, ether, benzene; relatively sol in acetic acid, phenol, pyridine, and in soln of alkali hydroxides and carbonates. Soluble in hot dil HCl and H2SO4.

In water, 1.6 mg/L at 25 °C; soluble up to about 1% in boiling water

0.0016 mg/mL

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antianaemia medicines

This chemical does not meet GHS hazard criteria for 92.6% (188 of 203) of all reports.

Not Classified

Aggregated GHS information provided per 203 reports by companies from 7 notifications to the ECHA C&L Inventory.

Chemical: L-Glutamic acid, N-[4-[[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-

Regulation (EC) No 178/2002 (amended)

REACH registered substance: Folic acid (EC: 200-419-0)

.beta.-D-ribo-2-Heptulopyranose, 2,7-anhydro-1,4-dideoxy-3-O-methyl-5-O-(phenylmethyl)-: Does not have an individual approval but may be used under an appropriate group standard

.beta.-D-Allopyranose, 1,6-anhydro-2,3-di-O-methyl-4-O-(phenylmethyl)-: Does not have an individual approval but may be used under an appropriate group standard

Folic acid: Does not have an individual approval but may be used under an appropriate group standard

Folic acid (CAS Reg. No. 59-30-3), also known as folacin or folate, may be safely used in food as a nutrient in accordance with the following prescribed conditions: (a) Folic acid is the chemical N-[4-[[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid. (b) Folic acid meets the specifications of the "Food Chemicals Codex," 4th ed. (1996), pp. 157-158, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. ... (c) Folic acid may be added to foods subject to a standard of identity established under section 401 of the Federal Food, Drug, and Cosmetic Act (the act) when the standard of identity specifically provides for the addition of folic acid. (d) Folic acid may be added, at levels not to exceed 400 micrograms (ug) per serving, to breakfast cereals, as defined under §170.3(n)(4) of this chapter, and to corn grits at a level such that each pound of corn grits contains not more than 1.0 milligram of folic acid. (e) Folic acid may be added to infant formula in accordance with section 412(i)(1) of the act or with regulations issued under section 412(i)(2) of the act which are codified in §107.100 of this chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), at levels not to exceed the amount necessary to meet the distinctive nutritional requirements of the disease or condition for which the food is formulated. (g) Folic acid may be added to food for special dietary use at levels not to exceed the amount necessary to meet the special dietary needs for which the food is formulated. (h) Folic acid may be added to foods represented as meal-replacement products, in amounts not to exceed: (1) Four hundred ug per serving if the food is a meal-replacement that is represented for use once per day; or (2) Two hundred ug per serving if the food is a meal-replacement that is represented for use more than once per day.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Folic acid is included in weight control drug products.

Anon; Maternal and Infant Folate Status Relationships Nutr Rev 48 (3): 157-9 (1990). A population based case control study was conducted to test the hypothesis that the risk of the occurrence of neural tube defects in infants with no other birth defects (isolated neural tube defects) is associated inversely with the maternal dietary intake of free and/or total folate in early pregnancy. Information was collected from the mothers of 77 case subjects with isolated neural tube defects who were born in Western Australia from 1982 to 1984, from the mothers of 77 control subjects with birth defects other than neural tube defects (control group 1) and from the mothers of 154 control subjects with no birth defects (control group 2). Crude and adjusted odds ratios showed a protective effect of an increasing intake of free folate in the first six weeks of pregnancy. These findings support the hypothesis that the dietary intake of folate in early pregnancy protects against the occurrence of isolated neural tube defects in infants. Measures of postpartum dietary folate and of postpartum serum and red cell folate levels showed no association with the occurrence of neural tube defects in infants.

Young SN, Ghadirian AM; Folic Acid and Psychopathology Prog Neuropsychopharmacol Biol Psychiatry 13 (6): 841-63 (1989).

Butterworth CE Jr, Tamura T; Folic Acid Safety and Toxicity: A Brief Review; Am J Clin Nutr 50 (2): 353-8 (1989). Oral folic acid (pteroylglutamic acid) is generally regarded as not toxic for normal humans but it may cause neurological injury when given to patients with undiagnosed pernicious anemia. The vitamin should be given with caution to drug-treated epileptic patients because seizure control may be affected. Some studies suggest that folic acid supplements interfere with intestinal zinc absorption in humans and animals but others do not confirm such an effect. The weight of current evidence favors the view that daily supplements of 5-15 mg folic acid do not have significant adverse effects on zinc nutriture in healthy nonpregnant subjects. Because antifolate medications are now being used to treat a wide range of malignant and nonmalignant disorders, further investigation is needed concerning folate metabolism and the safety of supplements in patients with these disorders.

Folic acid is exempted from the requirement of a tolerance when used as a synergist (maximum of 0.5% of formulation) in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only.

Acid solutions of FOLIC ACID are sensitive to heat, but towards neutrality, stability progressively increases. Solutions are inactivated by ultraviolet light and alkaline solutions are sensitive to oxidation. It is also inactivated by light. This chemical is incompatible with oxidizing agents, reducing agents and heavy metal ions. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with 5% acetic acid, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% acetic acid to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% acetic acid followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Folic acid is exempted from the requirement of a tolerance when used as a synergist (maximum of 0.5% of formulation) in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Folic acid is considered a member of the vitamin B complex and it is a natural component of the liver and kidney(1). The level of folic acid in human milk is 0.0020 mg/L(2).

FOLIC ACID IS EXCRETED IN HUMAN MILK. /FROM TABLE/

The use of high dose folic acid concomitantly with pyrimethamine to prevent bone marrow depression may cause a pharmacodynamic antagonism of the antiparasitic effect of pyrimethamine.

Nonsteroidal antiinflammatory drugs (NSAIDS), including ibuprofen, indomethacin, naproxen, mefenamic acid, piroxicam, and sulindac taken at high therapeutic dosages may exert antifolate activity.

Folic acid supplementation in mice was found to augment the therapeutic activity and ameliorate the adverse reactions of the ... antifolate cancer chemotherapeutic agent lometrexol.

The /daily/ use of folic acid ... was found to enhance the antidepressant action of fluoxetine ...

For more Interactions (Complete) data for FOLIC ACID (17 total), please visit the HSDB record page.

Neither normal nor excessively high intakes of folate are associated with liver injury or liver test abnormalities. In long term clinical trials, serum enzyme and bilirubin elevations were no more frequent with folic acid therapy than with placebo. Use of high doses of folic acid (up to 15 mg daily) has not been associated with appreciable adverse reactions, ALT elevations or hepatotoxicity.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a water solubility of 1.6 mg/L(2) and a regression-derived equation(3), indicates that folic acid is expected to have slight mobility in soil(SRC). The estimated pKa values of the two carboxylic acid moieties of folic acid are 3.5 and 4.3(4) indicating that this compound will primarily exist as an anion in the environment(5). Volatilization of folic acid from moist soil surfaces is not an important fate process(SRC) because anions do not volatilize. Folic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.2X10-20 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation is not expected to be an important environmental fate process in soil as indicated by a low BOD/COD ratio obtained using a sewage inoculum test(7).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a water solubility of 1.6 mg/L(2) and a regression-derived equation(3), indicates that folic acid is expected to adsorb to suspended solids and sediment(SRC). The estimated pKa values of the carboxylic acid moieties of folic acid are 3.5 and 4.3(3), indicating that this compound will primarily exist in anion form in the environment(4). Volatilization from water surfaces does not occur since anions do not volatilize. According to a classification scheme(5), an estimated BCF of 3.2(SRC), from its water solubility(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegadation is not expected to be an important environmental fate process in water as indicated by a low BOD/COD ratio obtained using a sewage inoculum test(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), folic acid, which has an estimated vapor pressure of 6.2X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase folic acid may be removed from the air by wet and dry deposition(SRC). Folic acid absorbs UV light >290 nm(3); therefore folic acid may be susceptible to photolysis although the rate is not known.

Folic acid is considered a member of the vitamin B complex and it is a natural component of liver, mushrooms, spinach, fresh fruit, and yeast(1). In Total Diet Studies conducted by the US Food and Drug Administration from the years 1987 to 1993, folic acid was tested for during 1991 through 1993; results were not published in this particular study(2).

Folic acid food sources include beans and legumes, citrus fruits and juices, wheat bran and other whole grains, dark green leafy vegetables, poultry, pork, shellfish, and liver(1). Many foods are now fortified with folic acid to help prevent neural tube birth defects such as spina bifida(1).

For the general population, a diet that contains a daily amount of folic acid below the established upper intake level of 1000 mcg has not been demonstrated to result conclusively in any adverse health outcomes. The U.S. National Toxicology Program (NTP) examined areas of previous concern, including cognition (relating to vitamin B12 deficiency), cancer, diabetes- and thyroid-related disorders, and hypersensitivity-related outcomes.

FOLIC ACID IS EXCRETED IN HUMAN MILK. /FROM TABLE/

Levels of folic acid in cows milk, goats milk, sheeps milk, mares milk, and human milk are 0.0023 mg/L, 0.0024 mg/L, 0.0024, 0.0012, and 0.0020 mg/L, respectively(2).

IDENTIFICATION: Folic acid is an antianaemic vitamin. Origin of the substance: Folic acid was isolated from green leafy vegetables, liver, yeast and fruits. Synthetic folic acid is commercially available. Yellow to orange brown crystalline powder which is odorless. Readily soluble in alkali, hydroxides and carbonates. Insoluble in alcohol, acetone, chloroform and ether. Solutions are inactivated by ultraviolet light. Alkaline solutions are sensitive to oxidation and acid solutions are sensitive to heat. Indications: For the prevention and treatment of vitamin B deficiency. For the treatment of megaloblastic anemia and macrocytic anemia due to folic acid deficiency. Folic acid supplements may be required in low birth weight infants, infants breastfed by folic acid deficient mothers, or those with prolonged diarrhea and infection. Other conditions which may increase folic acid requirements include alcoholism, hepatic disease, hemolytic anemia, lactation, oral contraceptive use and pregnancy. It has been given to pregnant mothers to reduce the risk of birth defects. HUMAN EXPOSURE: Main risks and target organs: Folic acid is relatively non-toxic. However, there have been reports of reactions to parenteral injections. Allergic reactions to folic acid have been rarely reported. Summary of clinical effects: Severe allergic reactions are characterized by hypotension, shock, bronchospasm, nausea, vomiting, rash, erythema. Itching may also occur. Adverse gastrointestinal and central nervous system effects have been reported. Treatment with folic acid is usually well tolerated except for rare reports of allergic reactions. Bioavailability: Folic acid is rapidly absorbed from gastrointestinal tract following oral administration. Peak folate activity in blood is 30 to 60 minutes after oral administration. Contraindications: It should be given with caution to patients with abnormal renal function. It is also contra-indicated in patients who show hypersensitivity reactions to folic acid. Caution is advised in patients who may have folate dependent tumours. Folic acid should never be given alone or in conjunction with inadequate amounts of Vitamin B12 for the treatment of undiagnosed megaloblastic anaemia. Although folic acid may produce a haematopoietic response in patients with megaloblastic anaemia due to Vitamin B12, it fails to prevent the onset of subacute combined degeneration of the cord. Absorption by route of exposure: Oral: Folic acid is rapidly absorbed from the proximal part of the gastrointestinal tract following oral administration. It is mainly absorbed in the proximal portion of the small intestine. The naturally occurring folate polyglutamate is enzymatically hydrolyzed to monoglutamate forms in the gastrointestinal tract prior to absorption. The peak folate activity in blood after oral administration is within 30 to 60 minutes. Enterohepatic circulation of folate has been demonstrated. Distribution by route of exposure: Tetrahydrofolic acid and its derivatives are distributed in all body tissues. The liver contains half of the total body stores of folate and is the principal storage site. Metabolism: Folic acid once absorbed is acted upon by hepatic dihydrofolate reductase to convert to its metabolically active form which is tetrahydrofolic acid. Following absorption, folic acid is largely reduced and methylated in the liver to N-5 methyltetrahydrofolic acid, which is the main transporting and storage form of folate in the body. Larger doses may escape metabolism by the liver and appear in the blood mainly as folic acid. Elimination by route of exposure: Oral: Following oral administration of single doses of folic acid in health adults, only a trace amount of the drug appears in urine. Following administration of large doses, the renal tubular reabsorption maximum is exceeded and excess folate is excreted unchanged in urine. Small amounts of orally administered folic acid have been recovered from feces. Pharmacodynamics: Folic acid is transformed into different coenzymes that are responsible for various reactions of intracellular metabolism mainly conversion of homocysteine to methionine, conversion of serine to glycine, synthesis of thymidylate, histidine metabolism, synthesis of purines and utilization or generation of formate. In man, nucleoprotein synthesis and the maintenance of normal erythropoiesis requires exogenous folate. Folic acid is the precursor of tetrahydrofolic acid which is active and acts as a co-factor for 1-carbon transfer reactions in the biosynthesis of purines and thymidylates of nucleic acids. Adults: There is little data available on folic acid toxicity in humans. A case of two patients who showed exacerbation of psychotic behavior during treatment with folic acid has been reported. Cytomorphological effects of folic acid were studied using in-vitro establishment human oral epithelium. A concentration twice that used clinically did not induce marked cytotoxic reaction in cultured cells. The most pronounced changes were cultures which showed degenerating cells showing edema, increased translucency of the cytoplasm, flattened cells and atypical filaments. Interactions: Folic acid therapy may increase phenytoin metabolism in folate deficient patients resulting in decreased phenytoin serum concentration. It has also been reported that concurrent administration of folic acid and chloramphenicol in folate deficient patients may result in antagonism of the hematopoietic response to folic acid. The use of ethotoin or mephenytoin concurrently with folic acid may decrease the effects of hydantoins by increasing hydantoin metabolism. Trimethoprim acts as a folate antagonist by inhibiting dihydrofolate reductase, so in patients receiving this drug leucovorin calcium must be given instead of folic acid. Folic acid may also interfere with the effects of pyrimethamine. Aminopterin (4 aminofolic acid) and methotrexate (4 amino- 10 methylfolic acid) antagonizes reduction of folic acid to tetrahydrofolic acid. Methotrexate continues to be used as an antineoplastic drug whose activity may be dependent on blocking certain syntheses, of purines, in which folic acid is required, thereby depriving neoplastic cells of compounds essential for their proliferation. Calcium leucovorin is used therapeutically as a potent antidote for the toxic effects of folic acid antagonists used as antineoplastic agents. Methotrexate or pyrimethamine or triamterene also acts as folate antagonist by inhibiting dihydrofolic reductase. Analgesics, anticonvulsants, antimalarials and corticosteroids may cause folic acid deficiency. Main adverse effects: Allergic reactions to folic acid have been rarely reported including erythema, rash, itching, general malaise and bronchospasm. Adverse gastrointestinal and central nervous system effects have been reported in patients receiving 15 mg of folic acid daily for one month. ANIMAL/PLANT STUDIES: Mode of action: Folic acid is relatively non-toxic. Toxicity studies in mice showed that folic acid could cause convulsions, ataxia and weakness. Histopathological studies in some strains of mice showed that toxic doses may also cause acute renal tubular necrosis. A possible relationship between folic acid neurotoxicity and cholinergic receptors in the pyriform cortex and amygdala has been shown.

Like other water-soluble vitamins, folic acid does not have significant storage in the body; hence toxicity is not a common concern. However, infrequent neurologic side effects have been noted in the context of folate supplementation in individuals with pernicious anemia.

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.

The Koc of folic acid is estimated as 3,400(SRC), using a water solubility of 1.6 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that folic acid is expected to have slight mobility in soil. The estimated pKas of the carboxylic acid moieties of folic acid are 3.5 and 4.5(4), indicating that this compound will primarily exist as an anion and generally do not absorb more strongly to organic carbon and clay than their neutral species(5). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(6,7), suggesting that mobility may be much lower in some soils(SRC).

Folic acid (CAS Reg. No. 59-30-3), also known as folacin or folate, may be safely used in food as a nutrient in accordance with the following prescribed conditions: (a) Folic acid is the chemical N-[4-[[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid. (b) Folic acid meets the specifications of the "Food Chemicals Codex," 4th ed. (1996), pp. 157-158, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. ... (c) Folic acid may be added to foods subject to a standard of identity established under section 401 of the Federal Food, Drug, and Cosmetic Act (the act) when the standard of identity specifically provides for the addition of folic acid. (d) Folic acid may be added, at levels not to exceed 400 micrograms (ug) per serving, to breakfast cereals, as defined under §170.3(n)(4) of this chapter, and to corn grits at a level such that each pound of corn grits contains not more than 1.0 milligram of folic acid. (e) Folic acid may be added to infant formula in accordance with section 412(i)(1) of the act or with regulations issued under section 412(i)(2) of the act which are codified in §107.100 of this chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), at levels not to exceed the amount necessary to meet the distinctive nutritional requirements of the disease or condition for which the food is formulated. (g) Folic acid may be added to food for special dietary use at levels not to exceed the amount necessary to meet the special dietary needs for which the food is formulated. (h) Folic acid may be added to foods represented as meal-replacement products, in amounts not to exceed: (1) Four hundred ug per serving if the food is a meal-replacement that is represented for use once per day; or (2) Two hundred ug per serving if the food is a meal-replacement that is represented for use more than once per day.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Folic acid is included in weight control drug products.

Folic acid is exempted from the requirement of a tolerance when used as a synergist (maximum of 0.5% of formulation) in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only.

B03BB01

V - Various

B - Blood and blood forming organs

QB - Blood and blood forming organs

QV - Various

B03BB01

The adequate intake of folate currently recommended by the National academy of Sciences for healthy infants up to 6 months of age is 65 ug daily and for those 6 to 12 months of age is 80 ug daily. ... The recommended daily allowance (RDA) of folate currently recommended ... for healthy children 1-3, 4-8, 9-13, 14-18 years of age is 0.15, 0.2, 0.3, or 0.4 mg of Dietary food folate Equivalents (DFE) daily, respectively. The RDA of folate for healthy adults 19- 50 years of age and 51 years and older is 0.4 mg of DFE daily.

Folate requirement increase substantially during pregnancy because of the acceleration in single-carbon transfer reactions.The RDA of folate recommended by the National Academy of Sciences for pregnant women is 0.6 mg dietary food folate equivalents daily.

Normal serum folate concentrations have been reported to range from 0.5 to 0.015 ug/mL. In general, serum folate concentrations below 0.005 ug/mL indicate folate deficiency and concentrations below 0.002 ug/mL usually result in megaloblastic anemia.

SYMPTOMS OF DEFICIENCY: ... Symptoms such as irritability, sleeplessness, and forgetfulness do appear during folate deficiency; such symptoms may be related to disordered cerebral metabolism. /Folate/

For more Bionecessity (Complete) data for FOLIC ACID (7 total), please visit the HSDB record page.

Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as [DB00563] as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.

Folic acid, after conversion to tetrahydrofolic acid, is necessary for normal erythropoiesis, synthesis of purine and thymidylates, metabolism of amino acids such as glycine and methionine, and the metabolism of histidine.

The principal biochemical function of folates is the mediation of one-carbon transfer reactions. 5-Methyltetrahydrofolate donates a methyl group to homocystine, in the conversion of homocystine to L-methionine. ... 5,10-Methyltetrahydrofolate is regenerated from tetrahydrofolate via the enzyme serine hydroxymethyltransferase, a reaction, which in addition to producing 5,10-methyltetrahydrofolate, yields glycine. ... 5,10-methyltetrahydrofolate, supplies the one carbon group for the methylation of deoxyuridylic acid to form the DNA precursor thymidylic acid. This reaction is catalyzed by thymidylate synthase and the folate product of the reaction is dihydrofolate. Dihydrofolate is converted to tetrahydrofolate via the enzyme dihydrofolate reductase ...

Folic acid is metabolized in the liver into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF) by the enzyme dihydrofolate reductase (DHFR).

Folic acid is converted (in the presence of ascorbic acid) in the liver and plasma to its metabolically active form (tetrahydrofolic acid) by dihydrofolate reductase.

Following absorption of 1 mg or less, folic acid is largely reduced and methylated in the liver to N-methyltetrahydrofolic acid... .

The folates are taken up by the liver and metabolized to polyglutamate derivatives (principally pteroylpentaglutamate), via the action of folypolyglutamate synthase. ... Folate polyglutamates are released from the liver to the systemic circulation and to the bile. When released from the liver into the circulation, the polyglutamate forms are hydrolyzed by gamma-glutamylhydrolase and reconverted to the monoglutamate forms.

Hepatic Route of Elimination: Folic Acid is metabolized in the liver to 7, 8-dihydrofolic acid and eventually to 5,6,7,8-tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide (DPNH) and folate reductases. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Folic Acid is also excreted in the milk of lactating mothers.

FOLIC ACID

Inhibition Small Intestine Fluid/Electrolyte Absorption [PE]; Vitamin B12 [EPC]; Vitamin B 12 [CS]; Analogs/Derivatives [Chemical/Ingredient]; Ascorbic Acid [CS]; Osmotic Laxative [EPC]; Magnesium Ion Exchange Activity [MoA]; Increased Large Intestinal Motility [PE]; Paramagnetic Contrast Agent [EPC]; Cations, Divalent [CS]; Vitamin C [EPC]; Phosphate Chelating Activity [MoA]; Copper Absorption Inhibitor [EPC]; Calcium [CS]; Stimulation Large Intestine Fluid/Electrolyte Secretion [PE]; Vitamin B6 Analog [EPC]; Blood Coagulation Factor [EPC]; Decreased Copper Ion Absorption [PE]; Vitamin A [EPC]; Vitamin D [EPC]; Calculi Dissolution Agent [EPC]; Phosphate Binder [EPC]; Vitamin B 6 [Chemical/Ingredient]; Vitamin A [CS]; Inhibition Large Intestine Fluid/Electrolyte Absorption [PE]; Magnetic Resonance Contrast Activity [MoA]; Vitamin D [CS]; Osmotic Activity [MoA]; Increased Coagulation Factor Activity [PE]

Agents which improve the quality of the blood, increasing the hemoglobin level and the number of erythrocytes. They are used in the treatment of anemias.

A group of water-soluble vitamins, some of which are COENZYMES.

Folic acid is absorbed rapidly from the small intestine, primarily from the proximal portion. Naturally occurring conjugated folates are reduced enzymatically to folic acid in the gastrointestinal tract prior to absorption. Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose; peak levels are generally reached within 1 hour.

After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. An oral dose of 5 mg in 1 study and a dose of 40 mcg/kg of body weight in another study resulted in approximately 50% of the dose appearing in the urine. After a single oral dose of 15 mg, up to 90% of the dose was recovered in the urine. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Small amounts of orally administered folic acid have also been recovered in the feces. Folic acid is also excreted in the milk of lactating mothers.

Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver.

Folic acid is absorbed rapidly from the GI tract following oral administration oral administration; the vitamin is absorbed mainly in the proximal portion of the small intestine.

The monoglutamate forms of folate, including folic acid, are transported across the proximal small intestine via a saturable pH-dependent process. Higher doses of the pteroylmonoglutamates, including folic acid, are absorbed via a nonsaturable passive diffusion process. The efficiency of absorption of the pteroylmonoglutamates is greater than that of pteroylpolyglutamates.

Following oral administration, peak folate activity in blood occurs within 30 to 60 minutes. Synthetic folate is almost 100% bioavailable when administered in fasting individuals. While the bioavailability of naturally occurring folate in food is about 50%, bioavailability of synthetic folic acid consumed with a meal ranges from 85 to 100%.

High concentrations in liver, kidney, mushrooms, spinach, yeast, and green leaves; Used as a vitamin (hematopoietic) and dietary requirement for poultry; [Merck Index] Used as a nutritional supplement; [FDA] Essential vitamin for erythropoiesis; Used in treatment of methanol poisoning; [Olson, p. 557]

Farming (Feed Additives) [Category: Industry]

MEDICATION

MEDICATION (VET)

Food additive

Vitamin. Nutritional factor.

... Condensation of 2,5,6-triamino-4(3H)-pyrimidinone, p-aminobenzoyl-L-glutamic acid, and 2,3-dibromopropanal.

Synthetic pteroylglutamic acid is made by the reaction of 2,3-di-bromopropanol,2,4,5-triamino-6-hydroxypyrimidine and para-aminobenzoyl glutamic acid

5 mg (base) per mL (Rx) [Folvite (benzyl alcohol 1.5 %)]; 10 mg per mL (Rx)

Folic acid (FOLVITE) is marketed as oral tablets containing 0.4, 0.8, and 1 mg and as an aqueous solution for injection. Tablets of folic acid contain either 0.1, 0.4, 0.8, or 1 mg of pteroylglutamic acid, as an aqueous solution for injection, and in combination with other vitamins and minerals

Injectable solutions are prepared by dissolving folic acid in normal sodium bicarbonate solution (which should be sterilized by filtration) or by preparing solutions of the sodium or methylglucamine salt.

Lexpec Folic Acid. Syrup containing folic acid 2.5 mg in each 5 mL (recommended diluent, Sorbitol Solution or Sorbitol Solution and water, equal parts).

10% feed grade, USP

L-Glutamic acid, N-[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-: ACTIVE

BOILING MILK FOR ... 5 SEC DECR FREE FOLIC ACID ACTIVITY 40-90% ... NO ... LOSSES DURING BLANCHING OF VEGETABLES. ... VEGETABLES EXHIBIT AN IRREGULAR PATTERN--SOME INCR & SOME DECR /CONTENT WHEN COOKED/. COOKING MEAT CAUSED SOME LOSSES.

Information available in 2005 indicated that Folic acid was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Australia, Austria, Bangladesh, Belgium, Bulgaria, Brazil, Canada, Chile, Colombia, Croatia, Cyprus, Czech Republic, Denmark, Dominican Republic, Ecuador, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Malaysia, Mexico, New Zealand, Norway, Poland, Portugal, Romania, South Africa, Singapore, Spain, Sweden, Switzerland, Thailand, Turkey, United Arab Emirates, United Kingdom, United States, Yugoslavia (1,2)

Information available in 2005 indicated that Sodium folate was used in the manufacture of pharmaceutical preparations in the following countries: Germany (1)