Editing Folate (section)

{{Short description|Vitamin B9; nutrient essential for DNA synthesis}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
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{{Use dmy dates|date=September 2024}}
{{Infobox drug
| drug_name = Folic acid
| image = Folic acid.svg
| image_class = skin-invert-image
| width = 260
| alt = Skeletal formula
| caption = 
| image2 = Folic-acid-from-xtal-3D-bs-17.png
| image_class2 = bg-transparent
| width2 = 280
| alt2 = <!-- Clinical data -->
| pronounce = {{IPAc-en|ˈ|f|oʊ|l|ɪ|k|,_|ˈ|f|ɒ|l|ɪ|k}}
| tradename = Folicet, Folvite
| Drugs.com = {{drugs.com|monograph|folic-acid}}
| MedlinePlus = a682591
| DailyMedID = Folic acid
| pregnancy_AU = A
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]], [[Intramuscular injection|intramuscular]], [[Intravenous therapy|intravenous]], [[Subcutaneous injection|subcutaneous]]
| class = 
| ATC_prefix = B03
| ATC_suffix = BB01
| ATC_supplemental = {{ATC|V04|CX02}} {{ATC|B03|AE02}} {{ATC|B03|AE01}} {{ATC|B03|BB51}}

<!-- Legal status -->| legal_AU = S4
| legal_AU_comment = /&nbsp;S2
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = /&nbsp;OTC
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->| bioavailability = 50–100%<ref name=AHFS2016/>
| protein_bound = 
| metabolism = [[Liver]]<ref name=AHFS2016/>
| metabolites = 
| onset = 
| elimination_half-life = 
| duration_of_action = 
| excretion = Urine<ref name=AHFS2016/>

<!-- Identifiers -->| index2_label = as salt
| CAS_number = 59-30-3
| CAS_number2 = 6484-89-5
| CAS_supplemental = 
| PubChem = 6037
| IUPHAR_ligand = 4563
| DrugBank = DB00158
| DrugBank2 = DBSALT001918
| ChemSpiderID = 5815
| ChemSpiderID2 = 21512
| UNII = 935E97BOY8
| UNII2 = 9P9W8GGU78
| KEGG = D00070
| KEGG2 = D07985
| ChEBI = 27470
| ChEMBL = 1622
| NIAID_ChemDB = 
| PDB_ligand = FOL
| synonyms = Wills factor, FA, ''N''-(4-<nowiki/>{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-<small>L</small>-glutamic acid, pteroyl-L-glutamic acid, folacin, vitamin B<sub>9</sub>;<ref name=NIH/> formerly, vitamin B<sub>c</sub> and vitamin M<ref name=Welch1983/>

<!-- Chemical and physical data -->| IUPAC_name = (2''S'')-2-<nowiki>[[</nowiki>4-[(2-Amino-4-oxo-1''H''-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid<ref>{{cite web|title=Folic Acid|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6037|publisher=The PubChem Project|url-status=live|archive-url=https://web.archive.org/web/20140407091703/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6037|archive-date=7 April 2014}}</ref>
| C = 19
| H = 19
| N = 7
| O = 6
| SMILES = n1c2C(=O)NC(N)=Nc2ncc1CNc3ccc(cc3)C(=O)N[C@H](C(O)=O)CCC(O)=O
| StdInChI = 1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1
| StdInChI_comment = 
| StdInChIKey = OVBPIULPVIDEAO-LBPRGKRZSA-N
| density = 1.6±0.1
| density_notes = <ref name="chemsrc">{{Cite web|url=https://www.chemsrc.com/en/cas/59-30-3_1191873.html|title=Folic Acid|website=ChemSrc|access-date=12 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828090610/https://www.chemsrc.com/en/cas/59-30-3_1191873.html|url-status=live}}</ref>
| melting_point = 250
| melting_high = 
| melting_notes = (decomposition)
| boiling_point = 
| boiling_notes = 
| solubility = 1.6
| sol_units = mg/L (25 °C)<ref name="chemsrc">{{Cite web|url=https://www.chemsrc.com/en/cas/59-30-3_1191873.html|title=Folic Acid|website=ChemSrc|access-date=12 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828090610/https://www.chemsrc.com/en/cas/59-30-3_1191873.html|url-status=live}}</ref>
| specific_rotation = 
}}

<!-- Definition and uses -->
'''Folate''', also known as '''vitamin B<sub>9</sub>''' and '''folacin''',<ref name="lpi">{{cite web|title=Folate|url=http://lpi.oregonstate.edu/mic/vitamins/folate|publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University|access-date=17 March 2018|date=2014|quote=Folate is a water-soluble B-vitamin, which is also known as vitamin B9 or folacin.|archive-date=19 August 2021|archive-url=https://web.archive.org/web/20210819075234/https://lpi.oregonstate.edu/mic/vitamins/folate|url-status=live}}</ref> is one of the [[B vitamins]].<ref name=AHFS2016>{{cite web|title=Folic Acid|url=https://www.drugs.com/monograph/folic-acid.html|website=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=1 September 2016|date=1 January 2010|url-status=live|archive-url=https://web.archive.org/web/20170808233930/https://www.drugs.com/monograph/folic-acid.html|archive-date=8 August 2017}}</ref> Manufactured '''folic acid''', which is converted into folate by the body, is used as a [[dietary supplement]] and in [[food fortification]] as it is more stable during processing and storage.<ref name=Choi2014>{{cite journal |vauthors=Choi JH, Yates Z, Veysey M, Heo YR, Lucock M |title=Contemporary issues surrounding folic Acid fortification initiatives |journal=Prev Nutr Food Sci |volume=19 |issue=4 |pages=247–60 |date=December 2014 |pmid=25580388 |pmc=4287316 |doi=10.3746/pnf.2014.19.4.247}}</ref> Folate is required for the body to make [[DNA]] and [[RNA]] and metabolise [[amino acids]] necessary for [[cell division]] and maturation of [[blood cell]]s.<ref name=NIH/><ref name=PKIN2020Folate>{{cite book |vauthors=West AA, Caudill MA, Bailey LB |title = Present Knowledge in Nutrition, Eleventh Edition |chapter = Folate |editor=BP Marriott |editor2=DF Birt |editor3=VA Stallings|editor4=AA Yates |publisher = Academic Press (Elsevier) |year=2020 |location = London, United Kingdom |pages = 273–88 |isbn=978-0-323-66162-1}}</ref> As the human body cannot make folate, it is required in the diet, making it an [[Nutrient#Essential nutrients|essential nutrient]].<ref>{{cite book|url=https://books.google.com/books?id=fedRNr2-UVAC&pg=PA551|title=Alcamo's Fundamentals of Microbiology: Body Systems|date=2009|publisher=Jones & Bartlett Publishers|isbn=978-0-7637-8712-7|page=511| vauthors = Pommerville JC |url-status=live|archive-url= https://web.archive.org/web/20170908213409/https://books.google.com/books?id=fedRNr2-UVAC&pg=PA551 |archive-date=8 September 2017 }}</ref> It occurs naturally in many foods.<ref name=lpi/><ref name=NIH/> The recommended adult daily intake of folate in the U.S. is 400 [[microgram]]s from foods or [[dietary supplement]]s.<ref name=NIH/>

<!-- Medical uses -->
Folate in the form of folic acid is used to treat [[anemia]] caused by [[folic acid deficiency|folate deficiency]].<ref name=AHFS2016 /> Folic acid is also used as a supplement by women during [[pregnancy]] to reduce the risk of [[neural tube defect]]s (NTDs) in the baby.<ref name=AHFS2016 /><ref>{{cite journal|vauthors=Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW, García FA, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phillips WR, Phipps MG, Pignone MP, Silverstein M, Tseng CW|s2cid=205077749|title=Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement|journal=JAMA|volume=317|issue=2|pages=183–189|date=January 2017|pmid=28097362|doi=10.1001/jama.2016.19438}}</ref> NTDs include [[anencephaly]] and [[spina bifida]], among other defects. Low levels in early [[pregnancy]] are believed to be the cause of more than half of babies born with NTDs.<ref name=NIH/> More than 80 countries use either mandatory or voluntary fortification of certain foods with folic acid as a measure to decrease the rate of NTDs.<ref name=Wald2018/> Long-term supplementation with relatively large amounts of folic acid is associated with a small reduction in the risk of [[stroke]]<ref name=Li2016>{{cite journal|vauthors=Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB|title=Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials|journal=Journal of the American Heart Association|volume=5|issue=8|pages=e003768|date=August 2016|pmid=27528407|pmc=5015297|doi=10.1161/JAHA.116.003768|url=https://dash.harvard.edu/bitstream/handle/1/29407892/5015297.pdf?sequence=1|access-date=4 November 2018|archive-date=27 April 2021|archive-url=https://web.archive.org/web/20210427034202/https://dash.harvard.edu/bitstream/handle/1/29407892/5015297.pdf?sequence=1|url-status=live}}</ref> and an increased risk of prostate cancer.<ref name=Wien2012/>  Maternal folic acid supplementation reduces [[autism]] risk, and [[folinic acid]] improves symptoms in autism with [[cerebral folate deficiency]]. Folate deficiency is linked to higher depression risk; folate supplementation serves as a beneficial [[Combination therapy|adjunctive]] treatment for depression. There are concerns that large amounts of supplemental folic acid can hide [[vitamin B12 deficiency|vitamin B<sub>12</sub> deficiency]].<ref name=NIH/>

<!-- Deficiency -->
Not consuming enough folate can lead to folate deficiency.<ref name=NIH/> This may result in [[megaloblastic anemia|a type of anemia]] in which red blood cells become abnormally large.<ref name=NIH/> Symptoms may include [[fatigue (medical)|feeling tired]], [[heart palpitations]], [[shortness of breath]], open sores on the tongue, and changes in the color of the skin or hair.<ref name=NIH/> Folate deficiency in children may develop within a month of poor dietary intake.<ref>{{cite book|vauthors=Marino BS, Fine KS|title=Blueprints Pediatrics|date=2009|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-8251-7|page=131|url=https://books.google.com/books?id=oqpSRIOcd8MC&pg=PA131|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908213408/https://books.google.com/books?id=oqpSRIOcd8MC&pg=PA131|archive-date=8 September 2017}}</ref> In adults, normal total body folate is between 10 and 30&nbsp;mg with about half of this amount stored in the liver and the remainder in blood and body tissues.<ref name=NIH/> In plasma, the natural folate range is 150 to 450&nbsp;nM.<ref>{{cite journal | vauthors = Fardous AM, Heydari AR | title = Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review | journal = Nutrients | volume = 15 | issue = 21 | page = 4699 | date = November 2023 | pmid = 37960352 | pmc = 10648405 | doi = 10.3390/nu15214699 | doi-access = free }}</ref>

<!-- History and culture -->
Folate was discovered between 1931 and 1943.<ref name=Pond>{{cite book| vauthors = Pond WG, Nichols BL, Brown DL |title=Adequate Food for All: Culture, Science, and Technology of Food in the 21st Century |date=2009 |publisher=CRC Press |isbn=978-1-4200-7754-4 |page=148 |url=https://books.google.com/books?id=wbS5FogT1-4C&pg=PA148 |language=en |quote=Folic acid's discovery started in 1931...}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> In 2022, it was the 65th most commonly prescribed medication in the United States, with more than 10{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Folic Acid Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/FolicAcid | access-date = 30 August 2024 | archive-date = 8 July 2020 | archive-url = https://web.archive.org/web/20200708065613/https://clincalc.com/DrugStats/Drugs/FolicAcid | url-status = live }}</ref> The term "folic" is from the Latin word {{lang|la|[[wikt:folium|folium]]}} (which means leaf) because it was found in dark-green leafy vegetables.<ref name=Chambers>{{cite book|title=Chambers Concise Dictionary|date=2004|publisher=Allied Publishers|isbn=978-81-86062-36-4|page=451|url=https://books.google.com/books?id=iwWuY9tAVq8C&pg=PA451|url-status=live|archive-url=https://web.archive.org/web/20170908213408/https://books.google.com/books?id=iwWuY9tAVq8C&pg=PA451|archive-date=8 September 2017}}</ref>
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