Editing Folate (section)

==Deficiency==
{{main|Folate deficiency}}
Folate deficiency can be caused by unhealthy diets that do not include enough vegetables and other folate-rich foods; diseases in which folates are not well absorbed in the digestive system (such as [[Crohn's disease]] or [[celiac disease]]); some genetic disorders that affect levels of folate; and certain medicines (such as phenytoin, [[sulfasalazine]], or trimethoprim-sulfamethoxazole).<ref name="nlm.nih.gov">{{Cite web|title=Folate deficiency: MedlinePlus Medical Encyclopedia|url=https://www.nlm.nih.gov/medlineplus/ency/article/000354.htm|website=nlm.nih.gov|access-date=16 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151117023226/https://www.nlm.nih.gov/medlineplus/ency/article/000354.htm|archive-date=17 November 2015}}</ref> Folate deficiency is accelerated by alcohol consumption, possibly by interference with folate transport.<ref>{{cite journal|vauthors=Hamid A, Wani NA, Kaur J|title=New perspectives on folate transport in relation to alcoholism-induced folate malabsorption–association with epigenome stability and cancer development|journal=The FEBS Journal|volume=276|issue=8|pages=2175–91|date=April 2009|pmid=19292860|doi=10.1111/j.1742-4658.2009.06959.x|s2cid=8591709|doi-access=free}}</ref>

Folate deficiency may lead to [[glossitis]], diarrhea, depression, confusion, anemia, and fetal neural tube and brain defects.<ref name="DRItext"/> Other symptoms include fatigue, gray hair, mouth sores, poor growth, and swollen tongue.<ref name="nlm.nih.gov"/> Folate deficiency is diagnosed by analyzing a [[complete blood count]] (CBC) and plasma vitamin B<sub>12</sub> and folate levels. A serum folate of 3&nbsp;μg/L or lower indicates deficiency.<ref name="DRItext"/> Serum folate level reflects folate status, but erythrocyte folate level better reflects tissue stores after intake. An erythrocyte folate level of 140&nbsp;μg/L or lower indicates inadequate folate status. Serum folate reacts more rapidly to folate intake than erythrocyte folate.<ref>{{cite journal|vauthors=Lohner S, Fekete K, Berti C, Hermoso M, Cetin I, Koletzko B, Decsi T|s2cid=26868696|title=Effect of folate supplementation on folate status and health outcomes in infants, children and adolescents: a systematic review|journal=International Journal of Food Sciences and Nutrition|volume=63|issue=8|pages=1014–20|date=December 2012|pmid=22574624|doi=10.3109/09637486.2012.683779}}</ref>

Since folate deficiency limits cell division, [[erythropoiesis]] (production of red blood cells) is hindered. This leads to [[megaloblastic anemia]], which is characterized by large, immature red blood cells. This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division, and produces abnormally large red cells 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 cells, although immature (reticulocytes), are released early from the marrow in an attempt to compensate for the anemia.<ref>{{cite book|title=Marks' Essential Medical Biochemistry, First edition|vauthors=Lieberman M, Marks AD, Smith C|publisher=Lippincott Williams & Wilkins|year=2007|isbn=978-0-7817-9340-7|location=Hagerstwon, MD}}{{page needed|date=May 2013}}</ref> Both adults and children need folate to make normal red and white blood cells and prevent anemia, which causes fatigue, weakness, and inability to concentrate.<ref name="Oldref_4">{{cite journal|vauthors=Zittoun J|title=Anémies par trouble du métabolisme des folates, de la vitamine B12 et des transcobalamines|trans-title=Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism|language=fr|journal=La Revue du Praticien|volume=43|issue=11|pages=1358–63|date=June 1993|pmid=8235383}}</ref><ref>{{cite web|url=http://www.healthlinkbc.ca/healthfiles/hfile68g.stm|title=Folate and Your Health – HealthLinkBC File #68g|publisher=Healthlink British Columbia|access-date=9 September 2012|url-status=live|archive-url=https://web.archive.org/web/20120709211636/http://www.healthlinkbc.ca/healthfiles/hfile68g.stm|archive-date=9 July 2012}}</ref>

Increased homocysteine levels suggest tissue folate deficiency, but homocysteine is also affected by vitamin B<sub>12</sub> and vitamin B<sub>6</sub>, renal function, and genetics. One way to differentiate between folate deficiency and vitamin B<sub>12</sub> deficiency is by testing for [[methylmalonic acid]] (MMA) levels. Normal MMA levels indicate folate deficiency and elevated MMA levels indicate vitamin B<sub>12</sub> deficiency.<ref name="DRItext"/> Elevated MMA levels may also be due to the rare metabolic disorder [[combined malonic and methylmalonic aciduria]] (CMAMMA).<ref>{{cite journal |vauthors=Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M, Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP  |title=Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria |journal=Nat Genet |volume=43 |issue=9 |pages=883–86 |date=August 2011 |pmid=21841779 |pmc=3163731 |doi=10.1038/ng.908 |url=}}</ref><ref>{{cite journal |vauthors=de Sain-van der Velden MG, van der Ham M, Jans JJ, Visser G, Prinsen HC, Verhoeven-Duif NM, van Gassen KL, van Hasselt PM  |title=A New Approach for Fast Metabolic Diagnostics in CMAMMA |journal=JIMD Rep |series=JIMD Reports |volume=30 |issue= |pages=15–22 |date=February 2016 |pmid=26915364 |pmc=5110436 |doi=10.1007/8904_2016_531 |isbn=978-3-662-53680-3 |url=}}</ref>

Folate deficiency is treated with supplemental oral folic acid of 400 to 1000&nbsp;μg per day. This treatment is very successful in replenishing tissues, even if deficiency was caused by malabsorption. People with megaloblastic anemia need to be tested for vitamin B<sub>12</sub> deficiency before treatment with folic acid, because if the person has vitamin B<sub>12</sub> deficiency, folic acid supplementation can remove the anemia, but can also worsen neurologic problems.<ref name="DRItext"/> Cobalamin (vitamin B<sub>12</sub>) deficiency may lead to folate deficiency, which, in turn, increases homocysteine levels and may result in the development of cardiovascular disease or birth defects.<ref>{{cite journal|vauthors=Varela-Moreiras G, Murphy MM, Scott JM|title=Cobalamin, folic acid, and homocysteine|journal=Nutrition Reviews|volume=67|pages=S69-72|date=May 2009|issue=Suppl 1 |pmid=19453682|doi=10.1111/j.1753-4887.2009.00163.x|hdl=2262/34510|hdl-access=free}}</ref>