Editing Folate (section)

===Safety===
The risk of toxicity from folic acid is low because folate is a water-soluble vitamin and is regularly removed from the body through urine. One potential issue associated with high doses of folic acid is that it has a masking effect on the diagnosis of [[pernicious anaemia]] due to vitamin B<sub>12</sub> deficiency, and may even precipitate or exacerbate neuropathy in vitamin B12-deficient individuals. This evidence justified development of a UL for folate.<ref name="DRItext" /> In general, ULs are set for vitamins and minerals when evidence is sufficient. The adult UL of 1,000&nbsp;μg for folate (and lower for children) refers specifically to folic acid used as a supplement, as no health risks have been associated with high intake of folate from food sources. The EFSA reviewed the safety question and agreed with United States that the UL be set at 1,000&nbsp;μg.<ref>{{cite web|title=Tolerable Upper Intake Levels For Vitamins And Minerals|publisher=European Food Safety Authority|year=2006|url=http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf|access-date=16 May 2016|archive-date=19 September 2017|archive-url=https://web.archive.org/web/20170919040144/http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf|url-status=live}}</ref> The Japan National Institute of Health and Nutrition set the adult UL at 1,300 or 1,400&nbsp;μg depending on age.<ref name=JapanDRI>{{cite journal |vauthors=Shibata K, Fukuwatari T, Imai E, Hayakawa T, Watanabe F, Takimoto H, Watanabe T, Umegaki K |title=Dietary Reference Intakes for Japanese 2010: Water-Soluble Vitamins |journal=Journal of Nutritional Science and Vitaminology |volume=2013 |issue=59 |pages=S67–S82 |year=2013 |url=https://www.jstage.jst.go.jp/article/jnsv/59/Supplement/59_S67/_pdf |doi=10.3177/jnsv.59.S67 |doi-access=free |access-date=27 September 2018 |archive-date=14 September 2019 |archive-url=https://web.archive.org/web/20190914033244/https://www.jstage.jst.go.jp/article/jnsv/59/Supplement/59_S67/_pdf |url-status=live }}</ref>

Reviews of clinical trials that called for long-term consumption of folic acid in amounts exceeding the UL have raised concerns. Excessive amounts derived from supplements are more of a concern than that derived from natural food sources and the relative proportion to vitamin B<sub>12</sub> may be a significant factor in adverse effects.<ref>{{cite web | title=Folic Acid Overload? | website=Tufts Health & Nutrition Letter | date=10 September 2019 | url=https://www.nutritionletter.tufts.edu/vitamins-supplements/folic-acid-overload/ | access-date=18 October 2021}}</ref> One theory is that consumption of large amounts of folic acid leads to detectable amounts of unmetabolized folic acid circulating in blood because the enzyme [[dihydrofolate reductase]] that converts folic acid to the biologically active forms is rate limiting. Evidence of a negative health effect of folic acid in blood is not consistent, and folic acid has no known cofactor function that would increase the likelihood of a causal role for free folic acid in disease development.<ref name=Obeid2012>{{cite journal | vauthors = Obeid R, Herrmann W | title = The emerging role of unmetabolized folic acid in human diseases: myth or reality? | journal = Current Drug Metabolism | volume = 13 | issue = 8 | pages = 1184–95 | date = October 2012 | pmid = 22746304 | doi = 10.2174/138920012802850137 }}</ref> However, low vitamin B<sub>12</sub> status in combination with high folic acid intake, in addition to the previously mentioned neuropathy risk, appeared to increase the risk of cognitive impairment in the elderly.<ref name="adavidsmith"/> Long-term use of folic acid dietary supplements in excess of 1,000&nbsp;μg/day has been linked to an increase in prostate cancer risk.<ref name=Wien2012/>