Editing Folate (section)

==Dietary recommendations==
Because of the difference in bioavailability between supplemented folic acid and the different forms of folate found in food, the dietary folate equivalent (DFE) system was established. One DFE is defined as 1&nbsp;μg of dietary folate. 1&nbsp;μg of folic acid supplement counts as 1.7&nbsp;μg DFE. The reason for the difference is that when folic acid is added to food or taken as a dietary supplement with food it is at least 85% absorbed, whereas only about 50% of folate naturally present in food is absorbed.<ref name=NIH/>

{| class="wikitable"
|+[[National Institutes of Health]] (U.S.) nutritional recommendations<ref name=NIH>{{cite web|publisher=Office of Dietary Supplements, US [[National Institutes of Health]]|title=Folate – Fact Sheet for Health Professionals|url=http://ods.od.nih.gov/factsheets/folate/|date=29 March 2021|access-date=29 April 2022|archive-date=2 April 2011|archive-url=https://web.archive.org/web/20110402200837/http://ods.od.nih.gov/factsheets/Folate/|url-status=live}}</ref><br />μg DFE per day for RDA, μg folic acid for [[Tolerable upper intake levels]] (UL)
|-
!  rowspan="2"|Age
!colspan="2"|Infants
! colspan="2"|Children and adults
! colspan="2"|Pregnant women
! colspan="2"|Lactating women
|-
! (AI)
! (UL)
! (RDA)
! (UL)
! (RDA)
! (UL)
! (RDA)
! (UL)
|-
| 0–6 months
| 65
| None set
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
|-
| 7–12 months
| 80
| None set
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
|-
| 1–3 years
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" |150
| style ="text-align: center;" |300
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
|-
| 4–8 years
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" |200
| style ="text-align: center;" |400
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" |&nbsp;–
|-
| 9–13 years
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" |300
| style ="text-align: center;" |600
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" | –
|-
| 14–18
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" |400
| style ="text-align: center;" |800
| style ="text-align: center;" |600
| style ="text-align: center;" |800
| style ="text-align: center;" |500
| style ="text-align: center;" |800
|-
| 19+
| style ="text-align: center;" | –
| style ="text-align: center;" | –
| style ="text-align: center;" |400
| style ="text-align: center;" |1000
| style ="text-align: center;" |600
| style ="text-align: center;" |1000
| style ="text-align: center;" |500
| style ="text-align: center;" |1000
|}

The U.S. Institute of Medicine defines Estimated Average Requirements (EARs), Recommended Dietary Allowances (RDAs), Adequate Intakes (AIs), and Tolerable upper intake levels (ULs) – collectively referred to as [[Dietary Reference Intake]]s (DRIs).<ref name=NIH/><ref name="DRItext">{{cite book|author=Institute of Medicine|title=Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline|chapter=Folate|publisher=The National Academies Press|year=1998|location=Washington, DC|pages=196–305|chapter-url=https://www.nap.edu/read/6015/chapter/10|access-date=25 September 2019|isbn=978-0-309-06554-2|author-link=Institute of Medicine|archive-date=25 September 2019|archive-url=https://web.archive.org/web/20190925102802/https://www.nap.edu/read/6015/chapter/10|url-status=live}}</ref> The [[European Food Safety Authority]] (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the United States. For women and men over age 18, the PRI is set at 330&nbsp;μg/day. PRI for pregnancy is 600&nbsp;μg/day, for lactation 500&nbsp;μg/day. For children ages 1–17 years, the PRIs increase with age from 120 to 270&nbsp;μg/day. These values differ somewhat from the U.S. RDAs.<ref>{{cite web|title=Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies|year=2017|url=https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf|url-status=live|archive-url=https://web.archive.org/web/20170828082247/https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf|archive-date=28 August 2017}}</ref> The United Kingdom's Dietary Reference Value for folate, set by the Committee on Medical Aspects of Food and Nutrition Policy in 1991, is 200&nbsp;μg/day for adults.<ref>{{cite web|title=Nutrition Requirements|url=https://www.nutrition.org.uk/attachments/article/234/Nutrition%20Requirements_Revised%20Oct%202016.pdf|publisher=British Nutrition Foundation|access-date=8 July 2018|archive-date=11 February 2019|archive-url=https://web.archive.org/web/20190211104805/https://www.nutrition.org.uk/attachments/article/234/Nutrition%20Requirements_Revised%20Oct%202016.pdf}}</ref>

===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/>

===Food labeling===
For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For folate labeling purposes, 100% of the Daily Value was 400&nbsp;μg. As of the 27 May 2016 update, it was kept unchanged at 400&nbsp;μg.<ref name="FedReg">{{cite web|url=https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf|title=Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels. FR page 33982.|access-date=30 August 2017|archive-date=7 October 2021|archive-url=https://web.archive.org/web/20211007100633/https://www.govinfo.gov/content/pkg/FR-2016-05-27/pdf/2016-11867.pdf|url-status=live}}</ref><ref>{{cite web | title=Daily Value Reference of the Dietary Supplement Label Database (DSLD) | website=Dietary Supplement Label Database (DSLD) | url=https://www.dsld.nlm.nih.gov/dsld/dailyvalue.jsp | access-date=16 May 2020 | archive-date=7 April 2020 | archive-url=https://web.archive.org/web/20200407073956/https://dsld.nlm.nih.gov/dsld/dailyvalue.jsp }}</ref> Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with [[US$]]10&nbsp;million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales.<ref name="FDAdelay">{{cite web | title=Changes to the Nutrition Facts Label | website=U.S. [[Food and Drug Administration]] (FDA) | date=27 May 2016 | url=https://www.fda.gov/food/food-labeling-nutrition/changes-nutrition-facts-label | access-date=16 May 2020 | archive-date=6 May 2018 | archive-url=https://web.archive.org/web/20180506080421/https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ucm385663.htm | url-status=dead }} {{PD-notice}}</ref><ref>{{cite web | title=Industry Resources on the Changes to the Nutrition Facts Label | website=U.S. [[Food and Drug Administration]] (FDA) | date=21 December 2018 | url=https://www.fda.gov/food/food-labeling-nutrition/industry-resources-changes-nutrition-facts-label | access-date=16 May 2020 | archive-date=25 December 2020 | archive-url=https://web.archive.org/web/20201225063145/https://www.fda.gov/food/food-labeling-nutrition/industry-resources-changes-nutrition-facts-label | url-status=dead }} {{PD-notice}}</ref> A table of the old and new adult daily values is provided at [[Reference Daily Intake]].

European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For folate, 100% RI was set at 200&nbsp;μg in 2011.<ref>{{cite journal|title=Regulation (EU) No 1169/2011 of the European Parliament and of the Council|journal=Official Journal of the European Union|volume=22|issue=11|pages=18–63|year=2011|url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:304:0018:0063:EN:PDF|access-date=26 September 2018|archive-date=26 July 2017|archive-url=https://web.archive.org/web/20170726215901/http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ%3AL%3A2011%3A304%3A0018%3A0063%3AEN%3APDF|url-status=live}}</ref>