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{{short description|Sweetener and sugar substitute}} {{about|the sweetener|other uses|Stevia (disambiguation)}} {{Use dmy dates|date=August 2020}} '''Stevia''' ({{IPAc-en|ˈ|s|t|iː|v|i|ə|,_|ˈ|s|t|ɛ|v|i|ə}})<ref>{{cite web |url=http://oxforddictionaries.com/definition/english/stevia |title=Stevia |series=British & World English |website=Oxforddictionaries.com |date=7 February 2013 |access-date=13 February 2013 |archive-url=https://web.archive.org/web/20130212042301/http://oxforddictionaries.com/definition/english/stevia |archive-date=12 February 2013 |url-status=dead}}</ref><ref>{{cite web |url=http://oxforddictionaries.com/definition/american_english/stevia |title=Stevia |series=US English |website=Oxforddictionaries.com |date=7 February 2013 |access-date=13 February 2013 |archive-url=https://web.archive.org/web/20130509020123/http://oxforddictionaries.com/definition/american_english/stevia |archive-date=9 May 2013 |url-status=dead}}</ref> is a sweet [[sugar substitute]] that is about 50 to 300 times [[sweetness|sweeter]] than [[sugar]].<ref>{{cite journal |journal=Plant Foods for Human Nutrition |year=1999 |volume=54 |number=2 |pages=119–129 |title=Measurement of the relative sweetness of stevia extract, aspartame and cyclamate/saccharin blend as compared to sucrose at different concentrations |first1=H.M.A.B. |last1=Cardello |first2=M.A.P.A. |last2=da Silva |first3=M.H. |last3=Damasio |doi=10.1023/A:1008134420339|pmid=10646559 |s2cid=38718610 }}</ref> It is [[extract]]ed from the leaves of ''[[Stevia rebaudiana]]'', a plant native to areas of [[Paraguay]] and [[Brazil]].<ref name="mbg">{{cite web |title=''Stevia rebaudiana'' |url=http://www.missouribotanicalgarden.org/PlantFinder/PlantFinderDetails.aspx?kempercode=e489 |publisher=Missouri Botanical Garden |access-date=30 October 2024 |date=2024}}</ref><ref name="kew">{{cite web|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:245468-2|title=''Stevia rebaudiana'' (Bertoni)|date=2024|publisher=Royal Botanic Gardens, Plants of the World Online|access-date=30 October 2024}}</ref> The active compounds in stevia are [[steviol glycoside]]s (mainly [[stevioside]] and [[rebaudioside]]).<ref name="Joint FAO/WHO2016">{{Cite tech report|last=Baines |first=J |collaboration=Joint FAO/WHO Expert Committee on Food Additives |date=2016 |title=Evaluation of Certain Food Additives: Eighty-second report of the Joint FAO/WHO Expert Committee on Food Additives|institution=WHO |number=1000 |language=en |isbn=978-92-4-069586-3 |url=https://apps.who.int/iris/bitstream/handle/10665/250277/9789241210003-eng.pdf?sequence=1 |url-status=live |access-date=10 December 2022 |archive-url=https://web.archive.org/web/20220806030120/https://apps.who.int/iris/bitstream/handle/10665/250277/9789241210003-eng.pdf?sequence=1 |archive-date=6 August 2022}}</ref>{{rp|54}} Stevia is heat-stable, [[pH]]-stable, and not [[fermentation (food)|fermentable]].<ref>{{cite report |last=Brandle |first=Jim |date=19 August 2004 |title=FAQ – Stevia, Nature's Natural Low Calorie Sweetener |publisher=Agriculture and Agri-Food Canada <!-- |access-date=11 Aug 2006 -->}}</ref> Humans cannot metabolize the [[glycosides]] in stevia, and it therefore has zero [[calorie]]s. Its taste has a slower onset and longer duration than that of sugar, and at high concentrations some of its extracts may have an [[aftertaste]] described as [[licorice]]-like or [[Bitter taste|bitter]]. Stevia is used in sugar- and calorie-reduced food and beverage products as an alternative for variants with sugar.<ref name="Samuel">{{cite journal | last1=Samuel | first1=Priscilla | last2=Ayoob | first2=Keith T | last3=Magnuson | first3=Bernadene A | last4=Wölwer-Rieck | first4=Ursula | last5=Jeppesen | first5=Per Bendix | last6=Rogers | first6=Peter J | last7=Rowland | first7=Ian | last8=Mathews | first8=Rebecca | title=Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential | journal=The Journal of Nutrition | volume=148 | issue=7 | date=2018-07-01 | issn=0022-3166 | doi=10.1093/jn/nxy102 | pages=1186S–1205S| pmid=29982648 |url=https://academic.oup.com/jn/article/148/7/1186S/5049670| doi-access=free | hdl=1983/618532e2-6caa-4fbe-bd6e-6eb0cb608981 | hdl-access=free }}</ref> The legal status of stevia as a [[food additive]] or [[dietary supplement]] varies from country to country. In the [[United States]], certain high-purity ''stevia glycoside'' extracts have been [[generally recognized as safe]] (GRAS) and may be lawfully marketed and added to food products, but stevia leaf and crude extracts do not have GRAS or [[Food and Drug Administration]] (FDA) approval for use in food.<ref name="FDA2017">{{cite web |url=https://www.fda.gov/aboutfda/transparency/basics/ucm194320.htm|publisher=US Food and Drug Administration|date=28 April 2017 |title=Has stevia been approved by FDA to be used as a sweetener? |access-date=27 July 2017 |archive-url=https://web.archive.org/web/20170729074803/https://www.fda.gov/AboutFDA/Transparency/Basics/ucm194320.htm |archive-date=29 July 2017 |url-status=dead}}</ref> The [[European Union]] approved ''Stevia rebaudiana'' additives in 2011.<ref name="eu-approved2">{{cite web |url=http://www.foodmanufacture.co.uk/Ingredients/Stevia-wins-final-EU-approval |title=Stevia wins final EU approval |first=Mike |last=Stones |work=foodmanufacture.co.uk |year=2011 |access-date=22 November 2011 |archive-url=https://web.archive.org/web/20111118163139/http://www.foodmanufacture.co.uk/Ingredients/Stevia-wins-final-EU-approval |archive-date=18 November 2011 |url-status=live}}</ref> In [[Japan]], stevia has been widely used as a sweetener for decades.<ref name="Japan">{{cite news |url=https://www.independent.co.uk/life-style/health-and-families/stevia-herb-shakes-up-global-sweetener-market-5531238.html |title=''Stevia'' herb shakes up global sweetener market |newspaper=The Independent |access-date=13 July 2017|archive-url=https://web.archive.org/web/20170728210745/http://www.independent.co.uk/life-style/health-and-families/stevia-herb-shakes-up-global-sweetener-market-5531238.html |archive-date=28 July 2017 |url-status=live|date=2010-03-28}}</ref> [[File:Stevia plant.jpg|thumb|''[[Stevia rebaudiana]]'']] The plant ''Stevia rebaudiana'' has been used for centuries by the [[Guaraní people]]s of South America, who called it ''ka'a he'ê'' ("sweet herb").<ref name="Misra-2011">{{cite journal |last1=Misra |first1=H. |last2=Soni |first2=M. |last3=Silawat |first3=N. |last4=Mehta |first4=D. |last5=Mehta |first5=B.K. |last6=Jain |first6=D.C. |title=Antidiabetic activity of medium-polar extract from the leaves of ''Stevia rebaudiana'' Bert. (Bertoni) on alloxan-induced diabetic rats |journal= J Pharm Bioallied Sci |volume=3 |issue=2 |pages=242–248 |date=April 2011 |doi=10.4103/0975-7406.80779 |pmid=21687353 |pmc=3103919 |doi-access=free }}</ref> The leaves have been used traditionally for hundreds of years in both Paraguay and Brazil to sweeten local teas, and as a "sweet treat".<ref name="Misra-2011"/> The genus was named for the Spanish botanist and physician [[Pedro Jaime Esteve]] (''Petrus James Stevus'', 1500–1556) a professor of botany at the [[University of Valencia]].<ref>{{cite book |author1=Parsons, W.T. |url=https://books.google.com/books?id=sRCrNAQQrpwC&q=%22Pedro%20Jaime%20Esteve%22%20stevia&pg=PA309 |title=Noxious Weeds of Australia, 2nd ed. |author2=Cuthbertson, E.G. |publisher=CSIRO Publishing |year=2001 |isbn=978-0-643-06514-7 |location=Collingswood, Australia |page=309}} Specifically, this reference refers to ''[[Stevia eupatoria]]'', a related weed with a similar name-origin.</ref> ==History== In 1899, Swiss botanist [[Moisés Santiago Bertoni]], while conducting research in eastern Paraguay, first described the plant and the sweet taste in detail.<ref>{{cite journal |last=Bertoni |first=Moisés Santiago |author-link=Moisés Santiago Bertoni |title=[no title cited] |journal=Revista de Agronomia de l'Assomption |volume=1 |page=35 |year=1899}}</ref> Only limited research was conducted on the topic until, in 1931, two French chemists isolated the [[glycoside]]s that give stevia its sweet taste.<ref>{{cite journal |last1=Bridel |first1=M. |last2=Lavielle |first2=R. |title=Sur le principe sucre des feuilles de kaa-he-e (''Stevia rebaundiana'' B) |journal=Comptes Rendus de l'Académie des Sciences |issue=Parts 192 |pages=1123–1125 |year=1931}}</ref> === Early regulation === During the 1990s, the United States [[Food and Drug Administration]] (FDA) received two petitions requesting that stevia be classified as [[generally recognized as safe]] (GRAS), but the FDA "disagreed with [the] conclusions [detailed in the petitions]".<ref>{{cite news |url=https://www.nytimes.com/2001/03/07/dining/so-sweet-so-natural-so-la.html |title=So sweet, so natural, so L.A. |access-date=15 September 2017 |archive-url=https://web.archive.org/web/20170906184459/http://www.nytimes.com/2001/03/07/dining/so-sweet-so-natural-so-la.html |archive-date=6 September 2017 |url-status=live|newspaper=[[The New York Times]] |date=2001-03-07 |last1=Drake |first1=Laurie }}</ref> Stevia remained banned for all uses until the [[Dietary Supplement Health and Education Act of 1994]], after which the FDA revised its stance and permitted stevia to be used as a [[dietary supplement]], although still not as a food additive.<ref name="McCaleb_1997_1">{{cite web |last=McCaleb |first=Rob |title=Controversial Products in the Natural Foods Market |publisher=Herb Research Foundation |year=1997 |url=http://herbs.org/greenpapers/controv.html#stevia |access-date=8 November 2006 |archive-url=https://web.archive.org/web/20061018132214/http://www.herbs.org/greenpapers/controv.html#stevia |archive-date=18 October 2006 |url-status=live}}</ref> In 1999, prompted by early studies, the [[European Commission]] banned stevia's use in food products within the European Union pending further research.<ref name="EC">{{cite report |publisher=[[European Commission]] |department=Scientific Committee on Food |date=June 1999 |url=http://ec.europa.eu/food/fs/sc/scf/out34_en.pdf |title=Opinion on stevioside as a sweetener |archive-url=https://web.archive.org/web/20061023103749/http://ec.europa.eu/food/fs/sc/scf/out34_en.pdf |archive-date=23 October 2006}}</ref> In 2006 and 2016, research data compiled in the safety evaluations released by the [[World Health Organization]] found no adverse effects.<ref name="WHO" /><ref name="Joint FAO/WHO2016" />{{rp|60}} In December 2008, the FDA gave a "no objection" approval for GRAS status to [[Truvia]]{{efn|[[Truvia]] is the [[brand-name]] of a sweetener developed by [[Cargill]] and the [[Coca-Cola Company]].}} and [[PureVia]],{{efn|[[PureVia]] is the [[brand-name]] of a sweetener developed by [[PepsiCo]] and the [[Whole Earth Sweetener Company]], a subsidiary of [[Merisant]].}} both of which use {{nowrap|[[rebaudioside A]]}} derived from the ''Stevia rebaudiana'' plant.<ref>{{cite news |last=Newmarker |first=Chris |title=Federal regulators give OK for Cargill's Truvia sweetener |newspaper=Minneapolis / St. Paul Business Journal |url=http://www.bizjournals.com/twincities/stories/2008/12/15/daily38.html |access-date=18 December 2008 |date=18 December 2008 |archive-url=https://web.archive.org/web/20090101145358/http://www.bizjournals.com/twincities/stories/2008/12/15/daily38.html |archive-date=1 January 2009 |url-status=live}}</ref> However, the FDA said that these products are not stevia, but a highly purified ''Stevia rebaudiana''-extract product.<ref>{{cite web |title=What refined ''Stevia'' preparations have been evaluated by FDA to be used as a sweetener? |url=https://www.fda.gov/AboutFDA/Transparency/Basics/ucm214865.htm |website=fda.gov |publisher=U.S. Food and Drug Administration |access-date=22 March 2014 |archive-url=https://web.archive.org/web/20140423015313/https://www.fda.gov/aboutfda/transparency/basics/ucm214865.htm |archive-date=23 April 2014|url-status=live}}</ref> In 2015, the FDA still regarded stevia as "not an approved food additive", and stated that it "has not been affirmed as GRAS in the United States due to inadequate toxicological information".<ref>{{cite report |publisher=[[Food and Drug Administration]] |edition=1995, rev 1996, 2005 |url=http://www.accessdata.fda.gov/cms_ia/importalert_119.html |series=Import Alert |id=Import Alert 45-06 |archive-url=https://web.archive.org/web/20151030052453/http://www.accessdata.fda.gov/cms_ia/importalert_119.html |archive-date=30 October 2015 |title=Automatic detention of ''Stevia'' leaves, extract of ''Stevia'' leaves, and food containing stevia}}</ref> In June 2016, the [[U.S. Customs and Border Protection]] issued an order of detention for stevia products made in China based on information that the products were made using [[prison labor]].<ref>{{cite web |url=https://www.cbp.gov/newsroom/national-media-release/cbp-commissioner-issues-detention-order-stevia-produced-china-forced |title=CBP Commissioner issues detention order on stevia produced in China with forced labor |date=1 June 2016 |access-date=14 April 2017 |archive-url=https://web.archive.org/web/20170508040816/https://www.cbp.gov/newsroom/national-media-release/cbp-commissioner-issues-detention-order-stevia-produced-china-forced |archive-date=8 May 2017 |url-status=live}}</ref> Certain high-purity ''stevia glycoside'' extracts have been [[generally recognized as safe]] (GRAS) and may be lawfully marketed and added to food products.<ref name=FDA2017/> === Commercial use === Use of stevia as a sweetener began in Japan,{{Primary source inline|date=July 2023}} with the [[aqueous]] [[extract]] of the leaves yielding purified steviosides developed as sweeteners. Japanese firm [[Morita Kagaku Kogyo Co., Ltd.|Morita Kagaku Kogyo]] claims they were the first, in 1971, to commercialize stevia sweetener production.<ref name="MoritaKagakuKogyo1">{{cite web |title=Stevia |publisher=Morita Kagaku Kogyo|date=2007|url=http://www.morita-kagaku-kogyo.co.jp/e/index.htm |access-date=5 July 2023 |url-status=dead |archive-url=https://web.archive.org/web/20131027055558/http://www.morita-kagaku-kogyo.co.jp/e/index.htm |archive-date=27 October 2013}}</ref> In the mid-1980s, stevia was commonly used in U.S. [[natural foods]] and [[health food]] industries, as a noncaloric natural sweetener for teas and weight-loss blends.<ref>{{cite magazine |last=Zeavin |first=Edna |via=Google Books |url=https://books.google.com/books?id=LLMXAQAAIAAJ&q=Stevia,+also+called+sweet+leaf+or+sweet+herb,+is+making+inroads+into+the+health+food+and+natural+foods+markets. |title=The outlaw herbal sweetener |magazine=East West Journal |date=February 1988 |page=28 |quote=''Stevia'', also called sweet leaf or sweet herb, is making inroads into the health food and natural foods markets.}}</ref><ref name=keville/> The makers of the synthetic sweetener [[NutraSweet]] (at the time Monsanto) asked the FDA to require testing of stevia extracts.<ref name=keville>{{cite magazine |last=Keville |first=Kathi |url=https://books.google.com/books?id=oQgAAAAAMBAJ&pg=PA47 |via=Google Books |title=Exploring South America's medicinal plants |magazine=[[Vegetarian Times]] |date=April 1987 |page=47}}</ref> <!-- DO NOT ADD ARBITRARY STEVIA PRODUCTS TO THIS SECTION - IS ABOUT SIGNIFICANT EVENTS, NOT A LIST OF PRODUCTS AND MANUFACTURERS --> In 2007, [[the Coca-Cola Company]] announced plans to obtain approval for its ''Stevia''-derived sweetener, [[Rebiana]], for use as a food additive within the United States by 2009, as well as plans to market Rebiana-sweetened products in 12 countries that allow stevia's use as a food additive.<ref>{{cite news |title=Coke and Cargill teaming on new drink sweetener |last=Stanford |first=Duane D. |newspaper=Atlanta Journal-Constitution |date=31 May 2007 |access-date=31 May 2007 |url=http://www.ajc.com/business/content/business/coke/stories/2007/05/31/0531bizcoke.html |archive-url=https://web.archive.org/web/20070603082921/http://www.ajc.com/business/content/business/coke/stories/2007/05/31/0531bizcoke.html |archive-date=3 June 2007 |url-status=dead}}</ref><ref>{{cite news |title=Coke, Cargill aim for a shake-up in sweeteners |last1=Etter |first1=Lauren |last2=McKay |first2=Betsy |name-list-style=amp |work=The Wall Street Journal|date=31 May 2007 |access-date=1 June 2007 |url=https://www.wsj.com/articles/SB118058140982419717?mod=rss_whats_news_us |archive-url=https://web.archive.org/web/20180124195624/https://www.wsj.com/articles/SB118058140982419717?mod=rss_whats_news_us |archive-date=24 January 2018 |url-status=live}}</ref> In May 2008, Coca-Cola and [[Cargill]] announced the availability of Truvia, a consumer-brand ''Stevia'' sweetener containing [[erythritol]] and Rebiana,<ref>{{cite web |url=http://www.truvia.com/about/ingredients/default.aspx |title=Truvia ingredients |access-date=15 May 2008 |url-status=dead |archive-url=https://web.archive.org/web/20090807113856/http://www.truvia.com/about/ingredients/default.aspx |archive-date=7 August 2009}}</ref> which the FDA permitted as a food additive in December 2008.<ref name="approval1">{{cite web |title=''Stevia'' sweetener gets US FDA go-ahead |url=http://www.foodnavigator-usa.com/Legislation/Stevia-sweetener-gets-US-FDA-go-ahead |date=18 December 2008 |access-date=11 May 2009 |agency=Decision News Media SAS |archive-url=https://web.archive.org/web/20090618165807/http://www.foodnavigator-usa.com/Legislation/Stevia-sweetener-gets-US-FDA-go-ahead |archive-date=18 June 2009 |url-status=live}}</ref> Coca-Cola announced intentions to release stevia-sweetened beverages in late December 2008.<ref name="preapproval">{{cite news |title=Coke to sell drinks with stevia; Pepsi holds off |agency=Associated Press |newspaper=The Seattle Times |date=15 December 2008 |access-date=16 December 2008 |url=http://seattletimes.nwsource.com/html/businesstechnology/2008522412_apdrinkssweetener.html |archive-url=https://web.archive.org/web/20081219112723/http://seattletimes.nwsource.com/html/businesstechnology/2008522412_apdrinkssweetener.html |archive-date=19 December 2008 |url-status=live}}</ref> From 2013 onwards, [[Coca-Cola Life]], containing stevia as a sweetener, was launched in various countries around the world.<ref name=Geller>{{cite news |last=Geller |first=Martinne |title=Coke to sell 'natural' mid-calorie cola in Argentina |url=https://www.reuters.com/article/cocacola-argentina-idUSL2N0F21Z020130626 |access-date=27 June 2013 |newspaper=[[Reuters]] |date=26 June 2013 |archive-url=https://web.archive.org/web/20130627122534/http://www.reuters.com/article/2013/06/26/cocacola-argentina-idUSL2N0F21Z020130626 |archive-date=27 June 2013 |url-status=live}}</ref> Shortly afterward, [[PepsiCo]] and [[Pure Circle]] announced PureVia, their brand of ''Stevia''-based sweetener, but withheld release of beverages sweetened with {{nowrap|rebaudioside A}} until receipt of FDA confirmation. Since the FDA permitted Truvia and PureVia, both the Coca-Cola Company and PepsiCo have introduced products that contain their new sweeteners.<ref name="nyt">{{cite news |title=FDA approves 2 new sweeteners |url=https://www.nytimes.com/2008/12/18/business/18sweet.html |date=17 December 2008 |access-date=11 May 2009 |newspaper=[[The New York Times]] |agency=Associated Press}}</ref> ==Industrial extracts== Rebaudioside A has the least [[bitter (taste)|bitterness]] of all the steviol glycosides in the ''Stevia rebaudiana'' plant. To produce steviol glycosides commercially, ''Stevia rebaudiana'' plants are dried and subjected to a hot water [[Extraction (chemistry)|extraction]] process.<ref name="Joint FAO/WHO2016" />{{rp|56}} This crude extract contains about 50% rebaudioside A. The various glycosides are separated and purified via [[crystallization]] techniques, typically using [[ethanol]] or [[methanol]] as [[solvent]].<ref>{{cite web |last=Purkayastha |first=S. |url=http://www.foodproductdesign.com/articles/guide-to-reb-a.html |title=A Guide to Reb-A |website=Food Product Design |access-date=28 March 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090326123009/http://www.foodproductdesign.com/articles/guide-to-reb-a.html |archive-date=26 March 2009}}</ref> The dried extract contains no less than 95% steviol glycosides.<ref name="Joint FAO/WHO2016" />{{rp|56}}<ref name="WHO Evaluations 2021" /> ''Stevia rebaudiana'' extracts and derivatives are produced industrially and marketed under different trade names. * [[Rebiana]] is an abbreviated name for the ''Stevia'' extract, {{nowrap|rebaudioside A}}.<ref name="pmid18554769">{{cite journal |vauthors=Prakash I, Dubois GE, Clos JF, Wilkens KL, Fosdick LE |title=Development of rebiana, a natural, non-caloric sweetener |journal=Food Chem. Toxicol. |volume=46 Suppl 7 |issue=7 |pages=S75–82 |date=July 2008 |pmid=18554769 |doi=10.1016/j.fct.2008.05.004}}</ref> * Truvia is the brand for an erythritol and rebiana sweetener concoction manufactured by [[Cargill]] and developed jointly with the Coca-Cola Company.<ref>{{cite news |url=http://www.startribune.com/new-cargill-sweetener-aims-at-the-giant-worldwide-cola-market/219040011/ |title=New Cargill sweetener aims at the giant worldwide cola market |newspaper=Star Tribune |place=Minneapolis, MN |date=10 August 2013 |author=Mike Hughlett|access-date=5 March 2017 |archive-url=https://web.archive.org/web/20170306134458/http://www.startribune.com/new-cargill-sweetener-aims-at-the-giant-worldwide-cola-market/219040011/ |archive-date=6 March 2017 |url-status=live}}</ref> * PureVia is PepsiCo's brand of rebiana.<ref name="nyt"/> * EverSweet, discovered and developed by Evolva,<ref>{{cite web |url=https://www.foodbev.com/news/evolva-signs-major-agreement-with-cargill-for-eversweet-sweetener/ |title=Evolva signs major agreement with Cargill for EverSweet sweetener |website=Foodbev Media |access-date=13 June 2021 }}</ref> and manufactured jointly by Cargill and [[DSM (company)|DSM]].<ref>{{cite web |url=https://www.foodingredientsfirst.com/news/cargill-dsm-joint-venture-starts-commercial-scale-production-of-eversweet.html |title=Cargill-DSM joint venture starts commercial-scale production of EverSweet |website=Food Ingredients First |access-date=13 June 2021 }}</ref><ref>{{cite web |url=https://www.confectioneryproduction.com/news/35211/cargill-and-dsms-eversweet-stevia-series-delivers-key-taste-and-sustainability-results/ |title=Cargill and DSM's Eversweet stevia series delivers key taste and sustainability results |website=Confectionery Production |access-date=13 June 2021 }}</ref> ==Mechanism of action== [[File:Steviol structure.svg|thumb|right|180px|[[Steviol]], the basic building block of stevia's [[steviol glycoside|sweet glycosides]] ]] Glycosides are molecules that contain glucose residues bound to other non-sugar substances called [[aglycones]] (molecules with other sugars are [[polysaccharide]]s). Preliminary experiments deduce that the tongue's [[taste receptor]]s react to the glycosides and transduce the sweet taste sensation and the lingering bitter aftertaste by direct activation of sweet and bitter receptors.<ref>{{cite journal |last1=Hellfritsch |first1=C. |last2=Brockhoff |first2=A. |last3=Stähler |first3=F. |last4=Meyerhof |first4=W. |last5=Hofmann |first5=T. |title=Human psychometric and taste receptor responses to steviol glycosides |journal=Journal of Agricultural and Food Chemistry |date=11 July 2012 |volume=60 |issue=27 |pages=6782–6793 |pmid=22616809 |doi=10.1021/jf301297n|bibcode=2012JAFC...60.6782H }}</ref> According to [[basic research]], steviol glycosides and steviol interact with a [[protein channel]] called [[TRPM5]], potentiating the signal from the sweet or bitter receptors, amplifying the taste of other sweet, bitter and umami tastants.<ref>{{cite journal |last1=Philippaert |first1=K. |last2=Pironet |first2=A. |last3=Mesuere |first3=M. |last4=Sones |first4=W. |last5=Vermeiren |first5=L. |last6=Kerselaers |first6=S. |last7=Pinto |first7=S. |last8=Segal |first8=A. |last9=Antoine |first9=N. |last10=Gysemans |first10=C. |last11=Laureys |first11=J. |last12=Lemaire |first12=K. |last13=Gilon |first13=P. |last14=Cuypers |first14=E. |last15=Tytgat |first15=J. |last16=Mathieu |first16=C. |last17=Schuit |first17=F. |last18=Rorsman |first18=P. |last19=Talavera |first19=K. |last20=Voets |first20=T. |last21=Vennekens |first21=R. |display-authors=6 |date=31 March 2017 |title=Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity |journal=Nature Communications |volume=8 |pages=14733 |pmid=28361903 |doi=10.1038/ncomms14733 |pmc=5380970|bibcode=2017NatCo...814733P }}</ref> The [[synergy|synergetic]] effect of the glycosides on the sweet receptor and TRPM5 explains the sweetness sensation. Some steviol glycosides (rebaudioside A) are perceived sweeter than others (stevioside).<ref>{{cite journal |pmid=24206531 |year=2013 |last1=Well |first1=C. |last2=Frank |first2=O. |last3=Hofmann |first3=T. |title=Quantitation of sweet steviol glycosides by means of a HILIC-MS/MS-SIDA approach|journal=Journal of Agricultural and Food Chemistry |volume=61 |issue=47 |pages=11312–11320 |doi=10.1021/jf404018g|bibcode=2013JAFC...6111312W }}</ref> Steviol is processed by intestinal microflora and is also taken up into the bloodstream, further metabolised by the liver to steviol glucuronide and several other metabolites, and excreted in the urine.<ref>{{cite journal |last1=Geuns |first1=J.M. |last2=Buyse |first2=J. |last3=Vankeirsbilck |first3=A. |last4=Temme |first4=E.H. |last5=Compernolle |first5=F. |last6=Toppet |first6=S. |title=Identification of steviol glucuronide in human urine |journal=Journal of Agricultural and Food Chemistry |date=5 April 2006 |volume=54 |issue=7 |pages=2794–2798 |pmid=16569078 |doi=10.1021/jf052693e|bibcode=2006JAFC...54.2794G }}</ref><ref name="Joint FAO/WHO2016" />{{rp|56–57}} A three-dimensional map of the [[protein]]s produced by the stevia plant, showing the crystalline structures that produce both the sensation of sweetness and bitter aftertaste in the sweetener, was reported in 2019.<ref>{{cite web |url=https://cen.acs.org/biological-chemistry/natural-products/enzyme-makes-stevia-sweet/97/i24 |title=This enzyme is what makes stevia so sweet |website=Chemical & Engineering News |language=en |access-date=2019-08-22}}</ref> ==Safety and regulations== A 2010 review found that the use of ''Stevia rebaudiana'' sweeteners as replacements for sugar might benefit children, people with [[diabetes]], and those wishing to lower their intake of calories.<ref name="Goyal-2010"/> Although both steviol and rebaudioside A have been found to be [[mutagenic]] in laboratory ''in vitro'' testing,<ref name=kobylewski>{{cite web |last1=Kobylewski |first1=Sarah |last2=Eckhert |first2=Curtis |title=Toxicology of rebaudioside A: A review |date=14 August 2008 |url=http://www.cspinet.org/new/pdf/stevia-report_final-8-14-08.pdf |access-date=19 August 2015 |archive-url=https://web.archive.org/web/20150910035854/http://www.cspinet.org/new/pdf/stevia-report_final-8-14-08.pdf |archive-date=10 September 2015 |url-status=live}}</ref> these effects have not been demonstrated for the doses and routes of administration to which humans are exposed.<ref name="WHO">{{Cite book |url=http://apps.who.int/iris/bitstream/10665/43265/1/9241660546_eng.pdf |title=Safety evaluation of certain food additives |date=2006 |publisher=World Health Organization, International Program on Chemical Safety |last1=Bend|first1=J.R.|collaboration=Food and Agriculture Organization of the United Nations, World Health Organization, International Program on Chemical Safety |isbn=978-92-4-166054-9 |location=Geneva |oclc=70637287|archive-url=https://web.archive.org/web/20080910124154/http://whqlibdoc.who.int/publications/2006/9241660546_eng.pdf |archive-date=10 September 2008 |url-status=live|page=140}}</ref><ref name="pmid14561506">{{cite journal |last=Geuns |first=J.M. |title=Stevioside |journal=[[Phytochemistry (journal)|Phytochemistry]] |volume=64 |issue=5 |pages=913–921 |year=2003 |pmid=14561506 |doi=10.1016/S0031-9422(03)00426-6|bibcode=2003PChem..64..913G }}</ref><ref name="pmid18556105">{{cite journal |last=Brusick |first=D.J. |title=A critical review of the genetic toxicity of steviol and steviol glycosides |journal=Food Chem Toxicol |volume=46 |issue=7 |pages=S83–S91 |year=2008 |pmid=18556105 |doi=10.1016/j.fct.2008.05.002}}</ref> Two 2010 review studies found no health concerns with ''Stevia rebaudiana'' or its sweetening extracts.<ref name="Goyal-2010">{{cite journal |last1=Goyal |first1=S.K. |last2=Samsher |last3=Goyal |first3=R.K. |title=Stevia (''Stevia rebaudiana'') a bio-sweetener: A review |journal=Int J Food Sci Nutr |volume=61 |issue=1 |pages=1–10 |date=February 2010 |doi=10.3109/09637480903193049 |pmid=19961353|s2cid=24564964 }}</ref><ref name="Ulbricht-2010">{{cite journal |last1=Ulbricht |first1=C. |last2=Isaac |first2=R. |last3=Milkin |first3=T. |last4=Poole |first4=E.A. |last5=Rusie |first5=E. |title=An evidence-based systematic review of stevia by the Natural Standard Research Collaboration |journal=Cardiovasc Hematol Agents Med Chem |volume=8 |issue=2 |pages=113–127 |date=April 2010 |doi=10.2174/187152510791170960 |pmid=20370653 |display-authors=etal |collaboration=Natural Standard Research Collaboration}}</ref> Used as an [[extract]], stevia leaves have been used traditionally in Paraguay as a women's [[Birth control|contraceptive]], administered as a daily drink. The effect has been tested in rats, finding a 57–79 percent reduction in fertility compared with the [[control group]], the lowered fertility continuing after withdrawal of the drug for up to two months.<ref>{{cite book |last1=Jaffe |first1=Louis|last2=Tribe|first2=Laurence |date=1971 |title=Environmental Protection: Issue 1 |url= https://books.google.com/books?id=laCwAAAAIAAJ&q=traditionally+contraceptive |publisher=Bracton Press |page=562}}</ref><ref>{{cite journal|last1=Planas|first1=Gladys|last2=Kuć|first2=Joseph|title=Contraceptive Properties of Stevia rebaudiana |journal=[[Science (journal)|Science]]|volume=162|issue=3857|page=1007|year=1968|pmid=17744732|doi=10.1126/science.162.3857.1007|bibcode=1968Sci...162.1007M }}</ref> The WHO's Joint Experts Committee on Food Additives has approved, based on long-term studies, an [[acceptable daily intake]] of steviol glycoside of up to 4 mg/kg of body mass.<ref name="WHO" /><ref name="Joint FAO/WHO2016" />{{rp|60}}<ref name="WHO Evaluations 2021">{{cite web |title=Evaluations of the Joint FAO/WHO Expert Committee on Food Additives (JECFA): Steviol Glycosides |url=https://apps.who.int/food-additives-contaminants-jecfa-database/Home/Chemical/267 |url-status=live |access-date=10 December 2022 |author=<!--Not stated--> |archive-url=https://web.archive.org/web/20221210230515/https://apps.who.int/food-additives-contaminants-jecfa-database/Home/Chemical/267 |archive-date=10 December 2022}}</ref> In 2010, The [[European Food Safety Authority]] established an acceptable daily intake of 4 mg/kg of steviol, in the form of steviol glycosides. Meanwhile, the [[Memorial Sloan Kettering Cancer Center]] warns that "steviol at high dosages may have weak mutagenic activity,"<ref name=mskcc>{{cite web |title=Stevia |url=https://www.mskcc.org/cancer-care/integrative-medicine/herbs/stevia |website=Memorial Sloan Kettering Cancer Center |access-date=19 August 2015 |archive-url=https://web.archive.org/web/20150912085756/https://www.mskcc.org/cancer-care/integrative-medicine/herbs/stevia |archive-date=12 September 2015 |url-status=live}}</ref> and a review "conducted for" the [[Center for Science in the Public Interest]] notes that there are no published carcinogenicity results for rebaudioside A (or stevioside).<ref name=kobylewski/> In August 2019, the US FDA placed an import alert on ''Stevia'' leaves and crude extracts – which do not have [[GRAS]] status – and on foods or dietary supplements containing them due to concerns about safety and potential for [[toxicity]].<ref name="fda19">{{cite web |title=Detention without physical examination of ''Stevia'' leaves, crude extracts of ''Stevia'' leaves and foods containing ''Stevia'' leaves and/or ''Stevia'' extracts |id=Import Alert 45-06 |url=https://www.accessdata.fda.gov/cms_ia/importalert_119.html |publisher=US Food and Drug Administration |access-date=23 November 2019 |date=16 August 2019}}</ref> ===Availability and legal status by country or area=== The plant may be grown legally in most countries, although some countries restrict its use as a sweetener. The legally allowed uses and maximum dosage of the extracts and derived products vary widely from country to country. * Argentina: available as of 2008, regulatory status uncertain<ref name="flexnews2008-07-01">{{cite web |title=Olam and Wilmar in 50:50 j.v. to acquire 20% stake in PureCircle, a leading producer of natural high-intensity sweeteners for USD 106.2 Mln |website=flex-news-food.com |date=1 July 2008 |url=http://www.flex-news-food.com/console/PageViewer.aspx?page=17487 |access-date=5 April 2012 |archive-url=https://web.archive.org/web/20120313225449/http://www.flex-news-food.com/console/PageViewer.aspx?page=17487 |archive-date=13 March 2012 |url-status=live}}</ref> * Australia: ** All steviol glycoside extracts were approved in 2008.<ref name="Aus-n-NZ-approval">{{cite news |url=https://www.foodnavigator.com/Article/2008/10/08/Stevia-gets-Australian-approval-for-food-and-beverages |title=Stevia gets Australian approval for food and beverages |date=7 October 2008|last1=Danielss|first1=Stephen|website=FoodNavigator|publisher=William Reed |access-date=3 December 2022|url-status=live|archive-url=https://web.archive.org/web/20220527024126/https://www.foodnavigator.com/Article/2008/10/08/Stevia-gets-Australian-approval-for-food-and-beverages|archive-date=27 May 2022}}</ref> * Brazil: stevioside extract approved as food additive since 2005.<ref>{{Cite web |url=http://www4.anvisa.gov.br/base/visadoc/CP/CP%5B12925-1-0%5D.PDF |title=Consulta Pública nº 86, de 7 de dezembro de 2005. D.O.U de 08/12/2005 |publisher=Agência Nacional de Vigilância Sanitária (ANVISA) |trans-title=Public Consultation nº 86, 7 December 2005 |access-date=2 February 2019 |archive-date=18 September 2017 |archive-url=https://web.archive.org/web/20170918145110/http://www4.anvisa.gov.br/base/visadoc/CP/CP[12925-1-0].PDF |url-status=dead }}</ref> * Canada (as of November 2012) ** Steviol glycosides became available as a food additive on 30 November 2012.<ref>{{cite report |title=Notice of modification to the list of permitted sweeteners to enable the use of steviol glycosides as a table-top sweetener and as a sweetener in certain food categories |id=Document Reference Number NOM/ADM-0002 |url=http://www.hc-sc.gc.ca/fn-an/consult/nom-adm-0002/document-consultation-eng.php |publisher=Health Canada |year=2012 |access-date=26 November 2013 |archive-url=https://web.archive.org/web/20131002113208/http://www.hc-sc.gc.ca/fn-an/consult/nom-adm-0002/document-consultation-eng.php |archive-date=2 October 2013 |url-status=live}}</ref> ** ''Stevia rebaudiana'' leaf and extracts are available as dietary supplements. * Chile: available as of 2008, regulatory status uncertain<ref name="flexnews2008-07-01"/> * China: available since 1984, regulatory status uncertain * Colombia: available as of 2008, regulatory status uncertain<ref name="flexnews2008-07-01"/> * [[European Union]]: Steviol glycosides were approved and regulated as food additives by the [[European Commission]] on 11 November 2011.<ref name="eu-approved2"/><ref name="ce1131">{{cite report |url=http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:295:0205:0211:EN:PDF |title=Commission Regulation (EU) No 1131/2011 |journal=Official Journal of the European Union |date=11 November 2011 |page=205|access-date= 15 November 2011 |quote=The CE regulation establishes steviol glycosides as food additive, and establishes maximum content levels in foodstuff and beverages. |archive-url=https://web.archive.org/web/20111120004818/http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:295:0205:0211:EN:PDF |archive-date=20 November 2011 |url-status=live}}</ref><ref>{{cite web |last=Halliday |first=Jess |title=France approves high Reb A ''Stevia'' sweeteners |website=foodnavigator.com |date=8 September 2009 |url=http://www.foodnavigator.com/On-your-radar/Healthier-products/France-approves-high-Reb-A-stevia-sweeteners |access-date=23 January 2010 |archive-url=https://web.archive.org/web/20100227220901/http://www.foodnavigator.com/On-your-radar/Healthier-products/France-approves-high-Reb-A-stevia-sweeteners |archive-date=27 February 2010 |url-status=live}}</ref> * Hong Kong: steviol glycosides approved as food additives since January 2010<ref>{{cite web |url=http://www.legislation.gov.hk/blis_ind.nsf/E1BF50C09A33D3DC482564840019D2F4/85E9080411B3696948257770001470C7?OpenDocument |title=Cap 132U Schedule |series=Sweeteners in Food Regulations; Ordinance |publisher=Public Health and Municipal Services |place=Hong Kong |website=legislation.gov.hk |year=2011 |access-date=22 June 2011}}</ref> * India: In a notification dated 13 November 2015, [[FSSAI]] has permitted its use in a range of products. This includes carbonated water, dairy-based desserts and flavoured drinks, yoghurts, ready-to-eat cereals, fruit nectars and jams.{{efn|Madhu-Tulsi (Sweeteners in Food Regulations; Public Health and Municipal Services Ordinance)}}<ref>{{cite news |url=http://www.business-standard.com/article/companies/sweetener-stevia-clears-fssai-hurdle-115112300973_1.html |title=Sweetener stevia clears FSSAI hurdle <!-- |series=Business Standard News |website=Business-standard.com --> |date=2015-11-24 |access-date=2016-09-22 |archive-url=https://web.archive.org/web/20151125040602/http://www.business-standard.com/article/companies/sweetener-stevia-clears-fssai-hurdle-115112300973_1.html |archive-date=25 November 2015 |url-status=live|newspaper=Business Standard |place=India |last1=Pinto |first1=Viveat Susan}}</ref> * Indonesia: (2012) ** Steviol glycosides are available as food additives since 2012.<ref>{{cite report |place=Indonesia |publisher=Ministry of Health |date=2012 |url=http://usdaindonesia.org/wp-content/uploads/2012/08/permenkes-033-2012-translation.pdf |title=Regulation of No. 033 on Food Additives |url-status=usurped |archive-url=https://web.archive.org/web/20130530205509/http://usdaindonesia.org/wp-content/uploads/2012/08/permenkes-033-2012-translation.pdf |archive-date=30 May 2013}}</ref> ** ''Stevia'' leaf is available as a dietary supplement. * Israel: approved as food additive since January 2012.<ref>{{cite web |url=http://www.greenprophet.com/2012/01/stevia-sweeteners-approved-in-israel/ |title=''Stevia'' sweeteners now approved in Israel |website=greenprophet.com |year=2012 |access-date=5 April 2012 |archive-url=https://web.archive.org/web/20120506105136/http://www.greenprophet.com/2012/01/stevia-sweeteners-approved-in-israel/ |archive-date=6 May 2012 |url-status=live}}</ref> * Japan: widely available since the 1970s and regulated as an existing additive since 1995.<ref>{{cite web |url=http://www.houko.com/00/01/H07/101.HTM |series=The Act for Partial Provisions of the Food Sanitation Act and the Nutrition Improvement Act |title=Supplementary Provisions Article 2 |website=houko.com |year=1995 |access-date=11 January 2018 |archive-url=https://web.archive.org/web/20160606011304/http://www.houko.com/00/01/H07/101.HTM |archive-date=6 June 2016 |url-status=live}}</ref> * Korea: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Malaysia: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Mexico: mixed steviol glycoside extract (not separate extracts) approved since 2009.{{third-party inline|date=March 2017}} * New Zealand: ** All steviol glycoside extracts were approved in 2008.<ref name=Aus-n-NZ-approval/> * Norway: ** Steviol glycoside approved as food additive (E 960) since June 2012.<ref name="Norwegian Institute of Public Health">{{cite journal |title=Norwegian stevia fact sheet, Norwegian Institute of Public Health |journal=EFSA Journal |volume=8 |issue=4 |pages=1537 |date=17 June 1999 |doi=10.2903/j.efsa.2010.1537 |doi-access=free}}</ref> ** The plant itself has not been approved as of September 2012. * Paraguay: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Peru: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Philippines: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Russian Federation: stevioside approved as food additive since 2008, in the "minimal dosage required" to achieve the goal.<ref name="russian">{{cite web |url=http://ec.europa.eu/food/international/trade/docs/allfood_05_en.pdf |at=Table 5 |title=Technical regulations for juice products from fruits and vegetables |series=Russian Federation Federal Law |website=ec.europa.eu |date=27 October 2008 |access-date=15 April 2011 |archive-url=https://web.archive.org/web/20121103180148/http://ec.europa.eu/food/international/trade/docs/allfood_05_en.pdf |archive-date=3 November 2012 |url-status=live}}</ref> Stevia leaves powder, syrups and crude extracts derived from it, have been banned. The ban is enacted on 27 February 2024. [[E960]] is still approved.<ref>{{Cite web |title=Какие пищевые добавки исключили из разрешенных? – Роскачество |trans-title=What food additives have been excluded form the approved ones?|url=https://roskachestvo.gov.ru/news/kakie-pishchevye-dobavki-isklyuchili-iz-razreshennykh/ |access-date=2024-02-28 |website=Roskachestvo}}</ref> * Saudi Arabia: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Singapore: steviol glycosides approved as food additive in certain foods, since 2005<ref>{{cite web |series=Sale of Food Act |at=Chapter 283, Section 56(1) |title=Food Regulations |url=http://www.ava.gov.sg/NR/rdonlyres/0CA18578-7610-4917-BB67-C7DF4B96504B/19280/2web_SOF_FoodRegulations15April2011.pdf |publisher=Agri-Food & Veterinary Authority |place=Singapore |year=2005 |url-status=dead |archive-url=https://web.archive.org/web/20120308150612/http://www.ava.gov.sg/NR/rdonlyres/0CA18578-7610-4917-BB67-C7DF4B96504B/19280/2web_SOF_FoodRegulations15April2011.pdf |archive-date=8 March 2012}}</ref> Previously it was banned.<ref name="sing">{{cite report |last=Li |first=Simon |publisher=Hong Kong Legislative Council Secretariat |department=Research and Library Services Division |date=27 March 2002 |title=Fact Sheet: Stevioside |url=http://www.legco.gov.hk/yr01-02/english/sec/library/0102fs04e.pdf |access-date=8 September 2003|archive-url=https://web.archive.org/web/20041210103724/http://www.legco.gov.hk/yr01-02/english/sec/library/0102fs04e.pdf |archive-date=10 December 2004 |url-status=live}}</ref> * South Africa: approved since September 2012 and widely available.<ref>{{cite web |url=http://www.foodstuffsa.co.za/news-stuff/latest-sa-news/2403-stevia-approved-for-use-in-south-africa |title=Stevia approved for use in South Africa |website=Foodstuffsa.co.za |date=2012-09-10 |access-date=2016-09-22 |archive-url=https://web.archive.org/web/20160923043151/http://www.foodstuffsa.co.za/news-stuff/latest-sa-news/2403-stevia-approved-for-use-in-south-africa |archive-date=23 September 2016 |url-status=live}}</ref> * Taiwan: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Thailand: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Turkey: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * United Arab Emirates: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * Uruguay: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> * United States (as of April 2017): ** Purified rebaudioside A has been allowed since December 2008 as a food additive (sweetener), sold under various trade names, and classified as "[[GRAS|generally recognized as safe]]" ("GRAS").<ref name=FDA2017/><ref name="FDA GRAS Notice">{{cite report |last=Curry |first=Leslie Lake |series=Agency Response Letter |title=GRAS Notice No. GRN 000287 |date=28 August 2009 |publisher=U.S. Food and Drug Administration |url=http://www.accessdata.fda.gov/scripts/fcn/fcnDetailNavigation.cfm?rpt=grasListing&id=287 |access-date=17 July 2020 <!-- 28 August 2010 --> |archive-url=https://web.archive.org/web/20110329092815/http://www.accessdata.fda.gov/scripts/fcn/fcnDetailNavigation.cfm?rpt=grasListing&id=287 |archive-date=29 March 2011 |url-status=dead}}</ref> ** ''Stevia rebaudiana'' leaf and crude extracts have been available as dietary supplements since 1995, but the 2008 FDA authorization does not extend to them, and they do not have GRAS status.<ref name=FDA2017/> In 2019, leaves and crude extracts were included in an FDA import alert with concerns about their safety for use in foods or supplements and potential for toxicity.<ref name=fda19/> * Vietnam: available as of 2008, regulatory status uncertain.<ref name="flexnews2008-07-01"/> ==See also== * [[Thaumatin]], a natural sweetener, derived from an African fruit * [[Miraculin]], a substance that modifies the perception of sour foods into sweet * [[Mogroside]], a natural sweetener extracted from [[Siraitia grosvenorii|monkfruit]] ==Footnotes== {{notelist|1}} ==References== {{reflist}} ==External links== * {{Commons category-inline|Stevia sugar}} {{Herbs & spices}} [[Category:Herbs]] [[Category:Sugar substitutes]]
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