Stevia

Stevia () is a natural sweetener and sugar substitute derived from the leaves of the plant species "Stevia rebaudiana", native to Brazil and Paraguay.
The active compounds are steviol glycosides (mainly stevioside and rebaudioside), which have 30 to 150 times the sweetness of sugar, are heat-stable, pH-stable, and not fermentable. The body does not metabolize the glycosides in stevia, so it contains zero calories, like artificial sweeteners. Stevia's taste has a slower onset and longer duration than that of sugar, and some of its extracts may have a bitter or licorice-like aftertaste at high concentrations.
The legal status of stevia as a food additive or dietary supplement varies from country to country. In the United States, high-purity "stevia glycoside" extracts have been generally recognized as safe (GRAS) since 2008, and are allowed in food products, but stevia leaf and crude extracts do not have GRAS or Food and Drug Administration (FDA) approval for use in food. The European Union approved "Stevia" additives in 2011, while in Japan, stevia has been widely used as a sweetener for decades.
The plant "Stevia rebaudiana" has been used for more than 1,500 years by the Guaraní peoples of South America, who called it "ka'a he'ê" ("sweet herb"). The leaves have been used traditionally for hundreds of years in both Brazil and Paraguay to sweeten local teas and medicines, and as a "sweet treat". The genus was named for the Spanish botanist and physician Petrus Jacobus Stevus.
In 1899, Swiss botanist Moisés Santiago Bertoni, while conducting research in eastern Paraguay, first described the plant and the sweet taste in detail. Only limited research was conducted on the topic until, in 1931, two French chemists isolated the glycosides that give stevia its sweet taste.
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]". 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. In 1999, prompted by early studies, the European Commission banned stevia's use in food products within the European Union pending further research. In 2006, research data compiled in the safety evaluation released by the World Health Organization found no adverse effects.
In December 2008, the FDA gave a "no objection" approval for GRAS status to Truvia and PureVia, both of which use derived from the "Stevia" plant. However, the FDA said that these products are not stevia, but a highly purified "Stevia"-extract product. 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". 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. As of 2017, high-purity "Stevia" glycosides are considered safe and allowable as ingredients in food products sold in the United States.
Commercial use.
In the early 1970s, sweeteners such as cyclamate and saccharin were gradually decreased or removed from a variant formulation of Coca-Cola. Consequently, use of stevia as an alternative began in Japan, with the aqueous extract of the leaves yielding purified steviosides developed as sweeteners. The first commercial "Stevia" sweetener in Japan was produced by the Japanese firm Morita Kagaku Kogyo Co., Ltd. in 1971. The Japanese have been using stevia in food products and soft drinks, (including Coca-Cola), and for table use. In 2006, Japan consumed more stevia than any other country, with stevia accounting for 40% of the sweetener market.
In the mid-1980s, stevia became popular in U.S. natural foods and health food industries, as a noncaloric natural sweetener for teas and weight-loss blends. The makers of the synthetic sweetener NutraSweet (at the time Monsanto) asked the FDA to require testing of the herb. 
As of 2006, China was the world's largest exporter of stevioside products. 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.
In May 2008, Coca-Cola and Cargill announced the availability of Truvia, a consumer-brand "Stevia" sweetener containing erythritol and Rebiana, which the FDA permitted as a food additive in December 2008. Coca-Cola announced intentions to release stevia-sweetened beverages in late December 2008. From 2013 onwards, Coca-Cola Life, containing stevia as a sweetener, was launched in various countries around the world.
Shortly afterward, PepsiCo and Pure Circle announced PureVia, their brand of "Stevia"-based sweetener, but withheld release of beverages sweetened with until receipt of FDA confirmation. Since the FDA permitted Truvia and PureVia, both Coca-Cola and PepsiCo have introduced products that contain their new sweeteners.
Industrial extracts.
Rebaudioside A has the least bitterness of all the steviol glycosides in the "Stevia rebaudiana" plant. To produce rebaudioside A commercially, "Stevia" plants are dried and subjected to a water extraction process. 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.
"Stevia" extracts and derivatives are produced industrially and marketed under different trade names.
Mechanism of action.
Glycosides are molecules that contain glucose residues bound to other non-sugar substances called aglycones (molecules with other sugars are polysaccharides). Preliminary experiments deduce that the tongue's taste receptors react to the glycosides and transduce the sweet taste sensation and the lingering bitter aftertaste by direct activation of sweet and bitter receptors.
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. The 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).
Steviol cannot be further digested in the digestive tract and is taken up into the bloodstream, metabolised by the liver to steviol glucuronide, and excreted in the urine.
A three-dimensional map of the proteins 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.
Safety and regulations.
A 2011 review found that the use of "Stevia" sweeteners as replacements for sugar might benefit children, people with diabetes, and those wishing to lower their intake of calories.
Although both steviol and rebaudioside A have been found to be mutagenic in laboratory "in vitro" testing, these effects have not been demonstrated for the doses and routes of administration to which humans are exposed. Two 2010 review studies found no health concerns with "Stevia" or its sweetening extracts.
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 weight. In 2010, The European Food Safety Authority established an acceptable daily intake of 4 mg/kg/day 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," 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).
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.
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.