Stevia: Difference between revisions

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The report also found no evidence of [[carcinogen]]ic activity. Furthermore, the report noted that "''stevioside has shown some evidence of [[pharmacological]] effects in patients with [[hypertension]] or with [[type-2 diabetes]]''"<ref name="WHO" /> but concluded that further study was required to determine proper dosage. 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 milligrams per kilogram of body weight.<ref>{{cite journal | title=Joint FAO/WHO Expert Committee on food additives, Sixty-ninth Meeting |url=http://docs.google.com/viewer?a=v&q=cache:_rH0bHkojQgJ:www.fao.org/ag/agn/agns/files/jecfa69_final.pdf+joint+experts+committee+world+health+organization+stevia&hl=en&gl=us&pid=bl&srcid=ADGEESj3s7eUmz81uTaMK5NKAENjR44MfBCLy_K-jkgDvg6NqNmyGPgUdLlMRGCXZhKafMVhs6zSX7H9VBIlTohniAZ_myM6RSeJjxifE11XT4h4F0AzK01AfvFDwVif9D9dThiv8lr3&sig=AHIEtbS4d201ZOfQ2jIHtWg3G2VtoM9jng |date=4 July 2008 |publisher=World Health Organization | format={{dead link|date=March 2010}}}}</ref>
The report also found no evidence of [[carcinogen]]ic activity. Furthermore, the report noted that "''stevioside has shown some evidence of [[pharmacological]] effects in patients with [[hypertension]] or with [[type-2 diabetes]]''"<ref name="WHO" /> but concluded that further study was required to determine proper dosage. 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 milligrams per kilogram of body weight.<ref>{{cite journal | title=Joint FAO/WHO Expert Committee on food additives, Sixty-ninth Meeting |url=http://docs.google.com/viewer?a=v&q=cache:_rH0bHkojQgJ:www.fao.org/ag/agn/agns/files/jecfa69_final.pdf+joint+experts+committee+world+health+organization+stevia&hl=en&gl=us&pid=bl&srcid=ADGEESj3s7eUmz81uTaMK5NKAENjR44MfBCLy_K-jkgDvg6NqNmyGPgUdLlMRGCXZhKafMVhs6zSX7H9VBIlTohniAZ_myM6RSeJjxifE11XT4h4F0AzK01AfvFDwVif9D9dThiv8lr3&sig=AHIEtbS4d201ZOfQ2jIHtWg3G2VtoM9jng |date=4 July 2008 |publisher=World Health Organization | format={{dead link|date=March 2010}}}}</ref>

The non-profit [[Center for Science in the Public Interest]], sent a letter in 2008 with comment by UCLA toxicologists to the [[Office of Food Additive Safety]] of the US [[Food and Drug Administration]] concerning the GRAS notification for Stevia extracts. The letter addressed studies that were published following the aforementioned 1985 study: “''However, importantly, several in vitro and in vivo genotoxicity tests of steviol and stevioside, which are closely related to rebaudioside A, found substance-related mutations, chromosome aberrations, and DNA breakage. Such findings indicate that rebaudioside A might cause similar problems, or cancer, in humans.''” The letter argues that GRAS status cannot be legitimately granted because of the inadequacy of the testing that has been conducted: “''Considering the genotoxic effects of rebaudioside A and the absence of a lifetime feeding study in mice, and considering that impartial toxicologists from UCLA (in contrast to the paid consultants to Cargill) are criticizing the testing and safety of rebaudioside A, this ingredient cannot be considered generally recognized as safe."" <ref name=CSPI>CSPI Letter to FDA [http://cspinet.org/new/pdf/stevia-cspi-cover-letter-8-4-08.pdf]</ref>


==Political controversy==
==Political controversy==

Revision as of 22:22, 2 July 2010

Stevia
Stevia rebaudiana flowers.
Scientific classification
Kingdom:
(unranked):
(unranked):
(unranked):
Order:
Family:
Tribe:
Genus:
Stevia

Species

About 240 species, including:
Stevia eupatoria
Stevia ovata
Stevia plummerae
Stevia rebaudiana
Stevia salicifolia
Stevia serrata

Stevia is a genus of about 240 species of herbs and shrubs in the sunflower family (Asteraceae), native to subtropical and tropical regions from western North America to South America. The species Stevia rebaudiana, commonly known as sweetleaf, sweet leaf, sugarleaf, or simply stevia, is widely grown for its sweet leaves. As a sweetener and sugar substitute, stevia's taste has a slower onset and longer duration than that of sugar, although some of its extracts may have a bitter or licorice-like aftertaste at high concentrations.

With its extracts having up to 300 times the sweetness of sugar, stevia has garnered attention with the rise in demand for low-carbohydrate, low-sugar food alternatives. Medical research has also shown possible benefits of stevia in treating obesity and high blood pressure. Because stevia has a negligible effect on blood glucose, it is attractive as a natural sweetener to people on carbohydrate-controlled diets.

The availability of stevia varies from country to country. In a few countries, it has been available as a sweetener for decades or centuries; for example, stevia is widely used as a sweetener in Japan where it has been available for decades. In some countries, stevia is restricted or banned. In other countries, health concerns and political controversies have limited its availability; for example, the United States banned stevia in the early 1990s unless labeled as a supplement, but in 2008 approved rebaudioside-A extract as a food additive. Over the years, the number of countries in which stevia is available as a sweetener has been increasing.

History and use

Steviol is the basic building block of stevia's sweet glycosides: Stevioside and rebaudioside A are constructed by replacing the bottom hydrogen atom with glucose and the top hydrogen atom with two or three linked glucose groups, respectively.

The genus Stevia consists of 240[1] species of plants native to South America, Central America, and Mexico, with several species found as far north as Arizona, New Mexico, and Texas.[2] They were first researched by Spanish botanist and physician Pedro Jaime Esteve, and the word stevia is a Latinized derivation of his surname.[3] Human use of the sweet species S. rebaudiana originated in South America. The leaves of the stevia plant have 30–45 times the sweetness of sucrose (ordinary table sugar).[4] The leaves can be eaten fresh, or put in teas and foods.

In 1899, the Swiss botanist Moisés Santiago Bertoni, during his research in eastern Paraguay first described the plant and the sweet taste in detail.[5] But only limited research was conducted on the topic until, in 1931, two French chemists isolated the glycosides that give stevia its sweet taste.[6] These compounds were named stevioside and rebaudioside, and are 250–300 times sweeter than sucrose, heat stable, pH stable, and non-fermentable.[7]

The exact structure of the aglycone and the glycoside were published in 1955.

In the early 1970s, Japan began cultivating stevia as an alternative to artificial sweeteners such as cyclamate and saccharin, which were suspected carcinogens. The plant's leaves, the aqueous extract of the leaves, and purified steviosides are used as sweeteners. Since the Japanese firm Morita Kagaku Kogyo Co., Ltd. produced the first commercial stevia sweetener in Japan in 1971,[8] the Japanese have been using stevia in food products, soft drinks (including Coca Cola),[9] and for table use. Japan currently consumes more stevia than any other country, with stevia accounting for 40% of the sweetener market.[10]

Today, stevia is cultivated and used in food elsewhere in east Asia, including in China (since 1984), Korea, Taiwan, Thailand, and Malaysia. It can also be found in Saint Kitts and Nevis, in parts of South America (Brazil, Colombia, Peru, Paraguay, and Uruguay) and in Israel. China is the world's largest exporter of stevioside.[10]

Stevia species are found in the wild in semi-arid habitats ranging from grassland to mountain terrain. Stevia does produce seeds, but only a small percentage of them germinate. Planting cloned stevia is a more effective method of reproduction.

Medicinal use

S. rebaudiana foliage
The stevia plant may be grown legally in most countries, although some countries restrict or ban its use as a sweetener.

For centuries, the Guaraní tribes of Paraguay, Bolivia and Brazil used stevia, which they called ka'a he'ê ("sweet herb"), as a sweetener in yerba mate and medicinal teas for treating heartburn and other ailments.[11] More recent medical research has shown promise in treating obesity[12] and hypertension.[13][14] Stevia has a negligible effect on blood glucose, even enhancing glucose tolerance;[15] therefore, it is attractive as a natural sweetener to diabetics and others on carbohydrate-controlled diets.[16]

Possible treatment of osteoporosis has been suggested by the patent application claim that eggshell breakage can be reduced by 75% by adding a small percentage of stevia leaf powder to chicken feed.[17] It has also been suggested that pigs fed stevia extract had twice as much calcium content in their meat, but these claims have been unverified.[18]

Availability

Current availability

Widely used as a sweetener
Available as a food additive (sweetener)
Available as a dietary supplement
Available as either a food additive or dietary supplement
  • Switzerland
    • Mixed steviol glycoside extracts with greater than 95% purity available as a food additive (2008)[23]
    • High purity rebaudioside A as a food additive (2009)[19]
  • United States
    • Stevia leaf and extracts are available as dietary supplements (1995)
    • Rebaudioside A is available (December 2008) as a food additive (sweetener).[24] It is available under multiple trade names including: Only Sweet, PureVia, Reb-A, Rebiana, SweetLeaf, and Truvia
Available (regulatory status unverified)
Banned

Availability notes

  • In the United States, rebaudioside A is generally recognized as safe (GRAS) as of December 2008.[24] The leaves and other extracts are available as dietary supplements.
  • In Australia and New Zealand, prior to their October 2008 approval of all steviol glycoside extracts, stevia leaves could be sold as food.[27]
  • The European Food Safety Authority is conducting a safety review and is expected to permit stevia extract to be used in the EU member states in 2010.[28]
    • A report was issued from this review, on March 10, 2010, indicating that steviol glycosides are safe up to an Acceptable Daily Intake (ADI) of 4 mg/kg body weight/day, but that those levels are likely to be exceeded at the proposed maximum use levels in both adults and children.[29]

Commercialization

Steviol glycosides were first commercialized as a sweetener in 1971 by the Japanese firm Morita Kagaku Kogyo Co., Ltd., a leading stevia extract producer in Japan.

Stevia has been grown on an experimental basis in Ontario, Canada since 1987 for the purpose of determining the feasibility of growing the crop commercially.

In 2007, The Coca-Cola Company announced plans to obtain approval for their 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.[30][31] In May 2008, Coke and Cargill announced the availability of Truvia, a consumer brand stevia sweetener containing erythritol and Rebiana,[32] which the FDA permitted as a food additive in December 2008.[33] Coca-Cola announced intentions to release stevia-sweetened beverages in late December 2008.[34]

Shortly afterward, PepsiCo and Pure Circle announced PureVia, their brand of stevia-based sweetener, but withheld release of beverages sweetened with rebaudioside A until receipt of FDA confirmation. Since the FDA permitted Truvia and PureVia, both Coca Cola and PepsiCo have announced products that will contain their new sweeteners.[35]

Extraction of sweet compounds

Rebaudioside A has the least bitterness of all the sweet compounds in the stevia 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 and is refined using ethanol, methanol, crystallization and separation technologies to separate the various glycoside molecules in the extract. This allows the manufacturer to isolate pure rebaudioside A.[36]

The National Research Council of Canada has patented a process for extracting sweet compounds from Stevia by column extraction at temperatures from 0-25°C , followed by purification by nanofiltration. A microfiltration pretreatment step is used to clarify the extract. Purification is by ultrafiltration followed by nanofiltration.[37]

Safety

A 1985 study reported that steviol, a breakdown product from stevioside and rebaudioside (two of the sweet steviol glycosides in the stevia leaf), is a mutagen in the presence of a liver extract of pre-treated rats[38] — but this finding was criticized on procedural grounds that the data were mishandled in such a way that even distilled water would appear mutagenic.[39] Over the following years bioassay, cell culture, and animal studies have shown mixed results in terms of toxicology and adverse effects of stevia constituents. While reports emerged that found steviol and stevioside to be weak mutagens,[40][41] the bulk of studies show an absence of harmful effects.[42][43] In a 2008 review, 14 of 16 studies cited showed no genotoxic activity for stevioside, 11 of 15 studies showed no genotoxic activity for steviol, and no studies showed genotoxicity for Rebaudioside A. No evidence for stevia constituents causing cancer or birth defects has been found.[42][43]

Other studies have shown stevia to improve insulin sensitivity in rats[44] and possibly even to promote additional insulin production,[45] helping to reverse diabetes and metabolic syndrome.[46] Preliminary human studies suggest that stevia can help reduce hypertension[47] although another study has shown it to have no effect on hypertension.[48] Indeed, millions of Japanese have been using stevia for over thirty years with no reported or known harmful effects.[49] Similarly, stevia leaves have been used for centuries in South America spanning multiple generations in ethnomedical tradition as a treatment for type II diabetes.[50]

In 2006, the World Health Organization (WHO) performed a thorough evaluation of recent experimental studies of stevioside and steviols conducted on animals and humans, and concluded that "stevioside and rebaudioside A are not genotoxic in vitro or in vivo and that the genotoxicity of steviol and some of its oxidative derivatives in vitro is not expressed in vivo."[51] The report also found no evidence of carcinogenic activity. Furthermore, the report noted that "stevioside has shown some evidence of pharmacological effects in patients with hypertension or with type-2 diabetes"[51] but concluded that further study was required to determine proper dosage. 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 milligrams per kilogram of body weight.[52]

Political controversy

In 1991, the United States Food and Drug Administration (FDA) labeled stevia as an "unsafe food additive" and restricted its import. The FDA's stated reason was "toxicological information on stevia is inadequate to demonstrate its safety."[53] This ruling was controversial, as stevia proponents pointed out that this designation violated the FDA's own guidelines under which natural substances used prior to 1958, with no reported adverse effects, should be generally recognized as safe (GRAS) as long as the substance was being used in the same way and format as prior to 1958.

Stevia occurs naturally, requiring no patent to produce it. As a consequence, since the import ban in 1991, marketers and consumers of stevia have shared a belief that the FDA acted in response to industry pressure.[27] Arizona congressman Jon Kyl, for example, called the FDA action against stevia "a restraint of trade to benefit the artificial sweetener industry."[54] To protect the complainant, the FDA deleted names in the original complaint in its responses to requests filed under the Freedom of Information Act.[27]

Stevia remained banned until after the 1994 Dietary Supplement Health and Education Act forced the FDA in 1995 to revise its stance to permit stevia to be used as a dietary supplement, although not as a food additive — a position that stevia proponents regard as contradictory because it simultaneously labels stevia as safe and unsafe, depending on how it is sold.[55]

Although unresolved questions remain about whether metabolic processes can produce a mutagen from stevia in animals, let alone in humans, the early studies nevertheless prompted the European Commission in 1999 to ban stevia's use in food in the European Union pending further research.[56] Singapore and Hong Kong have banned it also.[26] More recent data compiled in the safety evaluation released by the World Health Organization in 2006[51] suggest that these policies may be obsolete.

In December 2008, the FDA gave a "no objection" approval for GRAS status to Truvia (developed by Cargill and The Coca-Cola Company) and PureVia (developed by PepsiCo and the Whole Earth Sweetener Company, a subsidiary of Merisant), both of which use rebaudioside A derived from the Stevia plant.[57]

Names in other countries

Both the sweetener and the stevia plant Stevia rebaudiana (also known as Eupatorium rebaudianum[58]) are known simply as "stevia" in English-speaking countries (Template:PronEng) as well as in France, Germany, Greece, Italy, Portugal, Israel, Norway and Sweden — although some of these countries also use other terms as shown below. Similar pronunciations occur in Japan (sutebia or ステビア in katakana), and in Thailand (satiwia). In some countries (India, for example) the name translates literally as "sweet leaf." Below are some names for the stevia plant in various regions of the world:[59]

File:Stevia Sello Paraguay.JPG
Stamp of Paraguay, containing the Guarani and the scientific name of the plant.

See also

Further reading

  • Kirkland, James & Tanya. Sugar-Free Cooking With Stevia: The Naturally Sweet & Calorie-Free Herb. Crystal Health Publishing, Arlington Texas. p. 280. ISBN 192890615X. This book is an example that the FDA attempted to ban via destruction orders when stevia was first banned in the United States.

Notes and references

  1. ^ "Stevia". Flora of North America.
  2. ^ "Stevia Cav". USDA PLANTS.
  3. ^ Parsons, WT (2001). Noxious Weeds of Australia, 2nd ed. Collingswood, Australia: CSIRO Publishing. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help) This reference refers specifically to Stevia eupatoria, a related weed having the same nomenclature origin.
  4. ^ "Opinion on Stevia Rebaudiana plants and leaves" (PDF) (Press release). European Commission Scientific Committee on Food. 17 June 1999. Retrieved 27 January 2008.
  5. ^ Bertoni, Moisés Santiago (1899). Revista de Agronomia de l’Assomption. 1: 35. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  6. ^ Bridel, M. (1931). "Sur le principe sucre des feuilles de kaa-he-e (stevia rebaundiana B)". Academie des Sciences Paris Comptes Rendus (Parts 192): 1123–5. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Brandle, Jim (19 August 2004). "FAQ - Stevia, Nature's Natural Low Calorie Sweetener". Agriculture and Agri-Food Canada. Retrieved 8 November 2006. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  8. ^ "Stevia". Morita Kagaku Kogyuo Co., Ltd. 2004. Retrieved 6 November 2007.
  9. ^ Taylor, Leslie (2005). The Healing Power of Natural Herbs. Garden City Park, NY: Square One Publishers, Inc. pp. (excerpted at weblink). ISBN 0-7570-0144-0. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help)
  10. ^ a b Jones, Georgia (2006). "Stevia". NebGuide: University of Nebraska–Lincoln Institute of Agriculture and Natural Resources. Retrieved 4 May 2007. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help); Unknown parameter |month= ignored (help)
  11. ^ Tanvir, Ashraf (24 May 2005). "Sugar Leav – A new breed of 'sweetener'". Pakistan Agricultural Research Council. Retrieved 2 January 2009.
  12. ^ PubMed research articles related to treatments of obesity
  13. ^ PubMed research articles on stevia's effects on blood pressure
  14. ^ PubMed articles on stevia's use in treating hypertension
  15. ^ Curi R, Alvarez M, Bazotte RB, Botion LM, Godoy JL, Bracht A (1986). "Effect of Stevia rebaudiana on glucose tolerance in normal adult humans". Braz. J. Med. Biol. Res. 19 (6): 771–4. PMID 3651629.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Gregersen S, Jeppesen PB, Holst JJ, Hermansen K (2004). "Antihyperglycemic effects of stevioside in type 2 diabetic subjects". Metab. Clin. Exp. 53 (1): 73–6. PMID 14681845. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ "US Patent #6,500,471". Retrieved 29 August 2009.
  18. ^ "Stevia against Osteoporosis". OwnDoc.com. Retrieved 1 January 2010.
  19. ^ a b c d e "Stevia Timeline Important Dates and Events" (PDF). truvia.com. 01-Jan-2010. Retrieved 5 March 2010. {{cite web}}: Check date values in: |date= (help)
  20. ^ Stevia gets Australian approval for food and beverages
  21. ^ Halliday, Jess (08-Sep-2009). "France approves high Reb A stevia sweeteners". foodnavigator.com. Retrieved 23 January 2010. {{cite web}}: Check date values in: |date= (help)
  22. ^ Halliday, Jess (15-Sep-2009). "France's first stevia products around the corner". foodanddrinkeurope.com. Retrieved 23 January 2010. {{cite web}}: Check date values in: |date= (help)
  23. ^ Halliday, Jess (08-Jul-2009). "German-speaking countries show huge stevia interest". foodnavigator.com. Retrieved 5 March 2010. {{cite web}}: Check date values in: |date= (help)
  24. ^ a b Curry,Leslie Lake. "Agency Response Letter GRAS Notice No. GRN 000253". Retrieved 9 April 2010.
  25. ^ a b c "Olam and Wilmar in 50:50 JV to Acquire 20% Stake in PureCircle, a Leading Producer of Natural High-Intensity Sweeteners for USD 106.2 Mln". www.flex-news-food.com. 01-Jul-2008. Retrieved 8 March 2010. {{cite web}}: Check date values in: |date= (help)
  26. ^ a b c Li, Simon (27 March 2002). Fact Sheet: Stevioside (PDF). Hong Kong Legislative Council Secretariat Research and Library Services Division.
  27. ^ a b c Hawke, Jenny (February–March 2003). "The Bittersweet Story of the Stevia Herb" (PDF). Nexus magazine. 10 (2). Retrieved 9 July 2008.
  28. ^ Halliday, Jess (1 June 2009). "France and the rest of Europe prepare for stevia approval". Decision News Media.
  29. ^ "Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive". foodnavigator.com. 10-Mar-2010. Retrieved 16 April 2010. {{cite web}}: Check date values in: |date= (help)
  30. ^ Stanford, Duane D. (31 May 2007). "Coke and Cargill teaming on new drink sweetener". Atlanta Journal-Constitution. Retrieved 31 May 2007.
  31. ^ Etter, Lauren and McKay, Betsy (31 May 2007). "Coke, Cargill Aim For a Shake-Up In Sweeteners". Wall Street Journal. Retrieved 1 June 2007.{{cite news}}: CS1 maint: multiple names: authors list (link)
  32. ^ "Truvia ingredients". Retrieved 15 May 2008.
  33. ^ "Stevia sweetener gets US FDA go-ahead". Decision News Media SAS. 18 December 2008. Retrieved 11 May 2009.
  34. ^ Associated Press (15 December 2008). "Coke to sell drinks with stevia; Pepsi holds off". The Seattle Times. Retrieved 16 December 2008.
  35. ^ "FDA Approves 2 New Sweeteners". The New York Times. Associated Press. 17 December 2008. Retrieved 11 May 2009.
  36. ^ Purkayastha, S. ""A Guide to Reb-A," Food Product Design". Retrieved 28 March 2009.
  37. ^ "United States Patent 5,972,120 Extraction of sweet compounds from Stevia rebaudiana Bertoni".
  38. ^ Pezzuto JM, Compadre CM, Swanson SM, Nanayakkara D, Kinghorn AD (1985). "Metabolically activated steviol, the aglycone of stevioside, is mutagenic". Proc. Natl. Acad. Sci. U.S.A. 82 (8): 2478–82. doi:10.1073/pnas.82.8.2478. PMC 397582. PMID 3887402. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  39. ^ Procinska E, Bridges BA, Hanson JR (1991). "Interpretation of results with the [[8-azaguanine]] resistance system in Salmonella typhimurium: no evidence for direct acting mutagenesis by 15-oxosteviol, a possible metabolite of steviol". Mutagenesis. 6 (2): 165–7. doi:10.1093/mutage/6.2.165. PMID 2056919. {{cite journal}}: URL–wikilink conflict (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) – article text is reproduced here.
  40. ^ Matsui M, Matsui K, Kawasaki Y; et al. (1996). "Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays". Mutagenesis. 11 (6): 573–9. doi:10.1093/mutage/11.6.573. PMID 8962427. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  41. ^ Nunes AP, Ferreira-Machado SC, Nunes RM, Dantas FJ, De Mattos JC, Caldeira-de-Araújo A (2007). "Analysis of genotoxic potentiality of stevioside by comet assay". Food Chem Toxicol. 45 (4): 662–6. doi:10.1016/j.fct.2006.10.015. PMID 17187912.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ a b Geuns JM (2003). "Stevioside". Phytochemistry. 64 (5): 913–21. doi:10.1016/S0031-9422(03)00426-6. PMID 14561506.
  43. ^ a b Brusick DJ (2008). "A critical review of the genetic toxicity of steviol and steviol glycosides". Food Chem Toxicol. 46 (7): S83–S91. doi:10.1016/j.fct.2008.05.002. PMID 18556105.
  44. ^ Lailerd N, Saengsirisuwan V, Sloniger JA, Toskulkao C, Henriksen EJ (2004). "Effects of stevioside on glucose transport activity in insulin-sensitive and insulin-resistant rat skeletal muscle". Metab. Clin. Exp. 53 (1): 101–7. doi:10.1016/j.metabol.2003.07.014. PMID 14681850. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  45. ^ Jeppesen PB, Gregersen S, Rolfsen SE; et al. (2003). "Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat". Metab. Clin. Exp. 52 (3): 372–8. doi:10.1053/meta.2003.50058. PMID 12647278. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  46. ^ Dyrskog SE, Jeppesen PB, Colombo M, Abudula R, Hermansen K (2005). "Preventive effects of a soy-based diet supplemented with stevioside on the development of the metabolic syndrome and type 2 diabetes in Zucker diabetic fatty rats". Metab. Clin. Exp. 54 (9): 1181–8. doi:10.1016/j.metabol.2005.03.026. PMID 16125530. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ Hsieh MH, Chan P, Sue YM; et al. (2003). "Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study". Clin Ther. 25 (11): 2797–808. doi:10.1016/S0149-2918(03)80334-X. PMID 14693305. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  48. ^ Ferri LA, Alves-Do-Prado W, Yamada SS, Gazola S, Batista MR, Bazotte RB (2006). "Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertension". Phytother Res. 20 (9): 732–6. doi:10.1002/ptr.1944. PMID 16775813. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  49. ^ "Products and Markets - Stevia" ([HTML]). Food and Agriculture Organization of the United Nations - Forestry Department. Retrieved 4 May 2007.
  50. ^ Abudula R, Jeppesen PB, Rolfsen SE, Xiao J, Hermansen K (2004). "Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: studies on the dose-, glucose-, and calcium-dependency". Metab. Clin. Exp. 53 (10): 1378–81. doi:10.1016/j.metabol.2004.04.014. PMID 15375798. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  51. ^ a b c Benford, D.J. (2006). "Safety Evaluation of Certain Food Additives: Steviol Glycosides" (PDF – 18 MB). WHO Food Additives Series. 54. World Health Organization Joint FAO/WHO Expert Committee on Food Additives (JECFA): 140. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  52. ^ "Joint FAO/WHO Expert Committee on food additives, Sixty-ninth Meeting" ([dead link]). World Health Organization. 4 July 2008. {{cite journal}}: Cite journal requires |journal= (help)
  53. ^ Food and Drug Administration (1995, rev 1996, 2005). Import Alert #45-06: "Automatic Detention of Stevia Leaves, Extract of Stevia Leaves, and Food Containing Stevia"
  54. ^ Kyl, John (R-Arizona) (1993). Letter to former FDA Commissioner David Aaron Kessler about the 1991 stevia import ban, quoted at stevia.net safety studies.
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  59. ^ The Multilingual Multiscript plant name database has terms for the Stevia plant in various languages.

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