Stevia
Scientific Name(s): Stevia rebaudiana Bertoni. Family: Asteraceae (daisies)
Common Name(s): Stevia , Sweet Leaf of Paraguay , Caa-he-é , Ca-a-yupi , Eira-caa , Capim doce
Clinical Overview
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Uses of Stevia
Stevia is used as a sweetening agent. It also has been found to have hypotensive, hypoglycemic, and bactericidal properties. However, research reveals no clinical data regarding the use of stevia for any condition.
Stevia Dosing
Stevia leaf is used ad lib for sweetening foods.
Contraindications
Contraindications have not yet been identified.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Stevia Interactions
None well documented.
Stevia Adverse Reactions
No major contraindications, warnings, or side effects have been documented.
Toxicology
Stevioside was found to be nontoxic in acute toxicity studies in a variety of laboratory animals.
Botany
Stevia is a perennial shrub indigenous to northern South America, but commercially grown in areas such as Central America, Israel, Thailand, and China. The plant can grow to 1 m in height, with 2- to 3-cm long leaves. The leaves are the parts of the plant used. 1
History
Stevia has been used to sweeten tea for centuries, dating back to the Guarani Indians of South America. For hundreds of years, native Brazilians and Paraguayans have also employed the leaves of the plant as a sweetening agent. Europeans learned about stevia in the 16th century, whereas North American interest in the plant began in the 20th century when researchers heard of its sweetening properties. Paraguayan botanist Moises Bertoni documented stevia in the early 1900s. Glycosides responsible for the plant's sweetness were discovered in 1931. Stevia extracts are used today as food additives in Japan and Brazil as a non-caloric sweetener. In the US, however, use is limited to supplement status only. 1 , 2
Chemistry
Eight of stevia's glycosides were discovered and named in 1931. 3 Recently, the glycosides have been analyzed by capillary electrophoresis. Rebaudioside A and steviobioside have been isolated by HPLC methods. 4 Glycoside stevioside determination has been reported. 5 The main glycosides of stevia include stevioside and rebaudioside. Two glucosyl transferases acting on steviol and its glycosides have been isolated. 6 Stevioside (6 to 18% in leaves) is the sweetest glycoside and was tested and found to be 300 times sweeter than saccharose in one report. 7 Steviol hydroxylation has been reported. 8 Sterols in stevia include stigmasterol, beta-sitosterol, and campesterol. 9 Isolation of the principal sugars of stevia has also been studied. 10
Also found in stevia are certain vitamins (A, B, C), minerals (iron, zinc, calcium), electrolytes (sodium, potassium), protein and others. 1
Cultivation studies have been performed on the plant 11 , 12 as has tissue culture experimentation. 13
Stevia Uses and Pharmacology
Stevia has been used for centuries as a natural sweetener. 1 The plant contains sweet ent-kaurene glycosides, 14 with the most intense sweetness belonging to the species S. rebaudina . 15 Stevia has been evaluated for sweetness in animal response testing. 16 In humans, stevia as a sweetening agent works well in weight-loss programs to satisfy “sugar cravings,” and is low in calories. The Japanese are the largest consumers of stevia leaves and employ the plant to sweeten foods, such as soy sauce, confections, and soft drinks, as a replacement for aspartame and saccharin. 1
DiabetesAnimal data
Stevia may be helpful in treating diabetes. Steviol, isosteviol, and glucosilsteviol decreased glucose production in rat renal cortical tubules. 17 Oral use of stevia extract in combination with chrysanthemum to manage hyperglycemia has been discussed. 18
Clinical dataAqueous extracts of the plant increased glucose tolerance in 16 healthy volunteers, as well as markedly decreasing plasma glucose levels. 19
HypertensionAnimal data
Stevia's effects on blood pressure have been reported. The plant displayed vasodilatory actions in both normo- and hypertensive animals. 20 Stevia has also produced decreases in blood pressure, and has increased diuretic and natriuretic effects in rats. 21 , 22 The plant has cardiotonic actions, which normalize blood pressure and regulate heartbeat. 1
Clinical dataResearch reveals no clinical data for the use of stevia for hypertension.
Other usesStevia extract has exhibited strong bactericidal activity against a wide range of pathogenic bacteria, including certain E. coli strains. 23 Steviol is mutagenic toward salmonella and other bacterial strains, under various conditions, and toward certain cell lines. 24 , 25 , 26 , 27 Stevia may also be effective against Candida albicans . 1 One report addresses stevia's role against dental plaque. 28
Certain metabolic aspects of stevioside have been described, including rat liver effects, 29 , 30 , 31 and cell membrane transport. 32
Dosage
Stevia leaf is used ad lib for sweetening foods.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
No major contraindications, warnings, or side effects have been documented.
Toxicology
Stevia has been shown to not be mutagenic or genotoxic. 1 One report indicates that constituents of stevioside and steviol are not mutagenic in vitro. 33 Stevioside was found to be nontoxic in acute toxicity studies in a variety of laboratory animals. 1 Chronic administration of stevia to male rats had no effect in fertility vs. controls. 34 Another report concludes that stevioside in high doses affected neither growth nor reproduction in hamsters of both sexes. 35
Bibliography
1. Sousa M. Constituintes Quimicos Ativos De Planta Medicinais Brasileiras . Fortaleza, Brasil: Laboratorio de Produtos Naturais.2. Blumenthal M. Perspectives of FDA's new Stevia Policy. After four years, the agency lifts its ban — but only partially. Whole Foods Feb. 1996.
3. Bridel M, et al. J Pharm Chim 1931; 14:99.
4. Mauri P, et al. Analysis of Stevia glycosides by capillary electrophoresis. Electrophoresis 1996; 17(2):367–71.
5. Mitsuhashi H, et al. Studies on the cultivation of Stevia rebaudiana Bertoni. Determination of stevioside. Yakugaku Zasshi 1975; 95(1):127–30.
6. Shibata H, et al. Steviol and steviol-glycoside: glucosyltransferase activities in Stevia rebaudiana Bertoni — purification and partial characterization. Arch Biochem Biophys 1995; 321(2):390–96.
7. Samuelsson G. Drugs of Natural Origin Stockholm, Sweden: Swedish Pharmaceutical Press; 1992.
8. Kim K, et al. Hydroxylation of ent-kaurenoic acid to steviol in Stevia rebaudiana Bertoni — purification and partial characterization of the enzyme. Arch Biochem Biophys 1996; 332(2):223–30.
9. D'Agostino M, et al. Sterol in Stevia rebaudiana Bertoni. Boll Soc Ital Biol Sper 1984; 60(12):2237–40. Italian.
10. Aquino RP, et al. Isolation of the principal sugars of Stevia rebaudiana. Boll Soc Ital Biol Sper 1985; 61(9):1247–52. Italian.
11. Mitsuhashi H, et al. Studies on the cultivation of Stevia rebaudiana Bertoni. Determination of stevioside. II. Yakugaku Zasshi 1975; 95(12):1501–03.
12. Miyazaki Y, et al. Studies on the cultivation of Stevia rebaudiana Bertoni. III. Yield and stevioside content of 2–year old plants. Eisei Shikenjo Hokoku 1978; (96):86–89.
13. Handro W, et al. Tissue culture of Stevia rebaudiana, a sweetening plant. Planta Med 1977; 32(2):115–17.
14. Kinghorn A, et al. A phytochemical screening procedure for sweet ent-kaurene glycosides in the genus Stevia. J Nat Prod 1984; 47(3):439–44.
15. Soejarto D, et al. Potential sweetening agents of plant origin. III. Organoleptic evaluation of Stevia leaf herbarium samples for sweetness. J Nat Prod 1982; 45(5):590–99.
16. Jakinovich W, et al. Evaluation of plant extracts for sweetness using the Mongolain gerbil. J Nat Prod 1990; 53(1):190–95.
17. Yamamoto N, et al. Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules. Experientia 1985; 41(1):55–57.
18. White J, et al. Oral use of a topical preparation containing an extract of Stevia rebaudiana and the chrysanthemum flower int he management of hyperglycemia. Diabetes Care 1994; 17(8):940.
19. Curi R, et al. Effect of Stevia rebaudiana on glucose tolerance in normal adult humans. Braz J Med Biol Res 1986; 19(6):771–74.
20. Melis MS. A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats. Braz J Med Biol Res 1996; 29(5):669–75.
21. Melis MS, et al. Effect of calcium and verapamil on renal function of rats during treatment with stevioside. J Ethnopharmacol 1991; 33(3):257–62.
22. Melis MS. Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects. J Ethnopharmacol 1995; 47(3):129–34.
23. Tomita T, et al. Bactericidal activity of a fermented hot-water extract from Stevia rebaudiana Bertoni towards enterohemorrhagic Escherichia coli O157:H7 and other food-borne pathogenic bacteria. Microbiol Immunol 1997; 41(12): 1005–9.
24. Pezzuto J, et al. Metabolically activated steviol, the aglycone of stevioside, is mutagenic. Proc Natl Acad Sci 1985; 82(8):2478–82.
25. Pezzuto J, et al. Characterization of bacterial mutagenicity mediated by 13–hydroxy-ent-kaurenoic acid (steviol) and several structurally-related derivatives and evaluation of potential to induce glutathione S-transferase in mice. Mutat Res 1986; 169(3):93–103.
26. Matsui M, et al. Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays. Mutagenesis 1996; 11(6):573–79.
27. Klongpanichpak S, et al. Lack of mutagenicity of steviodside and steviol in Salmonella typhimurium TA 98 and TA 100. J Med Assoc 1997; 80 Suppl 1: S121–28.
28. Pinheiro C, et al. Effect of guarana and Stevia rebaudiana Bertoni (leaves) extracts, and stevioside, on the fermentation and synthesis of extracellular insoluble polysaccharides of dental plaque. Rev Odontol Univ Sao Paulo 1987; 1(4):9–13.
29. Kelmer-Bracht A, et al. Effects of Stevia rebaudiana natural products on rat liver mitochondria. Biochem Pharmacol 1985; 34(6):873–82.
30. Ishii E, et al. Stevioside, the sweet glycoside of Stevia rebaudiana, inhibits the action of atractyloside in the isolated perfused rat liver. Res Commun Chem Pathol Pharmacol 1986; 53(1):79–91.
31. Ishii-Iwamoto EL, et al. Stevioside is not metabolized in the isolated perfused rat liver. Res Commun Mol Pathol Pharmacol 1995; 87(2):167–75.
32. Constantin J, et al. Sensitivity of ketogenesis and citric acid cycle to steviosdie inhibition of palmitate transport across the cell membrane. Braz J Med Biol Res 1991; 24(8):767–71.
33. Suttajit M, et al. Mutagenicity and human chromosomal effect of stevioside, a sweetener from Stevia rebaudiana Bertoni. Environ Health Perspect 1993; 101 Suppl 3:53–56.
34. Oliveira-Filho RM, et al. Chronic administration of aqueous extract of Stevia rebaudiana (Bert.) Bertoni in rats: endocrine effects. Gen Pharmacol 1989; 20(2):187–91.
35. Yodyingyuad V, et al. Effect of stevioside on growth and reproduction. Hum Reprod 1991; 6(1):158–65.
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