Rebaudioside A

Stevia/Drug Interactions:

  • AntidiabeticsAntidiabetics: Stevioside and aqueous extracts of Stevia rebaudiana leaves have been shown to decrease glucose levels in human (5; 29) and animal (5; 29) research. Rebaudioside A, a glycoside found in stevia, has been found to stimulate the production and activity of insulin (2).
  • AntifungalsAntifungals: Methanol and ethyl acetate extracts of calli and tissue cultured from stevia plants showed antifungal activity against Alternaria alata (50).
  • AntihypertensivesAntihypertensives: Stevioside has been shown to decrease SBP and DBP in clinical studies (25; 24). The hypotensive effect in spontaneously hypertensive rats lasted for more than 60 minutes with a dose of 200mg/kg (26). Other animal research supports this observation (27). However, consumption of rebaudioside A did not produce clinically important changes in blood pressure in healthy adults with normal and low-normal blood pressure (48) and statistically significant changes in blood pressure were lacking when compared to placebo in other clinical trials (37; 36).
  • Anti-inflammatoriesAnti-inflammatories: In animal research, stevia has been shown to have anti-inflammatory activity (51).
  • AntilipemicsAntilipemics: Stevia rebaudiana Bertoni extract supplementation improved lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet, as evidenced by decreased triglyceride concentrations in serum and liver (52).
  • AntimicrobialsAntimicrobials: Stevia and constituents of stevia have shown toxic effects on Salmonella typhimurium TA 98 and TA 100 (53); antimicrobial activity against Gram-positive and Gram-negative bacteria, the yeast Candida albicans (10), and Staphylococcus aures (50); and bactericidal activity towards foodborne pathogenic bacteria, including enterohemorrhagic Escherichia coli O157:H7 (54). Stevia rebaudiana has been shown to exhibit larvicidal activity against Anopheles stephensi (55).
  • AntineoplasticsAntineoplastics: In in vitro research, isosteviol, a constituent of stevia, prevented the growth of human cancer cells (56).
  • AntiviralsAntivirals: In vitro, hot water extracts from Stevia rebaudiana inhibited the replication of all four serotypes of human rotavirus (12).
  • Appetite suppressantsAppetite suppressants: In human research, those who consumed stevia (compared with aspartame and sucrose) did not consume more at lunch and dinner meals, and self-reported hunger did not differ between the groups (57). However, stevia preloads significantly reduced postprandial glucose levels compared to sucrose preloads.
  • Calcium-channel blockersCalcium-channel blockers: In animal research, stevioside acted as a calcium antagonist (30). In animal research, verapamil (a calcium antagonist) tended to increase the renal and systemic effects of stevioside (30).
  • Cardiovascular agentsCardiovascular agents: Stevioside improved adipose tissue maturation and increased glucose transport, insulin signaling, and antioxidant defense in white visceral adipose tissue in obese insulin-resistant mice (58). Stevioside also reduced plaque volume in the aortic arch by decreasing the macrophage, lipid, and oxidized low-density lipoprotein (ox-LDL) content of the plaque.
  • DiureticsDiuretics: In animal research, stevioside was secreted by renal tubular epithelia and induced diuresis and natriuresis (59).
  • Fertility agentsFertility agents: Traditionally, stevia has been used by women in Paraguay to control fertility (3). In animal research, chronic administration (60 days) of a Stevia rebaudiana aqueous extract decreased testis weight, seminal vesicle weight, cauda epididymidis weight, the fructose content of accessory sex glands, epididymal sperm concentration, and plasma testosterone levels (32); the authors concluded that stevia treatment may decrease fertility in male rats. In other animal research, high doses of stevioside did not appear to have an effect on the growth and fertility of both sexes (39).
  • Hormonal agentsHormonal agents: In in vitro research, two terpene cyclases, (-)-copalyl diphosphate synthase (CPS) and (-)-kaurene synthase (KS), were determined to be part of the steviol glycoside biosynthetic pathway and that Stevia rebaudiana recruited two genes to secondary metabolism from a highly regulated pathway involved in hormone biosynthesis (60).
  • Memory-enhancing agentsMemory-enhancing agents: In scopolamine-treated rats, pretreatment with stevioside significantly reversed scopolamine-induced learning deficits (61); stevioside also attenuated scopolamine-induced increases in brain acetylcholinesterase enzyme activity and brain oxidative stress levels.
  • Sodium monoketocholate (MKC)Sodium monoketocholate (MKC): Combined pretreatment with stevia and sodium monoketocholate yielded lower values of glycemia in mice compared with that measured after treatment with stevia alone (62).
  • VasodilatorsVasodilators: In animal research, steviol had vasodilating effects (33; 25).

    • Stevia/Herb/Supplement Interactions:

  • AntifungalsAntifungals: Methanol and ethyl acetate extracts of calli and tissue cultured from stevia plants showed antifungal activity against Alternaria alata (50).
  • Anti-inflammatoriesAnti-inflammatories: In animal research, stevia has been shown to have anti-inflammatory activity (51).
  • AntilipemicsAntilipemics: Stevia rebaudiana Bertoni extract supplementation improved lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet, as evidenced by decreased triglyceride concentrations in serum and liver (52).
  • AntimicrobialsAntimicrobials: Stevia and constituents of stevia have shown toxic effects on Salmonella typhimurium TA 98 and TA 100 (53); antimicrobial activity against Gram-positive and Gram-negative bacteria, the yeast Candida albicans (10) and Staphylococcus aures (50); and bactericidal activity towards foodborne pathogenic bacteria, including enterohemorrhagic Escherichia coli O157:H7 (54). Stevia rebaudiana has been shown to exhibit larvicidal activity against Anopheles stephensi (55).
  • AntineoplasticsAntineoplastics: In in vitro research, isosteviol, a constituent of stevia, prevented the growth of human cancer cells (56).
  • AntioxidantsAntioxidants: An extract of Stevia rebaudiana reduced blood glucose levels in diabetic rats and decreased malondialdehyde (MDA) levels (63). In vitro, an ethanolic leaf extract of Stevia rebaudiana scavenged superoxides generated by EDTA/NBT (64). The extract also inhibited the hydroxyl radical, nitric oxide. In vitro, stevioside was shown to be superior to mannitol and sucrose in radical-scavenging abilities (65).
  • AntiviralsAntivirals: In vitro, hot water extracts from Stevia rebaudiana inhibited the replication of all four serotypes of human rotavirus (HRV) (12).
  • Appetite suppressantsAppetite suppressants: In human research, those who consumed stevia (compared with aspartame and sucrose) did not consume more at lunch and dinner meals, and self-reported hunger did not differ between the groups (57). However, stevia preloads significantly reduced postprandial glucose levels compared to sucrose preloads.
  • Cardiovascular agentsCardiovascular agents: Stevioside improved adipose tissue maturation and increased glucose transport, insulin signaling, and antioxidant defense in white visceral adipose tissue in obese insulin-resistant mice (58). Stevioside also reduced plaque volume in the aortic arch by decreasing the macrophage, lipid, and oxidized low-density lipoprotein (ox-LDL) content of the plaque.
  • CatechinCatechin: A human tasting panel determined that a combination of beta-cyclodextrin and rebaudioside A reduced the bitterness and astringency of (+)-catechin (21).
  • DiureticsDiuretics: In animal research, stevioside was secreted by renal tubular epithelia and induced diuresis and natriuresis (59).
  • Fertility agentsFertility agents: Traditionally, stevia has been used by women in Paraguay to control fertility (3). In animal research, chronic administration (60 days) of a Stevia rebaudiana aqueous extract decreased testis weight, seminal vesicle weight, cauda epididymidis weight, the fructose content of accessory sex glands, epididymal sperm concentration, and plasma testosterone levels (32); the authors concluded that stevia treatment may decrease fertility in male rats. In other animal research, high doses of stevioside did not appear to have an effect on the growth and fertility of both sexes (39).
  • Hormonal agentsHormonal agents: In in vitro research, two terpene cyclases, CPS and KS, were determined to be part of the steviol glycoside biosynthetic pathway, and Stevia rebaudiana recruited two genes to secondary metabolism from a highly regulated pathway involved in hormone biosynthesis (60).
  • HypoglycemicsHypoglycemics: Stevioside and aqueous extracts of Stevia rebaudiana leaves have been shown to decrease glucose levels in human (5; 29) and animal (5; 29) research. Rebaudioside A, a glycoside found in stevia, has been found to stimulate the production and activity of insulin (2).
  • HypotensivesHypotensives: Stevioside has been shown to decrease SBP and DBP in clinical studies (25; 24). The hypotensive effect in spontaneously hypertensive rats lasted for more than 60 minutes with a dose of 200mg/kg (26). Other animal research supports this observation (27). However, consumption of rebaudioside A did not produce clinically important changes in blood pressure in healthy adults with normal and low-normal blood pressure (48), and statistically significant changes in blood pressure were lacking when compared to placebo in other clinical trials (37; 36).
  • Memory-enhancing agentsMemory-enhancing agents: In scopolamine-treated rats, pretreatment with stevioside significantly reversed scopolamine-induced learning deficits (61); stevioside also attenuated scopolamine-induced increases in brain acetylcholinesterase enzyme activity and brain oxidative stress levels.
  • VasodilatorsVasodilators: In animal research, steviol had vasodilating effects (33; 25).

    • Stevia/Food Interactions:

  • SugarSugar: According to secondary sources, stevia extracts may be synergistic with sugar; the sugar provides the upfront sweetness that stevia extracts lack.
  • Sugar alcoholsSugar alcohols: According to secondary sources, sugar alcohols, such as erythritol, mannitol, xylitol, and sorbitol, may mask some of the negative aftertaste of stevia extracts.

    • Stevia/Lab Interactions:

  • Blood pressureBlood pressure: Stevioside has been shown to decrease SBP and DBP in clinical studies (25; 24). The hypotensive effect in spontaneously hypertensive rats lasted for more than 60 minutes with a dose of 200mg/kg (26). Other animal research supports this observation (27). However, consumption of rebaudioside A did not produce clinically important changes in blood pressure in healthy adults with normal and low-normal blood pressure (48), and statistically significant changes in blood pressure were lacking when compared to placebo in other clinical trials (37; 36).
  • ElectrolytesElectrolytes: In animal research, high doses of stevia affected renal activity and perfusion, sodium excretion, and urinary flow (30; 31; 32).
  • GlucagonGlucagon: According to a review, stevia suppressed glucagon release in human research (66).
  • Glucose levelGlucose level: Stevioside and aqueous extracts of Stevia rebaudiana leaves have been shown to decrease glucose levels in human (5; 29) and animal (5; 29) research. Rebaudioside A, a glycoside found in stevia, has been found to stimulate the production and activity of insulin (2).
  • Glucose tolerance testGlucose tolerance test: In human research in healthy volunteers, an extract of Stevia rebaudiana increased glucose tolerance (29).
  • LipidsLipids: Stevia rebaudiana Bertoni extract supplementation improved lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet, as evidenced by decreased triglyceride concentrations in serum and liver (52).