Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana.
Planta Med. 2005 Feb;71(2):108-13.
We have studied the effects of stevioside on the glucose and insulin metabolism in 2 models of diabetes in rats, STZ-induced diabetic rats and NIDDM diabetic rats induced by feeding with fructose. Stevioside (0.5 mg/kg), lowered the blood glucose levels in STZ-induced diabetic rats, peaking at 90 min. Stevioside administered twice daily also demonstrated dose-dependent effects in lowering the glucose levels in both diabetic rat models. Stevioside reduced the rise in glucose during glucose tolerance testing in normal rats. In conclusion, stevioside was able to regulate blood glucose levels by enhancing not only insulin secretion, but also insulin utilization in insulin-deficient rats; the latter was due to decreased PEPCK gene expression in rat liver by stevioside''''s action of slowing down gluconeogenesis. Further studies of stevia for the treatment of diabetes appear warranted.

Antihyperglycemic effects of stevioside in type 2 diabetic subjects.
Metabolism. 2004 Jan;53(1):73-6.
Stevioside is present in the plant Stevia rebaudiana Bertoni. Extracts of stevia have been used for the treatment of diabetes in, for example, Brazil, although a positive effect on glucose metabolism has not been unequivocally demonstrated. We studied the acute effects of stevioside in type 2 diabetic patients. We hypothesize that supplementation with stevia stevioside to a test meal causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients were included in an acute, paired cross-over study. A standard test meal was supplemented with either 1 g of stevioside or 1 g of maize starch (control). Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion of the test meal. Compared to control, stevioside reduced the incremental area under the glucose response curve by 18% (P =.013). The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside compared to control (P <.001). Stevioside tended to decrease glucagon levels, while it did not significantly alter the area under the insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide curves. In conclusion, stevioside reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism. Stevia Stevioside may be advantageous in the treatment of type 2 diabetes.
Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study.
Hsieh MH. Taipei Medical University--Wan Fang Hospital, Taipei City, Taiwan.
Clin Ther. 2003 Nov;25(11):2797-808.
BACKGROUND: Stevioside, a natural glycoside isolated from the plant Stevia rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan and Brazil for >20 years. Previous animal and human studies have indicated that stevioside (stevia) has an antihypertensive effect. OBJECTIVES: This study was undertaken to investigate the long-term (2-year) efficacy and tolerability of stevia in patients with mild essential hypertension. Secondary objectives were to determine the effects of stevia on left ventricular mass index (LVMI) and quality of life (QOL). METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese men and women aged between 20 and 75 years with mild essential hypertension (systolic blood pressure [SBP] 140-159 mm Hg and diastolic blood pressure [DBP] 90-99 mm Hg). Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years. RESULTS: After 2 years, the stevia group had significant decreases in mean (SD) SBP and DBP compared with baselineand compared with placebo). There were no significant changes in body mass index or blood biochemistry, and the results of laboratory tests were similar in the 2 groups throughout the study. No significant difference in the incidence of adverse effects was noted between groups, and QOL scores were significantly improved overall with stevia compared with placebo. Neither group had a significant change in mean LVMI. However, after 2 years, 6 of 52 patients (11.5%) in the stevia group had left ventricular hypertrophy (LVH), compared with 17 of 50 patients (34.0%) in the placebo group. Of those who did not have LVH at baseline, 3 of 46 patients (6.5%) in the stevia group had developed LVH after 2 years, compared with 9 of 37 patients (24.3%) in the placebo group. CONCLUSIONS: In this 2-year study in Chinese patients with mild hypertension, oral stevia significantly decreased SBP and DBP compared with placebo. QOL was improved, and no significant adverse effects were noted. baking with stevia sweetner stevia stevia safety
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Antihyperglycemic effects of stevioside in type 2 diabetic subjects.
Gregersen S,. Aarhus University Hospital, Denmark.
Metabolism. 2004 Jan;53(1):73-6.
Stevioside is present in the plant Stevia rebaudiana Bertoni (stevia). Extracts of stevia have been used for the treatment of diabetes in, for example, Brazil, although a positive effect on glucose metabolism has not been unequivocally demonstrated. We studied the acute effects of stevioside (stevia) in type 2 diabetic patients. We hypothesize that supplementation with stevia to a test meal causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients were included in an acute, paired cross-over study. A standard test meal was supplemented with either 1 g of stevioside or 1 g of maize starch (control). Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion of the test meal. Compared to control, stevia reduced the incremental area under the glucose response curve by 18%. The insulinogenic index was increased by approximately 40% by stevia compared to control. Stevia tended to decrease glucagon levels. In conclusion, stevia reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism. Stevia may be advantageous in the treatment of type 2 diabetes.

Stevia lowers blood pressure
Chan P, et al. A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. Taipei Wan Fang Hospital, Taiwan.: Br J Clin Pharmacol 2000 50(3):215-20
A multicentre, randomized, double-blind, placebo-controlled study was undertaken. This study group consisted of 106 Chinese hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to 75 years with 60 subjects (men 34, women 26) allocated to active treatment and 46 (men 19, women 27) to placebo treatment. Each subject was given capsules containing stevioside stevia (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year. RESULTS: After 3 months, the systolic and diastolic blood pressure of the stevia group decreased significantly (systolic: 166.0+/-9.4-152.6+/-6.8 mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6 mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry parameters including lipid and glucose showed no significant changes. No significant adverse effect was observed and quality of life assessment showed no deterioration. CONCLUSIONS: This study shows that oral stevia is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension. herb stevia book cook stevia buy stevia
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Stevia helpful for diabetes and hypertension
Jeppesen PB, et al. Stevioside acts directly on pancreatic beta cells to secrete insulin. Metabolism 2000 Feb;49(2):208-14.
The popularity of stevia continues to grow as more and more people find out about this amazing no-calorie herbal sweetener. One of the primary constituents of stevia that gives it its sweet taste is stevioside, which has been commercialized as a sweetener in Japan for more than 25 years. Lately, studies have shown that stevia, in addition to being a sweetener, has certain health benefits, too, particularly for diabetics and those with elevated blood pressure.
Stevia has been used for many years in the treatment of diabetes among Indians in Paraguay and Brazil. However, the mechanism for the blood glucose-lowering effect remains unknown. A study conducted at Aarhus University Hospital in Denmark found that stevioside enhances insulin secretion from mouse pancreatic islets in the presence of glucose. The researchers state, "Stevioside stimulates insulin secretion via a direct action on pancreatic beta cells. The results indicate that the compounds may have a potential role as an anti-hyperglycemic agent in the treatment of type 2 diabetes mellitus."
A double-blind, placebo-controlled study in Taiwan studied 106 Chinese hypertensive subjects ages ranging from 28 to 75 years. Each subject was given capsules containing 250 mg stevioside or placebo three times daily and followed-up at monthly intervals for 1 year (the average person who uses stevia ingests about 100 mg a day of stevioside). After 3 months, the systolic and diastolic blood pressure of the stevioside group decreased by about 6 points, and the effect persisted during the whole year. Blood biochemistry including lipid and glucose showed no major changes. No significant adverse effects were observed.

Third-Party Published Research on Stevia

All available third-party research on stevia be found at PubMed. A partial listing of the third-party published research on stevia is shown below:


Hypotensive & Heart Tonic Actions:
Wong, K. L., et al.”Antiproliferative Effect of Isosteviol on Angiotensin-II-Treated Rat Aortic Smooth Muscle Cells.” Pharmacology. 2006 Feb; 76(4): 163-169.
Wong, K. L., et al. “Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat.” Life Sci. 2004 Mar; 74(19): 2379-87.
Wong, K. L., et al. “Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells.” Planta Med. 2004; 70(2): 108-12.
Hsieh, M. H., et al. “Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study.” Clin. Ther. 2003; 25(11): 2797-808.
Chan, P., et al. “A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension.” Br. J. Clin. Pharmacol. 2000; 50(3): 215–20.
Melis, M. S. “A crude extract of Stevia rebaudiana increase the renal plasma flow of normal and hypertensive rats." Braz. J. Med. Biol. Res. 1996; 29(5): 669–75.
Melis, M. S. “Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects.” J. Ethnopharmacol. 1995; 47(3): 129–34.
Melis, M. S. “Stevioside effect on renal function of normal and hypertensive rats.” J. Ethnopharmacol. 1992; 36(3): 213–17.
Melis, M. S., et al. “Effect of calcium and verapamil on renal function of rats during treatment with stevioside.” J. Ethnopharmacol. 1991; 33(3): 257–62.
Boeckh, E. M., et al. “Stevia rebaudiana bertoni: Cardio-circulatory effects of total water extract in normal persons and of stevioside in rats and frogs." First Brazilian Seminar on Stevia rebaudiana, Inst. Technol. Aliment. Campinas, Brazil, June 25-26, 1981.
Humbolt, G., et al. “Steviosideo: Efeitos Cardio-circulatorios em Ratos.” V Simposio de Plantas Medicinais do Brasil. 1978; (4–6): 208.

Hypoglycemic & Anti-diabetic Actions:
Chang, J. C., et al. “Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.” Horm. Metab. Res. 2005; 37(10): 610-6.
Chen, T. H., et al. “Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana.” Planta Med. 2005; 71(2): 108-13.
Dyrskog, S. E., et al. “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.” Metabolism. 2005; 54(9): 1181-8.
Abudula, R., et al. “Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: studies on the dose-, glucose-, and calcium-dependency.” Metabolism. 2004; 53(10): 1378-81.
Lailerd, N., et al. “Effects of stevioside on glucose transport activity in insulin-sensitive and insulin-resistant rat skeletal muscle.” Metabolism. 2004; 53(1): 101-7.
Gregersen, S., et al. “Antihyperglycemic effects of stevioside in type 2 diabetic subjects.” Metabolism. 2004; 53(1):73-6.
Raskovic, A., et al. “Joint effect of commercial preparations of Stevia rebaudiana Bertoni and sodium monoketocholate on glycemia in mice.” Eur. J. Drug Metab. Pharmacokinet. 2004 Apr-Jun; 29(2): 83-6.
Raskovic, A., et al. “Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni).” Eur. J. Drug Metab. Pharmacokinet. 2004 Apr-Jun; 29(2):87
Gardana, C., et al. “Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora.” J. Agric. Food Chem. 2003 Oct; 51(22): 6618-22.
Koyama, E., et al. “Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans.” Food Chem.Toxicol. 2003; 41(6): 875-83.
Jeppesen, P. B., et al. “Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity.” Metabolism. 2000; 49(2): 208–14.
Yamamoto, N. S., et al. “Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules.” Experientia. 1985; 41(1): 55–7.
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.
Suzuki, H., et al. “Influence of the oral administration of stevioside on the levels of blood glucose and liver glycogen in intact rats.” Nogyo Kagaku Zasshi 1977; 51(3): 45
Oviedo, C. A., et al. “Hypoglycemic action of Stevia rebaudiana.” Excerpta Medica. 1970; 209: 92.

Antimicrobial Actions:
Pinheiro, C. E., 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. Odont. Usp. 1987; 1(4): 9–13.
Takahashi, K., et al. “Analysis of anti-rotavirus activity of extract from Stevia rebaudiana.” Antiviral Res. 2001; 49(1): 15–24.
Takaki, M., et al. “Antimicrobial activity in leaves extracts of Stevia rebaudiana Bert.” Rev. Inst. Antibiot. Univ. Fed. Pernambuco.1985; 22(1/2): 33–9.
Tomita, T., et al. “Bactericidal activity of a fermented hot-water extract from Stevia rebaudiana Bertoni towards enterohemorrhagic Escherichia coli 0157:h7 and other food-borne pathogenic bacteria." Microbiol. Immunol. 1997; 41(12): 1005–9.

Anti-inflammatory & Immune Modulation Actions:
Boonkaewwan, C., et al. “Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells.” J. Agric. Food Chem. 2006 Feb; 54(3): 785-9.
Mizushina, Y., et al. “Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors.” Life Sci. 2005 Sep; 77(17): 2127-40