stevioside and Hypertension

Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular risk factors, using data from randomised clinical trials (RCTs).. Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also searched Google Scholar, and hand searched the bibliography of retrieved full texts. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined the eligibility, assessed the reporting quality, and extracted the data.. Nine studies with a total of 756 participants were included. There was a variation in the reporting quality of included studies. Meta-analysis revealed a non-significant difference in systolic blood pressure between steviol glycoside and placebo, mean difference (MD): -2.98 mm Hg (-6.23 to 0.27). Significant reductions in diastolic blood pressure and fasting blood glucose were observed. There was no significant effect on blood lipid profile. Heterogeneity was significant. Adverse events included abdominal fullness, epigastric pain, and dizziness.. The evidence from published RCTs suggests that stevioside may generate reductions in blood pressure and fasting blood glucose. The sizes of the effects are small, and the substantial heterogeneity limits the robustness of any conclusions. Rebaudioside A does not appear to have any significant effects on blood pressure or cardiovascular risk factors. Available clinical trials vary in design and reporting quality, and some are characterised by inadequate sample sizes. In addition, the participants in most of the trials have high cardiovascular risk. Further clinical trials and regulatory assessments are warranted.

Topics: Blood Glucose; Blood Pressure; Cardiovascular Diseases; Chi-Square Distribution; Diabetes Mellitus; Dietary Supplements; Diterpenes, Kaurane; Glucosides; Humans; Hypertension; Protective Factors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sweetening Agents

Topics: Acetic Acid; Animals; Antihypertensive Agents; Catechin; Dioxoles; Diterpenes, Kaurane; Docosahexaenoic Acids; Eicosapentaenoic Acid; Functional Food; gamma-Aminobutyric Acid; Garlic; Glucosides; Humans; Hypertension; Lignans; Onions

Stevioside, an abundant component of Stevia rebaudiana leaf, has become well-known for its intense sweetness (250-300 times sweeter than sucrose) and is used as a non-caloric sweetener in several countries. A number of studies have suggested that, beside sweetness, stevioside along with related compounds, which include rebaudioside A (second most abundant component of S. rebaudiana leaf), steviol and isosteviol (metabolic components of stevioside) may also offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. It is of interest to note that their effects on plasma glucose level and blood pressure are only observed when these parameters are higher than normal. As steviol can interact with drug transporters, its role as a drug modulator is proposed. This review summarizes the current knowledge of the pharmacological actions, therapeutic applications, pharmacokinetics and safety of stevioside and related compounds. Although much progress has been made concerning their biological and pharmacological effects, questions regarding chemical purity and safety remain unsolved. These issues are discussed to help guide future research directions.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Carcinogens; Diterpenes, Kaurane; Diuretics; Drug Interactions; Glucosides; Humans; Hyperglycemia; Hypertension; Ion Pumps; Sweetening Agents

The antihypertensive effect of crude stevioside obtained from the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) on previously untreated mild hypertensive patients was examined. Patients with essential hypertension were submitted to a placebo phase for 4 weeks. The volunteers selected in this phase were randomly assigned to receive either capsules containing placebo during 24 weeks or crude stevioside 3.75 mg/kg/day (7 weeks), 7.5 mg/kg/day (11 weeks) and 15.0 mg/kg/day (6 weeks). All capsules were prescribed twice a daily (b.i.d.), i.e. before lunch and before dinner. After the placebo phase and after each dose of crude stevioside, body mass index, electrocardiogram and laboratory tests were performed. During the investigation blood pressure (BP) was measured biweekly and the remaining data were collected at the end of each stevioside dose step. All adverse events were prospectively recorded but no major adverse clinical effects were observed during the trial. Systolic and diastolic BP decreased (p < 0.05) during the treatment with crude stevioside, but a similar effect was observed in the placebo group. Therefore, crude stevioside up to 15.0 mg/kg/day did not show an antihypertensive effect. Moreover, the results suggest that oral crude stevioside is safe and supports the well-established tolerability during long term use as a sweetener in Brazil.

Topics: Adult; Antihypertensive Agents; Diterpenes, Kaurane; Double-Blind Method; Female; Glucosides; Humans; Hypertension; Male; Middle Aged; Phytotherapy; Prospective Studies; Stevia

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 has an antihypertensive effect.. This study was undertaken to investigate the long-term (2-year) efficacy and tolerability of stevioside in patients with mild essential hypertension. Secondary objectives were to determine the effects of stevioside on left ventricular mass index (LVMI) and quality of life (QOL).. 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. Blood pressure was measured at monthly clinic visits; patients were also encouraged to monitor blood pressure at home using an automated device. LVMI was determined by 2-dimensional echocardiography at baseline and after 1 and 2 years of treatment. QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey. Electrocardiographic, laboratory, and QOL parameters were assessed at the beginning of treatment, and at 6 months, 1 year, and 2 years.. One hundred seventy-four patients (87 men, 87 women) were enrolled in the study, and 168 completed it: 82 (42 men, 40 women; mean [SD] age, 52 [7] years) in the stevioside group and 86 (44 women, 42 men; mean age, 53 [7] years) in the placebo group. After 2 years, the stevioside group had significant decreases in mean (SD) SBP and DBP compared with baseline (SBP, from 150 [7.3] to 140 [6.8] mm Hg; DBP, from 95 [4.2] to 89 [3.2] mm Hg; P < 0.05) and compared with placebo (P < 0.05). Based on patients' records of self-monitored blood pressure, these effects were noted beginning approximately 1 week after the start of treatment and persisted throughout the study. 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 stevioside compared with placebo (P < 0.001). Neither group had a significant change in mean LVMI. However, after 2 years, 6 of 52 patients (11.5%) in the stevioside group had left ventricular hypertrophy (LVH), compared with 17 of 50 patients (34.0%) in the placebo group (P < 0.001). Of those who did not have LVH at baseline, 3 of 46 patients (6.5%) in the stevioside group had developed LVH after 2 years, compared with 9 of 37 patients (24.3%) in the placebo group (P < 0.001).. In this 2-year study in Chinese patients with mild hypertension, oral stevioside significantly decreased SBP and DBP compared with placebo. QOL was improved, and no significant adverse effects were noted.

Topics: Administration, Oral; Adult; Aged; Antihypertensive Agents; Blood Pressure; Diterpenes; Diterpenes, Kaurane; Double-Blind Method; Female; Glucosides; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Quality of Life

Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana which has been commercialized as a sweetener in Japan for more than 20 years. Previous animal studies have shown that stevioside has an antihypertensive effect. This study was to designed to evaluate the effect of stevioside in human hypertension.. 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; mean +/- s.d., 54.1+/-3.8 years) allocated to active treatment and 46 (men 19, women 27; mean +/- s.d., 53.7+/-4.1 years) to placebo treatment. Each subject was given capsules containing stevioside (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year.. After 3 months, the systolic and diastolic blood pressure of the stevioside 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.. This study shows that oral stevioside is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension.

Topics: Adult; Aged; Antihypertensive Agents; Diterpenes; Diterpenes, Kaurane; Double-Blind Method; Female; Glucosides; Humans; Hypertension; Male; Middle Aged; Patient Compliance; Quality of Life; Terpenes

Efficient treatment of hypertension is vital. The inhibition of angiotensin-converting enzyme activity has been one of the major strategies for treating hypertension. The ethanol extract of stevia leaves, steviol glycosides (with 95% purity; natural sweeteners widely used in the food industry) isolated from the ethanol extract and stevia leaf protein hydrolysates inhibited 26.60%, 59.56% and 74.38% of angiotensin-converting enzyme activities, respectively. Their effect was dose-dependent, which can be beneficial for avoiding hypertension or hypotension just by the proper control of the amount of their intake, and it was found to be superior to that of pharmaceutical drugs. A sensory test indicated that the application of the mixtures of steviol glycosides and stevia protein hydrolysates to decaffeinated coffee or tea as well as a formulated peanut protein drink was found to be well accepted, and an animal test showed that they had a significantly antihypertensive effect in spontaneously hypertensive rats. Steviol glycosides and stevia leaf protein hydrolysates can be good ingredients for making functional or healthy food products or beverages targeted for the prevention or treatment of hypertension.

Topics: Animals; Antihypertensive Agents; Diterpenes, Kaurane; Enzyme Inhibitors; Female; Glucosides; Humans; Hypertension; Male; Peptidyl-Dipeptidase A; Plant Extracts; Plant Leaves; Plant Proteins; Protein Hydrolysates; Rats; Rats, Inbred SHR; Stevia; Taste

Stevioside is a natural sweet-tasting glycoside isolated from the herb Stevia rebaudiana, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used commercially as sugar substitute. Previous study has shown that it can lower blood pressure in anesthetized spontaneously hypertensive rats (SHR). This study was undertaken to evaluate the antihypertensive effect of stevioside in different strains of hypertensive rats and to observe whether there is difference in blood pressure lowering effect.. Noninvasive tail-cuff method was employed to measure blood pressure. Stevioside at the concentrations of 50, 100 and 200 mg/kg were administered intraperitoneally (ip) to normotensive Wistar-Kyoto rats (NTR), SHR, deoxycorticosterone acetate-salt (DOCA-NaCl) sensitive hypertensive rats (DHR) and renal hypertensive rats (RHR).. Significant hypotensive effect of stevioside administered ip was noted in different strains of rats at the dose of 50 mg/kg. When stevioside was increased to the concentrations of 100 and 200 mg/kg, ip, it also caused slow and persistent lowering of blood pressure in SHR and NTR. Data also showed that stevioside given at the concentrations of 100, 200 and 400 mg/kg ip resulted in lowering of blood pressure in SHR dose-dependently. Blood pressure returned to previous levels after the drug was discontinued for 2-3 days. Drinking of 0.1% stevioside solution in mature SHR could have antihypertensive effect and also prevented hypertension in immature SHR.. This study reconfirmed stevioside has hypotensive effect and the effect is more prominent in hypertensive rats.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Diterpenes; Diterpenes, Kaurane; Glucosides; Hypertension; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Terpenes

Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves of Stevia rebaudiana (Compositae). It has been used popularly in Japan and Brazil as a sugar substitute for decades. Previous study has shown that it lowered blood pressure in spontaneously hypertensive rats (SHRs) when administered intravenously. This study shows that intraperitoneal injection of stevioside 25 mg/kg also has antihypertensive effect in SHRs. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel. This phenomenon was further confirmed in cultured aortic smooth muscle cells (A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic rings, showing that this vasorelaxation effect was not related to nitric oxide. The present data show that the vasorelexation effect of stevioside was mediated mainly through Ca(2+) influx inhibition.

Topics: Animals; Antihypertensive Agents; Aorta; Asteraceae; Calcium; Diterpenes; Diterpenes, Kaurane; Dose-Response Relationship, Drug; Glucosides; Hypertension; In Vitro Techniques; Injections, Intraperitoneal; Muscle, Smooth, Vascular; Phytotherapy; Plant Extracts; Rats; Rats, Inbred SHR; Terpenes; Vasoconstriction