The hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure
Introduction
Rebaudioside A and stevioside are naturally occurring steviol glycosides from the leaves of the plant Stevia rebaudiana Bertoni (JECFA, 2005). Stevia extracts have been used for many years as high-intensity sweeteners in several countries, primarily in South America and Asia. Stevioside and rebaudioside A differ by one additional glucose moiety on rebaudioside A. Both are metabolized to steviol in the gastrointestinal tract (JECFA, 2005). Because of the similarities in their metabolism, rebaudioside A and stevioside are expected to produce similar physiological effects.
Steviol glycosides have been reported to have antihypertensive properties in animals and humans (Melis and Sainati, 1991a, Melis and Sainati, 1991b, Melis, 1992a, Melis, 1992b, Chan et al., 1998, Hsieh et al., 2003, Jeppesen et al., 2003, Liu et al., 2003). Results from long-term clinical trials (1–2 years) in China studying men and women with mild to moderate essential hypertension have suggested antihypertensive effects of stevioside at intakes of 750 and 1500 mg/day (Chan et al., 2000, Hsieh et al., 2003). However, other studies have not shown measurable effects of steviol glycosides on blood pressure in humans. Geuns et al. (2007) reported that administration of stevioside (750 mg/day for 3 days) failed to significantly alter blood pressure in nine subjects with normal blood pressure. Ferri et al. (2006) also reported a lack of any antihypertensive effect of stevioside in patients with untreated, mild hypertension following 6 weeks of stevioside administration at dosages up to 15.0 mg kg−1 day−1.
Most studies assessing antihypertensive properties have evaluated stevioside, steviol, or mixtures of steviol glycosides (i.e., Stevia extracts). To date, little information has been generated regarding consumption of rebaudioside A alone (also referred to by the common name of rebiana). Maki et al. (2008) showed that consumption of 1000 mg/day of rebaudioside A for 16 weeks did not alter blood pressure or glucose homeostasis in subjects with type 2 diabetes mellitus.
The present investigation was designed to examine the potential effects of 4 weeks of daily consumption of 1000 mg of rebaudioside A on blood pressure and heart rate (HR) in healthy men and women with normal baseline blood pressure (<120 mmHg systolic blood pressure (SBP) and <80 mmHg diastolic blood pressure (DBP) as defined in the Seventh Report on Prevention, Detection, Evaluation and Treatment of High Blood Pressure; Chobanian et al., 2003). The study was conducted as part of a clinical program designed to address questions raised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) pertaining to the potential for pharmacological effects of steviol glycosides (JECFA, 2005).
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Study conduct
This was a randomized, double-blind, placebo-controlled trial conducted at six clinical research sites in the United States. It was performed under Good Clinical Practice Guidelines, the Declaration of Helsinki (2000), and US 21 Code of Federal Regulations (Part 50 – Protection of Human Subjects). An institutional review board (Schulman Associates Institutional Review Board, Inc., Cincinnati, OH) approved the protocol before the initiation of the study. All subjects provided informed consent
Subjects characteristics
A total of 100 healthy subjects with normal blood pressure were randomly assigned to receive either rebaudioside A 1000 mg/day (n = 50) or placebo (n = 50). Two subjects (both in the placebo group) did not complete the study. One was lost to follow-up in week 3, and the other discontinued the study during the final week of the treatment period due to a serious adverse event (gastroenteritis). The investigator judged this event to be unrelated to the study product.
Baseline and demographic
Discussion
Several studies in the published literature have examined the effects of steviol glycosides, primarily stevioside, on blood pressure in animals and humans. A number of these have reported antihypertensive properties (Chan et al., 1998, Chan et al., 2000, Hsieh et al., 2003, Jeppesen et al., 2003, Liu et al., 2003, Dyrskog et al., 2005, Ferri et al., 2006). Although results from some of the studies support a blood pressure-lowering effect of stevioside (Chan et al., 1998, Chan et al., 2000,
Conflict of interest statement
Authors Tarka and Bisognano received financial support from Cargill for consulting services.
Acknowledgement
The authors gratefully acknowledge Ashley Roberts, PhD for assistance with the design and interpretation of the study results; and Rachel Hubacher for technical assistance.
References (22)
- et al.
Overview: the history, technical function and safety of rebaudioside A, a naturally occurring steviol glycoside, for use in food and beverages
Food Chem. Toxicol.
(2008) - et al.
The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats
Life Sci.
(1998) - et al.
Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study
Clin. Ther.
(2003) - et al.
Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat
Metabolism
(2003) - et al.
Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus
Food Chem. Toxicol.
(2008) - et al.
Effect of calcium and verapamil on renal function of rats during treatment with stevioside
J. Ethnopharmacol.
(1991) The use of a sweetener substitution method to predict dietary exposures for the intense sweetener rebaudioside A
Food Chem. Toxicol.
(2008)- et al.
How long shall the patient rest before clinic blood pressure measurement?
Am. J. Hypertens.
(2006) - et al.
Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men
Food Chem. Toxicol.
(2008) - et al.
A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension
Br. J. Clin. Pharmacol.
(2000)