Stevia Rebaudiana Studies
Efficacy and Tolerability of Oral Stevioside in Patients with Mild Essential Hypertension: A Two-Year,Randomized,Placebo-Controlled Study 2003 [PDF]
Background: Stevioside, a natural glycoside isolated from the plant Stevia re-
baudiana Bertoni, has been used as a commercial sweetening agent in Japan and
Brazil for >20 years. Previous animal and human studies have indicated that ste-
vioside has an antihypertensive effect.
Objectives: This study was undertaken to investigate the long-term (2-year) ef-
ficacy and tolerability of stevioside in patients with mild essential hypertension.
Secondary objectives were to determine the effects of stevioside on left ventricu-
lar 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. 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.
Results: 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  years) in the stevioside group and 86 (44 women, 42 men; mean age, 53  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 ~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 through-
out 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 pa-
tients (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).
Conclusions: 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. (Clin Ther. 2003;25:
2797?2808) Copyright ? 2003 Excerpta Medica, Inc.
Key words: stevioside, hypertension, adverse effect, quality of life.