Safety evaluation of certain food additives - ipcs inchem

STEVIOL GLYCOSIDES (addendum) 201
local ethics committee and met the requirements of the Declaration of Helsinki
(Barriocanal et al., 2006, 2008). The Committee previously noted that this product
did not meet the proposed specification of “not less than 95% steviol glycosides”
and that the study was conducted in a small number of subjects.
A study of antihypertensive effects was conducted in previously untreated
mild hypertensive patients with crude stevioside obtained from the leaves of
S. rebaudiana. Patients with essential hypertension were subjected to a placebo
phase for 4 weeks and then received either capsules containing placebo for 24
weeks or crude stevioside at consecutive doses of 3.75 mg/kg bw per day (7 weeks),
7.5 mg/kg bw per day (11 weeks) and 15 mg/kg bw per day (6 weeks). Comparison
of patients receiving stevioside with those on placebo showed neither antihypertensive
nor adverse effects of stevioside. This study was approved by the local
ethics committee and met the requirements of the Declaration of Helsinki (Ferri et
al., 2006). The product in this study also did not meet the proposed specification.
According to a study available in abstract form only, a randomized placebocontrolled
double-blind control study was conducted in subjects with type 2
diabetes. Fifty-five subjects received 500 mg stevioside (purity unspecified) or
placebo (maize starch) 3 times daily for 3 months. Compared with the placebo,
stevioside did not reduce the incremental area under the glucose response curve
and maintained the insulin response and HbA1c and fasting blood glucose levels.
HbA1c is an indicator of mean glucose levels and is used in identifying effects on the
control of diabetes. No difference in lipids or blood pressure was observed. It is not
clear whether this study was approved by the local ethics committee or met the
requirements of the Declaration of Helsinki (Jeppesen et al., 2006).
A number of other studies were available on steviol-related material of
unspecified composition, for which the administered dose of steviol could not be
identified or the reports were insufficiently detailed to make an assessment of
their quality (Oviedo et al., 1970; Alvarez et al., 1981; Boeckh & Humboldt, 1981;
Boeckh-Haebisch, 1992; Hsieh et al., 2003).
In addition, a study of skin prick allergy testing with 10% stevioside
conducted in infants (50 per group, aged 4 months to 2 years) indicated a higher
prevalence of sensitization to stevioside in infants with allergic diseases compared
with healthy infants (Kimata, 2007).
At the current meeting, the Committee was presented with the results of
additional studies in human volunteers, including those that were in progress at the
time of the sixty-eighth meeting.
A placebo-controlled double-blind trial was carried out in 49 hyperlipidaemic
patients (aged 20–70 years, number of males and females not supplied) not
undergoing treatment. The study was approved by the local ethics committee and
complied with the principles of the Declaration of Helsinki. Individuals were divided
into two groups, with 24 subjects receiving placebo capsules and 25 receiving
capsules containing a dose of 50 mg steviol glycosides (70% stevioside, 20%
rebaudioside A), equivalent to 1.04 mg steviol/kg bw per day, using the mean body
weight of the treatment group, 72.7 kg. Two capsules were taken before lunch and
two before dinner each day for 90 days. Six subjects withdrew from the study, four