Safety evaluation of certain food additives - ipcs inchem

200 STEVIOL GLYCOSIDES (addendum)
The effects of isosteviol (99% purity) on Sprague-Dawley rats with heart
ischaemia–reperfusion injury were observed. Animals were divided into eight
groups with 10–12 animals per group: one sham-operated control and seven groups
with ischaemia–reperfusion injury—one ischaemia–reperfusion control group, three
groups pretreated with isosteviol (0.5, 1 and 2 mg/kg bw), one group pretreated
with ligustrazine and another with 5-hydroxydecanoate, and one group pretreated
with 5-hydroxydecanoate and isosteviol. The ischaemia–reperfusion injury was
produced by occluding the left coronary artery for 30 min followed by reopening
of the artery for 90 min. All compounds were administered intravenously.
Haemodynamic parameters, heart rate, ventricular tachycardia and ventricular
fibrillation were determined during the ischaemia–reperfusion period, and the
myocardial infarct size and serum lactate dehydrogenase and creatine kinase
activities were determined at the end of the study. In the groups receiving isosteviol,
the indicators of heart injury were statistically significantly improved compared with
those in groups not receiving isosteviol. The mitochondrial ATP-sensitive potassium
channel blocker, 5-hydroxydecanoate, partially attenuated the reduction in heart
damage seen in the isosteviol groups (Xu et al., 2007).
A number of studies were available on steviol-related material of unspecified
composition, for which the equivalent dose of steviol could not be identified (Sainati
et al., 1986; De-Yi et al., 1990; Toskulkao et al., 1994a, 1994b; Chang et al., 2006;
Sehar et al., 2008).
2.3 Observations in humans
At its sixty-eighth meeting, the Committee was presented with a number of
studies of observations in humans.
Four male and five female healthy volunteers (aged 21–29 years) were
provided with capsules containing 250 mg stevioside (97% purity) to be taken
3 times per day for 3 days. Doses, expressed as steviol, were 288 mg/day or
4.4 mg/kg bw per day for females and 3.9 mg/kg bw per day for males. Twenty-fourhour
urine samples were taken before dosing on day 1 and after dosing on day 3.
Fasting blood samples were taken before dosing on day 1, and six samples were
taken at different time points on day 3 after dosing. Fasting blood pressure
measurements were taken before the first capsule and at six different time intervals
after the first dose. Urine was analysed for creatinine, sodium, potassium, calcium
and urea. Blood was analysed for plasma glucose, plasma insulin, alkaline
phosphatase, ALT, GPT, creatine kinase and lactate dehydrogenase. The clinical
analyses of blood, blood pressure and urine showed no differences between
samples taken before or after dosing. This study was approved by the local ethics
committee (Temme et al., 2004).
In a study unpublished at the time of the sixty-eighth meeting, 250 mg of a
product containing 91.7% total steviol glycosides, including 64.5% stevioside and
18.9% rebaudioside A, was administered to groups of type 1 (n = 8) and type
2 diabetics (n = 15) and non-diabetics (n = 15) 3 times daily for 3 months in a doubleblind,
placebo-controlled trial. Control groups with the same number of subjects
received a placebo. After 3 months, there were no significant changes in systolic or
diastolic blood pressure, glycated haemoglobin (HbA1c), blood lipids, or renal or
hepatic function. No side-effects were reported. This study was approved by the