Title: Alternative Sweeteners

Stevioside 177
gene, an actual active metabolite of steviol responsible for this activity has not
yet been structurally elucidated. However, it has been pointed out by investigators
at the National Institute of Health Sciences in Tokyo that the mutagenicity observed
in in vitro experiments on activated steviol does not appear to be significant
biologically, given the lack of carcinogenicity found in F344 rats after a 2year
feeding study of stevioside. It was specifically demonstrated during this
study that steviol was generated by enzymatic hydrolysis and the levels of this
aglycone of stevioside were quantitated by high-performance liquid chromatography
(24).
C. Effects on Reproduction
It was first documented in 1968 that the Paraguayan Matto Grosso Indians use
teas produced from the leaves and stems of S. rebaudiana for their contraceptive
and antifertility effects and that an aqueous extract of S. rebaudiana leaves led
to reduced fertility in female rats (1). These effects were not duplicated under
similar conditions in experimental animals examined in other laboratories (1).
However, a further report has appeared more recently from Brazil that suggests
a deleterious effect on the fertility of mature female mice as a result of the intragastric
administration of teas prepared from S. rebaudiana leaves. Fertility was
reduced by 20% and 40%, respectively, by treatment with 1% and 5% infusions,
during the 12-day period before mating, using small groups of mice (up to seven
in a group). The 1% infusion when given during the mating period reduced the
number of uterine implants but had no effect if given before mating began. Because
stevioside was not used as part of the protocol, the authors of the study
were unclear as to whether the S. rebaudiana sweet glycosides or some other
leaf constituents were responsible for the observed effects (30). In contrast, two
reports have appeared in which no adverse endocrine effects were seen in male
rats fed S. rebaudiana leaf extracts (31, 32).
Stevioside and steviol have also been evaluated for their effects on reproduction.
Stevioside administered to male and female rats at concentrations of up
to 3% of the diet produced no abnormal responses in mating performance or
fertility of any of the groups, and no external, internal, or skeletal anormalities
were seen in the fetuses (2). More recently, stevioside was administered to Wistar
rats by gavage at daily doses up to 1 g/kg body weight, from days 6 through 15
of pregnancy. After death at day 20, it was determined that stevioside caused no
fetal abnormalities and no toxic signs in the pregnant rats and fetuses (33). However,
when steviol was studied in pregnant hamsters, it was determined that doses
of 0.75 and 1.0 g/kg body weight were toxic to both dams and fetuses. The
dams experienced a decrease of body weight and increased mortality relative to
controls, and the number of live fetuses per litter and the mean fetal weight decreased.
However, no dose-related teratogenesis was detected. The levels of stev-