Title: Alternative Sweeteners

178 Kinghorn et al.
iol administered were proportional to about 80 times that of an acceptable intake
of stevioside for humans (7.938 mg/kg body weight per day) (34).
No follow-up has been published on a compound of apparently unknown
structure that was referred to as ‘‘dihydroisosteviol’’ and reported in 1960 to
exhibit a statistically significant antiandrogenic effect in a chick-comb bioassay
at a dose of 3.0 mg/comb (2). ‘‘Dihydroisosteviol’’ was not found to be effective
in inhibiting the action of testosterone at total dose levels of 5 and 20 mg per
animal when injected subcutaneously in 28-day-old Charles River male castrated
rats. The origin of ‘‘dihydroisosteviol’’ was not stipulated in this study, and no
compound with such a structure seems to have been determined subsequently as
a metabolic or degradative product of any of the S. rebaudiana sweet constituents
(2).
D. Effects on Carbohydrate Metabolism
Mention has been made earlier in this chapter of the use of S. rebaudiana extracts
in Paraguay as a remedy for diabetes. Hypoglycemic effects in humans and rats
using S. rebaudiana extracts have been claimed in several scientific publications
from South America, thereby providing some credence for the medicinal use of
this plant as a hypoglycemic agent. However, a number of other investigators
have found no significant effects on blood glucose levels in rats (1, 2).
Stevioside has been found to affect monosaccharide transport in an isolated,
perfused liver preparation (2). Glucose absorption was inhibited in hamsters fed
2.5 g/kg/day stevioside for 12 weeks, which was attributed to both a decrease
in intestinal Na / K -ATPase activity and a decreased absorptive area in the intestines
(35). Stevioside (0.2 mM), when given orally both with fructose (0.2 mM)
and alone to rats fasted for 24 hr, led to increased glycogen deposition in the
liver (36). Steviol (1 mM) inhibited glucose intake and altered the morphology
of intestinal absorptive cells (37).
E. Other Biological Activities
A hypotensive effect in human subjects was noted in a Brazilian study wherein
S. rebaudiana tea was administered daily for 30 days (2). It was mentioned also
in the previous version of this chapter that stevioside resulted in alterations of
mean blood pressure and renal function when tested on normal Wistar rats (2).
In the last decade, there has been increasing evidence that S. rebaudiana extracts
and stevioside have demonstrable vasoactive properties. When aqueous S. rebaudiana
extracts (2 ml of an extract corresponding to 66.7 g S. rebaudiana/100
ml) were administered to normal Wistar rats for 40 and 60 days, such chronic
administration led to hypotension, diuresis, and natiuresis. For the 60-day treated
group, an increase in renal plasma flow was observed (38). In Wistar rats, stevio-