Title: Alternative Sweeteners

Neotame 143
of metabolism and pharmacokinetic data in animals and humans demonstrates
that the species used in the toxicology studies are relevant for predicting human
safety.
G. Overview of Clinical Studies
The results from clinical studies demonstrate that neotame is safe and well tolerated
in humans even in amounts well above projected chronic consumption levels.
These clinical studies included single doses ranging from 0.1 to 0.5 mg/kg body
weight, repeated doses of 0.25 mg/kg hourly for 8 hours totaling 2 mg/kg/day,
and daily doses including 1.5 mg/kg/day for up to 13 weeks in healthy populations,
including male and female subjects and doses of 1.5 mg/kg/day in a population
of male and female individuals with non-insulin-dependent diabetes mellitus
(type 2). Specifically, there were no clinically significant or neotame-related
changes in any vital signs, electrocardiogram results, or ophthalmologic examinations.
There were no neotame-related observations of clinical significance in any
biochemical, hematological, physiological, or subjective findings. There were no
statistically significant differences between neotame and placebo treatments in
reported adverse experiences. Furthermore, neotame had no significant effect on
plasma glucose or insulin concentrations or glycemic control in the population
with non-insulin-dependent diabetes mellitus.
The 0.25 mg/kg hourly dose in the repeated dose study is equivalent to
consuming about 1 liter of beverage sweetened with 100% neotame every hour
for an 8-hour period. The high dose of 1.5 mg/kg/day in the 13-week study is
equivalent to consuming about 6 liters of beverage sweetened with neotame daily
for 13 weeks. Thus, the results of the clinical studies with neotame with doses
up to 40 times the projected 90th percentile consumption clearly confirm the
safety of neotame for use by the general population.
VI. PATENTS
Neotame was invented by the French scientists Claude Nofre and Jean-Marie
Tinti and patented in 1992 (1, 2). The NutraSweet Company holds the rights to
a wide range of patents related to neotame.
VII. REGULATORY STATUS
Neotame is currently undergoing regulatory review for use as a general sweetener
and flavor enhancer. A petition limited to tabletop use was submitted to the U.S.
Food and Drug Administration (FDA) in December, 1997 (10), and a petition