Effects on blood glucose and type 2 diabetes
This section presents data on the effects of IS consumption
on glucose homeostasis and risk of diabetes, in healthy
subjects, type 1 diabetics and type 2 diabetics Thirty-one
clinical trials and two reviews assessed the short-term effects
(less than one week) of IS consumption on glucose
homeostasis. To date, the data on the long-term risk of developing
diabetes are still limited and have been taken from
seven observational epidemiological studies.
Effects on glucose homeostasis
Regarding the acute effects (i.e. less than 24 hrs.), the
available studies did not show any effects related to
the consumption of aspartame on an empty stomach
[39–44], saccharine [45] or sucralose [46, 47] on
blood glucose and insulin levels. Other studies assessed
acute effects of IS on post-prandial glycaemic parameters
after a test meal [48–52]. These studies generally showed
that consuming IS before a test meal did not modify
post-prandial glycaemic and insulin responses compared
to a placebo, and reduced these responses compared
to a sucrose preload. These effects were reported
irrespective of the tested IS (aspartame, stevia extract,
sucralose, beverage containing acesulfame K and sucralose).
It should also be noted that the parameters of
these studies were highly variable with differences in
the composition of test meals, the time between the
preload and the meal, the studied subject groups (age,
sex, healthy overweight or obese subjects) and the preload
form (solid or liquid). Several studies also showed
that consuming IS before a meal resulted in increased
secretion of GLP1 (Glucagon-like peptide), a gastrointestinal
hormone that usually increases insulin secretion,
slows down gastric emptying and reduces glucagon
secretion [53]. This increase in GLP1 may be
induced by IS activating sweetness receptors, as suggested
by data in rats [54].
When considering short- and medium-term effects, several
studies assessed the effect of regular IS intake (one to
three times per day, for a few days to several weeks), in
capsule form or in beverages, on maintaining blood sugar
control (glucose and insulin concentrations measured
after a night of fasting, glycated haemoglobin HbA1c). For
type 2 diabetics, the consumption of sucralose [55] or aspartame
[56–58] for periods of up to 18 weeks did not
change fasting glucose levels) compared to sucrose or a
placebo. Furthermore, fasting plasma glucose and insulin,
and HOMA-IR (insulin sensitivity calculated from the
HOMA index) were not modified in non-diabetic obese
subjects who had consumed a beverage sweetened with
aspartame for six months compared to groups who had
consumed sugar-sweetened drinks, water or milk [21].
Other studies covering unspecified IS compared to sucrose
in obese or overweight subjects [59] confirm these
results. Regarding stevia extracts, the data show either a
lack of effect on glucose control in healthy [59] or diabetic
[59] subjects or a slight significant decrease in blood glucose
levels in healthy subjects [59] or hypertensive subjects
[60].
Overall, the vast majority of studies do not show any
acute effects of IS intake on blood glucose or insulin
concentrations measured on an empty stomach or after
a test meal, in healthy subjects or in diabetics. Some
studies reported a modest increase in GLP-1 secretion,
but with no repercussions on insulin secretion or blood
glucose concentrations. IS consumption has no effect on
short- and medium-term blood glucose parameters in
healthy subjects or in diabetics.

Effects on the risk of type 2 diabetes (T2D)
The seven observational studies dealing with IS consumption
and the incidence of T2D showed diverging
results. Four cohort studies of good quality (three undertaken
in North American populations and one in a
European population), over periods of nine to 24 years,
did not show any relationship between the consumption
of artificially sweetened beverages and the risk of developing
T2D after adjustment for BMI and energy intake
of subjects [61–63, 26]. Three other cohort studies suggested
a positive association between the consumption
of artificially sweetened beverages and the incidence of
T2D [64–66]. Among them a French study, [64], showed
that the incidence of T2D was significantly higher (HR
(95 % CI) 2.21 [1.56-3.14]) in the group of women consuming
the largest amounts of artificially sweetened beverages
(over 600 mL per week) who were monitored for
14 years, with a linear and dose-dependent relationship.
The second study, undertaken in the United States for
seven years, reported an increase in the incidence of
T2D in subjects consuming more than one artificially
sweetened beverage per day in a model with adjustment
for the primary confounding factors (HR (95 % CI) 1.67
[1.27–2.20]. The third study, which reported an increased
incidence of T2D in subjects consuming more
than one artificially sweetened beverage per week (HR
(95 % CI) 1.70 [1.13–2.55], focused on a limited-sized
Japanese population not representative of the general
population, monitored for seven years. It is important to
underline the heterogeneity of these data, particularly in
terms of the characteristics of the populations and the
monitoring periods (from seven to 24 years). Furthermore,
in these studies, the consumption of artificially
sweetened beverages was recorded when the subjects
were first included, often through self-administered frequency
questionnaires, with no updating of dietary data
over time.
In conclusion, the long-term epidemiological studies
on the risk of developing T2D show heterogeneous results,
but the most robust studies do not report any
effects.
Other effects
Effects on lipid parameters
Of the 20 randomised controlled experimental studies
analysed, the majority focused on aspartame or stevia extracts.
Compared to a placebo, aspartame consumption
had no effects on triglycerides or cholesterol concentrations
(either total, HDL, LDL or VLDL cholesterol) in
various populations (healthy, T2D and overweight subjects)
for periods ranging from 13 to 28 weeks. Compared
to a caloric sweetener (sucrose, glucose or fructose), of the
five identified studies, two showed a modest significant
improvement in lipid profile (TG and/or total cholesterol)
in the group that received aspartame, still with no differences
compared to the placebo. Three studies, two in T2D
patients, assessed the effect of stevia extracts on lipid parameters
and showed no differences compared to a placebo.
Studies using other types of IS (cyclamate, sucralose,
IS mixture or unspecified IS) also showed no effects on
the assessed lipid parameters. Of the four identified cohort
studies, most showed no effects on lipid parameters related
to the consumption of artificially sweetened beverages.
A single study reported a positive association
between the consumption of these beverages and an increase
in TG concentrations associated with a lowering of
HDLc [67].
In conclusion, the majority of observational studies
showed no effects on lipid profile related to IS. Two
studies reported that replacing sugars with aspartame reduced
plasma triglyceride concentrations but the data
are too limited to conclude that IS have a beneficial
effect on lipid profile.
Effects on pre-term deliveries
Two epidemiological studies are available. In the first
[68], a dose-effect relationship was observed, which
meant that the risk of pre-term delivery was higher
in the heaviest consumers of artificially sweetened
beverages (OR (95 % CI) 1.38 [1.15-1.65] for ≥ 1 serving
of artificially sweetened carbonated soft drinks/d).
In addition to this Danish study, another study, with
a similar methodology and including over 60,000
pregnant women, suggested that the consumption of
artificially sweetened beverages and sugar-sweetened
beverages was associated with an increased risk of
spontaneous or induced pre-term delivery (OR (95 % CI)
1.11 [1.00-1.24] for ≥ 1 serving of artificially sweetened soft
drinks/d). However, although the association was stronger
for sugar-sweetened beverages, the authors concluded that
they could not determine whether this risk was caused by
the effects of these beverages or by other associated dietary
or socio-economic factors [69].
Based on the available data, it is not possible to identify
any benefits or draw any conclusions regarding the
risk related to the consumption of intense sweeteners
during pregnancy, in terms of maternal health, obstetrical
parameters or newborn health.