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Zùsto: A new sweetening agent with low glycemic index

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Background & aims: Sweetening agents are sugar substitutes with a low glycemic index, used to obtain a better glycemic control in diabetes patients. However, they also may have a role in other subjects, as a high glycemic index is thought to cause many pathological conditions. Unfortunately, not all artificial sweeteners are perceived as sweet as sugar by patients. Consumers refer often to an after taste present in foods sweetened with intensive sweeteners. The objective of this study was to explore whether Zùsto®had a low glycemic index, to replace glucose as a sweetener. Methods: In this study, the glycemic index (GI) of a new sweetening agent, Zùsto®, is compared to that of glucose 25 g, a standard sugar-loaded drink used in the oral glucose tolerance test to detect diabetes, as primary endpoint. Zùsto®is composed of non-digestible, water soluble fibers and sweeteners. 10 healthy, female non-obese volunteers received glucose and Zùsto®, albeit by an interval of a week. Evolution of glycemia, C-peptide and insulin release was measured at different time-points after intake. Results: The results show that, when calculating the mean incremental Area Under the Curve (AUC), the AUC of glucose was around five times as high as that of Zùsto®; a GI of 22 for Zùsto®was calculated. Furthermore, Zùsto®had no significant effect on the glycemia, contrary to glucose, for at least 60'. This was also the case concerning C-peptide and insulin release, but the difference lasted even for 180'. Moreover, Zùsto®was perceived as sweet by all volunteers, with no particular aftertaste. Conclusion: Zùsto®could be a viable alternative for fast sugars and other sweetening agents, both for diabetic patients and other subjects, requiring however a larger trial to confirm these results. CLINICALTRIALS.GOV: NCT02607345.
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Original article
Zùsto: A new sweetening agent with low glycemic index
Joeri Jan Pen
a
,
1
, Galina Khorosheva
a
,
1
, Ursule Van de Velde
a
, Corinne Debroye
a
,
Andr
e Huyghebaert
b
, Raoul Rottiers
c
, Bart Keymeulen
a
,
*
a
Diabeteskliniek UZ Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium
b
Food Safety and Quality, Faculty Bioscience Engineering, Ghent University (UGent), Ghent, Belgium
c
Dienst Endocrinologie, UZ Gent, Universiteit Gent (UGent), Ghent, Belgium
article info
Article history:
Received 23 March 2017
Accepted 28 November 2017
Keywords:
Glycemia
Glycemic index
Zùsto
®
summary
Background &aims: Sweetening agents are sugar substitutes with a low glycemic index, used to obtain a
better glycemic control in diabetes patients. However, they also may have a role in other subjects, as a
high glycemic index is thought to cause many pathological conditions. Unfortunately, not all articial
sweeteners are perceived as sweet as sugar by patients. Consumers refer often to an after taste present in
foods sweetened with intensive sweeteners. The objective of this study was to explore whether Zùsto
®
had a low glycemic index, to replace glucose as a sweetener.
Methods: In this study, the glycemic index (GI) of a new sweetening agent, Zùsto
®
, is compared to that of
glucose 25 g, a standard sugar-loaded drink used in the oral glucose tolerance test to detect diabetes, as
primary endpoint. Zùsto
®
is composed of non-digestible, water soluble bers and sweeteners. 10 healthy,
female non-obese volunteers received glucose and Zùsto
®
, albeit by an interval of a week. Evolution of
glycemia, C-peptide and insulin release was measured at different time-points after intake.
Results: The results show that, when calculating the mean incremental Area Under the Curve (AUC), the
AUC of glucose was around ve times as high as that of Zùsto
®
; a GI of 22 for Zùsto
®
was calculated.
Furthermore, Zùsto
®
had no signicant effect on the glycemia, contrary to glucose, for at least 60'. This
was also the case concerning C-peptide and insulin release, but the difference lasted even for 180'.
Moreover, Zùsto
®
was perceived as sweet by all volunteers, with no particular aftertaste.
Conclusion: Zùsto
®
could be a viable alternative for fast sugars and other sweetening agents, both for
diabetic patients and other subjects, requiring however a larger trial to conrm these results.
Clinicaltrials.gov: NCT02607345.
©2017 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.
1. Introduction
The glycemic index (GI) is a tool to rank the capacity of foods to
raise glycemia after a meal. Food with a low GI is preferred in
diabetic patients, as regulation of the glycemia is primordial. High
GI-containing food is known to lead to fast, high and longstanding
postprandial hyperglycemia, making it more difcult to control
diabetes and prevent complications [1e4].
Sweetening agents are sugar substitutes that are articially
designed to replace fast sugars. They are generally used in diabetic
patients due to their low GI and their sweet taste. They do not cause
a postprandial hyperglycemia and are therefore good agents to
obtain glucose control, contrary to fast sugars. One problem with
these agents is that in some cases, health concerns on the long term
have been raised. Also, these agents are not all perceived as sweet
by all patients, as sweetness can be accompanied by other tastes,
inherent to the molecule [5,6].
A higher GI is also linked to many pathological conditions in
non-diabetic individuals, and is thought to give rise to obesity and
diabetes (even after risk correction for obesity) [7e9], cancer [10]
and cognitive functioning [11], also in children [12]. Moreover, in
pregnancy, food intake with a higher GI is linked to the develop-
ment of obesity and metabolic disturbances in the newborn [13,14].
This appears also to be the case with sugar-sweetened beverages.
Sweetening agents have been shown to diminish those risks, even
in the absence of diabetes [15e18].
In this study, a novel sweetening agent, Zùsto
®
, is tested for its
GI, as compared to glucose. Glycemia, C-peptide release and
*Corresponding author.
E-mail address: Bart.Keymeulen@uzbrussel.be (B. Keymeulen).
1
These authors contributed equally to this work.
Contents lists available at ScienceDirect
Clinical Nutrition ESPEN
journal homepage: http://www.clinicalnutritionespen.com
https://doi.org/10.1016/j.clnesp.2017.11.009
2405-4577/©2017 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.
Clinical Nutrition ESPEN xxx (2017) e1ee4
Please cite this article in press as: Pen JJ, et al., Zùsto: A new sweetening agent with lowglycemic index, Clinical Nutrition ESPEN (2017), https://
doi.org/10.1016/j.clnesp.2017.11.009
insulinemia after ingestion are assessed. Moreover, the sweet taste
of Zùsto
®
is tested on healthy volunteers, and no particular after-
taste is recorded.
2. Materials and methods
2.1. Subjects
We conducted a randomized, controlled, single-blinded trial in
the University Hospital Brussel (UZ Brussel), Belgium. The study
was approved by the Institutional Review Board of the hospital and
performed in accordance with the Declaration of Helsinki and Good
Clinical Practice guidelines. Written informed consent was ob-
tained from all patients.
Ten healthy female adult volunteers with normal insulin
secretory beta cell function and normal insulin sensitivity, partici-
pated in the study (Table 1). Exclusion criteria were diabetes in rst
degree relatives, intake of medication which inuences blood
glucose levels, pregnancy or breastfeeding, or people following a
diet for weight loss.
2.2. Study design and procedures
After selection, healthy volunteers were split in two groups of
ve subjects. Group 1 received glucose 25 g (Glucomedics
®
) solved
in 100 ml water (standard drink), while group 2 received 25 g
Zùsto
®
solved in 100 ml water. Both drinks had to be taken in a time
period of 5'. Subjects had to have fasted for 8 h prior to testing.
Blood samples for glucose and insulin were taken at 15' and 0'.
Blood samples for glucose, insulin and C-peptide were taken at 15',
30', 60', 90', 120' and 180' after the start of the intake. After one
week interval, groups were switched and the same procedure took
place.
2.3. Properties of Zusto
Zùsto is a blend of several ingredients optimized in order to
approach the sweet taste of regular sugar or sucrose (saccharose).
The blend is further optimized so it can be applied in a one to one
ratio to sucrose. No particular adaptation of recipes in the eld of
solid or semisolid sweet products, like desserts, frozen desserts or
ne bakery ware, is necessary. It is not intended to be applied in
liquid products.
In detail, Zùsto is a sugar substitute marketed with a proprietary
formula on the EU market. It contains polydextrose, erythritol,
inulin, fructo-oligosaccharides, maltodextrins, isomaltulose and
sucralose in quantities that allow to mimic the organoleptic and
functional properties of sugar, while providing only 97 kcal/100 g.
The sweetening power is adjusted to match that of table sugar by
the use of 0.14 g/100 g of Sucralose. In addition, non-digestible
carbohydrates with ber properties are added to provide bulk
and mimic the technological properties of sugar. The full compo-
sition is described in the patent (World Intellectual Property
Organization. Patentscope). https://patentscope.wipo.int/search/
en/detail.jsf?docId¼WO2015158735&redirectedID¼true. Last
accessed on 19 October 2018.
The individual components of the formula have all demon-
strated effects on blood glucose in various trials. The aim of this
study was to investigate the effect of the specic composition of
Zusto on blood glucose levels. The study was designed to conrm
the validity of the concept and the absence of unexpected
phenomena.
In addition to the sweet taste, particular attention has been
given to the functional properties of the formula. The blend shows
good functional properties in terms of water solubility, texture
formation, caramellisation, browning reactions and crystallization.
2.4. Outcomes
The primary outcome of this study is comparison of the GI of
glucose and Zùsto
®
, by means of calculating the AUC. The secondary
endpoints are the evaluation of C-peptide and insulin levels after
ingestion of either glucose or Zùsto
®
.
2.5. Statistical analysis
Baseline subject characteristics are expressed as mean with
standard deviations. The primary outcomes measured were the
differences between changes from baseline for glucose, plasma C-
Peptide and insulin after intake of glucose and Zùsto
®
. The differ-
ences between changes from baseline were analyzed by using the
Related-Samples Wilcoxon Signed Rank Test. The glycemic index
was calculated by expressing each participant's glucose incre-
mental area under the curve (iAUC) for both intake with glucose
and Zùsto
®
according to a previously described formula [19].Re-
sults are reported as mean ±standard error of the mean (SEM). The
signicance of differences was calculated by using the Man-
neWhitney-U test. All statistical tests were performed two-sided at
the 5% level of signicance.
3. Results
All participants completed the study.
Volunteers took either glucose or Zùsto
®
, and blood samples
were taken at different timepoints. The incremental Area Under the
Curve (AUC) of glucose as compared to Zùsto
®
was calculated
(Fig. 1). For glucose, the mean iAUC was 2262 ±431. For Zùsto
®
, the
mean iAUC was 353 ±77.
Table 1
Subject characteristics (n ¼10).
Age (y) 41,3 (5,3)
Body weight (kg) 68,0 (5,8)
BMI (kg/m
2
) 25 (2,7)
Fasting glycemia (mg/dL) 87 (4)
Homa
%B 109 (29)
%S 141 (51)
IR 0.8 (0.4)
All data are expressed as mean (SD).
Fig. 1. Incremental Area Under the Curve (iAUC) of glycemia for glucose 25 g (right) as
compared to Zùsto®25 g (left). Box plots with mean and SEM. The GI of Zùsto®is 22.
J.J. Pen et al. / Clinical Nutrition ESPEN xxx (2017) e1ee4e2
Please cite this article in press as: Pen JJ, et al., Zùsto: A new sweetening agent with low glycemic index, Clinical Nutrition ESPEN (2017), https://
doi.org/10.1016/j.clnesp.2017.11.009
An expected 360% increase of glycemia after ingestion with
glucose was measured, but this increase was minor with Zùsto
®
(plus 40%). After 60', glycemia after glucose had fallen again to a
level not signicantly different from that with Zùsto
®
(Fig. 2, upper
panel). Plasma C-peptide was elevated after glucose during 180 min
the last timepoint measured (Fig. 2, middle panel). This was also the
case with insulin secretion after intake (Fig. 2, lower panel). In
contrast, no signicant increase of plasma C-peptide and insulin
levels were measured after intake of Zùsto
®
. Moreover, at 180',
plasma glucose was slightly lower after intake of glucose (6 mg/dl)
than after intake of Zùsto
®
(Fig. 1, upper panel), presumably
reecting the strong stimulus of insulin secretion after intake of
glucose.
All volunteers tended to designate Zùsto
®
as sweet. No volun-
teer remarked an added taste or aftertaste.
4. Discussion
This study shows that a novel sweetening agent, Zùsto
®
, can be
used as a replacement for fast sugars, as it has a low GI. Its taste is
perceived as sweet and it has no effect on postprandial glycemia, C-
peptide release and insulinemia, unlike fast sugars.
The fact that postprandial glycemia is not altered by Zùsto
®
,is
important because both the GI as the glycemia itself are thought of
having an effect on a patient's overall health, as well as their well-
being. Moreover, insulinemia is not altered, which is the case with
the standard drink glucose as well as food with a higher GI.
Hyperinsulinemia has been correlated with a higher prevalence of
increased appetite and weight gain, (pre)diabetes, cardiovascular
disease and even cancer (see Introduction), although none of these
associations have been studied in this small pilot trial. By conse-
quence, Zùsto
®
's non-metabolic disturbance is of signicant
importance, as the absence of hyperinsulinemia after ingestion
suggests that the appetite, and by consequence weight gain, will
not be increased. These hypotheses need to be suggested in a larger
trial.
The GI is typically low to 0 in sweetening agents, as they are
articially designed to replace fast sugars. Biochemically, they are
multiple times as sweet as normal fast sugars. The problem with
many sweetening agents is that their overall taste is not universally
appreciated by all patients. Stevioside, saccharin and aspartame are
sweeteners with a GI of 0 [20], but the rst two are perceived as
having a bitter aftertaste by many patients, and are not even
tolerated in a small fraction of them [5,6,21], while aspartame is
unstable at high temperatures [22,23]. This is not the case with
Zùsto
®
, although the sample size is small. Another advantage of
Zùsto
®
is that one dose is composed of only 25 g of carbohydrates,
as compared to classical food (bread, potatoes). While Zùsto
®
was
indeed perceived as sweet by all participants, it should be noted
that this was not an endpoint of the study.
In conclusion, Zùsto
®
is a novel sweetening agent that can be
used as an alternative to fast sugars, both in diabetic and other
patients.
Acknowledgements
The UZ Brussel investigators declare no conict of interest. RR
declares no conict of interest. AH has been consulted during the
development of the formula but has no nancial interest.
RR, AH and BK concepted and designed the study. GK, UVDV and
CD executed the study. JP, AH, RR and BK interpreted the results.
This academic study was performed thanks to a grant provided
by SDC (Sweet D'Light Creations NV) Belgium.
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doi.org/10.1016/j.clnesp.2017.11.009
... allow consumers who are diabetic to consume SUITENA™ as the sweetener since it will not induce a spike in the blood glucose level upon consumption. Most commercially-available sugar replacers have low to zero GI, but some were reported to have a bitter aftertaste or unstable at high temperatures [8]. As for SUITENA™, most of the participants perceived the sugar replacer to be sweeter than dextrose without any aftertaste. ...
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The present study is a secondary analysis of the ROLO study, a randomised control trial of a low-glycaemic index (GI) diet in pregnancy to prevent the recurrence of fetal macrosomia. The objectives of the present study were to identify which women are most likely to respond to a low-GI dietary intervention in pregnancy with respect to three outcome measures: birth weight; maternal glucose intolerance; gestational weight gain (GWG). In early pregnancy, 372 women had their mid-upper arm circumference recorded and BMI calculated. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. At delivery, infant birth weight was recorded and fetal glucose, C-peptide and leptin concentrations were measured in the cord blood. Women who benefited in terms of infant birth weight were shorter, with a lower education level. Those who maintained weight gain within the GWG guidelines were less overweight in both their first and second pregnancies, with no difference being observed in maternal height. Women who at 28 weeks of gestation developed glucose intolerance, despite the low-GI diet, had a higher BMI and higher glucose concentrations in early pregnancy with more insulin resistance. They also had significantly higher-interval pregnancy weight gain. For each analysis, women who responded to the intervention had lower leptin concentrations in early pregnancy than those who did not. These findings suggest that the maternal metabolic environment in early pregnancy is important in determining later risks of excessive weight gain and metabolic disturbance, whereas birth weight is mediated more by genetic factors. It highlights key areas, which warrant further interrogation before future pregnancy intervention studies, in particular, maternal education level and inter-pregnancy weight gain.
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Epidemiologic evidence for the relation between carbohydrate quality and risk of type 2 diabetes (T2D) has been mixed. We prospectively examined the association of dietary glycemic index (GI) and glycemic load (GL) with T2D risk. We prospectively followed 74,248 women from the Nurses' Health Study (1984-2008), 90,411women from the Nurses' Health Study II (1991-2009), and 40,498 men from the Health Professionals Follow-Up Study (1986-2008) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by using a validated questionnaire and updated every 4 y. We also conducted an updated meta-analysis, including results from our 3 cohorts and other studies. During 3,800,618 person-years of follow-up, we documented 15,027 cases of incident T2D. In pooled multivariable analyses, those in the highest quintile of energy-adjusted GI had a 33% higher risk (95% CI: 26%, 41%) of T2D than those in the lowest quintile. Participants in the highest quintile of energy-adjusted GL had a 10% higher risk (95% CI: 2%, 18%) of T2D. Participants who consumed a combination diet that was high in GI or GL and low in cereal fiber had an ∼50% higher risk of T2D. In the updated meta-analysis, the summary RRs (95% CIs) comparing the highest with the lowest categories of GI and GL were 1.19 (1.14, 1.24) and 1.13 (1.08, 1.17), respectively. The updated analyses from our 3 cohorts and meta-analyses provide further evidence that higher dietary GI and GL are associated with increased risk of T2D.