Effect of Acute or Chronic Ingestion of Sucralose on Serum Insulin in Young and Healthy Adults: a Randomized, Double-blind, Placebo-controlled Trial
Phase: NA
Conditions: Healthy
Sponsor: Hospital General de México Dr. Eduardo Liceaga

 
 
Study protocol 
México CDMX. a January  20th 2016 
 
Effect of Acute or Chronic Ingestion of Sucralose on Serum Insulin in Young 
and Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. 
 
Background 
Relevance of the estudy 
Hypothesis 
Principal outcome 
Materials and Methods 
Ethical considerations 
 
 
 

 
 
 
México CDMX. a January  20th 2016 
 
Effect of Acute or Chronic Ingestion of Sucralose on Serum Insulin in Young 
and Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. 
 
Background 
Since the last 30 years, the prevalence of overweight and obesity have been 
considerably increasing worldwide (1); this is directly associated with a greater 
incidence of non-transmissible chronic disease such as Type 2 Diabetes Mellitus 
(DM2) (2, 3). Consequently, in recent years the consumption of Non-Caloric 
Sweeteners (NCS) has increased in young and healthy adults as a healthy 
alternative to reduce the ingestion of calories with the sweet taste in food or 
beverages (4). One of the NCS (No Caloric Sweetener) more consumed in the world 
is the sucralose, because is the 600 times sweeter than sugar but without calories 
intake (5, 6).  
Nevertheless, there are some studies that suggest a correlation between high 
consumption of NCS and high levels of blood glucose, insulin, and metabolic 
hormones as C-peptide, Gastric Inhibitory Polypeptide (GIP) and Glucagon-Like 
Peptide-1 (GLP-1), these systemic inflammatory factors can have an impact role on 
the development of DM2, obesity and cardiovascular diseases  (7).  On the other 

 
hand, a study in animal models shown that the chronic exposure to sucralose for 10 
weeks increases the values of area under the curve (AUC) of glucose tolerance test, 
which was attributed to a change of the intestinal microbiota (8). However, these 
studies did not take in to consideration the effect of acute or chronic exposure to 
NCS over the systemic inflammatory response; which has been repeatedly 
documented as a previous step in the development of glucose intolerance in the 
obese patient (9-11). 
Furthermore, it has not been studied until now whether the acute or prolonged 
consume of NCS such as sucralose is capable to cause a systemic inflammatory 
state and if this is related to the development of glucose intolerance in healthy 
individuals. This has generated in the scientific community a polemical discussion 
about the possible association between the consume of sweeteners and the 
development of glucose intolerance; which is characterized by the elevation in the 
AUC of insulin, glucose, C peptide, glucagon, GIP and GLP-1, as well as the rise of 
systemic inflammatory factors. Whence the aim of this research was measure the 
effect of the acute and chronic exposure to sucralose on blood glucose, insulin, C-
peptide, GIP and GLP-1 levels and the reduction of interleukins 4, 10, 13 in young 
and healthy adults.  
Relevance of the study 
Until now, the international agencies safety assessment of non-caloric sweeteners 
has been enough to recommend their use in humans. This confidence has led to a 
mass production and use of these additives for the western population of all ages, 
complemented by the absence of epidemiological evidence focused on trade 

 
adversities to the consumption of these substances. However, recent studies have 
revealed some studies that relate a state of glucose intolerance and insulin 
resistance with the chronic consumption of some of these available in the market 
products, as in the case of sucralose. Unfortunately, the results of these studies have 
been criticized for the lack of methodology robustness used and for omitting the 
presence of other markers that are directly involved with metabolic dysfunctions; the 
only consideration was the symptom of sucralose on the intestinal microbiota. 
Therefore, it is necessary to determine if the acute or chronic consumption of 
sucralose is capable of inducing a glucose intolerance and insulin resistance state 
in humans, through the performance of a dependable robust prospective, 
randomized, double blind study and placebo controlled, which allows us to issue 
reliable recommendations on the habitual use of non-caloric sweeteners in our 
population. 
 
Hypothesis 
In healthy, young volunteers, subjected to an oral glucose tolerance curve of 180 
minutes, acute or chronic exposure to 48 - 96 mg of sucralose in a single dose or 10 
weeks daily intake, respectively, causes an increase in the average levels of the 
area under the curve of insulin, glucose and other intolerance to this carbohydrate 
markers when compared with water as a placebo. 
 
Principal outcome  
To evaluate the effect of acute and chronic exposure to 48 - 96 mg of sucralose in a 
single dose or for 10 weeks, respectively, on the average levels of the area under 

 
the insulin curve in healthy, young volunteers, subjected to an oral glucose tolerance 
curve at 180 minutes, in a randomized, double-blind, placebo-controlled study. 
 
Materials and Methods  
This is a randomized, double-blind, placebo-controlled trial in young and healthy 
adults, the study at the General Hospital of Mexico, Dr. Eduardo Liceaga from April 
2016 to June 2018, and the present study meets with the criteria of CONSORT. 
To evaluate the acute effect of sucralose, the experimental groups will receive 48 
mg / 60 ml and 96 mg / 60 ml of fasting sucralose in a single shot, while the control 
group will receive 60 ml of water as a placebo, before undergoing a CTOG with 75 
g of glucose during 180 min. During this procedure, 4 ml of blood will be taken at -
15 (sucralose intake or placebo) and 0 (75 g glucose intake) as a base and then at 
15, 30, 45, 60, 75, 90, 105, 120 and 180 minutes post-load glucose for the 
quantification of insulin, glucose, C-peptide, glucagon, GLP-1, and GPI levels. 
Subsequently, to evaluate the chronic effect of sucralose, the experimental group 
will continue with the daily intake of 48 – 96 mg / 60ml of sucralose for 10 consecutive 
weeks, while the control group will receive 30 ml of water daily as a placebo during 
the same period of time. At the end of 10 weeks of treatment with sucralose or 
placebo, a second CTOG (75g / 180 min) will be carried out, taking again 4 ml of 
blood at -15 and time zero, and subsequently 4 ml at 15, 30, 45, 60, 75, 90, 105, 120 
and 180 minutes after glucose loading. To evaluate the acute exposure to the 
sweetener, the area under the curve (AUC) of the blood glucose levels obtained 
during the CTOG in each participant will be calculated and the average differences 

 
between the sucralose groups versus placebo will be compared, adjusting for BMI. 
In the case of chronic exposure to the sweetener, the AUC values between the 
sucralose groups versus placebo will be compared after 10 weeks, and the AUC 
values will be compared at the beginning and end of the study in the group that 
received sucralose, adjusting in both cases for BMI. In addition to the determination 
of glucose levels during the two CTOGs, the circulating levels of insulin, glucagon, 
C peptide, GIP, GLP-1, TNF-, pCr, IFN-, IL-1, IL- will be quantified. 4, IL-6, IL-10, 
IL-12, IL-13, IL-17, IL-23, and inflammatory monocytes CD14hiCD16 + CD11c + 
CCR2hiCX3CR1lowCD206-, with the purpose of comparing their values in the acute 
exposure scheme and chronic to sucralose, adjusting for BMI. The samples of 
excrement from acute and chronic exposure will be processed to extract the DNA 
and run them in PCR in real time and the percentage of each bacteria present in 
feces will be compared at the beginning and at the end. The difference between the 
two samples will be analyzed by means of square chi.  
Ethical considerations  
This study will be carried out in compliance with the guidelines of the protocol, with 
the ethical principles of the Declaration of Helsinki in its most recent version 
approved during the 64th Assembly of the World Association of Physicians, in 
Fortaleza Brazil, in October 2013, in accordance to the principles that govern human 
research in the General Health Law and in accordance with the ethical and research 
guidelines of the General Hospital of Mexico "Dr. Eduardo Liceaga. 
 
 

 
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