Applied nutritional investigationEffects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial
Introduction
As a result of the rapid increases in the prevalence of type 2 diabetes mellitus and obesity, non-nutritive sweeteners (NNS) have become popular as alternatives to added sugars because they contain no or fewer calories while preserving palatability [1], [2]. Unexpectedly, an accumulation of studies have suggested that NNS may increase the risk of excessive weight gain [3], metabolic syndrome [4], [5], and type 2 diabetes mellitus [6], [7]. There are several potential mechanisms that may induce NNS to cause glucose intolerance. One of these is that NNS could interfere with the release of insulin, gut hormones, and neurotransmitters by interaction with sweet taste receptors (T1 R2/T1 R3) expressed throughout the gastrointestinal tract [8], [9], [10]. This has been documented in healthy adolescents and young adults [11], obese insulin-sensitive subjects [12], and youth with type 1 diabetes mellitus [13]. These sweet taste receptors are also expressed in multiple organs including brain, tongue, respiratory system, pancreas, liver, adipose tissue, urinary bladder, and testes [14]. A recent in vitro study demonstrated the activation of the sweet taste receptor on pancreatic beta-cells involved in first phase insulin secretion [15]. However, the mechanisms of sweet taste receptors are still not fully understood. Other explanations include cognitive mechanisms. NNS may stimulate appetite and hunger via cephalic phase responses and can activate the reward system that contributes to glycemic control and energy homeostasis [16]. Perceptions in consumption of low calorie diets can influence the estimation of energy intake and lead to rebound eating [17]. Moreover, a recent experimental study in mice and humans showed that NNS consumption can induce glucose intolerance by alterations of gut microbiota [18].
Among the US Food and Drug Administration approved NNS, sucralose is one of the most widely used [19], [20]. Several human studies demonstrated that a single exposure of sucralose can affect the glycemic, insulin, and incretin responses to an oral glucose load [11], [12], [13], [21], [22]. In contrast, others showed no effects of sucralose [23], [24], [25]. Thus, the impact of a single exposure of sucralose on metabolic effects is still unknown. Despite the fact that the long-term effects of sucralose have been studied with regard to safety, a study of chronic exposure of sucralose on metabolic effects is still lacking. Thus, we aim to determine the effect of long-term sucralose exposure on glycemic responses, insulin secretion, insulin sensitivity, and GLP-1 release in healthy subjects using a randomized, double-blind crossover study.
Section snippets
Material and methods
The study protocol was approved by the Committee on Human Rights Related to Research Involving Human Subjects of the Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. All the participants provided written informed consent before enrollment.
Baseline characteristics
Fifteen healthy Thai subjects (11 females, 4 males) with normal oral glucose tolerance were included in the study. The mean baseline characteristics were age 31.9 ± 10 y, body mass index 23.1 ± 3 kg/m2, waist circumference 80.9 ± 9.2 cm, waist-height ratio 0.51 ± 0.06, systolic blood pressure 109.3 ± 11 mmHg, and diastolic blood pressure 70 ± 6.5 mmHg. Mean serum results were aspartate transaminase 26.3 ± 6.7 IU/L, alanine transaminase 20.8 ± 10.8 IU/L, and creatinine 68 ± 14.1 µmol/L. Mean
Discussion
In this randomized, double-blind, crossover study, we showed that daily oral ingestion of 200 mg sucralose for 4 wk decreased total body and hepatic insulin sensitivities in healthy volunteers. Not surprisingly, the insulin secretion indexed from OGTTs was also increased because of the compensatory response in insulin resistant subjects. AIR derived from IVGTTs was reduced after exposure to sucralose. In addition, glucose-stimulated GLP-1 secretion was enhanced after exposure to sucralose.
We
Acknowledgments
We thank all participants for their time and willingness to be part of this project. The authors would like to thank Sukanya Siriyotha for her outstanding support in statistical analysis. We also thank Professor Chatchalit Rattarasarn for technical assistance in measurement of insulin secretion and sensitivity.
References (37)
- et al.
Low-calorie sweetener consumption is increasing in the United States
Am J Clin Nutr
(2012) - et al.
Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort
Am J Clin Nutr
(2013) - et al.
Altered processing of sweet taste in the brain of diet soda drinkers
Physiol Behav
(2012) - et al.
Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes
J Am Diet Assoc
(2003) - et al.
Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus
Food Chem Toxicol
(2008) - et al.
Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women
Nutr Res
(2011) - et al.
Allelic polymorphism within the TAS1 R3 promoter is associated with human taste sensitivity to sucrose
Curr Biol
(2009) - et al.
Use of caloric and noncaloric sweeteners in US consumer packaged foods, 2005–2009
J Acad Nutr Diet
(2012) - et al.
Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain
Obesity (Silver Spring)
(2008) - et al.
Diet soda intake is associated with long-term increases in waist circumference in a biethnic cohort of older adults: the San Antonio Longitudinal Study of Aging
J Am Geriatr Soc
(2015)
Chronic low-calorie sweetener use and risk of abdominal obesity among older adults: a cohort study
PLoS ONE
Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Diabetes Care
Expression of sweet taste receptors of the T1 R family in the intestinal tract and enteroendocrine cells
Biochem Soc Trans
Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1
Proc Natl Acad Sci USA
T1 R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1
Proc Natl Acad Sci USA
Ingestion of diet soda before a glucose load augments glucagon-like peptide-1 secretion
Diabetes Care
Sucralose affects glycemic and hormonal responses to an oral glucose load
Diabetes Care
Effects of diet soda on gut hormones in youths with diabetes
Diabetes Care
Cited by (58)
The effect of regular consumption of four low- or no-calorie sweeteners on glycemic response in healthy women: A randomized controlled trial
2023, NutritionCitation Excerpt :In addition, LNCS may possibly affect the cephalic phase response and alter gut microbiota, consequently inducing glucose intolerance [13,33,34]. However, only a few studies have assessed the long-term effects of LNCS on glucose tolerance and release of insulin and GLP-1 in humans [35–37]. There were some limitations of those studies, and a larger, longer-term controlled study with different LNCS at doses similar to daily life in a healthy population was needed.
Sugar reduction and sweeteners to improve foods
2023, Strategies to Improve the Quality of FoodsSugar reduction in beverages: Current trends and new perspectives from sensory and health viewpoints
2022, Food Research InternationalNon-nutritive sweeteners: Mechanisms of action, effects on eating behavior and glycemic control
2022, Medecine des Maladies Metaboliques
Conflict of Interest: The authors declare that they have no conflict of interest.
Funding: This work was supported by Faculty of Medicine Ramathibodi Hospital, Mahidol University, and by the Endocrine Society of Thailand. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The abstract was presented at the ENDO2017, April 1–4, 2017, in Orlando, FL. USA.