Elsevier

Nutrition

Volumes 55–56, November 2018, Pages 125-130
Nutrition

Applied nutritional investigation
Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial

https://doi.org/10.1016/j.nut.2018.04.001Get rights and content

Highlights

  • A 4-week consumption of sucralose was found to decrease insulin sensitivities in healthy volunteers.

  • An acute insulin response (AIR) was also reduced after sucralose consumption.

  • A glucose-stimulated glucagon-like peptide-1 (GLP-1) secretion was enhanced after chronic sucralose exposure.

  • Although sucralose is not metabolically inactive, it has an effect on insulin and GLP-1 responses.

Abstract

Objectives

Emerging evidence shows that non-nutritive sweeteners might induce glucose intolerance. This study aims to determine the effects of chronic exposure to sucralose on glycemic response, insulin secretion and sensitivity, and glucagon-like peptide-1 (GLP-1) release in healthy subjects.

Methods

Healthy volunteers who did not use non-nutritive sweeteners and were normoglycemia after oral glucose tolerance test (OGTT) were recruited. Subjects underwent a 75-g OGTT on two separate occasions, preceded by blindly consuming pills containing either 200 mg sucralose or placebo for 4 wk in a randomized crossover trial. Plasma glucose, insulin, and active GLP-1 levels were obtained after ingesting 75-g glucose. On the following day, intravenous glucose tolerance test (IVGTT) was performed to evaluate the acute insulin response (AIR).

Results

Fifteen participants (11 females, age 31.9 ± 10 y, body mass index 23.1 ± 3 kg/m2) participated in the study. AIR was lower after exposure to sucralose than placebo (58.9 ± 48.61 versus 69.94 ± 73.81 µU/mL, P < 0.001). Whole-body insulin sensitivity (estimated using the Matsuda index) was lower in sucralose than placebo (4.69 ± 1.67 versus 5.31 ± 2.56, P < 0.005). AUC of active GLP-1 was significantly higher in the sucralose than placebo (23.16 ± 18.86 versus 18.5 ± 22.22 pmol/L ⋅ 120 min, P < 0.001).

Conclusions

The continuous exposure to sucralose reduced AIR, decreased insulin sensitivity, and enhanced GLP-1 release in healthy subjects. However, the clinical significance of these results needs to be investigated in longer follow-up studies.

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.

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    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.

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