Non-nutritive sweeteners and their role in the gastrointestinal tract

J Clin Endocrinol Metab. 2012 Aug;97(8):2597-605. doi: 10.1210/jc.2012-1475. Epub 2012 Jun 7.


Context: Non-nutritive sweeteners can bind to sweet-taste receptors present not only in the oral cavity, but also on enteroendocrine and pancreatic islet cells. Thus, these sweeteners may have biological activity by eliciting or inhibiting hormone secretion. Because consumption of non-nutritive sweeteners is common in the United States, understanding the physiological effects of these substances is of interest and importance.

Evidence acquisition: A PubMed (1960-2012) search was performed to identify articles examining the effects of non-nutritive sweeteners on gastrointestinal physiology and hormone secretion.

Evidence synthesis: The majority of in vitro studies showed that non-nutritive sweeteners can elicit secretion of gut hormones such as glucagon-like peptide 1 and glucose-dependent insulinotropic peptide in enteroendocrine or islet cells. In rodents, non-nutritive sweeteners increased the rate of intestinal glucose absorption, but did not alter gut hormone secretion in the absence of glucose. Most studies in humans have not detected effects of non-nutritive sweeteners on gut hormones or glucose absorption. Of eight human studies, one showed increased glucose-stimulated glucagon-like peptide 1 secretion after diet soda consumption, and one showed decreased glucagon secretion after stevia ingestion.

Conclusions: In humans, few studies have examined the hormonal effects of non-nutritive sweeteners, and inconsistent results have been reported, with the majority not recapitulating in vitro data. Further research is needed to determine whether non-nutritive sweeteners have physiologically significant biological activity in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Gastrointestinal Hormones / metabolism
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose / metabolism
  • Humans
  • Intestinal Absorption / drug effects
  • Metagenome / drug effects
  • Sweetening Agents / pharmacology*
  • Taste Perception / drug effects


  • Gastrointestinal Hormones
  • Sweetening Agents
  • Glucagon-Like Peptide 1
  • Glucose