Effects of saccharin on insulin sensitivity in overweight individuals without diabetes: a pilot study
Context It has been suggested that consumption of saccharin, a widely used artificial sweetener, decreases insulin sensitivity in rodents and humans, but studies show conflicting results.  Aim To investigate if saccharin affects insulin sensitivity in a proof-of-concept study in humans using hyperinsulinemic-euglycemic clamp. Methods In an open label pilot study, we recruited 14 overweight participants without diabetes of mean 60.5 (SD 4.1) years of age and body mass index 27.6 (SD 0.7). Insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, was determined before and after consumption of 5 mg/kg saccharin/day for three months. Blood was collected for analyses of diabetes-related biomarkers. Stool samples were collected before, during and after saccharin consumption for microbiota profiling by 16S rRNA gene sequencing.  Results Thirteen of the 14 participants (6 men, 7 women) completed the study. There was no change in insulin sensitivity (mean M value difference (?M) -0.1, p=0.85) or body weight (mean difference -0.1 kg, p=0.70) after consumption of saccharin. However, the mean HbA1c decreased from 38.7 mmol/mol (SD 3.0) at visit 1 to 36.8 (SD 3.4) at visit 4 (p=0.003). Overall, there was no change in composition or richness of the gut microbiota at the end of the study.  Conclusion This study did not demonstrate an association between saccharin intake and impaired insulin sensitivity in overweight participants without diabetes assessed by hyperinsulinemic-euglycemic clamp.