Effects of Sucralose on Drug Absorption and Metabolism (The SweetMeds Study)

National Institute On Alcohol Abuse And Alcoholism

Investigators

Abstract

Non-nutritive sweeteners (NNS) are 100-20,000 times sweeter than sucrose and provide sweet taste with no or minimal contribution to caloric intake. Consumption of NNS has steadily increased in both children and adults in the US. This trend will likely continue since sugar intake has been linked to the development of obesity, and NNS offers a palatable alternative. However, several large cross-sectional studies have suggested adverse metabolic effects of NNS resulting in similar consequences as high sugar intake, including weight gain, insulin resistance, fatty liver disease, diabetes and cardiovascular disease. In a previous pilot study, we observed that diet soda (Diet Rite Cola) augments glucose-stimulated GLP-1 secretion in young, healthy volunteers. Subjects 12 to 25 years of age participated in two 75-gram oral glucose tolerance tests (OGTT) on separate days. Ten minutes prior to the glucose load, subjects drank 240 mL of either caffeine-free diet soda (Diet Rite cola) sweetened with sucralose and acesulfame-potassium or unflavored carbonated water in randomized order, with each subject serving as his/her own control. In the ongoing study, Dr. Rother showed that the NNS sucralose and acesulfame-potassium in diet soda partially contribute to the observed increase in GLP-1. However, the taste of diet soda or other ingredients also plays a role. Furthermore, we found that insulin secretion is slightly higher when study participants receive NNS (either in water or in diet soda) before an OGTT compared to water as a pretreatment. We speculate this may be due to pancreatic beta cell sweet taste receptor activation. We are also studying the effects of NNS in individuals who have undergone bariatric surgery. (Roux-en-Y) since these persons have very high incretin concentrations, which may be important for their weight loss and lack of weight regain. It is unknown whether NNS can further induce GLP-1 responses. We are also testing the effects of the sweet taste receptor inhibitor lactisole on GLP-1 secretion and measuring GLP-1 in saliva. The protocol was restarted this July 2024 with the support of NIH Pharmacy. Enrolling!