Effects of Low/No Calorie Sweeteners on Glucose Tolerance

Excessive sugar consumption has been related to chronic metabolic problems, including obesity, type 2 diabetes, neuroinflammatory diseases, etc. Therefore, it is recommended to decrease added sugar intake below 10% of total energy intake. Low/no calorie sweeteners (LNCS) may seem as a good alternative to added sugars because they provide sweetness without adding calories to the diet. Although they may reduce energy intake and prevent weight gain, studies investigating the short and long term effects of these sweeteners on metabolic profile are controversial. Therefore, there is a need for future studies to shed light on metabolic effects of these compounds in humans. Some observational and clinical studies show that they may cause insulin resistance and type 2 diabetes. There are possible mechanisms that may explain this relationship. One of these possible mechanisms is interaction with sweet taste receptors (STRs). It has been shown that STRs not only found in oral cavity but also in extra-oral tissues, such as gastrointestinal tract, pancreas, brain, etc. In vitro studies with sucralose, it has been shown that it may activate STRs in L-cells and stimulate GLP-1 release in a similar manner with glucose. However, these results were not confirmed in vivo. There are at least six different LNCS approved for human use worldwide. However, each of them have different biological fate in terms of absorption, metabolism and excretion characteristics in the body. Therefore, result of a study with one of LNCS cannot be extrapolated for all LNCS; each of them should be studied in well-designed studies. In this study it is hypothesized that LNCS may activate STRs in intestinal L-cells and alter release of GLP-1; as a result impair glucose tolerance. In acute human studies, these effects are tested and there are controversial results in regard to glucose tolerance or incretin release. However, individuals who want to consume fewer calories or to better control their blood glucose use LNCS in place of sugar for longer period of time. For this reason, we wanted to test the effects of regular use of LNCS on glucose tolerance and incretin release.