Accumulating evidence link sugar-containing foods and beverages to adverse health outcomes. Non-Caloric Sweeteners (NCSs) are an alternative sugar source that lead to reduction in calories, and may mitigate body weight gain and hyperglycemia, especially in patients with diabetes. Yet, contradicting studies suggest that NCSs may mediate metabolic derangements. Here, we aim to assess long-term metabolic effects of chronic consumption of NCSs. To this aim, mice consuming either regular diet or high fat diet (HFD) were supplemented with NCSs in their drinking water at concentrations consumed by humans. Under HFD, mice consuming reb M or sucralose had significant lower body weight compared to fructose. In comparison to fructose consumption, a significantly lower blood glucose levels were observed in mice under chow diet drinking either sucralose or reb M. Under HFD, a significant decrease in blood glucose levels was found only in mice consuming ace-k. On HFD, all NCSs other than saccharin, resulted in significantly improved insulin sensitivity compared to fructose. A significant decrease in fasting glucose was found only in sucralose and reb M groups under these conditions. A trend towards higher levels of plasma insulin was observed in mice under HFD drinking either fructose or saccharin. None of the interventions caused a decrease in fluid consumption as compared to water, nor were significant differences in daily food intake, daily caloric intake or energy expenditure. RER displayed a normal nocturnal pattern in all groups and no significant change in voluntary physical activity was observed. As compared to fructose, NCS consumption decreased markers of NAFLD in obesity.

In summary, our results suggest that chronic consumption of NCS do not result in any observed metabolic alternations, and may attenuate some of the metabolic derangements associated with fructose and high fat-based diet.


M.Rathaus: None. L.Azem: None. R.Livne: None. S.Ron: None. I.Ron: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company.

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