Sucralose, Stevia Effects May Persist Across Mouse Generations

Diet sodas and other reduced-calorie products use non-nutritive sweeteners such as sucralose and stevia for sweetness without sugar's calories. Some health organizations have asked whether these additives disrupt energy metabolism over time and raise the risk of diabetes or cardiovascular disease. A new mouse study, published in Frontiers in Nutrition, adds to that discussion.

Researchers led by Dr. Francisca Concha Celume of the Universidad de Chile divided 47 male and female mice into three groups: one drank plain water, the other two drank water containing sucralose or stevia, at doses meant to resemble a normal human diet. The mice were bred for two more generations, and unlike the originals, these later ones drank only plain water.

Each generation was tested for oral glucose tolerance, a measure of how well the body handles glucose and an early sign of insulin resistance. Researchers examined fecal samples for gut microbiome changes and short-chain fatty acid levels — compounds made by gut bacteria that can influence gene regulation — and measured the activity of five liver and intestine genes linked to inflammation, gut-barrier integrity, and metabolism.

Sucralose and stevia produced different effects that shifted across generations. In the first generation, impaired glucose tolerance appeared only in males descended from sucralose-exposed mice; by the second generation, researchers found elevated fasting blood sugar in male descendants of the sucralose group and female descendants of the stevia group. Mice from either sweetener group developed more diverse fecal microbiomes but lower short-chain fatty acid levels; that reduction also appeared in both later generations.

Sucralose's effects were stronger and lasted longer: it appeared to increase activity of inflammation-linked genes and reduce activity of metabolism-linked genes, effects still detectable two generations after the original exposure. Stevia also altered gene activity, but more weakly, and did not persist past the first generation. Concha said the animals did not develop diabetes; researchers observed subtler changes in glucose regulation and gene activity instead.