April 23, 2026, 8:24 am | Read time: 6 minutes
Sweeteners are almost indispensable: They dominate not only in the fitness bubble in the form of drink syrups and flavor powders. They are also a popular tool among the general public for easily saving calories, such as through light drinks. However, sweeteners and their long-term effects are repeatedly criticized: They are said to alter gut flora and possibly promote metabolic diseases in this way. A new study suggests that this effect could even be intergenerational. However, it is based on mouse experiments, and further studies with humans are still lacking.
Are Sweeteners Really Harmless?
A sugar-rich diet has been proven to promote the development of obesity, type 2 diabetes, and other chronic diseases. Consequently, numerous calorie-free and low-calorie sweeteners have been developed to mitigate the negative effects of sugar on metabolism and facilitate weight control. And their consumption is increasing worldwide.1 According to a U.S. study, this is also true for women of childbearing age.2
But now the World Health Organization questions the long-term benefits of sweeteners. In a guideline published in 2023, the WHO emphasizes that there are indications of an increased risk of type 2 diabetes, cardiovascular diseases, and mortality associated with long-term sweetener consumption (but not short-term). However, the evidence is still inconclusive.3
This prompted Dr. Francisca Concha Celume from the Universidad de Chile to delve into sweeteners: “We found it remarkable that despite the increasing consumption of these additives, the prevalence of obesity and metabolic disorders like insulin resistance has not decreased. This does not mean that sweeteners are responsible for these trends, but it raises the question of whether they affect metabolism in ways we do not yet fully understand.”4
Intergenerational Experiment
The scientists divided 47 male and female mice into three groups.5 In addition to unrestricted access to standard food, the mice received, depending on the group:
- Water
- Water with Stevia
- Water with Sucralose
Both sweeteners were given at a concentration of 0.1 milligrams per milliliter of drinking water. This corresponds to approximately five to 15 milligrams per kilogram of body weight per day and falls within the range of the acceptable daily intake (ADI) for humans. After six weeks of treatment, the mice were paired. Offspring were bred over two generations, with neither generation receiving sweeteners. Each group was monitored until the 20th week of life.
Concha explains: “Animal models allow us to control environmental conditions very precisely and isolate the effect of a specific factor, such as a food component, while simultaneously tracking multiple generations within a relatively short time.”
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Glucose and Stool Samples
Each generation underwent an oral glucose tolerance test. This test shows how well the body handles glucose after a sugar load and provides clues to impaired insulin action–an early warning sign for diabetes. Additionally, researchers analyzed stool samples to detect changes in the gut microbiome and short-chain fatty acids. These substances are produced by gut bacteria and can influence gene activity. The authors suspect a possible mechanism here through which sweeteners could pass biological effects to offspring.
The team also examined the activity of genes related to inflammation, gut barrier, and metabolism in the liver and gut. The researchers aimed to determine whether molecular patterns emerged that matched the observed changes in metabolism and the gut.
Study Showed Different Effects–Depending on Sweetener and Generation
The research team found that different sweeteners caused varying effects, which also changed across generations. In the first generation (children of the sweetener mice), only the male offspring of sucralose mice showed signs of impaired glucose tolerance. In the second generation (grandchildren of the sweetener mice), the same group exhibited elevated fasting blood sugar levels. Both are early indications that blood sugar regulation could be out of balance.
And what about the female mice? In the second generation, they also showed elevated fasting blood sugar levels, but among the offspring of stevia mice.
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Changes in the Gut Microbiome
The composition of the gut flora changed in all generations. Additionally, the mice had lower concentrations of short-chain fatty acids in the gut, indicating that gut bacteria produce fewer beneficial metabolic products. In sucralose mice and their offspring, the changes in the microbiome were more pronounced than in stevia mice–their feces contained more pathogenic and fewer beneficial bacterial species.
Sucralose, like stevia, increased the activity of genes related to inflammatory processes while simultaneously inhibiting metabolism-relevant gene activity. In sucralose, these effects persisted into the second generation of offspring. Stevia also influenced gene activity, but overall weaker and only up to the first generation of offspring.
“Comparing the generations, these effects were generally most pronounced in the first generation and tended to decrease in the second generation,” said Concha. “Overall, the effects associated with sucralose were more consistent and persistent across generations.”
Interpretation and Significance of the Study
The results suggest that calorie-free sweeteners may not be entirely biologically neutral. Notable were changes in glucose metabolism and the gut microbiome. In this mouse study, sucralose was associated with stronger and longer-lasting effects than stevia. At the same time, the authors urge caution: “The observed changes in glucose tolerance and gene expression could be interpreted as early biological signals related to metabolic or inflammatory processes,” said Concha. But: “The animals did not develop diabetes, for example.” No manifest diseases were observed, but rather early shifts in biological regulatory circuits. These shifts, however, could increase susceptibility to metabolic diseases under certain conditions, such as a high-fat diet.
It is also important to note: The study shows correlations but does not prove a direct cause-and-effect relationship, and results from animal experiments cannot be directly applied to humans. Accordingly, Concha emphasizes: “The aim of this study is not to spread panic, but to highlight the need for further research. It seems advisable to moderate the consumption of these additives and continue to explore their long-term biological effects.”