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Increasing consumption of artificial sweeteners raises scientific alert about possible heritable metabolic effects and silent changes in the body over generations, even without direct ingestion of the analyzed substances.
A study conducted by researchers from the University of Chile has raised a new alert about the consumption of calorie-free sweeteners by pointing out that exposure to sucralose and stevia in mice was associated with metabolic changes, alterations in gut microbiota, and modifications in the expression of genes linked to inflammation and metabolism that extended for up to two generations.
The analyzed descendants did not consume these compounds directly, yet they still exhibited some of the effects observed in the initially exposed animals.
Study on sweeteners and metabolic impact
The results were published on April 10, 2026, in the scientific journal Frontiers in Nutrition and reinforce a line of investigation that seeks to understand whether sugar substitutes, widely used in “zero” beverages, processed foods, and weight control diets, may produce more complex biological impacts than previously thought.
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The authors emphasize that the work was done in an animal model and, therefore, does not allow for conclusions to be drawn about the same occurring in humans.
The research evaluated 47 male and female mice, divided into three groups.
One group received only water, while the others consumed water supplemented with sucralose or stevia for 16 weeks.
After that, the animals were bred to form the first generation of descendants and then the second.
Both the F1 and F2 generations received only water, without direct contact with the sweeteners, which allowed researchers to observe whether the effects associated with parental consumption could persist in the offspring and grandchildren.
Changes in glucose and effects over generations
Among the main findings, scientists identified subtle yet consistent changes in how the body handled glucose.
In the parental generation, there was no significant difference in the oral glucose tolerance test.
In the next generation, male descendants of the animals exposed to sucralose showed a slight alteration in glycemic response.
In the second generation, this group continued to show unfavorable metabolic signs, with elevated fasting blood glucose levels.
In the case of stevia, the metabolic effects appeared in a more limited manner and tended to diminish over time.
Impact on gut microbiota and inflammation
The work also describes changes in gut microbiota, impacting the composition of the bacteria present in the intestine and reducing short-chain fatty acids, substances considered important for the metabolic and inflammatory balance of the body.
According to the researchers, this decline was observed in both the exposed animals and their descendants.
In the sucralose group, the changes were more pronounced and persistent, with indications of a higher presence of potentially harmful bacterial species and a lower presence of microorganisms associated with beneficial functions.
In addition to the intestine, scientists examined genes related to inflammation, the intestinal barrier, and metabolism.
The study points to an increase in the expression of Tlr4 and Tnf in the intestines of the animals in the sucralose group, both in the directly exposed generation and in the following generation.
A lower expression of Srebp1 in the liver was also observed, an alteration that persisted from the parental generation to the second generation in this same group.
In the case of stevia, there was an increase in inflammatory genes in the first generation, but this effect did not persist in the second.
Differences between sucralose and stevia
These findings led the authors to argue that the analyzed sweeteners did not produce the same pattern of response.
Sucralose appeared to be associated with more stable and lasting effects, while stevia demonstrated a more restricted and less persistent impact.
Nevertheless, the researchers refrain from treating the results as proof of established clinical harm.
The animals did not develop diabetes during the experiment, and the very group responsible for the work describes what they found as early biological signs, capable of indicating greater susceptibility to metabolic changes under certain conditions.
Epigenetics and transmission of effects
The hypothesis raised by the team involves mechanisms that go beyond the simple presence of the sweetener in the diet.
The authors discuss the possibility of the involvement of gut microbiota in this process, as changes in intestinal bacteria and the production of metabolites can influence genetic activity.
This is a field related to epigenetics, an area that investigates changes in how genes are expressed without direct alteration of the DNA sequence.
The study, however, does not claim that this mechanism has been definitively proven in humans.
Scientific debate and limits of the study
The dissemination of the results has reignited a debate that already exists in the scientific community.
The replacement of sugar with low or no-calorie sweeteners is often presented as a strategy to reduce energy intake and limit glycemic spikes, especially in products aimed at those wishing to lose weight or control sugar consumption.
At the same time, some recent research has investigated whether the relationship between these compounds and metabolic health is more complex than the logic of “fewer calories, less risk” suggests.
Experts consulted by the Science Media Centre after publication urged caution in interpreting the data.
They emphasized that studies with mice help formulate hypotheses and identify possible mechanisms, but cannot be automatically transported to human reality.
One of the points raised is that the transmission of microbiota between animals may occur differently than between people, which limits direct comparisons.
It was also noted that the article analyzes a specific set of genes and markers, without allowing for disease diagnosis based on these isolated results.
Use of sweeteners in daily life
Even with these reservations, the study broadens the discussion about the routine use of sweeteners in soft drinks, desserts, yogurts, supplements, and other daily consumption items.
The Chilean team states that the goal is not to provoke alarm, but to draw attention to the need for further investigation into long-term effects, especially in contexts of frequent exposure and sensitive phases of reproductive life.
Until there is more robust evidence in humans, the recommendation presented by the researchers is moderation, without turning the findings into a definitive condemnation of these products.
The central point of the research is less spectacular than the public debate sometimes suggests, but no less relevant.
Instead of showing established diseases, the study describes gradual changes in processes related to metabolism, inflammation, and the intestinal environment, with persistence in descendants who did not receive the sweeteners.
It is precisely this silent nature, measured in biological markers and not in evident symptoms, that helps explain why the topic has begun to mobilize increasing attention among researchers in nutrition and metabolic health.
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