Health organizations have expressed growing concern about the long-term effects of artificial sweeteners, substances used to provide a sweet taste without calories.
Although it seems like an ideal alternative to sugar, there are concerns that it may interfere with energy metabolism and increase the risk of developing diabetes and heart disease in the future.
Now, a new study conducted on mice has revealed that the common sweeteners sucralose and stevia have negative effects on the gut microbiome and gene expression, which may harm metabolic health, and, more seriously, these effects can be passed down through generations.
Dr. Francesca Concha Selomé of the University of Chile, lead author of the study published in the journal Frontiers in Nutrition, says it is interesting that despite the increased consumption of these additives, rates of obesity and metabolic disorders such as insulin resistance have not decreased.
She explains that this does not mean that sweeteners are directly responsible for these trends, but it does raise an important question about whether they affect metabolism in ways that science is still unable to fully understand.
To conduct the study, the scientists divided 47 mice into three groups, with each group receiving either plain water or water with added doses of sucralose or stevia, equivalent to the amount a human might consume as part of their normal diet.
These groups were then raised for three consecutive generations, but subsequent generations received only plain water free of any sweeteners. Concha explained that animal models allow scientists to precisely control environmental conditions and isolate the effect of a specific factor, such as a nutrient, while also being able to monitor several generations in a relatively short period.
Each generation underwent an oral glucose tolerance test, which measures insulin resistance, an early warning sign of diabetes. Researchers also collected stool samples to detect changes in the gut microbiome and short-chain fatty acid concentrations, which may indicate genetic variations passed down from parents to children.
In addition, the scientists looked at the expression of five genes associated with inflammation, intestinal barrier function, and metabolism in the liver and intestines, with the aim of identifying potential genetic influences that might explain the negative health effects of non-nutritive sweeteners.
The researchers found that each sweetener had a different effect, and these effects changed over time across generations. In the first generation, only male offspring of mice fed sucralose showed signs of impaired glucose tolerance, but by the second generation, both male offspring of mice fed sucralose and female offspring of mice fed stevia showed elevated fasting blood sugar.
Both groups that consumed the sweeteners had more diverse fecal microbiomes, but with lower concentrations of short-chain fatty acids, suggesting that the beneficial bacteria were producing less of the beneficial metabolites. This decline continued in subsequent generations as well.
It turned out that sucralose was the most effective and persistent, as the mice were more severely affected by it, with more pathogenic and less beneficial types of bacteria appearing in their feces
Sucralose appears to stimulate the expression of genes associated with inflammation and decrease the expression of genes associated with metabolism, with these effects persisting for up to two generations after its consumption. While stevia also affects gene expression, its effects are smaller and do not extend beyond one generation.
Concha commented on these results, saying that the changes observed in glucose tolerance and gene expression can be interpreted as early biological signals related to metabolic processes or inflammation. She explained that the animals did not develop diabetes fully, but rather showed mild changes in how the body regulates sugar and in the activity of genes associated with inflammation, which may increase susceptibility to metabolic disorders under certain conditions such as following a high-fat diet
However, the team emphasizes that this research identifies correlations between different health status changes, but does not definitively prove causal relationships, and that the effect of these sweeteners on mice may not accurately reflect their effect on humans.
Concha concludes by saying that the aim of this research is not to cause panic among consumers, but to highlight the need for further scientific investigation, noting that it may be reasonable to adopt moderation in the consumption of these additives and to continue studying their long-term biological effects before trusting them as a completely safe alternative to sugar
