A long-term trial suggests that replacing sugar with low-calorie sweeteners can enhance beneficial gut microbes and help sustain weight loss. The study, involving over 300 overweight Europeans, found participants using sweeteners maintained greater weight reduction after 10 months. However, experts caution that the microbiome changes might stem from weight loss itself.
Concerns about low-calorie sweeteners have grown in recent years, with studies linking them to increased hunger, elevated blood sugar, and higher risks of heart attacks and strokes. In 2023, the World Health Organization advised against their use for weight control due to insufficient long-term evidence.
Ellen Blaak at Maastricht University in the Netherlands led a study to address this gap. Researchers recruited 341 overweight or obese adults across Europe and placed them on a low-calorie diet for two months, resulting in an average 10-kilogram weight loss. Participants then shifted to a healthy diet with less than 10 percent of calories from sugar for weight maintenance.
Of the group, 171 avoided sweeteners entirely, while the remaining 170 were encouraged to substitute sugary foods and drinks with options using at least 16 varieties of low-calorie sweeteners, allowing individual choice in types and amounts.
After 10 months, the sweetener group sustained a 1.6-kilogram greater weight loss compared to the non-sweetener group. They also showed higher levels of gut bacteria producing short-chain fatty acids, compounds that prior research links to blood sugar regulation, heart health support, and weight management.
“This shows that at least replacing sugars in the diet with non-caloric sweeteners may help you in maintaining body weight,” says Blaak. She attributes differences from prior studies to the trial's longer duration, its focus on sweeteners within a healthy diet, and the use of multiple varieties together.
Eran Elinav at the Weizmann Institute of Science in Israel notes that microbiome understanding remains nascent, making it hard to gauge health impacts. It is unclear whether bacterial shifts resulted from the sweeteners, the weight loss, or both.
The findings appear in Nature Metabolism (DOI: 10.1038/s42255-025-01381-z).