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Researchers at Maastricht University and the University of Copenhagen report that incorporating sweeteners and sweetness enhancers within a healthy, sugar-reduced diet supported one-year weight loss maintenance and coincided with microbiota shifts toward short-chain fatty acid and methane-producing taxa in adults with overweight or obesity.
Global rises in overweight and obesity continue to elevate the risk for type 2 diabetes and cardiovascular disease. Dietary patterns rich in saturated fat and added sugar have been proposed as key contributors, and guidance from the World Health Organization recommends keeping free sugars under 10% of energy, preferably under 5%.
Debate over long-term health effects of non-sugar sweeteners has persisted, with observational reports raising concerns of increased weight gain and short-term trials often showing neutral or beneficial outcomes.
In the study, "Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study," published in Nature Metabolism, researchers conducted a multi-center randomized controlled trial to test whether replacing sugar-rich products with sweetener-containing options aids weight loss maintenance and alters gut microbiota over one year.
Participants included 341 adults and 38 children recruited across four European sites in Athens, Copenhagen, Maastricht and Pamplona. Enrollment spanned June 2020 to October 2021, with clinical investigation days at baseline, after a 2-month weight loss or weight stability phase, mid-maintenance and 12 months.
A microbiota subgroup comprised 137 adults stratified by age, sex and center. Completion at one year fell to 203 adults and 22 children, with dropouts frequently linked to pandemic-related disruptions.
Adults first followed a two-month low-energy diet targeting at least 5% weight loss, then transitioned to a 10-month healthy ad libitum diet capped at less than 10% of energy from sugars. Randomization allocated households to either a sugar group that avoided sweeteners or a sweeteners and sweetness enhancers (S&SEs) group that replaced sugar-rich foods and drinks with commercially available S&SE products.
As participants were free to choose which non-sugar alternative they preferred through product choices, no specific evaluation of a sweetener or sweetness enhancers was made.
Examples of what was commercially available include high-potency sweeteners such as aspartame, acesulfame-K, saccharin, thaumatin, neotame and stevia glycosides, along with polyols (lower calorie sugar alcohols) like erythritol, sorbitol, mannitol, isomalt, maltitol, lactitol and xylitol. Slowly digestible carbohydrates listed include sucromalt and isomaltulose, and sweet fibers or oligosaccharides include inulin-type oligosaccharides.
Primary outcomes covered one-year changes in body weight and gut microbiota composition in adults. Secondary outcomes included cardiometabolic markers, intrahepatic lipid in a Maastricht subgroup, gastrointestinal symptoms, adverse events and children's BMI-for-age z-score.
Adults maintained substantial weight loss across 12 months, with intention-to-treat analysis showing a larger loss in the S&SEs group than the sugar group by 1.6 ± 0.7 kg at one year.
Time-point comparisons showed lower body weight in the S&SEs group at months four, six, nine and 12, with differences ranging from 1.0 to 2.1 kg, all with significant P values.
Per-protocol findings scaled with compliance, culminating in a 3.7 ± 1.4 kg advantage for those meeting all four compliance criteria. Sugar intake fell more in the S&SEs group, including a 12.0 ± 5.5 g per day greater reduction in total sugar and a 2.4 ± 0.9 percentage-point greater drop in energy from sugar.
Microbiota composition shifted over time in a group-dependent manner, with a significant interaction between time and intervention by multiple distance metrics.
A total of 46 taxa displayed differential trends between groups, with the S&SEs group showing increased relative abundance of multiple short-chain fatty acid-associated genera, including Megasphaera, Megamonas, Dialister, Catenibacterium, Eubacterium eligens, Prevotella, Alloprevotella, Porphyromonas, Butyricimonas, Oscillospira, Eubacterium siraeum and CAG:56. Methanolobus, a methane-producing genus, also rose in the S&SEs group.
Three taxa decreased in the S&SEs group relative to the sugar group, including Saccharimonadales, Candidatus Competibacter and Clostridium sensu stricto 1.
Pathway predictions indicated upregulation of methanogenesis and several fermentation pathways in the S&SEs group, along with signals for degradation of aromatic compounds and l-arabinose, vitamin and cofactor biosynthesis, and reductions in photosynthesis-related and lipid remodeling pathways.
Six-month changes favored the S&SEs group for BMI, total cholesterol, LDL-C, HDL-C and non-HDL-C, with differences not persisting to 12 months except for a greater reduction in hip circumference.
Cardiometabolic markers did not differ between groups at 12 months, and intrahepatic lipid changes in the Maastricht subset were similar between groups. Children experienced a decrease in BMI-for-age z-score over the year with no between-group differences and no other significant changes.
Adverse events during weight maintenance were more frequent in the S&SEs group, including a higher number of gastrointestinal symptoms such as abdominal pain or cramps, loose stools and excess intestinal gas, with reported P values indicating significance. Serious adverse events were uncommon across groups and not attributed to the intervention. Both groups showed firmer stools after weight loss.
The authors conclude that prolonged use of sweeteners and sweetness enhancers within a healthy, sugar-reduced diet is a safe strategy for adults with overweight or obesity aiming to maintain weight loss, accompanied by shifts toward short-chain fatty acid-linked taxa and methanogenesis pathways without adverse cardiometabolic signals over one year. The findings in children show no between-group differences.
Written for you by our author Justin Jackson, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.
More information: Michelle D. Pang et al, Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study, Nature Metabolism (2025). DOI: 10.1038/s42255-025-01381-z
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Citation: A year of dieting with non-sugar sweeteners shows weight loss can stay lost (2025, October 22) retrieved 7 December 2025 from https://medicalxpress.com/news/2025-10-year-dieting-sugar-sweeteners-weight.html
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