Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study

Author(s): Pang MD, Kjølbæk L, Bastings JJAJ, Andersen SSH, Umanets A, Sost MM, Navas-Carretero S, Reppas K, Finlayson G, Hodgkins CE, Del Álamo M, Lam T, Moshoyiannis H, Feskens EJM, Adam TCM, Goossens GH, Halford JCG, Harrold JA, Manios Y, Martinez JA, Blaak EE, Raben A.
Publication name: Nat Metab. 2025 Oct 7. https://doi.org/10.1038/s42255-025-01381-z (open access)
Publication year: 2025

Abstract

Consumption of sweeteners and sweetness enhancers (S&SEs) is a popular strategy to reduce sugar intake, but the role of S&SEs in body weight regulation and gut microbiota composition remains debated. Here, we show that S&SEs in a healthy diet support weight loss maintenance and beneficial gut microbiota shifts in adults with overweight or obesity. In this multi-centre, randomized, controlled trial, we included 341 adults and 38 children with overweight or obesity. Adults followed a 2-month low-energy diet for ≥5% weight loss, followed by a 10-month healthy ad libitum diet with <10% energy from sugars. One group replaced sugar-rich products with S&SE products (S&SEs group), while the other did not (sugar group). Primary outcomes included changes in body weight and gut microbiota composition at 1 year. Secondary outcomes included changes in cardiometabolic parameters. The S&SEs group, compared to the sugar group, maintained greater weight loss at 1 year (1.6 ± 0.7 kg, P = 0.029) and exhibited distinct gut microbiota shifts, with increased short-chain fatty acid and methane-producing taxa (q ≤ 0.05). No significant differences were observed in cardiometabolic markers or in children. Overall, our findings indicate that prolonged consumption of S&SEs in a healthy diet is a safe strategy for obesity management.

Summary

The SWEET study, a large multi-centre European clinical trial, has found that using low/no calorie sweeteners (LNCS) as part of a healthy, reduced-sugar diet can help people with overweight or obesity maintain more efficiently their weight loss over a year without harming gut microbiota or cardiometabolic health.

The study followed 341 adults across four European countries who first lost weight on a low-calorie diet and then entered a year-long maintenance phase. Those who replaced sugar with LNCS kept off about 1.6 kilograms more than those who avoided sweeteners, with the most consistent users maintaining 3.8 kilograms more of the initial weight loss.

Gut microbiome analysis revealed positive changes in gut microbiota composition in the LNCS group, with increases in short-chain fatty acid–producing species linked to improved metabolic function. These shifts may have contributed to better weight maintenance in the group that used sweeteners. No signs of harm or gut dysbiosis were observed, and cardiometabolic markers such as glucose, cholesterol, and liver fat remained stable across groups.

Overall, the SWEET study adds high-quality, long-term evidence that LNCS can be a useful part of sugar-reduction strategies and support long-term weight management challenging earlier guidance that discouraged their use.

 

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