Results from the SWEET Randomised Controlled Trial
Highlights:
- A new landmark clinical trial shows that incorporating low/no calorie sweeteners into a healthy, low-sugar diet can help people with overweight or obesity in keeping the lost weight off over one year.
- The study also found beneficial shifts in gut microbiota composition associated with improved metabolic function, which may help explain the better weight maintenance in the sweeteners group, with no signs of gut dysbiosis.
- The findings contrast with the World Health Organization’s (WHO) 2023 conditional recommendation against using non-sugar sweeteners for weight control.
Low/no calorie sweeteners (LNCS) have long sparked debate in nutrition science. Are they helpful tools for managing weight, or do they hinder weight loss? The newly published SWEET study, one of the largest and longest clinical trials to date, provides robust new data on how LNCS affect weight maintenance, gut microbiota, and cardiometabolic health..
Inside the SWEET study
The SWEET project is an EU Horizon 2020 research programme designed to investigate the long-term safety and effects of sweeteners and sweetness enhancers. As part of the project, a long-term, 1-year randomised controlled trial (RCT) studied the impact of LNCS use in weight management, gut microbiota, and cardiometabolic risk markers in 341 adults and 38 children with overweight or obesity from Denmark, Greece, Spain, and the Netherlands.
In the first phase, adults followed an eight-week low-energy diet and lost an average of 10 kilograms. Those who achieved this weight loss entered a ten-month weight maintenance phase and were randomised to one of two groups: the LNCS group who replaced sugar-rich foods and drinks with alternatives containing sweeteners such as aspartame, sucralose, and stevia as part of a healthy diet; and the control group who were instructed to avoid LNCS but continued to consume a healthy, low-sugar diet, with less than 10% of total energy intake from sugars.
Low/no calorie sweeteners can help sustain weight loss over the long term
After one year, both groups maintained more than half of their initial weight loss, but those using LNCS achieved better results. The LNCS group maintained an average of 7.2kg of weight loss compared with 5.6kg in the control group, a difference of 1.6 kilograms in favour of the sweetener group. Among those with the highest level of dietary compliance, the weight difference reached 3.8 kilograms, suggesting that consistent substitution of sugar with sweeteners may produce even greater benefits.
Importantly, participants in the LNCS group reduced their sugar intake by roughly twice as much as those in the control group, confirming that LNCS were being used in their intended purpose of use, meaning as replacements for sugar rather than as additional sources of sweetness.
The smaller cohort of 38 children also showed improved BMI-for-age z-scores in both groups, but there was no significant difference between LNCS and control groups. Because the number of participating children was small, these results were considered exploratory.
Notably, LNCS have also shown modest benefits in reducing liver fat, fat mass, and body weight, particularly when they replace sugars in beverages.11 In addition, it is well established that, compared to sugars, LNCS cause a lower blood glucose rise after consumption.12 This evidence reinforces that LNCS, when used as sugar substitutes, may confer modest advantages in cardiometabolic risk reduction.3
Gut Microbiome: A Key Piece of the Puzzle
The study also explored how sweeteners affect the gut microbiota in a subgroup of 137 adults. Researchers observed distinct changes in microbial composition between the groups, with participants in the LNCS group showing a higher abundance of short-chain fatty acid–producing bacteria, as well as methane-producing taxa. These shifts are associated with improved metabolic regulation and may help explain why the LNCS group maintained more of their weight loss over one year.
No signs of dysbiosis or harmful microbial patterns were detected. Interestingly, the researchers found that baseline microbiota profiles could predict which individuals would respond best to the intervention, particularly in terms of avoiding weight regain and changes in HbA1c levels. This finding suggests that gut bacteria may influence how different people respond to sweetener use, opening the door for more personalised dietary approaches.
Cardiometabolic Outcomes
No significant differences were seen between groups in key diabetes markers like glucose, insulin, and HbA1c. At six months, the LNCS group showed reductions in total, LDL-, and HDL-cholesterol levels, though these changes were not sustained at 12 months, likely due to fewer participants completing the full follow-up.
A major European study challenges WHO’s guideline on non-sugar sweeteners
The findings, published in Nature Metabolism in October 2025, stand in sharp contrast to the World Health Organization’s (WHO) 2023 conditional recommendation suggesting against using non-sugar sweeteners for weight control. Unlike the low-certainty observational evidence that informed the WHO guideline, the one-year SWEET trial demonstrated that incorporating LNCS into a healthy, low-sugar diet supports weight loss maintenance and favourable gut microbiota changes without adverse effects on cardiometabolic health.
Implications for health and policy
The SWEET study delivers one of the strongest pieces of evidence yet that LNCS can safely support long-term weight management as part of a balanced, low-sugar diet. By showing sustained weight loss, gut microbiota benefits, and no harm to cardiometabolic health, it challenges lingering concerns from observational studies and policy debates.
In a commentary, Dr. Sarah Schmitz and Dr. Louis Aronne emphasised the importance of the trial’s findings by addressing one of the hardest challenges in obesity management: keeping the weight off over the long term. By including a wide variety of real-world foods and drinks containing sweeteners, and recruiting participants from multiple European countries, the SWEET study better reflects everyday consumption patterns and enhances the generalisability of its results across different dietary and cultural settings.
Taken together with previous clinical research, these findings strengthen the overall body of evidence indicating that low/no calorie sweeteners can be a valuabe tool in sugar reduction and long-term weight management when used as substitutes for added sugars in the context of an overall healthy diet.