Obesity rates continue to climb in nearly every region of the world, raising the risks of type 2 diabetes, liver disease, stroke and heart failure across generations. Diets loaded with saturated fat and added sugars remain a major driver of that crisis, prompting global guidelines to urge people to curb free sugars to 10% of daily energy at most, and ideally to half that. But replacing sugar is easier said than done. For decades, scientists, doctors and food regulators have debated whether non-sugar sweeteners truly help — or whether they silently backfire over time, promoting weight gain or metabolic distress.
A new one-year, multi-country randomized controlled trial published in Nature Metabolism offers one of the most detailed answers to date. The SWEET study, led by researchers in Maastricht and Copenhagen, found that adults who replaced sugar with commercially available sweeteners, while following a healthy reduced-sugar diet, were better able to maintain weight loss across a full year. Their gut microbiota also shifted in a direction consistent with increased production of short-chain fatty acids — a change widely linked to beneficial metabolic effects. Crucially, no harmful cardiometabolic signals emerged over 12 months.
Inside a Rare, Long-Term Human Trial of Real-World Eating
The trial was unusually large and pragmatic in design. A total of 341 adults with overweight or obesity — plus 38 children from the same households — were recruited at four European sites. Adults first underwent a two-month low-energy diet until they lost at least 5% of their body weight, simulating the real-world situation where successful weight loss has already occurred and the challenge then becomes keeping it off. After that, for 10 months, households were randomly assigned to one of two paths: either avoid sweeteners entirely and consume only sugar in moderation, or use sweeteners and sweetness enhancers in place of sugar-rich foods and drinks while still keeping total sugar under 10% of energy.
No single sweetener was tested. Participants freely chose from what is currently on the market — the same products that millions of consumers reach for. These included high-potency sweeteners like aspartame, acesulfame-K, stevia glycosides and saccharin, as well as sugar alcohols like erythritol and xylitol, and slowly digestible sweet carbohydrates such as isomaltulose and sucromalt. This design answered not a laboratory question but the public-health question: what happens when ordinary people swap sugar for sweetener-containing foods over a full year as part of a healthier diet they actually live with?
Sweeteners Helped Stabilize Lost Weight
Adults using sweeteners held on to more of their weight loss than those avoiding them. The difference, modest in absolute terms but consistent across time, averaged 1.6 kilograms after one year in intention-to-treat analysis. When researchers looked only at people who consistently followed the protocol, the gap widened to nearly 4 kilograms — a meaningful margin in clinical, metabolic and psychological terms. Maintaining even small fractions of weight loss is notoriously difficult, with many people regaining most of it within a year. Anything that helps preserve progress matters.
Sugar intake dropped further in the sweetener group, as expected. They cut an extra 12 grams of sugar per day on average, and a larger share of their total energy no longer came from sugar. Simply put, they replaced sugar with something less caloric without losing the sweet taste that makes foods and beverages pleasant and sustainable.
The Gut Microbiome Shifted — and in a Direction Linked to Metabolic Benefit
The microbiota arm of the trial looked at 137 adults with sequencing data across the year. The gut ecosystems of participants did not merely drift over time; they changed in group-specific ways. Forty-six microbial taxa showed different trajectories between groups. The sweetener group developed higher relative abundance of bacteria associated with production of short-chain fatty acids — compounds such as butyrate that help sustain the intestinal lining, reduce inflammation and support metabolic health. There was also an increase in methane-producing microbes, suggesting a shift in fermentation dynamics.
Only three taxa declined more in the sweetener group than in the sugar group, and the broader functional predictions suggested enhanced fermentation and vitamin-related pathways without concerning signals in lipid remodeling or cardiometabolic pathways. This matters because critics have long suggested that sweeteners might “damage” the microbiome or trigger unhealthy dysbiosis. This year-long, controlled evidence instead points toward adaptive, SCFA-linked restructuring under sugar-reduced conditions.
Safety and Side Effects
Gastrointestinal symptoms such as abdominal cramping, loose stools and gas were more common among people in the sweetener group — not surprising given the known effects of polyols and certain fibers. Serious adverse events were rare in both groups and not attributed to the intervention. Cardiometabolic markers such as cholesterol improved modestly at six months in favor of the sweetener group, though these differences faded by one year. Children in the study maintained or reduced weight for age regardless of group, and showed no differential effects.
Overall, the profile that emerged was one of benefit on weight maintenance without metabolic harm — with GI discomfort as the main trade-off for some participants.
A Study That Shifts the Frame of the Debate
For years, the literature around sweeteners has been split between observational studies that hint at long-term harm and short-term trials showing neutral or beneficial outcomes. Observational studies are vulnerable to reverse causation — people who already struggle with weight may switch to diet products, making sweeteners look guilty by association. Short trials are too brief to reveal real-world maintenance effects. This study is rare in overcoming those gaps: it is randomized, controlled, transnational, one year in duration and embedded in realistic dietary choices.
The takeaway is not that sweeteners alone cause weight loss, nor that they are nutrition saviours. The core message is narrower and more defensible: when people who have already lost weight try to keep it off within a healthy, sugar-reduced diet, using sweetened alternatives instead of returning to sugary foods appears to help — and does not introduce detectable cardiometabolic harm across a year.
What This Means for Households Trying to Eat Better
People do not relapse because they stop knowing what is healthy; they relapse because pleasure, habit and sustainability overwhelm intention. Most people find abrupt removal of sweetness intolerable, and diets built on deprivation tend to fail. The SWEET study suggests that replacing rather than eliminating sweetness can help freeze the gains of weight loss, making realistic diets stay realistic over time.
This does not give license to binge on “diet” foods, nor does it guarantee outcomes for every individual. But it weakens the claim that long-term sweetener intake in the context of a healthier diet is risky or useless. It points to a pragmatic middle road: keep sugars low, use sweeteners as tools rather than indulgences, and anchor eating patterns around whole, nutrient-dense foods rather than caloric sugar loads.
The Next Questions
The trial leaves open key frontiers. Would benefits persist past one year? Do different sweeteners produce distinct microbiome or metabolic effects if isolated? How do genetics, baseline microbiota or behavioral traits shape who responds best? Could the microbiota changes partly mediate the improved weight maintenance, or are they parallel consequences of dietary substitution? Ongoing mechanistic work will be needed.
For now, however, the study moves the conversation. It suggests that long-term fears of sweeteners in weight-managed adults may be overstated, and that the dominant nutritional hazard is still excess sugar itself. In a world where sugar is easy, cheap and omnipresent, and where regaining lost weight is the norm, having a safe, usable alternative matters — not as a cure, but as a stabilizer. In that sense, the science now supports what a great many people were already doing out of practical intuition: swapping sugar for sweetness without the calories can help hold the line.
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
