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One of the largest artificial sweetener studies has just been released, helping to answer important questions that previous research left open. The World Health Organization issued a conditional recommendation against artificial sweeteners for weight control or to reduce the risk of developing diabetes [1]. Yet many people who struggle to give up sugary drinks want to know whether zero-sugar alternatives are actually a safer option—or whether switching could come with its own set of risks.
Previous research on this question has been largely observational, making it difficult to separate cause from effect. Now, a major new randomised controlled trial—the SWEET study—directly compared sugary drinks to artificially sweetened drinks in a rigorous, year-long design. The study also examined how each type of drink affects the gut microbiome, shedding new light on the mechanisms behind earlier concerns and providing the clearest evidence yet on the question of safety and efficacy.
The puzzle
The logic for choosing artificially sweetened drinks seems straightforward: replacing high-calorie sugary beverages with low- or no-calorie alternatives should cut overall calorie intake and help with weight management.
However, some observational studies paint a surprising picture: people who consume more artificial sweeteners tend to have a higher body weight. One study found that artificial sweetener intake was generally associated with higher BMI, body weight, and waist circumference—and was linked to a stronger increase in these metrics over a 25-year period [2].
After reviewing multiple observational studies showing the same pattern, the authors cautioned against replacing natural sugars with artificial ones:
"Coupled with previous evidence, alternatives to national recommendations to replace added sugar with [artificial sweeteners] should be considered since both may have health consequences." [2]
Several mechanisms have been proposed to explain these findings:
- Microbiome disruption: These substances may disrupt the gut microbiome, which has profound implications for metabolic processes, including glucose metabolism.
- Insulin signaling interference: Certain artificial sweeteners may alter insulin signaling by disrupting insulin receptor sensitivity or glucose transporter expression [3].
- Psychological compensation: Consuming artificially sweetened foods may trigger a feeling of having "saved" calories, leading to overindulgence elsewhere.
- Reverse causality: People struggling with weight may be more likely to use artificial sweeteners in the first place.
Observational data has also surfaced troubling associations between artificial sweeteners and several health conditions. One large cohort analysis found a potential direct association between higher artificial sweetener consumption—especially aspartame, acesulfame potassium, and sucralose—and increased cardiovascular risk [4].
The study
Observational studies alone cannot establish causation. Randomised controlled trials (RCTs) are needed to disentangle what is really going on. The SWEET study was designed to do exactly this [1].
The aim was to investigate the effects of artificial sweeteners and sweetness enhancers (S&SEs) in both food and drink on weight, cardiometabolic risk factors, and the gut microbiome in individuals with overweight or obesity. While the study enrolled both children and adults, the analysis below focuses on the adult participants, as the number of children enrolled was small and dietary compliance was a challenge in that group.
Study Design
- Participants: 341 adults and 38 children (adult results are the focus)
- Phase 1: 2-month calorie-restricted diet targeting a 5% weight loss
- Phase 2: 10-month healthy ad libitum diet with <10% of energy from sugars
- Groups:
- One group replaced sugar-rich products with S&SE alternatives (e.g. aspartame, erythritol, xylitol)
- The other group consumed sugar as usual
The primary outcomes were changes in body weight and gut microbiota composition after one year. Secondary outcomes included cardiometabolic markers such as blood pressure and fasting glucose.
Results
After the 2-month weight-loss phase, the artificial sweetener group maintained 1.6 kg (around 3.5 pounds) more weight loss than the sugar group at the end of the year [1].
That is a real and meaningful difference—and it may be an underestimate of the true effect. In the subset of the S&SE group with the highest dietary compliance, the weight difference was 3.8 kg [1].
"The highest level of dietary compliance resulted in the largest weight difference (3.8 kg), suggesting that more consistent adherence could further amplify the observed differences." [1]
Gut microbiome findings
One major concern raised by critics of artificial sweeteners is their potential effect on the gut microbiome—the trillions of bacteria that influence metabolism, immunity, and even appetite. The SWEET study directly measured this. Researchers confirmed that artificial sweeteners do impact the gut microbiome. They observed differences in 46 distinct bacterial taxa between the two groups over the course of the year-long study [1].
Notably, the artificial sweetener group showed an increase in short-chain fatty acid (SCFA)-producing bacteria [1].
Why does that matter?
Short-chain fatty acids (SCFAs) are associated with several beneficial health effects, including:
- Increased energy expenditure via enhanced lipid oxidation
- Improved satiety through gut–brain signaling
- Anti-inflammatory effects
- Protection against:
- Obesity
- Type 2 diabetes
- Cancer
- Cardiovascular disease [5]
However, the artificial sweetener group also experienced a shift toward more methane-producing bacteria, particularly Methanolobus, which may explain the increased gastrointestinal discomfort reported by some participants [1].
"Increased CH₄ may contribute to gastrointestinal symptoms by inhibiting motility, potentially causing slow-transit constipation and abdominal pain." [1]
The science of the gut microbiome is still evolving. While the SWEET study found significant microbial changes, the long-term implications are not yet fully understood. A one-year study is substantial, but longer follow-up is needed before definitive conclusions can be drawn.
Safety
It is worth highlighting what was not found in the SWEET study.
Despite prior concerns from observational research, this randomised controlled trial found no adverse effects in the artificial sweetener group on:
- Fasting glucose
- Insulin levels
- LDL cholesterol
- Blood pressure
- Risk markers for type 2 diabetes or cardiovascular disease [1]
The study found no evidence of the harmful metabolic impacts suggested by observational data. Some of the microbiome changes even hint at potential benefits.
The trial was not industry-funded. It was supported by the European Union's Horizon 2020 programme [1].
"The trial is funded by the Horizon 2020 programme: 'Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability' (SWEET; grant no. 774293)" [1]
However, 5 researchers involved had some connections to food and beverage companies:
"A.R. has received honoraria from Nestlé, Unilever and the International Sweeteners Association and is currently employed by Novo Nordisk. J.C.G.H. and J.H. have received project funds from the American Beverage Association. T.L. works for a company (NetUnion) that has no conflict of interest. C.E.H.'s research centre provides consultancy to organizations supported by food and drink companies. The remaining authors declare no competing interests." [1]
Additionally, the trial was conducted during the COVID-19 pandemic, which led to:
- Disrupted participant follow-up
- Logistical challenges
- A 40% dropout rate (higher than the expected 30%), reducing statistical power [1]
Recommendations
While some questions remain, this and other randomised controlled trials collectively suggest:
- Artificial sweeteners can modestly help with weight loss maintenance
- They do not appear to increase metabolic risk, despite earlier concerns
- They may even induce positive microbiome changes
These findings align with a 2023 meta-analysis of six RCTs involving 1,729 participants. That analysis found that switching from sugar-sweetened beverages to artificially sweetened or unsweetened drinks led to an average 1 kg (2.2 lbs) long-term weight reduction [6].
Even more surprisingly, another RCT found that participants drinking artificially sweetened beverages maintained greater weight loss than those drinking water [7].
At 1 year:
- Water group: 2.45 kg weight loss
- Artificial sweetener group: 6.21 kg weight loss
- (P < 0.001) [7]
Researchers tracked activity levels and found no differences between groups. They speculated that avoiding sweetness in drinks (as in the water group) may have driven participants to seek sweetness from other foods, increasing total calorie intake [7].
Final Verdict
There are still open questions about long-term safety, but the direction of the current evidence is clear:
- Artificially sweetened drinks are less harmful than sugary drinks
- They may even be preferable to water in certain weight-loss scenarios
- No significant safety issues were observed over one year
For people who struggle to reduce consumption of sugary drinks, artificially sweetened alternatives represent a viable and potentially beneficial option based on current RCT evidence. However, those who experience gastrointestinal discomfort when consuming them may wish to limit intake or consult a healthcare professional.
References
- https://www.nature.com/articles/s42255-025-01381-z
- https://www.nature.com/articles/s41366-023-01336-y
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11501561/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9449855/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9498509/
- https://pubmed.ncbi.nlm.nih.gov/37880814/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4744961/
