One of the largest artificial sweetener studies has just been released.
It helps answer important questions because previous studies have raised concerns about the potential risks of artificial sweeteners. The World Health Organization even issued a conditional recommendation against them for weight control or to reduce the risk of developing diabetes [1].
But I see patients at the clinic who are struggling to kick the habit of drinking sugary drinks. They often ask me if they should switch to a zero-sugar option with artificial sweeteners instead. And it’s been a tricky question to answer.
Now, with this new study that directly compared sugary drinks to artificially sweetened drinks, I can give my patients a clear answer. Plus, the study uncovered some interesting effects on the gut microbiome from artificial sweeteners, which shed some light on the risk conversation.
Table of Contents
The puzzle
So why might we consider artificially sweetened drinks? The logic seems straightforward. Consuming low- or no-calorie drinks instead of their sugary counterparts should mean a substantial cut in calorie consumption. And that should help us lose, or at least manage, weight.
But some observational studies paint a surprising picture, where people who consume more artificial sweeteners tend to have a higher body weight. One study, for example, found that artificial sweetener intake was generally associated with a higher BMI, body weight, and waist circumference. It was also linked to a stronger increase in these metrics over a 25-year period [2].
In their discussion, the authors reviewed several other observational studies, which revealed the same basic pattern. On the strength of their findings and existing research, they cautioned against the strategy of 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]
What explains these findings? Several ideas have been proposed:
- 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.
Moreover, observational data has surfaced troubling associations between artificial sweeteners and several health problems, including type 2 diabetes, heart disease, and cancer. 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 don’t give us a very clear picture. We want randomized controlled trials (RCTs) to disentangle what’s really going on. And the new SWEET study uncovered some important new data [1].
The aim of the study 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 included children and adults, we’ll focus on the adults, as the number of children enrolled was small and compliance was a challenge.
Study Design
- Participants: 341 adults and 38 children (we're focusing on adults)
-
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 like 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’s not a huge amount, but it’s a real and meaningful difference.
And it may be an underestimate of the true effect. In a 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
So what happened with the gut microbiome?
The SWEET study found that artificial sweeteners did impact the gut microbiome. There were differences in 46 distinct bacterial taxa between the groups over the course of the study [1].
Importantly, the artificial sweetener group showed an increase in short-chain fatty acid (SCFA)-producing bacteria [1].
Why does that matter?
SCFAs promote several beneficial health effects, including:
- Increased energy expenditure via enhanced lipid oxidation
- Improved satiety through gut–brain signaling
- Anti-inflammatory effects
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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 participants [1].
“Increased CH₄ may contribute to gastrointestinal symptoms by inhibiting motility, potentially causing slow-transit constipation and abdominal pain.” [1]
Our understanding of the gut microbiome is still developing. While the study found microbial changes, the long-term implications aren’t fully known. A one-year study is significant, but longer studies are needed.
Safety
It’s also worth highlighting what wasn’t found in the SWEET study.
Despite prior concerns from observational research, this randomized 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]
This is important. The study found no evidence of the harmful impacts suggested by observational data. And some of the microbiome changes even hint at potential benefits.
The trial was also 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 did have 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]
Also, 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
So what’s the takeaway?
While some questions remain, this and other randomized controlled trials suggest:
- Artificial sweeteners can modestly help with weight loss maintenance
- They don’t appear to increase metabolic risk, despite earlier concerns
-
They may even induce positive microbiome changes
These findings line up with a 2023 meta-analysis of six RCTs with 1,729 participants. That study 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. They speculated that avoiding sweetness in drinks (as in the water group) may have driven people to seek sweetness from other foods, increasing total calorie intake [7].
Final Verdict
There are still 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
So for patients who struggle to cut down on sugary drinks, artificially sweetened alternatives are a viable and potentially beneficial option.
References
1. https://www.nature.com/articles/s42255-025-01381-z
2. https://www.nature.com/articles/s41366-023-01336-y
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC11501561/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC9449855/
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC9498509/
6. https://pubmed.ncbi.nlm.nih.gov/37880814/
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC4744961/
