Artificial sweeteners may be affecting the body in unexpected ways, with new evidence linking them to altered metabolism and gut health
The study, published in Current Atherosclerosis Reports, examined evidence from both randomized clinical trials and large observational studies to assess how non-nutritive sweeteners—including artificial and other low-calorie sweeteners—affect cardiometabolic health
Researchers from Tufts University’s Food is Medicine Institute reviewed 21 randomized clinical trials involving adults and conducted a meta-analysis of the findings
“What makes our analysis notable is that, by focusing on noncaloric comparators, we better isolated the direct physiological effects of the sweeteners themselves, not the calories they replace,” said first author Meng Wang, a research assistant professor at the institute
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When compared with noncaloric controls such as water or placebo, sweetener consumption was associated with higher fasting insulin levels and higher HbA1c, a marker used to measure long-term blood sugar control. The analysis also found a trend toward worsening insulin sensitivity
The findings challenge the long-held assumption that artificial sweeteners are metabolically inert—meaning they pass through the body without affecting biological processes
Non-nutritive sweeteners are widely used in products such as diet soft drinks, sugar-free chewing gum, protein bars and other foods marketed as lower-sugar alternatives
Researchers say there is growing evidence that these compounds may exert direct effects on metabolism
However, Bryan Quoc Le, a food scientist, food industry consultant and author of 150 Food Science Questions Answered, cautioned that the established benefits of reducing sugar intake should not be overlooked
“We know that long-term, high consumption of sugars leads to many chronic conditions, and so the benefits of switching out sugar are known and well-established,” he told Newsweek
Le explained that artificial sweeteners are a broad category that includes both synthetic products and naturally derived alternatives such as ste
Many of the studies highlighted in the review focus primarily on synthetic high-intensity sweeteners such as aspartame, saccharin and acesulfame potassium, Le said, adding that more research is needed to understand how different sweeteners affect the body at the doses typically consumed by the general population
Le also pointed to growing interest in newer protein-based sweeteners being developed by the food industry, which work differently from traditional artificial sweeteners and may not produce the same biological effects
One possible explanation involves the gut microbiome, the vast community of microbes that lives in the digestive tract and plays an important role in digestion, immunity and metabolic health
Artificial and low-calorie sweeteners typically pass through the gut, where they come into direct contact with these microorganisms
According to the review, evidence from one of the studies examined showed that certain low-calorie sweeteners altered both the composition and function of gut bacteria
Researchers used detailed microbiome profiling and experiments involving the transfer of microbes from humans to mice to help identify these changes
Whether these microbiome changes ultimately translate into meaningful long-term health consequences remains unclear, Le said
“This is still a matter of debate, especially factoring in the complexity of the gut microbiome, variations between individuals, and different types of non-nutritive sweeteners at various concentrations over time,” he added
Le said that scientists are still working to understand how different sweeteners—including naturally ence the gut microbiome in different ways
The authors also reviewed observational studies tracking health outcomes in large populations
These generally found links between consuming non-nutritive sweeteners and a higher risk of developing cardiometabolic diseases
However, the researchers cautioned that such studies cannot prove cause and effect because people already at greater risk of these conditions may be more likely to choose low-calorie sweeteners
Another challenge is that sweeteners are often studied as a single group, despite important differences between individual products
The researchers noted that distinct sweeteners may have different biological effects, meaning some could be more problematic than others
Experts say this distinction is important because the category includes both synthetic and naturally derived sweeteners, which may not affect the body in the same way
Wang, M., Wu, O.Y., Wallen, O. et al. Artificial and Other Non-Nutritive Sweeteners, the Microbiome, and Cardiometabolic Health. Curr Atheroscler Rep 28, 65 (2026). https://doi.org/10.1007/s11883-026-01429-9
