Study Reveals New Health Risks of Artificial Sweeteners

Artificial sweeteners, long considered a safe alternative to sugar for those looking to reduce calorie intake, may have more complex effects on the body than previously thought. Recent research suggests that these substances could influence metabolism and gut health in ways that are not yet fully understood.

The study, published in Current Atherosclerosis Reports, looked at evidence from both randomized clinical trials and large observational studies to evaluate how non-nutritive sweeteners affect cardiometabolic health. These include artificial sweeteners as well as other low-calorie alternatives.

Researchers from Tufts University’s Food is Medicine Institute reviewed 21 randomized clinical trials involving adults and conducted a meta-analysis of their findings. According to Meng Wang, a research assistant professor at the institute and the first author of the study, “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.”

When compared with noncaloric controls such as water or placebo, consumption of sweeteners 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. These findings challenge the assumption that artificial sweeteners are metabolically inert—meaning they pass through the body without affecting biological processes.

Non-nutritive sweeteners are commonly found in diet soft drinks, sugar-free chewing gum, protein bars, and other products marketed as lower-sugar alternatives. Researchers say there is growing evidence that these compounds may directly impact metabolism.

However, Bryan Quoc Le, a food scientist and author of 150 Food Science Questions Answered, cautioned that the 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 said.

Le explained that artificial sweeteners are a broad category that includes both synthetic products and naturally derived alternatives such as stevia and monk fruit. Many of the studies highlighted in the review focus primarily on synthetic high-intensity sweeteners like aspartame, saccharin, and acesulfame potassium. He added 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. These sweeteners work differently from traditional artificial ones 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 contact with these microorganisms.

According to the review, evidence from one of the studies 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 sourced products that have been consumed for centuries—might influence 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.

Reference
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.