A new Tufts University review finds growing evidence that artificial and other low-calorie sweeteners may disrupt gut bacteria and impair blood sugar control.
Researchers say common sugar substitutes were linked to higher fasting insulin and HbA1c levels in an analysis of 21 randomized clinical trials.
Experts stress the findings do not prove sugar substitutes are unsafe but suggest more research is needed into their long-term metabolic effects.
For decades, artificial sweeteners have been marketed as a healthier alternative to sugar, offering sweetness without the calories. But a growing body of research suggests those substitutes may not be as metabolically harmless as once believed.
A new review and meta-analysis by researchers at Tufts University's Food is Medicine Institute concludes that non-nutritive sweeteners — including artificial and other low-calorie sugar substitutes — may alter the gut microbiome in ways that negatively affect blood sugar regulation and metabolic health. The findings were published in the journal Current Atherosclerosis Reports.
The researchers analyzed data from 21 randomized clinical trials involving adults. Compared with participants who consumed water or a placebo, those who consumed non-caloric sweeteners had higher fasting insulin levels and higher HbA1c, a measure of long-term blood sugar control. The analysis also found a trend toward reduced insulin sensitivity, an early marker associated with type 2 diabetes.
‘Metabolic harms’
"What makes our analysis notable is that by focusing on non-caloric comparators, we better isolated the direct physiological effects of the sweeteners themselves, not the calories they replace," said lead author Meng Wang, a research assistant professor at Tufts' Friedman School of Nutrition Science and Policy. "When pooling findings from individual trials, we see signals that these compounds may have metabolic harms."
Researchers believe one possible explanation lies in the gut microbiome. Unlike sugar, many non-nutritive sweeteners pass through the digestive tract largely unchanged, coming into direct contact with the trillions of microbes that inhabit the intestine.
Laboratory and animal studies suggest some sweeteners can alter the composition and activity of these microbial communities, potentially affecting glucose metabolism and inflammation.
Not all sweeteners are the same
The review examined a variety of sweeteners, including saccharin, sucralose, aspartame, stevia, and sugar alcohols. However, the researchers said evidence varies by compound, and not all sweeteners appear to have identical effects. They also noted that people's responses may differ depending on the makeup of their individual gut microbiome.
Despite the findings, the authors cautioned against drawing sweeping conclusions. Most sweeteners approved for use in the United States have been deemed safe by regulators when consumed within recommended daily intake levels, and the new review does not establish that sugar substitutes directly cause diabetes or other metabolic diseases.
Instead, the researchers say the evidence highlights the need for larger, longer-term human studies to determine which sweeteners may pose risks, who may be most susceptible, and how gut microbes influence those outcomes.
"Our findings don't suggest people should automatically abandon all non-nutritive sweeteners," Wang said. "But they do challenge the assumption that these compounds are biologically inert and underscore the importance of understanding how they interact with the gut microbiome and metabolism."