A recent study has suggested a link between calorie-free sweeteners and blood sugar control, with researchers saying their findings confirm others that warn about the potential long-term risk of cardiometabolic diseases associated with non-nutritive sweeteners (NNS) intake and short-term harmful effects of NNS on glycaemia.
Since the first introduction of saccharin, artificial and other non-nutritive (low-calorie or calorie-free) sweeteners have become ubiquitous in food supply. However, a growing body of research suggests that these compounds are not inert in the body and may be disrupting our metabolism.
This new review and meta-analysis by researchers from the Food is Medicine Institute at the Gerald J and Dorothy R Friedman School of Nutrition Science and Policy at Tufts University, published in Current Atherosclerosis Reports, pulls together the best available evidence on how non-nutritive sweeteners affect health.
Across 21 randomised clinical trials in adults, the researchers observed that artificial and other low-calorie sweeteners, compared with non-caloric controls like water or placebo, raised fasting insulin and HbA1c, a marker of long-term blood sugar control, and showed a trend toward worsening insulin sensitivity.
“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 first author Meng Wang, a research Assistant Professor at the Friedman School of Nutrition Science and Policy. “When pooling findings from individual trials, we see signals that these compounds may have metabolic harms.”
One explanation based on the current evidence, the researchers say, involves the gut microbiome. Non-nutritive sweeteners generally pass through the gut and come into direct contact with these microbes. In one trial they reviewed that used detailed microbiome profiling along with experiments transferring microbes from humans to mice, certain low-calorie sweeteners were shown to alter both the composition and the function of the gut microbiota.
In addition to randomised trials, the researchers reviewed large observational studies, which generally found that consuming non-nutritive sweeteners is linked to a higher risk of developing cardiometabolic diseases. The team notes that these studies have limitations as people already at risk for these conditions may be more likely to choose these products.
Different sweeteners may also have different health effects, so grouping them together may obscure the full picture. Combined with the clinical trial findings, however, the researchers say the overall body of evidence raises concern.
“The rapidly increasing use of these sweeteners has outpaced our understanding of their long-term health effects,” said study senior author Dariush Mozaffarian, cardiologist and director of the Food is Medicine Institute.
“Until we know more, caution is needed. If you’re replacing large amounts of added sugar in your diet, such as in multiple servings of soda, these low-calorie sweeteners may be a better alternative. But we can’t simply assume they are safe and innocuous, and avoiding them whenever possible appears a prudent choice.”
Finally, the researchers highlight a gap in US labelling policy that hinders the research. Current regulations require manufacturers to list non-nutritive sweeteners in the ingredient list, but not the amount included. This makes it difficult for researchers to accurately assess non-nutritive sweetener intake and generate more definitive evidence about their health risk in large community or population studies.
The review underscores the need for additional carefully designed randomised controlled trials of both cardiometabolic risk factors and mechanistic pathways.
Complete information on authors, methodology and conflicts of interest is available in the published paper.
Study details
Artificial and Other Non-Nutritive Sweeteners, the Microbiome, and Cardiometabolic Health
Published in Current Atherosclerosis Reports on 25 June 2026
Meng Wang, Olivia Wu, Olivia Wallen & Dariush Mozaffarian.
Abstract
Purpose of review
In this narrative review complemented by a novel meta-analysis, we critically analysed current scientific evidence from RCTs and cohort studies regarding the impact of non-nutritive sweeteners (NNS) on cardiometabolic health, and assessed the interplay with the gut microbiome as a potential mechanistic pathway. We focused on the question of direct physiological effects of NNS, rather than the additional effects of energy displacement by NNS, to inform future research and the development of dietary and clinical guidelines.
Recent findings
Cohort studies assessing NNS from all dietary sources suggest that total NNS and each commonly used NNS are associated with higher risk of type 2 diabetes, and that total intake and specific agents are associated with certain cardiovascular disease outcomes. These findings are consistent with prior evidence from cohorts focusing on NNS in beverages. Such observational evidence may be confounded by reverse causation: people at higher cardiometabolic risk choosing to use NNS. However, our new meta-analysis of RCTs with non-caloric comparators and a recent RCT on glycaemia outcomes with human-to-mice microbiota transplant suggest that NNS have harmful effects on glucose-insulin homeostasis including fasting insulin, HbA1c, and glucose area under the curve during oral glucose tolerance test (OGTT), potentially mediated by effects on the composition and functional potential of the gut microbiome.
Summary
The summed evidence supports potential long-term risk of cardiometabolic diseases associated with NNS intake and short-term harmful effects of NNS on glycaemia. Future clinical trials of physiologic effects and molecular mechanisms will strengthen interpretations and causal inference. Given potential for harm, caution is warranted for the use of NNS.
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Artificial sweeteners found to be toxic to gut microbes
Non-nutritive sweeteners linked to heart disease and cancer
Artificial sweeteners’ link to higher risk of heart disease – French study