They're sold as diet-friendly, "guilt free" sugar alternatives-but a new study suggests one common sweetener may not be so harmless after all. Research from Washington University in St. Louis, published in Science Signaling, reveals that sorbitol, a widely used sugar alcohol found in sugar free gums and candies, may behave much like fructose, the natural sugar long linked to fatty liver disease and metabolic disorders. The findings challenge decades of assumptions about sugar substitutes and raise new questions about how they affect the liver and metabolism.
Sweeteners like aspartame (Equal), sucralose (Splenda), and sugar alcohols such as sorbitol and xylitol are marketed as safer ways to enjoy sweetness without spiking blood sugar. But the new study, led by Dr. Gary Patti, Professor of Chemistry and Medicine at WashU, shows how the body may actually convert sorbitol into harmful fructose derivatives—potentially undermining the very purpose of using these substitutes in the first place.
Using zebrafish models, Patti’s team discovered that enzymes in the gut can naturally produce sorbitol from glucose after a meal, even in people without diabetes. From there, sorbitol travels to the liver, where it is transformed into fructose like molecules. While this pathway had been recognized in diabetic conditions before, the new study shows it can occur under normal metabolic circumstances, meaning sorbitol’s effects may extend beyond people with high blood sugar.
The researchers also found that gut bacteria play a crucial protective role. Strains of Aeromonas can break down sorbitol into harmless byproducts—but not everyone has these microbes in abundance. When beneficial bacteria are missing or overwhelmed, excess sorbitol reaches the liver, increasing the likelihood of fat accumulation and metabolic stress.
At low concentrations—such as those found in fruits—sorbitol is generally safe. Problems arise when glucose or sorbitol intake is excessive, as gut microbes can’t keep up. This imbalance can push sorbitol metabolism into overdrive, contributing to fatty liver changes and systemic inflammation.
According to Dr. Patti, “there is no free lunch” when it comes to artificial sweeteners. Even sugar alcohols thought to pass harmlessly through the body can end up influencing the same pathways as sugar itself. The study suggests a need for reevaluating “sugar free” labeling and understanding how both diet and microbiome diversity shape our metabolic health.
REFERENCE: Madelyn M. Jackstadt, Ronald Fowle-Grider, Mun-Gu Song, Matthew H. Ward, Madison Barr, Kevin Cho, Hector H. Palacios, Samuel Klein, Leah P. Shriver, Gary J. Patti. Intestine-derived sorbitol drives steatotic liver disease in the absence of gut bacteria. Science Signaling, 2025; 18 (910) DOI: 10.1126/scisignal.adt3549
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