Sweeteners like aspartame, sucralose, and sugar alcohols are often marketed as healthier options compared to refined sugars. However, new research suggests that the sugar alcohol sorbitol may not be as safe as previously believed.
A recent study published in Science Signaling indicates that sorbitol could contribute to steatotic liver disease. This work builds on earlier findings from Gary Patti's laboratory at Washington University in St. Louis, which have shown that fructose can harm the liver and support cancer cell growth. According to Patti, "The most surprising finding from the current work is that because sorbitol is essentially 'one transformation away from fructose,' it can induce similar effects."
The research team used zebrafish models to show that sorbitol—commonly found in "low-calorie" candies, gum, and certain fruits—can be produced by enzymes in the gut and later converted into fructose by the liver. Patti noted, "There are many roads to fructose in the liver, and potential detours, depending on a person's sorbitol and glucose consumption patterns, along with the bacterial populations colonizing their gut."
While previous studies focused on how sorbitol production occurs due to high glucose levels in diabetes, this new research found that even healthy individuals can produce enough gut glucose after eating to generate sorbitol. Patti explained, "The enzyme that produces sorbitol has a low affinity for glucose, so glucose levels must be high for it to take effect. That is why sorbitol production has primarily been associated with diabetes... But even in healthy settings, glucose levels in the gut become high enough after feeding to drive sorbitol production within the intestine."
Some strains of Aeromonas bacteria can degrade sorbitol into harmless byproducts. However, Patti warned: "However, if you don't have the right bacteria, that's when it becomes problematic. Because in those conditions, sorbitol doesn't get degraded and as a result, it is passed on to the liver." In such cases, the unprocessed sorbitol reaches the liver where it is turned into a derivative of fructose.
This issue raises concerns for people who consume large amounts of alternative sweeteners or rely on them due to metabolic disorders like diabetes. While gut bacteria can typically clear small amounts of naturally occurring sorbitol (such as from fruit), higher quantities—from excessive dietary intake or increased glucose-derived production—may overwhelm these microbes.
Patti commented on his own experience: "Avoiding both sugar and alternative sweeteners is increasingly complicated... I was bemused to discover my own favorite protein bar was chock full of sorbitol." He added that more research is needed on how bacteria clear sorbitol but cautioned against assuming all polyols are harmless: "We do absolutely see that sorbitol given to animals ends up in tissues all over the body."
Patti concluded: "Bottom line: it's becoming more apparent that 'there is no free lunch' when trying to find sugar alternatives, with many roads leading to liver dysfunction."
