A new study has revealed potential health risks associated with common sugar substitutes such as sorbitol, challenging the widespread belief that they are harmless alternatives to sugar.
Researchers found that sorbitol can be converted into fructose in the liver, triggering metabolic effects similar to those caused by regular sugar. The findings, published in Science Signaling, were led by Prof. Gary Patti, a professor of chemistry, genetics, and medicine in the Arts & Sciences faculty. Patti explained that sorbitol is “one transformation away from fructose,” meaning it can contribute to the same health concerns linked to excess sugar consumption.
Using zebrafish as a model, the researchers showed that enzymes in the gut can produce sorbitol from dietary sources. This sorbitol is then transported to the liver, where it is converted into fructose. Patti noted that the liver can receive fructose through multiple metabolic pathways, depending on an individual’s glucose and sorbitol intake, as well as the composition of their gut microbiome.
While certain gut bacteria, including Aeromonas strains, can break down sorbitol into harmless by-products, the absence of these microbes allows sorbitol to accumulate and reach the liver, potentially placing stress on metabolic functions. “If you have the right bacteria, it doesn’t matter. But if you don’t, that’s when it becomes problematic,” Patti said.
The study also highlighted that even in people without diabetes, sorbitol can be produced naturally in the gut after meals, especially when glucose levels rise. Low levels of sorbitol, such as those found in whole fruits, are usually managed efficiently by gut bacteria. Problems arise when glucose or sorbitol consumption exceeds what these microbes can process, increasing metabolic strain on the liver.
Patti warned that modern diets, which often combine multiple sweeteners in processed foods, compound the risk, as metabolic pathways from sugar substitutes can ultimately converge in ways that damage liver function.
The research builds on earlier work examining how fructose affects the liver and other organs. Patti has previously shown that fructose processed by the liver can be diverted to fuel cancer cell growth, while other studies have linked fructose to steatotic liver disease, a condition that affects about 30 per cent of adults globally.
“Most people assume sugar alcohols, also known as polyols, are eliminated without harm, but we do see that sorbitol given to animals ends up in tissues throughout the body,” Patti said. “There is no free lunch when it comes to sugar alternatives, and many metabolic pathways can ultimately lead back to liver dysfunction.”
The researchers said the findings raise important questions about the safety of so-called “healthy” sweeteners, particularly for individuals with metabolic conditions, and called for further studies into how gut bacteria regulate sorbitol and other sugar alcohols.
