Study Challenges Sorbitol Safety as Sugar Substitute

Sweeteners like aspartame in Equal packets, sucralose in Splenda, and sugar alcohols appear in products as healthier alternatives to refined sugar. Recent research questions this view, particularly for sorbitol, once considered harmless. The study, published in Science Signaling, builds on findings from Gary Patti's lab at Washington University in St. Louis about fructose's negative effects on the liver and other systems.

Patti previously showed fructose processed in the liver can fuel cancer cells. His prior studies also linked fructose to steatotic liver disease, which affects 30% of adults worldwide. The new study reveals sorbitol, being “one transformation away from fructose,” produces similar outcomes.

Zebrafish experiments demonstrated that sorbitol, used in low-calorie candy, gum, and found in stone fruits, forms via gut enzymes and converts to fructose in the liver. Multiple pathways lead to liver fructose, influenced by sorbitol and glucose intake plus gut bacteria. Although most of the research on sorbitol metabolism has focused on its production due to glucose overload in pathological settings such as diabetes, sorbitol can be naturally produced in the gut from glucose after eating, Patti said.

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, where blood glucose levels can become elevated. But, even in healthy settings, glucose levels in the gut become high enough after feeding to drive sorbitol production within the intestine, 

“It can be produced in the body at significant levels,” said Patti. “But if you have the right bacteria, turns out, it doesn’t matter.” Sorbitol-degrading Aeromonas strains turn it into harmless byproducts. “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,” he said. There, it becomes a fructose derivative.

Gut bacteria do a good job of clearing sorbitol when it is present at modest levels, such as those found in fruit. But problems arise when sorbitol quantities become higher than what gut bacteria can degrade. This can occur when excessive amounts of glucose are consumed in the diet, which lead to high levels of glucose-derived sorbitol, or when dietary sorbitol itself is too high.

The lab plans more research to understand the specific mechanisms for how bacteria clears sorbitol, but the basic idea that these sugar alcohols, called polyols, are harmlessly expelled, may not hold true. “We do absolutely see that sorbitol given to animals ends up in tissues all over the body,” Patti added.