Sorbitol, a sweetener used in beverages, chewing gum and a range of processed foods in place of sugar, converts into fructose that can drive liver damage and cancer cell growth when gut microbes are scarce, according to a new study. The finding suggests that alternative sweeteners in "sugar-free" or "reduced-sugar" products do not necessarily pass through the body without affecting metabolism.
A team led by Professor Gary J. Patti at Washington University in St. Louis published the results in the international journal Science Signaling, tracking how sorbitol is metabolized in the body using zebrafish.
The researchers found that in adult zebrafish with sharply reduced gut microbes, sorbitol traveled to the liver. There it was converted into fructose 1-phosphate, a process that activated glucose metabolism in the liver and increased the accumulation of fat and glycogen in the organ.
Sorbitol is a type of sugar alcohol that provides sweetness with fewer calories than sugar. It is used as a sweetener in gum, candy and other foods, and occurs naturally in stone fruits such as peaches and plums.
The notable part of the study is how sorbitol itself is metabolized. In zebrafish with normal gut microbes, the researchers confirmed that some bacteria break down sorbitol. In zebrafish depleted of gut microbes, by contrast, undigested sorbitol moved to the liver.
The team also identified certain bacteria in the genus Aeromonas as capable of breaking down sorbitol. When sorbitol-degrading Aeromonas strains were reintroduced into zebrafish whose gut microbes had been removed, symptoms associated with fatty liver eased.
Conversely, zebrafish given high concentrations of sorbitol from an external source showed fat accumulation in the liver. On that basis, the researchers suggested that excessive sorbitol intake may be linked to the risk of fatty liver when gut microbes cannot break down enough of the compound. The study did not, however, establish a causal relationship between sorbitol intake and fatty liver in humans.
Another central finding is that sorbitol is closely tied to fructose in the body's metabolism. The researchers concluded that once sorbitol is converted into fructose in the liver, it activates hepatic glucokinase and increases glycolytic flux, which can lead to greater accumulation of fat and glycogen in the liver.
Fructose is not only a leading cause of fatty liver disease, which affects 30% of adults worldwide, but is also dangerous because its metabolic byproducts serve as a key energy source that helps cancer cells spread and grow.
The researchers also noted that sorbitol does not enter the body through food alone. Intestinal cells can convert glucose taken in after a meal into sorbitol. The composition and volume of gut microbes, along with the amount of sorbitol produced internally or consumed, can therefore all affect the metabolic process.
The team stressed that replacing sugar with another sweetener does not eliminate every effect that can arise during metabolism. Patti said there is no free lunch in the search for sugar substitutes, cautioning against overconsuming processed foods based solely on a sugar-free label.
The study is limited by the fact that it was conducted in zebrafish. The researchers said further work is needed to determine how excessive sorbitol intake affects human metabolic function. These results alone make it difficult to conclude that all zero-sugar or sugar-free products containing sorbitol are harmful to human health.
