A recent study found that artificial sweeteners, including sugar alcohols like sorbitol, may not be as harmless as previously thought. Published in Science Signaling, the research highlights how these sugar substitutes can affect liver metabolism and contribute to steatotic liver disease, raising concerns about their widespread use.
Considering that artificial sweeteners are often perceived as healthier alternatives to sugar, particularly for individuals seeking weight loss or managing diabetes, this study could change how people view “sugar-free” products. While these sweeteners offer fewer calories and are widely promoted as safe, the new evidence suggests that their impact on the liver and other organs may be more significant than assumed.
What the study found
The study, conducted by researchers at Washington University in St. Louis, builds on years of research into how fructose affects liver metabolism. Gary Patti, the Michael and Tana Powell Professor of Chemistry in Art & Sciences and of Genetics and Medicine at WashU Medicine, previously demonstrated that fructose processed by the liver can fuel cancer cell growth. Other research has linked fructose to steatotic liver disease, a condition affecting roughly 30 per cent of adults worldwide.
Using zebrafish as a model, the team investigated how sorbitol, a sugar alcohol, interacts with liver metabolism. The researchers found that “metabolic dysfunction–associated steatotic liver disease (MASLD) is linked to a shift in the composition of the gut microbiome. Here, we found that depletion of the gut microbiome in adult zebrafish led to the development of steatotic liver disease in animals on standard diets.”
Through metabolomics and isotope tracing, the study showed that dietary glucose could be converted to sorbitol by host intestinal cells. “Although bacteria degraded sorbitol in control animals, sorbitol was transferred to the livers of fish when the gut microbiome had been depleted. Within the liver, sorbitol was converted into fructose 1-phosphate, which subsequently activated glucokinase and increased glycolytic flux, leading to increased hepatic glycogen and fat content,” the researchers wrote.
The team further observed that inhibiting sorbitol production in microbiome-depleted animals prevented the development of steatotic liver disease. Moreover, colonising the intestines of microbiome-depleted fish with sorbitol-degrading Aeromonas bacterial strains rescued the liver phenotype. Conversely, “exogenous administration of high concentrations of sorbitol phenocopied gut microbiota depletion and induced hepatic steatosis.”
One of the study’s key insights is that sorbitol is essentially “one transformation away from fructose,” meaning it can trigger metabolic effects similar to those caused by fructose itself. Patti explained, “It can be produced in the body at significant levels. But if you have the right bacteria, turns out, it doesn’t matter.” Certain bacterial strains in the gut are capable of breaking down sorbitol into harmless byproducts, preventing its harmful accumulation in the liver.
The findings challenge the notion that sugar alcohols, such as sorbitol, are entirely safe. Even individuals without diabetes may produce significant amounts of sorbitol in the gut after meals, depending on glucose levels and the gut microbiome composition.
When sorbitol intake overwhelms the system
The study also revealed that problems arise when the amount of sorbitol exceeds the gut microbiome’s capacity to degrade it. Patti explained, "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.”
Once in the liver, sorbitol is converted into a fructose derivative, which can trigger metabolic changes leading to hepatic steatosis. At low levels, such as those naturally found in stone fruits or typical dietary sources, gut bacteria are generally effective at processing sorbitol. Trouble begins when high amounts of glucose are consumed, boosting internal sorbitol production, or when diets contain large quantities of sorbitol itself.
Patti noted that even products marketed as “low-calorie” or “sugar-free” can contain surprising levels of sorbitol. He was surprised to learn that his own favourite protein bar contained a significant amount of sorbitol.
However, further research is needed to understand exactly how gut bacteria clear sorbitol. What is becoming clear, however, is that the long-held assumption that sugar alcohols, also known as polyols, are simply eliminated without harm may not be accurate. “There is no free lunch,” Patti added, emphasising that many metabolic pathways can ultimately lead back to liver dysfunction.
Additional studies support these observations. A 2022 animal study evaluating the effects of short- and long-term sorbitol consumption in mice found that bolus feeding of sorbitol significantly increased plasma insulin concentrations and decreased fasting blood glucose levels. Long-term administration induced glucose intolerance and altered the gut microbiome. Specifically, sorbitol intake decreased beneficial bacteria such as Bifidobacterium and increased others like Helicobacter and Alistipes, suggesting that prolonged consumption may disrupt gut balance and contribute to metabolic disorders.
Are artificial sweeteners better?
The assumption that sugar substitutes are inherently safer is increasingly being questioned. According to Harvard Health Publishing, “By offering the taste of sweetness without any calories, artificial sweeteners seem like they could be one answer to effective weight loss.” Diet sodas, for instance, provide zero calories compared to sugar-sweetened beverages, which typically deliver around 150 calories per 12-ounce serving.
The American Heart Association (AHA) and the American Diabetes Association (ADA) have cautiously endorsed non-nutritive sweeteners (NNS) as tools to reduce obesity, metabolic syndrome, and diabetes risk. “While they are not magic bullets, smart use of non-nutritive sweeteners could help you reduce added sugars in your diet, therefore lowering the number of calories you eat,” Harvard Health notes. Reduced calorie intake can contribute to maintaining a healthy body weight and lowering heart disease risk.
However, some studies suggest that artificial sweeteners may have unintended consequences. Research indicates they can interfere with the brain’s ability to associate sweetness with caloric intake, potentially increasing sugar cravings and preference for sweet foods. The San Antonio Heart Study found that participants who consumed more than 21 diet drinks per week were twice as likely to become overweight or obese compared to those who didn’t consume diet sodas.
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Animal studies suggest another layer of concern: artificial sweeteners may be addictive. In experiments, rats previously exposed to cocaine chose oral saccharin over intravenous cocaine, indicating a potential preference and reinforcing the addictive nature of sweeteners.
A 2016 review highlighted that while NNS provide greater sweetness with fewer calories and have been approved as safe by the FDA, evidence for their long-term health benefits remains inconclusive. Pregnant and lactating women, children, diabetics, and patients with migraine or epilepsy may be particularly vulnerable to adverse effects, and the widespread use of NNS remains controversial. The review emphasised that, “It is the duty of the health-care providers to be aware of the latest evidence-based dietary guidelines and to inform the consumers regarding the potential risks associated with NNS use.”
Non-alcoholic fatty liver disease (NAFLD), a condition marked by excess fat accumulation in the liver, is also linked to gut microbiome disruptions. Studies suggest that artificial sweeteners can alter gut bacteria and contribute to dysbiosis, potentially increasing NAFLD risk.
This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS.
