Excess fructose, present in ultra-processed foods, causes bowel changes and is connected to a possible risk of type 2 diabetes and liver disease; consumed in fresh fruit, sugar does not cause issues
In tests with animals on a fructose diet, after four weeks, glucose was no longer efficiently removed from the blood, and, by the end of the study, there was an accumulation of fat in the liver, which can develop into more serious conditions, such as cirrhosis – Photo: Freepik
Researchers from Canada's Université Laval (Ulaval) and USP's Institute of Biomedical Sciences (ICB) have discovered that excessive consumption of fructose, common in diets high in ultra-processed foods, modifies the way the bowel responds to glucose, increasing its absorption and compromising blood sugar control. These effects precede glucose intolerance and the accumulation of fat in the liver, two factors connected to the development of type 2 diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The article describing the study, High fructose rewires gut glucose sensing via glucagon-like peptide 2 to impair metabolic regulation in mice , was on the cover of the March issue of the scientific journal Molecular Metabolism.
The research, funded by the São Paulo Research Foundation (FAPESP), was carried out by Paulo Evangelista Silva, a doctoral student in the Graduate Studies of the ICB's Department of Functional and Molecular Biology, in co-authorship with Eya Sellami, a researcher at Ulaval, and Caio Jordão Teixeira, a post-doctoral student at the ICB's Department of Physiology and Biophysics. The work was coordinated by Fernando Forato Anhê, assistant professor at the Université Laval's Faculty of Medical Sciences and researcher at the Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ).
In the study, for seven weeks, mice were fed a diet that contained 8.5% of its energy from fructose—a proportion considered high but still close to the average human consumption. In just three days, the animals already showed an increase in the bowel's ability to absorb glucose, even before glucose intolerance appeared. After four weeks, the glucose was no longer efficiently removed from the blood. By the end of the trial, fat accumulation was noticed in the liver, a condition that can develop into more serious illnesses such as cirrhosis.
Interestingly, despite these adverse effects, the mice did not develop insulin resistance in their muscles or adipose tissue, indicating that the initial lack of glycemic control is due to changes in the bowel, rather than a failure in the peripheral insulin response. The explanation for this phenomenon may lie in the action of a hormone called GLP-2, produced by intestinal cellsl. The researchers found that excessive consumption of fructose increases circulating levels of GLP-2, a hormone that stimulates the growth of the bowel surface and enhances nutrient absorption. By blocking the receptor for this hormone (Glp2r) with a drug, it was possible to prevent the increased absorption of glucose, avoiding both intolerance and the accumulation of fat in the liver.
Blocking
However, the strategy of blocking Glp2r is not easily applicable to humans, as this same receptor is involved in protecting the bowel barrier against infection and inflammation. This reinforces the complexity of GLP-2's role in metabolic health. “We showed that the increase in glucose absorption by the bowel occurs before glucose intolerance. This paves the way for using this mechanism as an early biomarker,” professor Anhê says. “The bowel glucose absorption test is cheap, safe, and already used in humans – we just need to apply it in a new context.”
A new phase of research, supported by the Canadian Institutes of Health Research (CIHR), will investigate how the bowel microbiome can be manipulated to reduce the harmful effects of excess fructose. Researcher Evangelista Silva emphasizes that the study's results relate to the consumption of fructose added to ultra-processed foods. “Fresh fruit is rich in fiber, which helps slow down the absorption of glucose and increases satiety. They also contain nutrients that are beneficial for bowel and liver health,” he explains.
The nutritional poverty of ultra-processed foods, with their low fiber content and high levels of added sugars, such as corn syrup and cane sugar, overloads the body. Evangelista Silva recommends prioritizing fresh foods, as recommended by the Food Guide for the Brazilian Population, developed by the Ministry of Health with the support of PAHO/Brazil. Sugarcane sugar and corn syrup are examples of fructose-rich sugars widely used by the industry in ultra-processed foods.
Ultra-processed foods with a high concentration of fructose include soft drinks and industrialized juices (even “100% fruit” nectars), breakfast cereals and sweetened bars, stuffed cookies and industrialized sweets, ready-made breads and cakes (such as bread rolls and slides breads), ready-made teas and sweetened sports drinks, industrialized sauces (ketchup, barbecue, etc.), sweetened yogurts, dairy desserts and jams. The study was supported by the Fonds de Recherche du Québec – Santé (FQRS), Fondation IUCPQ, and FAPESP.
From the ICB Communications Office