Excess fructose consumption may cause leaky gut, lead to fatty liver disease

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Excessive consumption of fructose can result in non-alcoholic fatty liver disease (NAFLD), but contrary to previous understanding, researchers at University of California San Diego School of Medicine reported in a new study published in Nature Metabolism that fructose only adversely affects the liver after it reaches the intestines, where the sugar disrupts the epithelial barrier protecting internal organs from bacterial toxins in the gut.

The new study, conducted in mice, looked at the specific role and risk for high fructose corn syrup in the development of fatty liver disease. Multiple studies in animals and humans have linked increased high fructose corn syrup consumption with the nation's obesity epidemic and numerous inflammatory conditions, such as diabetes, heart disease, and cancer. Fructose is broken down in the human digestive tract by an enzyme called fructokinase, which is produced both by the liver and the gut.

Using mouse models, researchers found that excessive fructose metabolism in intestinal cells reduces production of proteins that maintain the gut barrier, a layer of tightly packed epithelial cells covered with mucus that prevent bacteria and microbial products, such as endotoxins, from leaking out of the intestines and into the blood.

The researchers found that leaked endotoxins reaching the liver provoked increased production of inflammatory cytokines and stimulated the conversion of fructose and glucose into fatty acid deposits. They also said that feeding mice with high amounts of fructose and fat results in particularly severe adverse health effects.

Additionally, the research team said they found that when fructose intake was reduced below a certain threshold, no adverse effects were observed in mice, suggesting only excessive and long-term fructose consumption represents a health risk. Moderate fructose intake through normal consumption of fruits is well-tolerated, they said.

Developing treatments that prevent intestinal barrier disruption could protect the liver from NAFLD, the researchers said.