(August 26th, 2020) Excessive consumption of fructose -- a sweetener ubiquitous in the American diet -- can result in non-alcoholic fatty liver disease (NAFLD), which is comparably abundant in the United States. But contrary to previous understanding, researchers at University of California San Diego School of Medicine report 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.
Developing treatments that prevent intestinal barrier disruption, the authors conclude in a study published August 24, 2020 in Nature Metabolism, could protect the liver from NAFLD, a condition that affects one in three Americans.
"NAFLD is the most common cause of chronic liver disease in the world. It can progress to more serious conditions, such as cirrhosis, liver cancer, liver failure and death," said senior author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine. "These findings point to an approach that could prevent liver damage from occurring in the first place."
Fructose consumption in the U.S. has skyrocketed since the 1970s and the introduction of high fructose corn syrup (HFCS), a cheaper sugar substitute that is broadly used in processed and packaged foods, from cereals and baked goods to soft drinks. Multiple studies in animals and humans have linked increased HFCS consumption with the nation's obesity epidemic and numerous inflammatory conditions, such as diabetes, heart disease and cancer. The U.S. Food and Drug Administration, however, currently regulates it similar to other sweeteners, such as sucrose or honey, and advises only moderation of intake.
The new study, however, defines a specific role and risk for HFCS in the development of fatty liver disease. "The ability of fructose, which is plentiful in dried figs and dates, to induce fatty liver was known to the ancient Egyptians, who fed ducks and geese dried fruit to make their version of foie gras," said Karin.
Interestingly, the research team 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.
"Unfortunately, many processed foods contain HFCS and most people cannot estimate how much fructose they actually consume," said Karin. "Although education and increased awareness are the best solutions to this problem, for those individuals who had progressed to the severe form of NAFLD known as nonalcoholic steatohepatitis, these findings offer some hope of a future therapy based on gut barrier restoration."