Scientists have discovered a surprising link between sugar metabolism and alcohol addiction, identifying a potential new therapeutic target for treating alcohol-associated liver disease (ALD) and alcohol use disorder (AUD).
A new study, published in Nature Metabolism, shows that alcohol triggers a metabolic pathway in the body that leads to the internal production of fructose — the same type of sugar found in sweetened foods and beverages.
This reaction, driven by the enzyme ketohexokinase (KHK), appears to play a crucial role both in reinforcing alcohol consumption behavior and accelerating liver damage.
Researchers found that mice lacking the KHK enzyme showed a significantly reduced tendency to consume alcohol.
They drank less in various tests — including voluntary consumption models and reward-based models — and displayed reduced activity in brain regions associated with addiction.
An Unexpected Link Between Sugar and Alcohol Metabolism
A key finding is that alcohol-induced liver damage was virtually absent when KHK activity was blocked, either genetically or through pharmacological treatment.
The livers of these mice showed fewer fat deposits, less inflammation, and reduced fibrosis, suggesting that targeting fructose metabolism could halt or even prevent the progression of alcohol-related liver disease.
“Our findings show that alcohol doesn’t just directly affect the liver, it hijacks sugar metabolism in the body in a way that amplifies the desire to drink and worsens liver damage,” said Miguel A. Lanaspa, Associate Research Professor at CU Anschutz and lead author of the study.
“By targeting fructose metabolism, we could break this vicious cycle and develop new treatments for both alcohol addiction and liver disease.”
Promising Perspectives for Treatment Development
Because both alcohol-associated liver disease (ALD) and metabolic-associated steatotic liver disease (MASLD) involve mechanisms influenced by fructose, the results suggest that therapies inhibiting fructose metabolism could help a broad range of patients affected by diet- or alcohol-related liver disease.
“This discovery highlights an unexpected link between sugar and alcohol metabolism,” explained Richard Johnson, MD, Professor at CU Anschutz and co-author of the study.
“It opens promising avenues for developing therapies that target a shared pathway underlying both metabolic and alcohol-related liver diseases.”
This research therefore provides a new and promising direction for combating liver disease and alcohol addiction, two conditions for which effective treatments are still limited, according to EurekAlert.
