Fructose could Drive Brain Inflammation and Increase the Risk of Dementia

Alzheimer’s disease (AD) is currently the sixth leading cause of death and is characterized by cognitive decline and cerebral atrophy associated with β-amyloid plaques and tau-protein aggregation (neurofibrillary tangles) in neurons.

 Treatments to reduce β-amyloid and/or tau protein aggregation carry promise but have generally not been as successful as predicted , consistent with a prior hypothesis that more basic mechanisms may drive the disease. In this regard, preclinical and early manifestations of AD include reduced cerebral glucose metabolism, mitochondrial dysfunction, neuroinflammation, and intracellular energy depletion. 

These observations have led to dietary, behavioral, and therapeutic strategies to improve metabolic parameters with promising early results. Nevertheless, the underlying mechanism(s) driving AD, especially the late-onset sporadic variant, is not fully understood.

Fructose could drive Alzheimer’s disease

Richard Johnson, MD, professor at the University of Colorado School of Medicine and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

When threatened with the possibility of starvation, early humans developed a survival response which sent them foraging for food. Yet foraging is only effective if metabolism is inhibited in various parts of the brain. Foraging requires focus, rapid assessment, impulsivity, exploratory behavior and risk taking. It is enhanced by blocking whatever gets in the way, like recent memories and attention to time. Fructose, a kind of sugar, helps damp down these centers, allowing more focus on food gathering.

In fact, the researchers found the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals.

The researchers noted that fructose reduces blood flow to the brain’s cerebral cortex involved in self-control, as well as the hippocampus and thalamus. Meanwhile, blood flow increased around the visual cortex associated with food reward. All of this stimulated the foraging response.

Fructose produced in the brain can lead to inflammation and ultimately Alzheimer’s disease, the study said. Animals given fructose show memory lapses, a loss in the ability to navigate a maze and inflammation of the neurons.

The study suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease


Richard J. Johnson, Dean R. Tolan, Dale Bredesen, Maria Nagel, Laura G. Sánchez-Lozada, Mehdi Fini, Scott Burtis, Miguel A. Lanaspa, David Perlmutter. Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? The American Journal of Clinical Nutrition, January 11,  2023; DOI: 10.1016/j.ajcnut.2023.01.002