Clues to the development and possible treatment of Alzheimer’s disease may come from an ancient human instinct to seek food, fueled by the production of fructose in the brain, according to new research.
Researchers say an evolutionary foraging instinct that relied on fructose sugar may now be fueling the formation of
Recently published in THE
“A basic principle of life is to ensure enough food, water and oxygen to survive,” the study said. “A lot of attention has focused on acute survival responses to hypoxia and starvation. However, nature has developed a clever way to protect animals before the crisis actually occurs.
When threatened with starvation, early humans developed a survival response that sent them searching for food. Yet foraging is only effective if metabolism is inhibited in various parts of the brain. Foraging requires concentration, quick assessment, impulsiveness, exploratory behavior and risk taking. It is enhanced by blocking out anything that gets in the way, such as recent memories and attention to time. Fructose, a type of sugar, helps cushion these centers, allowing you to focus more on collecting food.
In fact, the researchers found that the entire foraging response was triggered by the metabolism of fructose, whether consumed or produced in the body. Metabolize fructose and its by-product, intracellular uric
“We believe that initially, the fructose-dependent reduction in brain metabolism in these regions was reversible and expected to be beneficial,” Johnson said. “But a chronic and persistent reduction in brain metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and loss of neurons with all the hallmarks of AD.”
Johnson suspects that the survival response, what he calls the “survival switch”, which helped ancient humans through times of scarcity, is now stuck in the “on” position in times of relative abundance. This leads to overeating of high fat, sweet and salty foods, leading to excess production of fructose.
Fructose produced in the brain can lead to inflammation and ultimately Alzheimer’s disease, according to the study. Animals given fructose exhibit memory lapses, loss of ability to navigate a maze, and inflammation of neurons.
“One study found that if you keep lab rats on fructose long enough, they get tau and beta-amyloid proteins in the brain, the same proteins seen in Alzheimer’s disease,” Johnson said. “You can also find high levels of fructose in the brains of people with Alzheimer’s disease.”
Johnson suspects that the tendency of some AD patients to wander off may be a holdover from the old foraging response.
The study indicated that more research is needed on the role of fructose and uric acid metabolism in AD.
“We suggest that dietary and pharmacological trials aimed at reducing fructose exposure or blocking fructose metabolism be performed to determine if there is any potential benefit in the prevention, management, or treatment of this disease,” said Johnson said.
Reference: “Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by the intracerebral metabolism of fructose and uric acid?” by Richard J. Johnson, Dean R. Tolan, Dale Bredesen, Maria Nagel, Laura G. Sánchez-Lozada, Mehdi Fini, Scott Burtis, Miguel A. Lanaspa and David Perlmutter, January 11, 2023, American Journal of Clinical Nutrition.
DOI: 10.1016/j.ajcnut.2023.01.002
The study’s co-authors are Dean R. Tolan, Dale Bredesen, Laura G. Sanchez-Lozada, Mehdi Fini, Scott Burtis, Miguel A. Lanaspa, and David Pearlmutter.