AURORA, Colo. — An ancient human survival instinct still embedded deep within our brains may be driving dementia onset thanks to an unlikely accomplice — fructose, a kind of sugar. Researchers from the University of Colorado Anschutz say this instinctual foraging mechanism, fueled by fructose production in the brain, could provide new clues into both the development and possible treatment of Alzheimer’s disease, the most common form of dementia.
Study authors believe their findings present a unique take on an awful-yet-common disease, which develops due to abnormal accumulations of proteins in the brain, eventually resulting in the deterioration of both memory and cognition.
“We make the case that Alzheimer’s disease is driven by diet,” says the study’s lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension, in a media release.
What does Alzheimer’s have to do with being hungry?
Prof. Johnson and his team explain that Alzheimer’s may be a harmful adaptation of an evolutionary survival pathway used by animals and our distant ancestors during times of scarcity for centuries.
“A basic tenet of life is to assure enough food, water and oxygen for survival,” study authors explain. “Much attention has focused on the acute survival responses to hypoxia and starvation. However, nature has developed a clever way to protect animals before the crisis actually occurs.”
Starvation was an everyday threat for early humans. So, they developed a survival response that sent them searching for food. However, foraging for food is only effective if metabolism is inhibited in various parts of the brain. Successful food foraging hinges on focus, rapid assessment, impulsivity, exploratory behavior, and risk taking. In other words, it’s helpful to block out whatever gets in the way, like recent memories and attention to time, while out searching for food. Meanwhile, fructose can help dampen these brain centers, facilitating more focus on food gathering.
Moreover, the research team notes that the entire foraging response sets in motion through the metabolism of fructose, regardless of whether the person eats or produces their own fructose. The metabolization of fructose, and its byproduct intracellular uric acid, is essential to both human and animal survival.
Fructose restricts blood flow to the brain’s cerebral cortex, which is involved in self-control, as well as the hippocampus and thalamus. Simultaneously, blood flow increases around the visual cortex, a region associated with food reward. All of this together helps stimulate the foraging response.
“We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial,” Prof. Johnson adds. “But chronic and persistent reduction in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD.”
The human ‘survival switch’ results in overeating today
Prof. Johnson theorizes that this survival response, which he calls a “survival switch,” helped ancient humans survive periods of extreme scarcity. Today, however, that survival switch is still on, so to speak, in a time of relative abundance. This promotes the overeating of high fat, sugary and salty foods resulting in excess fructose production.
Fructose created in the brain can promote inflammation and eventual Alzheimer’s disease, the study concludes. For example, animals consuming fructose display memory lapses, a loss in the ability to navigate a maze, and neuronal inflammation.
“A study found that if you keep laboratory rats on fructose long enough they get tau and amyloid beta proteins in the brain, the same proteins seen in Alzheimer’s disease,” Prof. Johnson comments. “You can find high fructose levels in the brains of people with Alzheimer’s as well.”
Prof. Johnson also theorizes that the tendency of some Alzheimer’s patients to wander off could be an evolutionary holdover linked to this ancient foraging response. All in all, the study concludes more research is necessary, examining the role of fructose and uric acid metabolism in dementia.
“We 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,” Prof. Johnson concludes.
The study is published in the American Journal of Clinical Nutrition.