Fructose fueled “evolutionary” scouring a strong indicator of Alzheimer’s, study finds

14 Mar 2023 --- An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer’s disease (AD), according to researchers from the University of Colorado Anschutz Medical Campus (CU Anschutz). 

The researchers hold that the study confirms that overproduction of fructose from a modern lifestyle activates the “evolutionary” instinct, stimulating a build-up of proteins that eventually triggers parts of the brain responsible for memory. 

NutritionInsight delves into the research with Dr. Richard Johnson, professor of medicine, renal diseases and hypertension, CU Anschutz. 

“Our work has found that when fructose is metabolized, it can act like any type of food in terms of carrying calories, but that it is metabolized differently from glucose such that it preferentially stimulates fat production as a type of stored energy as opposed to making ATP (adenosine triphosphate), which is the immediate energy,” says Johnson. 

The study, published in The American Journal of Clinical Nutrition, demonstrates that AD, which is fatal, can be characterized by abnormal accumulations of proteins in the brain, a spin-off of fructose production that slowly erodes memory and cognition.

Harmful adaptation of survival pathwayThe CU Anschutz researchers believe natural fruits do not affect AD formation because they have less fructose.
The researchers suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity, whereby nature developed a way to protect animals before a crisis occurs.

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

When early humans were threatened by starvation, they would forage for food. However, foraging is only effective if metabolism is inhibited in various parts of the brain. It requires focus, rapid assessment, impulsivity, exploratory behavior and risk-taking, the researchers argue. 

The effects are enhanced by blocking whatever gets in the way, like recent memories and attention to time. Fructose damps down these centers, allowing more focus on food gathering.

“This inhibition is associated with reducing brain activity in these regions by reducing the amount of glucose available. The process of providing less energy essentially acts to starve that part of the brain, and it is associated with impaired energy production and inflammation,” Johnson explains.

“Over time, this can lead to brain damage including shrinkage of the brain, loss of neurons and the formation of amyloid plaques.”

Fructose stimulates foraging
While most of our fructose comes from sugar and high fructose corn syrup, the body and brain can make fructose from glucose. Therefore, fructose production is high in conditions where food is high in glucose, such as starchy foods and salty foods that stimulate the enzymes that convert glucose to fructose.

“As part of this process, the fructose stimulates hunger and foraging. “Foraging is a specific behavior that involves traveling into areas that may not be safe and being a risk taker. This requires impulsivity. It turns out that fructose does this by inhibiting certain regions of the brain involved in self-control and memory,” Johnson observes.

“Natural fruits do not seem to play a role as they have less fructose and also contain counteracting substances such as vitamin C and antioxidants,” says Johnson.

High levels of fructose have been found in the brains of people with Alzheimer’s. The tendency of some AD patients to wander off has been identified as a vestige of the ancient foraging response.

In other developments, neuroimaging has revealed a positive association between adherence to the MIND and Mediterranean diets and the reduction of tau tangles and amyloid plaques in the brain – the key signatures of Alzheimer’s disease.

Survival switch constantly onThe researchers have recommended further research into the role of fructose and uric acid metabolism.
Initially, the fructose-dependent reduction in cerebral metabolism in the hippocampus and thalamus was reversible and meant to be beneficial. But the 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.

“Administering fructose to rats can replicate these findings, which suggest that it can cause Alzheimer’s disease. Fructose levels are also high in the brains of patients with Alzheimer’s disease,” says Johnson. 

“What’s more, foods that increase the risk for Alzheimer’s involve foods that can stimulate the production of fructose in the brain, such as high sugar diets, high salt diets and high glycemic carbohydrates,” he outlines.

In essence, the research posits that the survival response, coined the “survival switch,” which helped ancient humans deal with scarcity, is stuck in the “on position” in a time of abundance, which leads to overeating of foods high in fat, sugar and salt leading to excess fructose production.

Fructose produced in the brain can lead to inflammation and, ultimately, Alzheimer’s disease, the study says. Fructose administered to test animals demonstrates lapses in memory, inability to navigate a maze and inflammation of the neurons.

“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,” Johnson says. 

The study stresses that more research is needed on the role of fructose and uric acid metabolism in AD.

“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,” Johnson concludes.

Meanwhile, high levels of fructose consumption cause inflammation in the immune system and damage cells that contribute to the healthy functioning of organs and body systems, according to researchers at the University of Swansea, UK.

By Inga de Jong