An American Journal of Clinical Nutrition paper ties together research explaining how fructose was essential for our ancestors’ survival with studies that show why this simple sugar is bad for the brain and may be a prime driver of Alzheimer’s disease.
Some fructose occurs naturally in the brain, but it is also found in fruit, some vegetables, and honey. In the modern world, it is a basic component in table sugar, while high fructose corn syrup is a frequent additive used to sweeten processed foods and beverages.
“We make the case that Alzheimer’s disease is driven by diet,” said the study’s lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension.
How might this work? Fructose helps conserve energy during times of scarcity by triggering a neural response that encourages food and water intake, slows down metabolism, and stores fat and glycogen, the paper explained. It also reduces insulin sensitivity which helps preserve glucose, a primary energy source for the brain.
At the same time, the sugar signals the brain to block out distractions so it can zero in on tasks like exploration and risk taking. All good when finding food is an imperative for survival. Less desirable in a world that requires very little foraging.
In fact, the researchers found the entire foraging instinct 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, they said. And in addition, the researchers noted fructose escalates the foraging response by reducing blood flow to the brain’s cerebral cortex involved in self-control, as well as the hippocampus and thalamus. Meanwhile, it increases blood flow around the visual cortex associated with food reward.
When long term high fructose intake pushes the setting on our “survival switch” to high, the brain is constantly on the hunt for high fat, sugary, and salty foods–all of which are readily available on supermarket shelves and the drive through. In turn, this pushes the brain to produce even more fructose which can ultimately lead to neural inflammation and create the conditions that lead to Alzheimer’s, the scientists proposed.
“We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial,” Johnson said. “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.”
One study the paper cited as evidence for this idea found that laboratory rats fed a constant diet of fructose begin to build up tau and amyloid beta proteins in the brain, the same proteins that are associated with Alzheimer’s. Johnson goes so far as to speculate that when some Alzheimer’s patients wander off, it may be a vestige of the foraging response.
Of course, this is all just theory for now. Scientists need more lab data to understand how fructose metabolism might cause Alzheimer’s disease and other forms of dementia in a real world setting. In the meantime, they suggested it can’t hurt to test dietary and drug interventions that reduce fructose exposure or block fructose metabolism to see if they can prevent, manage, or treat the disease.
