The risk of Alzheimer’s Disease (AD), the 6th leading cause of death, is known to be increased by diets high in table sugar (sucrose) or High Fructose Corn Syrup (HFCS), high glycemic carbohydrates, salty foods, and alcohol. Likewise, processed meats rich in umami also increase the risk of dementia. All of these foods are associated with fructose production.
Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain.
A basic tenet of life is to ensure enough food, water, and oxygen for survival a la a survival mechanism. This “survival mechanism” is mediated by the metabolism of fructose that is either ingested or produced in the body. The key question is how the survival mechanism affects brain metabolism and function given that the brain has high energy requirements, accounting for 20% of the daily amount of ATP used by the body despite constituting only 2% of the body mass.
The survival mechanism also involves reducing brain energy expenditure so long as critical brain function is supported. Research has found evidence that animals in nature use excessive intake and metabolism of fructose to activate a survival response that prepares them for periods when food, water, or oxygen may not be adequately available. The evidence suggests that the survival pathway in humans during our primitive years was beneficial in reducing the risk of starvation but, in today’s environment, may predispose us to not only obesity and diabetes but also AD. The study revealed that the survival mechanism has a major role in the development of Alzheimer’s Disease and may account for many of the early features.
Basically the survival mechanism involves going into a “low-power” mode in which both ATP (i.e. energy production) production and usage are reduced. This is accomplished by reducing energy metabolism at rest while allowing sufficient energy for critical activities, such as foraging. Both food and water intake are encouraged by stimulating hunger and arousal by blocking satiety (i.e. fullness) and stimulating foraging. The demand for oxygen is reduced by slowing mitochondrial respiration, with a shift toward glycolysis (i.e. oxidizing glucose in order to obtain energy for the cell).
The storage of fat and glycogen in the liver is also encouraged by stimulating their production and inhibiting fatty acid oxidation, lipolysis (i.e. stimulation of body fat to usable energy), and glycogenolysis (i.e. the breakdown of glycogen to glucose to useable energy). Glucose metabolism in muscles is reduced by decreasing glucose uptake (via insulin resistance) and inhibiting insulin secretion from the pancreas. This reduces total energy expenditure while providing more glucose to the brain, where insulin is not fully required for uptake.
Humans have put this biological switch into overdrive by the means of 2 historic events.
1st, we are more sensitive to the effects of fructose because the enzyme uricase was lost in our primate ancestors because of a series of mutations in the uricase gene millions of years ago, leading to higher uric acid levels and a greater metabolic response.
2nd is the intake of added sugars that contain fructose and glucose, such as table sugar (sucrose) and high-fructose corn syrup (HFCS). The Western diet contains a high amount of fructose (primarily from sucrose and HFCS) and foods that stimulate fructose production (high glycemic carbohydrates, alcohol, and salty foods) or those that readily generate uric acid (umami-rich foods), all of which engage the survival mechanism to fructose.
The study suggests that local (i.e. brain) fructose generation and metabolism may be the critical factor for how fructose induces AD. The chronic and persistent decrease in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD.
Source: Study Finds…Research, in a nutshell