A new study led by a team of researchers at the Icahn School of Medicine at Mount Sinai Hospital in New York recently revealed that compounds called glycotoxins found in over-cooked foods may increase the risk for age-related dementia, with Alzheimer’s disease the most common type of dementia. The study is entitled “Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans” and was published in the journal Proceedings of the National Academy of Sciences (PNAS).
Diet is known to influence cognitive function. Caloric restriction in particular has a positive result in the aging brain, and this is thought to be through the restoration of a protein called sirtuin 1 (SIRT1), a protein involved in the regulation of neuronal, endocrine and immune responses that was found to be down-regulated in disorders like Alzheimer’s disease and metabolic syndrome, an obesity-related disorder linked to hyperglycemia and insulin resistance.
Glycotoxins, also called advanced glycation end products (AGEs), abundant in cooked, heated, fried or grilled food products at high temperatures, correspond to a class of agents that have been reported to be contributing factors in the development of chronic diseases like diabetes, heart disease and kidney disease, and also in aging and brain injury due to Alzheimer’s disease. Once inside the body, AGEs adhere to tissues, oxidizing them and causing inflammation. Studies in mice models have shown that diets with AGE restriction induced a delay in metabolic and vascular diseases, while extending the animal lifespan. On the other hand, a diet supplemented with AGE induced inflammation, a decrease in SIRT1 levels and caused metabolic syndrome in mice. In humans, AGE restriction has been reported to improve insulin resistance and inflammation.
Researchers hypothesized that, besides causing metabolic syndrome, AGEs may predispose people to dementia. To test their hypothesis, the team used mice models fed throughout life either with a diet supplemented with AGEs or with an AGE-restricted diet. Researchers found that cognitive and motor deficits develop concomitantly with metabolic changes in old mice fed with AGE-rich diet but not in mice fed with an AGE-restricted diet. Interestingly, mice fed with a high amount of AGEs were found to have a decrease in SIRT1 levels and an increase in beta amyloid proteins, which are proteins characteristic of Alzheimer’s disease that aggregate and form amyloid plaques in the brain.
The research team also assessed AGEs in blood samples from 93 individuals aged over 60 years for a 9-month period. Data on the participants’ cognitive function and eating habits, especially of food products rich in glycotoxins, was analyzed. The insulin sensitivity of each participant was also determined, as it represents a major biomarker for metabolic syndromes, including obesity and diabetes. Similar to the results in mice, participants with higher blood levels of AGEs experienced more cognitive decline and a reduction in insulin sensitivity, suggesting that regular consumption of AGEs in over-cooked food may lead to diabetes and obesity.
The team concluded that food-derived AGEs are a modifiable risk factor for both metabolic syndrome disorders and Alzheimer’s disease, and suggest that an AGE-restricted diet may provide an effective therapeutic strategy for both disorders.