Advanced Glycation End Products (AGEs) and Cognitive Decline

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AGEs may be one explanation for why those who consume meat may have up to three times the risk of developing dementia compared with vegetarians.

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Although it is known that plant-based foods are important for physical health, less is known about the relationship between plant-based foods and cognitive health. In terms of preventing Alzheimer’s and other forms of actual dementia, there’s data that those who consume meat, including poultry and fish, have two to three times the risk of developing dementia compared with vegetarians. But what about just day-to-day function? Greater adherence to a more plant-based dietary pattern was related to better performance on all cognitive tasks researchers measured.

One possible mechanism that could have been thought to underlie the results is body weight: plant-based diets reduce BMI, and lower BMI has been associated with better cognitive function. But they still found a connection between more plants and better brain function, even after controlling for weight. Another possible mechanism linking diet and cognition is inflammation. That’s how saturated fat impairs the memory of lab rats––through brain inflammation. And since fiber can be anti-inflammatory, and meat can be pro-inflammatory, that may help explain some of the eects of plant-based diets on health and cognition.

The saturated fat connection appears to extend to human cognition. A systematic review and meta-analysis covering nine studies found that increased saturated fat intake—which is found mostly in meat, dairy, and junk—was associated with a 40 percent increased risk of cognitive impairment and nearly 90 percent higher risk of Alzheimer’s disease. So wait does that mean if you put people on a low-carb diet it impairs their brain function? Yes, it does. A high-fat diet not only impairs the heart but also cognitive function.

Men were randomized to just five days of a high-fat, low-carbohydrate diet or a lower-fat diet, and on the low-carb diet, cognitive tests showed they suffered impaired attention, speed, and mood, again—just within days. Conclusion: raising the level of fat in your blood not only decreased energy production in the heart, but reduced cognition––which suggests that a high-fat diet is detrimental to the heart and brain. Now, they were thinking the impaired energy production may have accounted for the brain dysfunction as well, but oral glycotoxins may also link high-fat eating with a loss of cognitive capacity.

Glycotoxins, also known as advanced glycation end products, or AGEs, are a class of oxidant stress-promoting agents, free radical-promoting agents implicated in diabetes and aging––including brain injury due to Alzheimer’s disease and stroke. The development of Alzheimer’s disease in the first place is thought to involve the accumulation of these AGEs, which encourage the formation and deposition of the two hallmarks of Alzheimer’s disease: neurofibrillary tangles and amyloid plaques in the brain, discovered on autopsy. But it’s not just full-blown dementia. Evidence suggests that AGEs contribute to cognitive decline in general. 

Dietary advanced glycation end products are associated with decline in memory, and “[s]ince modifying the levels of AGEs in the diet may be relatively easy, these preliminary results suggest a simple strategy to diminish cognitive compromise.” What are the major sources of dietary AGEs to stay away from? Meat cooked using high, dry heat, such as in broiling, grilling, frying, and roasting. In my video The Best Diet for Healthy Aging, there’s a list of all the most AGE-contaminated foods.

AGEs are not only associated with getting Alzheimer’s in the first place, but also the progression of Alzheimer’s disease, as well as lower cognitive performance in general as tracked, interestingly enough, via skin autofluorescence. AGEs have a natural fluorescence that you can pick up using a special detector, enabling a simple non-invasive assessment of advanced glycation end product accumulation in the body.

The more meat you eat, the more of the AGE skin autofluorescence you get, which then correlates with cognitive impairment. In fact, one of these days, these fluorescence scanners may be included in routine medical check-ups. Since meat is the main high-AGE food, it should be no surprise that AGE skin autofluorescence measurements are significantly lower in those eating more plant-based. So, the data suggest reduction of food-derived AGEs is feasible, and may provide an effective treatment strategy for our epidemics of Alzheimer’s and metabolic disease.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Although it is known that plant-based foods are important for physical health, less is known about the relationship between plant-based foods and cognitive health. In terms of preventing Alzheimer’s and other forms of actual dementia, there’s data that those who consume meat, including poultry and fish, have two to three times the risk of developing dementia compared with vegetarians. But what about just day-to-day function? Greater adherence to a more plant-based dietary pattern was related to better performance on all cognitive tasks researchers measured.

One possible mechanism that could have been thought to underlie the results is body weight: plant-based diets reduce BMI, and lower BMI has been associated with better cognitive function. But they still found a connection between more plants and better brain function, even after controlling for weight. Another possible mechanism linking diet and cognition is inflammation. That’s how saturated fat impairs the memory of lab rats––through brain inflammation. And since fiber can be anti-inflammatory, and meat can be pro-inflammatory, that may help explain some of the eects of plant-based diets on health and cognition.

The saturated fat connection appears to extend to human cognition. A systematic review and meta-analysis covering nine studies found that increased saturated fat intake—which is found mostly in meat, dairy, and junk—was associated with a 40 percent increased risk of cognitive impairment and nearly 90 percent higher risk of Alzheimer’s disease. So wait does that mean if you put people on a low-carb diet it impairs their brain function? Yes, it does. A high-fat diet not only impairs the heart but also cognitive function.

Men were randomized to just five days of a high-fat, low-carbohydrate diet or a lower-fat diet, and on the low-carb diet, cognitive tests showed they suffered impaired attention, speed, and mood, again—just within days. Conclusion: raising the level of fat in your blood not only decreased energy production in the heart, but reduced cognition––which suggests that a high-fat diet is detrimental to the heart and brain. Now, they were thinking the impaired energy production may have accounted for the brain dysfunction as well, but oral glycotoxins may also link high-fat eating with a loss of cognitive capacity.

Glycotoxins, also known as advanced glycation end products, or AGEs, are a class of oxidant stress-promoting agents, free radical-promoting agents implicated in diabetes and aging––including brain injury due to Alzheimer’s disease and stroke. The development of Alzheimer’s disease in the first place is thought to involve the accumulation of these AGEs, which encourage the formation and deposition of the two hallmarks of Alzheimer’s disease: neurofibrillary tangles and amyloid plaques in the brain, discovered on autopsy. But it’s not just full-blown dementia. Evidence suggests that AGEs contribute to cognitive decline in general. 

Dietary advanced glycation end products are associated with decline in memory, and “[s]ince modifying the levels of AGEs in the diet may be relatively easy, these preliminary results suggest a simple strategy to diminish cognitive compromise.” What are the major sources of dietary AGEs to stay away from? Meat cooked using high, dry heat, such as in broiling, grilling, frying, and roasting. In my video The Best Diet for Healthy Aging, there’s a list of all the most AGE-contaminated foods.

AGEs are not only associated with getting Alzheimer’s in the first place, but also the progression of Alzheimer’s disease, as well as lower cognitive performance in general as tracked, interestingly enough, via skin autofluorescence. AGEs have a natural fluorescence that you can pick up using a special detector, enabling a simple non-invasive assessment of advanced glycation end product accumulation in the body.

The more meat you eat, the more of the AGE skin autofluorescence you get, which then correlates with cognitive impairment. In fact, one of these days, these fluorescence scanners may be included in routine medical check-ups. Since meat is the main high-AGE food, it should be no surprise that AGE skin autofluorescence measurements are significantly lower in those eating more plant-based. So, the data suggest reduction of food-derived AGEs is feasible, and may provide an effective treatment strategy for our epidemics of Alzheimer’s and metabolic disease.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

The video I mentioned is The Best Diet for Healthy Aging. Glycation is actually one of the pathways of aging I cover in my upcoming book How Not to Age. (As always, all proceeds go to charity.) Stay tuned! 

For more videos on brain health, see:

Can Alzheimer’s Disease Be Reversed with a Plant-Based Diet? Check out the video. What does improving the cognition and function of Alzheimer’s patients with lifestyle medicine actually translate to in terms of human impact? See the video.

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