Why can a single meal high in saturated fat impair cognition?
The Role of Endotoxins in Alzheimer’s and Dementia
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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.
Intro: When it comes to diet and cognitive decline, I’ve talked previously about glycotoxins, which are created when high-fat, high-protein foods are exposed to high dry heat like broiling or roasting. In this video, we look at endotoxins, which are inflammatory components of bacteria that can end up in our bloodstream. How might the presence of these toxins relate to Alzheimer’s? Watch to find out.
Having a high cholesterol level in your early 40s is associated with an increased risk of Alzheimer’s and vascular dementia decades later. And your cholesterol doesn’t have to be that high to increase dementia risk. A 57 percent higher risk of developing Alzheimer’s at a total cholesterol of 240 compared to under 200. I’ve done a bunch of videos talking about the clogging of the cerebral arteries inside of the brain with the same atherosclerosis that causes heart attacks and strokes, choking off blood flow to the memory centers in the brain.
This may be why higher saturated fat intake was found to be associated with the development of worse global cognitive function and memory decline, an apparent acceleration of brain aging as if you were six years older. How can we cut down on saturated fat? By cutting down on cheese, cake, ice cream, and chicken––essentially the top sources in the American diet, but also pork, burgers, and beef in general.
In my video on the role of glycotoxins in cognitive decline, I profiled this study, showing that just five days of a high-fat, low-carb diet impairs energy metabolism in the heart, as well as cognitive function, concluding such diets are detrimental to the heart and brain. Now, they were thinking the impaired energy production may have accounted for the brain dysfunction as well, but high levels of dietary glycotoxins, so-called AGEs, are also associated with cognitive decline. So, we may want to cut down our intake of baked, broiled, or grilled meat, chicken, or fish, as well as certain dairy products. But there’s another possibility.
“Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans?” Endotoxins are highly pro-inflammatory components of certain types of bacteria, like E. coli, that are released when bacteria die. They can end up being absorbed through our gut wall and end up in the bloodstream, resulting in what’s called endotoxemia. The highest levels of these endotoxins are found, not surprisingly, in foods like meat that are contaminated with bacteria––both red meat and white meat. And having elevated levels of endotoxins circulating in your bloodstream may be detrimental for healthy aging––associated with a large range of diseases, such as obesity, type 2 diabetes, heart disease, and depression.
Put people on a high-fat, low-carb diet for five days, and endotoxin levels in the bloodstream roughly double. Endotoxin levels before and after a few days on a high-fat diet. In fact, even a single meal can do it. Give people some sausage and egg McMuffins with hash browns, and you can get a significant increase within hours after the meal. How do we know it wasn’t the refined carbs in the muffin or something? Because the control meal had a muffin too, but lower fat and no sausage and egg. In fact, you can have people chug straight sugar water, and no change in endotoxin levels, whereas there was a big jump within hours drinking straight cream, which is pretty much straight fat. And not just any kind of fat, but mostly saturated fat.
A double-blind, randomized crossover trial demonstrated that a single meal high in saturated fat can impede attention (meaning the cognitive ability to distinguish target stimuli from distractors in a computer game), compared with an identical meal high in the kind of fat found more in nuts, seeds, and avocados. And this cognitive deficit was present five hours after the meal, and who knows how much longer after that.
There are two ways to cut down on endotoxin bursts after meals. One is to not eat so many in the first place. But if you do eat meat and dairy, the addition of fiber-rich foods can blunt the endotoxin surge. The same sausage and egg McMuffin endotoxin bomb, but with or without Fiber One Original cereal, which would be like 30 grams of fiber, and it seemed to glom on to the endotoxins, preventing the bump of endotoxemia three hours after the meal. The fiber also reduced the oxidative stress, the free radicals generated by such a meal––showing clearly that the addition of fiber to the high-fat, high-calorie meal had profound effects on metabolic and inflammatory events after the meal. And over time, meal after meal, this could have long-term implications.
Recent investigations reported higher abundance of endotoxins in the brains of patients with Alzheimer’s disease on autopsy—endotoxins building up in the memory center of the brain, the region of the brain that develops the earliest and most profound neuropathology in Alzheimer’s. Some advanced Alzheimer’s patients had up to a 26-fold increase in endotoxin levels over age-matched controls without dementia. And where were the endotoxins concentrated? Smack dab in the middle of the amyloid plaques, a pathology characteristic of Alzheimer’s. The endotoxins are staining red here, and the amyloid staining green. You can see how they superimpose right over each other, suggesting endotoxins may be playing a role in the formation of these plaques, like happens in the brains of other animals.
For these and other reasons, proper nutrition has been proposed as a promising non-medical strategy to prevent cognitive decline and subsequent dementia.
Please consider volunteering to help out on the site.
- Solomon A, Kivipelto M, Wolozin B, Zhou J, Whitmer RA. Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later. Dement Geriatr Cogn Disord. 2009;28(1):75-80.
- Okereke OI, Rosner BA, Kim DH, et al. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol. 2012;72(1):124-134.
- National Cancer Institute. Identification of top food sources of various dietary components. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2019.
- Holloway CJ, Cochlin LE, Emmanuel Y, et al. A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects. Am J Clin Nutr. 2011;93(4):748-755.
- West RK, Moshier E, Lubitz I, et al. Dietary advanced glycation end products are associated with decline in memory in young elderly. Mech Ageing Dev. 2014;140:10-12.
- Kellow NJ, Coughlan MT, Reid CM. Association between habitual dietary and lifestyle behaviours and skin autofluorescence (Saf), a marker of tissue accumulation of advanced glycation endproducts (Ages), in healthy adults. Eur J Nutr. 2018;57(6):2209-2216.
- André P, Laugerette F, Féart C. Metabolic endotoxemia: a potential underlying mechanism of the relationship between dietary fat intake and risk for cognitive impairments in humans? Nutrients. 2019;11(8):1887.
- Erridge C. Accumulation of stimulants of Toll-like receptor (Tlr)-2 and TLR4 in meat products stored at 5 °C. J Food Sci. 2011;76(2):H72-79.
- Bowser SM, McMillan RP, Boutagy NE, et al. Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans. Metabolism. 2020;103:154041.
- Anderson AS, Haynie KR, McMillan RP, et al. Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity. Obesity (Silver Spring). 2015;23(4):720-724.
- Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009;32(12):2281-2287.
- Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care. 2010;33(5):991-997.
- Madison AA, Belury MA, Andridge R, et al. Afternoon distraction: a high-saturated-fat meal and endotoxemia impact postmeal attention in a randomized crossover trial. Am J Clin Nutr. 2020;111(6):1150-1158.
- Ghanim H, Batra M, Abuaysheh S, et al. Antiinflammatory and ros suppressive effects of the addition of fiber to a high-fat high-calorie meal. J Clin Endocrinol Metab. 2017;102(3):858-869.
- Zhao Y, Jaber V, Lukiw WJ. Secretory products of the human gi tract microbiome and their potential impact on alzheimer’s disease (Ad): detection of lipopolysaccharide (Lps) in ad hippocampus. Front Cell Infect Microbiol. 2017;7:318.
- Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology. 2016;87(22):2324-2332.
Motion graphics by Avo Media
- advanced glycation end-products (AGEs)
- aging
- Alzheimer’s disease
- animal products
- baking
- barbecuing
- beef
- brain health
- cardiovascular disease
- cardiovascular health
- cholesterol
- cognition
- cooking methods
- dairy
- dementia
- depression
- diabetes
- E. coli
- endotoxins
- fat
- fiber
- free radicals
- glycotoxins
- heart disease
- inflammation
- low-carb diets
- low-fat diets
- metabolism
- obesity
- oxidative stress
- pork
- saturated fat
- standard American diet
- stroke
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.
Intro: When it comes to diet and cognitive decline, I’ve talked previously about glycotoxins, which are created when high-fat, high-protein foods are exposed to high dry heat like broiling or roasting. In this video, we look at endotoxins, which are inflammatory components of bacteria that can end up in our bloodstream. How might the presence of these toxins relate to Alzheimer’s? Watch to find out.
Having a high cholesterol level in your early 40s is associated with an increased risk of Alzheimer’s and vascular dementia decades later. And your cholesterol doesn’t have to be that high to increase dementia risk. A 57 percent higher risk of developing Alzheimer’s at a total cholesterol of 240 compared to under 200. I’ve done a bunch of videos talking about the clogging of the cerebral arteries inside of the brain with the same atherosclerosis that causes heart attacks and strokes, choking off blood flow to the memory centers in the brain.
This may be why higher saturated fat intake was found to be associated with the development of worse global cognitive function and memory decline, an apparent acceleration of brain aging as if you were six years older. How can we cut down on saturated fat? By cutting down on cheese, cake, ice cream, and chicken––essentially the top sources in the American diet, but also pork, burgers, and beef in general.
In my video on the role of glycotoxins in cognitive decline, I profiled this study, showing that just five days of a high-fat, low-carb diet impairs energy metabolism in the heart, as well as cognitive function, concluding such diets are detrimental to the heart and brain. Now, they were thinking the impaired energy production may have accounted for the brain dysfunction as well, but high levels of dietary glycotoxins, so-called AGEs, are also associated with cognitive decline. So, we may want to cut down our intake of baked, broiled, or grilled meat, chicken, or fish, as well as certain dairy products. But there’s another possibility.
“Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans?” Endotoxins are highly pro-inflammatory components of certain types of bacteria, like E. coli, that are released when bacteria die. They can end up being absorbed through our gut wall and end up in the bloodstream, resulting in what’s called endotoxemia. The highest levels of these endotoxins are found, not surprisingly, in foods like meat that are contaminated with bacteria––both red meat and white meat. And having elevated levels of endotoxins circulating in your bloodstream may be detrimental for healthy aging––associated with a large range of diseases, such as obesity, type 2 diabetes, heart disease, and depression.
Put people on a high-fat, low-carb diet for five days, and endotoxin levels in the bloodstream roughly double. Endotoxin levels before and after a few days on a high-fat diet. In fact, even a single meal can do it. Give people some sausage and egg McMuffins with hash browns, and you can get a significant increase within hours after the meal. How do we know it wasn’t the refined carbs in the muffin or something? Because the control meal had a muffin too, but lower fat and no sausage and egg. In fact, you can have people chug straight sugar water, and no change in endotoxin levels, whereas there was a big jump within hours drinking straight cream, which is pretty much straight fat. And not just any kind of fat, but mostly saturated fat.
A double-blind, randomized crossover trial demonstrated that a single meal high in saturated fat can impede attention (meaning the cognitive ability to distinguish target stimuli from distractors in a computer game), compared with an identical meal high in the kind of fat found more in nuts, seeds, and avocados. And this cognitive deficit was present five hours after the meal, and who knows how much longer after that.
There are two ways to cut down on endotoxin bursts after meals. One is to not eat so many in the first place. But if you do eat meat and dairy, the addition of fiber-rich foods can blunt the endotoxin surge. The same sausage and egg McMuffin endotoxin bomb, but with or without Fiber One Original cereal, which would be like 30 grams of fiber, and it seemed to glom on to the endotoxins, preventing the bump of endotoxemia three hours after the meal. The fiber also reduced the oxidative stress, the free radicals generated by such a meal––showing clearly that the addition of fiber to the high-fat, high-calorie meal had profound effects on metabolic and inflammatory events after the meal. And over time, meal after meal, this could have long-term implications.
Recent investigations reported higher abundance of endotoxins in the brains of patients with Alzheimer’s disease on autopsy—endotoxins building up in the memory center of the brain, the region of the brain that develops the earliest and most profound neuropathology in Alzheimer’s. Some advanced Alzheimer’s patients had up to a 26-fold increase in endotoxin levels over age-matched controls without dementia. And where were the endotoxins concentrated? Smack dab in the middle of the amyloid plaques, a pathology characteristic of Alzheimer’s. The endotoxins are staining red here, and the amyloid staining green. You can see how they superimpose right over each other, suggesting endotoxins may be playing a role in the formation of these plaques, like happens in the brains of other animals.
For these and other reasons, proper nutrition has been proposed as a promising non-medical strategy to prevent cognitive decline and subsequent dementia.
Please consider volunteering to help out on the site.
- Solomon A, Kivipelto M, Wolozin B, Zhou J, Whitmer RA. Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later. Dement Geriatr Cogn Disord. 2009;28(1):75-80.
- Okereke OI, Rosner BA, Kim DH, et al. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol. 2012;72(1):124-134.
- National Cancer Institute. Identification of top food sources of various dietary components. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2019.
- Holloway CJ, Cochlin LE, Emmanuel Y, et al. A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects. Am J Clin Nutr. 2011;93(4):748-755.
- West RK, Moshier E, Lubitz I, et al. Dietary advanced glycation end products are associated with decline in memory in young elderly. Mech Ageing Dev. 2014;140:10-12.
- Kellow NJ, Coughlan MT, Reid CM. Association between habitual dietary and lifestyle behaviours and skin autofluorescence (Saf), a marker of tissue accumulation of advanced glycation endproducts (Ages), in healthy adults. Eur J Nutr. 2018;57(6):2209-2216.
- André P, Laugerette F, Féart C. Metabolic endotoxemia: a potential underlying mechanism of the relationship between dietary fat intake and risk for cognitive impairments in humans? Nutrients. 2019;11(8):1887.
- Erridge C. Accumulation of stimulants of Toll-like receptor (Tlr)-2 and TLR4 in meat products stored at 5 °C. J Food Sci. 2011;76(2):H72-79.
- Bowser SM, McMillan RP, Boutagy NE, et al. Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans. Metabolism. 2020;103:154041.
- Anderson AS, Haynie KR, McMillan RP, et al. Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity. Obesity (Silver Spring). 2015;23(4):720-724.
- Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009;32(12):2281-2287.
- Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care. 2010;33(5):991-997.
- Madison AA, Belury MA, Andridge R, et al. Afternoon distraction: a high-saturated-fat meal and endotoxemia impact postmeal attention in a randomized crossover trial. Am J Clin Nutr. 2020;111(6):1150-1158.
- Ghanim H, Batra M, Abuaysheh S, et al. Antiinflammatory and ros suppressive effects of the addition of fiber to a high-fat high-calorie meal. J Clin Endocrinol Metab. 2017;102(3):858-869.
- Zhao Y, Jaber V, Lukiw WJ. Secretory products of the human gi tract microbiome and their potential impact on alzheimer’s disease (Ad): detection of lipopolysaccharide (Lps) in ad hippocampus. Front Cell Infect Microbiol. 2017;7:318.
- Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology. 2016;87(22):2324-2332.
Motion graphics by Avo Media
- advanced glycation end-products (AGEs)
- aging
- Alzheimer’s disease
- animal products
- baking
- barbecuing
- beef
- brain health
- cardiovascular disease
- cardiovascular health
- cholesterol
- cognition
- cooking methods
- dairy
- dementia
- depression
- diabetes
- E. coli
- endotoxins
- fat
- fiber
- free radicals
- glycotoxins
- heart disease
- inflammation
- low-carb diets
- low-fat diets
- metabolism
- obesity
- oxidative stress
- pork
- saturated fat
- standard American diet
- stroke
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Title
The Role of Endotoxins in Alzheimer’s and Dementia
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
The video I mentioned about glycotoxins just came out recently. See Advanced Glycation End Products (AGEs) and Cognitive Decline.
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.
My videos on the clogging of cerebral arteries include:
- Flashback Friday: Alzheimer’s and Atherosclerosis of the Brain
- Cholesterol and Alzheimer’s Disease
- Oxidized Cholesterol as a Cause of Alzheimer’s Disease
Check out these two videos on the connection between supplements and Alzheimer’s: Can Vitamin E or Selenium Supplements Prevent or Treat Alzheimer’s? and Centrum Multivitamin, Vitamin C, Beta Carotene, Souvenaid, Zinc, or Calcium Supplements to Prevent Alzheimer’s.
Does Aluminum Cause Alzheimer’s Disease? Check out the video.
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