One way a diet rich in animal-sourced foods like meat, eggs, and cheese may contribute to heart disease, stroke, kidney failure, and death is through the production of toxin called TMAO.
How to Treat Heart Failure & Kidney Failure with Diet
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.
One way a diet rich in animal-sourced foods—meat, eggs, and cheese—may contribute to heart disease, stroke, and death is through the production of an atherosclerosis-inducing substance called TMAO. With the help of certain gut bacteria, the choline and carnitine found concentrated in animal products can get converted into TMAO. But, wait a second: I thought atherosclerosis—hardening of the arteries—was about the buildup of cholesterol.
“Cholesterol is still king.” TMAO just appears to accelerate the process. TMAO appears to increase the ability of inflammatory cells within the atherosclerotic plaque in the artery wall to bind to LDL cholesterol, which makes it “more prone to gobble up [that] cholesterol.” So, it’s just “another piece of the puzzle [of] how cholesterol causes heart disease.”
And, TMAO doesn’t just appear to worsen atherosclerosis—contributing to strokes and heart attacks—but also heart failure and kidney failure. If you look at a really high-risk group, like diabetics after a heart attack, nearly all those who started out with the most TMAO in their bloodstream went on to develop heart failure within 2,000 days—about five years, whereas only about 20% of those starting out with medium levels in the blood went into heart failure, and none in the low-TMAO group.
Not only do those with heart failure have higher levels of TMAO than controls, and those with worse heart failure have higher levels than those with lesser stage disease, if you follow people with heart failure over time, within six years, half of those who started out with the highest levels were dead. This finding has since been replicated in two other independent populations of heart failure patients.
The question is, why? It’s “probably unlikely” to just be additional atherosclerosis, since that takes years. For most of those that die of heart failure, the heart muscle just conks out, or there’s a fatal heart rhythm. So, maybe TMAO has toxic effects beyond just the accelerated buildup of cholesterol.
What about kidney failure? People with chronic kidney disease are at particularly “increased risk for the development of cardiovascular disease,” thought to be because of a diverse array of “uremic toxins.” These are toxins that would normally be filtered out by the kidneys into the urine, but may build up in the bloodstream as our kidney function declines. When we think of uremic toxins, we usually think of the toxic byproducts of protein, putrefying in our gut—which is why specially formulated, plant-based diets have been used for decades to treat chronic kidney failure. Those who eat vegetarian form less than half of these uremic toxins in the first place. But, those aren’t the only uremic toxins. TMAO, from the breakdown of choline and carnitine, in mostly meat and eggs, may be increasing heart disease risk in kidney patients as well, by apparently downregulating “reverse cholesterol transport”—meaning subverting our own bodies’ attempt at pulling cholesterol out of our arteries.
And indeed, the worse people’s kidney function gets, the higher their TMAO levels rise, and those elevated levels correlate with the amount of plaque they have clogging up the arteries in their heart. But, get a kidney transplant, get a working kidney going, and kidney patients can drop their TMAO levels right back down. So, TMAO was thought to be kind of a biomarker for declining kidney function. But then, this study was published from the Framingham Heart Study, which found that elevated choline and TMAO levels among individuals with normal kidney function predicted increased risk for developing chronic kidney disease—suggesting TMAO is both a biomarker and itself a kidney toxin.
Indeed, when you follow kidney patients over time, and assess their freedom from death, those with higher TMAO—even controlling for kidney function—lived significantly shorter lives, indicating this is a diet-induced mechanism for progressive kidney scarring and dysfunction, strongly implying “the need to focus preventi[ti]ve efforts on dietary [modification].”
What might that look like? Well, maybe we should reduce “dietary sources of TMAO generation, such as some species of deep-sea fish, eggs, and meat.” But, it also depends on what kind of gut bacteria you have. Remember, you can feed a vegan a steak, and they still don’t really make any TMAO, because they haven’t been fostering the carnitine-eating bacteria in their gut. Researchers are hoping, however, that one day, they’ll find a way to replicate the effects of a vegetarian diet “by selective prebiotic, probiotic, or [antibiotic] therapies.”
Please consider volunteering to help out on the site.
- Torres N, Guevara-Cruz M, Velázquez-Villegas LA, Tovar AR. Nutrition and Atherosclerosis. Arch Med Res. 2015 Jul;46(5):408-26.
- Cannon JA, McMurray JJ. Gut feelings about heart failure. J Am Coll Cardiol. 2014 Nov 4;64(18):1915-6.
- Tang WH, Wang Z, Shrestha K, Borowski AG, Wu Y, Troughton RW, Klein AL, Hazen SL. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Card Fail. 2015 Feb;21(2):91-6.
- Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, Li XS, Levison BS, Hazen SL. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015 Jan 30;116(3):448-55.
- Willyard C. Pathology: At the heart of the problem. Nature. 2013 Jan 31;493(7434):S10-1.
- Moraes C, Fouque D, Amaral AC, Mafra D. Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet. J Ren Nutr. 2015 Nov;25(6):459-65.
- (authors unknown) Cleveland Clinic. Gut Flora-Dependent TMAO: New Studies Extend Its Reach Beyond the Arteries to the Heart and Kidneys. Feb. 12, 2015 / Heart & Vascular / Research.
- Trøseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, Aakhus S, Gude E, Bjørndal B, Halvorsen B, Karlsen TH, Aukrust P, Gullestad L, Berge RK, Yndestad A. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med. 2015 Jun;277(6):717-26.
- Vanholder R, De Smet R, Lesaffer G. p-cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity. Nephrol Dial Transplant. 1999 Dec;14(12):2813-5.
- Barsotti G, Morelli E, Cupisti A, Meola M, Dani L, Giovannetti S. A low-nitrogen low-phosphorus Vegan diet for patients with chronic renal failure. Nephron. 1996;74(2):390-4.
- Patel KP, Luo FJ, Plummer NS, Hostetter TH, Meyer TW. The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. Clin J Am Soc Nephrol. 2012;7(6):982-8.
- Tang WH. Trimethylamine N-Oxide as a Novel Therapeutic Target in CKD. J Am Soc Nephrol. 2016;27(1):8-10.
Image credit: Monsterkoi via Pixabay. Image has been modified.
- animal products
- antibiotics
- cardiovascular disease
- carnitine
- cheese
- cholesterol
- choline
- dairy
- eggs
- fish
- Framingham Heart Study
- gut flora
- heart disease
- heart failure
- kidney disease
- kidney failure
- kidney function
- LDL cholesterol
- meat
- microbiome
- mortality
- Plant-Based Diets
- prebiotics
- probiotics
- standard American diet
- stroke
- TMAO
- vegans
- vegetarians
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.
One way a diet rich in animal-sourced foods—meat, eggs, and cheese—may contribute to heart disease, stroke, and death is through the production of an atherosclerosis-inducing substance called TMAO. With the help of certain gut bacteria, the choline and carnitine found concentrated in animal products can get converted into TMAO. But, wait a second: I thought atherosclerosis—hardening of the arteries—was about the buildup of cholesterol.
“Cholesterol is still king.” TMAO just appears to accelerate the process. TMAO appears to increase the ability of inflammatory cells within the atherosclerotic plaque in the artery wall to bind to LDL cholesterol, which makes it “more prone to gobble up [that] cholesterol.” So, it’s just “another piece of the puzzle [of] how cholesterol causes heart disease.”
And, TMAO doesn’t just appear to worsen atherosclerosis—contributing to strokes and heart attacks—but also heart failure and kidney failure. If you look at a really high-risk group, like diabetics after a heart attack, nearly all those who started out with the most TMAO in their bloodstream went on to develop heart failure within 2,000 days—about five years, whereas only about 20% of those starting out with medium levels in the blood went into heart failure, and none in the low-TMAO group.
Not only do those with heart failure have higher levels of TMAO than controls, and those with worse heart failure have higher levels than those with lesser stage disease, if you follow people with heart failure over time, within six years, half of those who started out with the highest levels were dead. This finding has since been replicated in two other independent populations of heart failure patients.
The question is, why? It’s “probably unlikely” to just be additional atherosclerosis, since that takes years. For most of those that die of heart failure, the heart muscle just conks out, or there’s a fatal heart rhythm. So, maybe TMAO has toxic effects beyond just the accelerated buildup of cholesterol.
What about kidney failure? People with chronic kidney disease are at particularly “increased risk for the development of cardiovascular disease,” thought to be because of a diverse array of “uremic toxins.” These are toxins that would normally be filtered out by the kidneys into the urine, but may build up in the bloodstream as our kidney function declines. When we think of uremic toxins, we usually think of the toxic byproducts of protein, putrefying in our gut—which is why specially formulated, plant-based diets have been used for decades to treat chronic kidney failure. Those who eat vegetarian form less than half of these uremic toxins in the first place. But, those aren’t the only uremic toxins. TMAO, from the breakdown of choline and carnitine, in mostly meat and eggs, may be increasing heart disease risk in kidney patients as well, by apparently downregulating “reverse cholesterol transport”—meaning subverting our own bodies’ attempt at pulling cholesterol out of our arteries.
And indeed, the worse people’s kidney function gets, the higher their TMAO levels rise, and those elevated levels correlate with the amount of plaque they have clogging up the arteries in their heart. But, get a kidney transplant, get a working kidney going, and kidney patients can drop their TMAO levels right back down. So, TMAO was thought to be kind of a biomarker for declining kidney function. But then, this study was published from the Framingham Heart Study, which found that elevated choline and TMAO levels among individuals with normal kidney function predicted increased risk for developing chronic kidney disease—suggesting TMAO is both a biomarker and itself a kidney toxin.
Indeed, when you follow kidney patients over time, and assess their freedom from death, those with higher TMAO—even controlling for kidney function—lived significantly shorter lives, indicating this is a diet-induced mechanism for progressive kidney scarring and dysfunction, strongly implying “the need to focus preventi[ti]ve efforts on dietary [modification].”
What might that look like? Well, maybe we should reduce “dietary sources of TMAO generation, such as some species of deep-sea fish, eggs, and meat.” But, it also depends on what kind of gut bacteria you have. Remember, you can feed a vegan a steak, and they still don’t really make any TMAO, because they haven’t been fostering the carnitine-eating bacteria in their gut. Researchers are hoping, however, that one day, they’ll find a way to replicate the effects of a vegetarian diet “by selective prebiotic, probiotic, or [antibiotic] therapies.”
Please consider volunteering to help out on the site.
- Torres N, Guevara-Cruz M, Velázquez-Villegas LA, Tovar AR. Nutrition and Atherosclerosis. Arch Med Res. 2015 Jul;46(5):408-26.
- Cannon JA, McMurray JJ. Gut feelings about heart failure. J Am Coll Cardiol. 2014 Nov 4;64(18):1915-6.
- Tang WH, Wang Z, Shrestha K, Borowski AG, Wu Y, Troughton RW, Klein AL, Hazen SL. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Card Fail. 2015 Feb;21(2):91-6.
- Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, Li XS, Levison BS, Hazen SL. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015 Jan 30;116(3):448-55.
- Willyard C. Pathology: At the heart of the problem. Nature. 2013 Jan 31;493(7434):S10-1.
- Moraes C, Fouque D, Amaral AC, Mafra D. Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet. J Ren Nutr. 2015 Nov;25(6):459-65.
- (authors unknown) Cleveland Clinic. Gut Flora-Dependent TMAO: New Studies Extend Its Reach Beyond the Arteries to the Heart and Kidneys. Feb. 12, 2015 / Heart & Vascular / Research.
- Trøseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, Aakhus S, Gude E, Bjørndal B, Halvorsen B, Karlsen TH, Aukrust P, Gullestad L, Berge RK, Yndestad A. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med. 2015 Jun;277(6):717-26.
- Vanholder R, De Smet R, Lesaffer G. p-cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity. Nephrol Dial Transplant. 1999 Dec;14(12):2813-5.
- Barsotti G, Morelli E, Cupisti A, Meola M, Dani L, Giovannetti S. A low-nitrogen low-phosphorus Vegan diet for patients with chronic renal failure. Nephron. 1996;74(2):390-4.
- Patel KP, Luo FJ, Plummer NS, Hostetter TH, Meyer TW. The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. Clin J Am Soc Nephrol. 2012;7(6):982-8.
- Tang WH. Trimethylamine N-Oxide as a Novel Therapeutic Target in CKD. J Am Soc Nephrol. 2016;27(1):8-10.
Image credit: Monsterkoi via Pixabay. Image has been modified.
- animal products
- antibiotics
- cardiovascular disease
- carnitine
- cheese
- cholesterol
- choline
- dairy
- eggs
- fish
- Framingham Heart Study
- gut flora
- heart disease
- heart failure
- kidney disease
- kidney failure
- kidney function
- LDL cholesterol
- meat
- microbiome
- mortality
- Plant-Based Diets
- prebiotics
- probiotics
- standard American diet
- stroke
- TMAO
- vegans
- vegetarians
Republishing "How to Treat Heart Failure & Kidney Failure with Diet"
You may republish this material online or in print under our Creative Commons licence. You must attribute the article to NutritionFacts.org with a link back to our website in your republication.
If any changes are made to the original text or video, you must indicate, reasonably, what has changed about the article or video.
You may not use our material for commercial purposes.
You may not apply legal terms or technological measures that restrict others from doing anything permitted here.
If you have any questions, please Contact Us
How to Treat Heart Failure & Kidney Failure with Diet
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
For more on this revolutionary TMAO story, see:
- Carnitine, Choline, Cancer, and Cholesterol: The TMAO Connection
- Egg Industry Response to Choline and TMAO
- How to Develop a Healthy Gut Ecosystem
- How Our Gut Bacteria Can Use Eggs to Accelerate Cancer
- How to Reduce Your TMAO Levels
For more on kidney failure, see Preventing Kidney Failure Through Diet and Treating Kidney Failure Through Diet.
If you haven't yet, you can subscribe to our free newsletter. With your subscription, you'll also get notifications for just-released blogs and videos. Check out our information page about our translated resources.