Carnitine, Choline, Cancer, & Cholesterol: The TMAO Connection

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Expanding on the subject of my upcoming appearance on The Dr. Oz Show, a landmark new article in the New England Journal of Medicine shows that choline in eggs, poultry, dairy, and fish produces the same toxic TMAO as carnitine in red meat—which may help explain plant-based protection from heart disease and prostate cancer.

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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.

Earlier this month, a research team at the Cleveland Clinic offered a novel explanation as to why meat intake may be related to mortality. “Numerous studies have suggested a decrease in atherosclerotic disease risk [heart disease, our #1 killer] in vegan and vegetarian individuals compared to omnivores; [but, we’ve just assumed this was due to reduced intake] of dietary cholesterol and saturated fat…”

But, what these researchers found was that within 24 hours of carnitine consumption—eating a sirloin steak, taking a carnitine supplement—certain gut bacteria metabolize the carnitine to a toxic substance called trimethylamine, which then gets oxidized in our liver to TMAO (trimethylamine-n-oxide), which then circulates throughout our bloodstream.

The way we know it’s the gut bacteria that’s doing it, is that if you give people antibiotics to wipe out gut bacteria, you can apparently eat all the steak you want without making any TMAO. But then, if you wait a couple weeks, until your gut bacteria grows back, you’re back to the same problem. 

What’s so bad about this TMAO stuff? Well, it may increase the risk of buildup of cholesterol in the inflammatory cells in the atherosclerotic plaques in our arteries, increasing our risk of heart attack, stroke, death—and, if that isn’t enough, cardiac surgery, as well.

So, how do you stay away from carnitine? Well, there’s zero dietary requirement; our body normally makes all that we need. The problem is that the bodies of other animals also makes all that they need, so when we eat them, their carnitine can end up in our gut for those bacteria to feast upon—resulting in TMAO. Some animals make more than others; carnitine is concentrated in red meat. So, then, why is there also clip art of white meat, dairy, and eggs?

That is what most media reports missed—even though it’s the very first sentence of the paper. How do you think the researchers even thought to look into carnitine? Because gut bacteria can turn choline into TMAO, too! Given the similarity in structure between carnitine and choline, they figured that the same kind of transformation would occur into TMAO. And, that’s exactly what they found.

“Eggs, milk, liver, red meat, poultry, shell fish, and fish,…[all] believed to be major dietary sources of choline, and, hence TMAO production.” So it’s not just red meat. The good news is that this may mean a new approach “to prevent or treat heart disease,” the most obvious of which would be “to limit dietary choline intake.” But, if that means decreasing egg, meat, and dairy consumption, then the new approach sounds an awful lot like the old approach.

Unlike carnitine, we do need to take in some choline, so should vegans be worried about the choline they’re getting from beans, veggies, grains, and fruit? And, same question with carnitine. There’s a small amount of carnitine found in fruits, veggies, and grains, as well. Of course, it’s not the carnitine itself we’re worried about, but the toxic TMAO, and you can feed a vegan a steak—literally, an eight-ounce sirloin (anything in the name of science). Same whopping carnitine load, but, essentially no TMAO was produced.

Apparently, the vegans don’t develop those TMAO-producing bacteria in their gut. And, why should they? It’s like the whole prebiotic story. You eat a lot of fiber, and you select for fiber-consuming bacteria.  And, some of the compounds they make with fiber are beneficial, like the propionate I’ve talked about, that appears to have an anti-obesity effect.

So, eat fiber; select for fiber-eating bacteria. Well, if we eat a lot of animal products, we may instead be selecting for animal product-digesting bacteria, and it appears some of those waste products, like the trimethylamine, may be harmful.

Even if you eat vegan, though, you’re not necessarily out of the woods. If you regularly drink carnitine-containing energy drinks, or take carnitine supplements, or lecithin supplements, which contain choline, presumably you’d foster and maintain those same kinds of TMAO-producing bacteria in your gut, and increase your risk of heart disease and, perhaps, cancer.

About two million men in the U.S. are living with prostate cancer, but that’s better than dying from prostate cancer. Catch it when it’s localized, and your five-year survival is practically guaranteed. But, once it really starts spreading, your chances drop to about one in three.

“Thus, identification of modifiable factors that affect the progression of prostate cancer is [something that deserves study].” So, researchers at Harvard took more than a thousand men with early stage prostate cancer, and followed them for a couple years to see if there was anything in their diet associated with a resurgence of the cancer, such as a spread to the bone.

Compared to men who hardly ate any eggs, men who ate even less than a single egg a day had “a significant 2-fold increased risk of prostate cancer progression.” And, maybe it’s the choline.

“A plausible mechanism that may explain [the]…association between eggs and prostate cancer progression is high dietary choline.” Egg consumption is a determinant of how much choline you have in your blood, and higher blood choline has been associated with “a greater risk” of getting prostate cancer in the first place. So, the choline in eggs may both increase one’s risk of getting it, and then, having it spread, and, also, having it kill you.

“Choline intake and [the] risk of lethal prostate cancer.” Choline consumption is associated not just with getting cancer, and spreading cancer, but also with a significantly increased risk of dying from it. Those who ate the most “had a 70% increased risk of lethal prostate cancer.”

Another recent study found that men who consumed two and a half or more eggs per week—that’s just like one egg every three days—”had an 81% increased risk of lethal prostate cancer.” Now, it could just be the cholesterol in eggs that’s increasing fatal cancer risk, but it could also be that choline.

Maybe that’s why meat, milk, and eggs have all been associated with advanced prostate cancer, because of the choline. In fact, choline is so concentrated in cancer cells, if you follow choline uptake in the body, you can track the spread of cancer throughout your body.

But why may dietary choline increase the risk of lethal prostate cancer? It may be the TMAO, the trimethylamine oxide. The Harvard researchers speculated that the TMAO from the “high dietary choline [intake] may increase inflammation, and this may promote progression of prostate cancer to lethal disease.”

In fact, just yesterday, in the New England Journal of Medicine, that same Cleveland Clinic research team that did the carnitine study repeated the study. But, this time, instead of feeding people a steak, they fed people some hard-boiled eggs. And, just as they suspected, a similar spike in that toxic TMAO. So, it’s not just the red meat. And the link between TMAO levels in the blood and strokes, heart attacks, and death was seen even in low-risk groups like those with low-risk cholesterol levels. So, eating eggs may increase our risk regardless what our cholesterol is, because of the choline. 

It’s ironic that the choline content of eggs is something the egg industry actually boasts about. And, the industry is aware of the cancer data. Through the Freedom of Information Act, I was able to get my hands on an email from the executive director of the industry’s Egg Nutrition Center to an American Egg Board executive talking about how choline may be a culprit in promoting cancer progression: “Certainly worth keeping in mind as we continue to promote choline as another good reason to consume eggs.”

Please consider volunteering to help out on the site.

Image thanks to Nature

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.

Earlier this month, a research team at the Cleveland Clinic offered a novel explanation as to why meat intake may be related to mortality. “Numerous studies have suggested a decrease in atherosclerotic disease risk [heart disease, our #1 killer] in vegan and vegetarian individuals compared to omnivores; [but, we’ve just assumed this was due to reduced intake] of dietary cholesterol and saturated fat…”

But, what these researchers found was that within 24 hours of carnitine consumption—eating a sirloin steak, taking a carnitine supplement—certain gut bacteria metabolize the carnitine to a toxic substance called trimethylamine, which then gets oxidized in our liver to TMAO (trimethylamine-n-oxide), which then circulates throughout our bloodstream.

The way we know it’s the gut bacteria that’s doing it, is that if you give people antibiotics to wipe out gut bacteria, you can apparently eat all the steak you want without making any TMAO. But then, if you wait a couple weeks, until your gut bacteria grows back, you’re back to the same problem. 

What’s so bad about this TMAO stuff? Well, it may increase the risk of buildup of cholesterol in the inflammatory cells in the atherosclerotic plaques in our arteries, increasing our risk of heart attack, stroke, death—and, if that isn’t enough, cardiac surgery, as well.

So, how do you stay away from carnitine? Well, there’s zero dietary requirement; our body normally makes all that we need. The problem is that the bodies of other animals also makes all that they need, so when we eat them, their carnitine can end up in our gut for those bacteria to feast upon—resulting in TMAO. Some animals make more than others; carnitine is concentrated in red meat. So, then, why is there also clip art of white meat, dairy, and eggs?

That is what most media reports missed—even though it’s the very first sentence of the paper. How do you think the researchers even thought to look into carnitine? Because gut bacteria can turn choline into TMAO, too! Given the similarity in structure between carnitine and choline, they figured that the same kind of transformation would occur into TMAO. And, that’s exactly what they found.

“Eggs, milk, liver, red meat, poultry, shell fish, and fish,…[all] believed to be major dietary sources of choline, and, hence TMAO production.” So it’s not just red meat. The good news is that this may mean a new approach “to prevent or treat heart disease,” the most obvious of which would be “to limit dietary choline intake.” But, if that means decreasing egg, meat, and dairy consumption, then the new approach sounds an awful lot like the old approach.

Unlike carnitine, we do need to take in some choline, so should vegans be worried about the choline they’re getting from beans, veggies, grains, and fruit? And, same question with carnitine. There’s a small amount of carnitine found in fruits, veggies, and grains, as well. Of course, it’s not the carnitine itself we’re worried about, but the toxic TMAO, and you can feed a vegan a steak—literally, an eight-ounce sirloin (anything in the name of science). Same whopping carnitine load, but, essentially no TMAO was produced.

Apparently, the vegans don’t develop those TMAO-producing bacteria in their gut. And, why should they? It’s like the whole prebiotic story. You eat a lot of fiber, and you select for fiber-consuming bacteria.  And, some of the compounds they make with fiber are beneficial, like the propionate I’ve talked about, that appears to have an anti-obesity effect.

So, eat fiber; select for fiber-eating bacteria. Well, if we eat a lot of animal products, we may instead be selecting for animal product-digesting bacteria, and it appears some of those waste products, like the trimethylamine, may be harmful.

Even if you eat vegan, though, you’re not necessarily out of the woods. If you regularly drink carnitine-containing energy drinks, or take carnitine supplements, or lecithin supplements, which contain choline, presumably you’d foster and maintain those same kinds of TMAO-producing bacteria in your gut, and increase your risk of heart disease and, perhaps, cancer.

About two million men in the U.S. are living with prostate cancer, but that’s better than dying from prostate cancer. Catch it when it’s localized, and your five-year survival is practically guaranteed. But, once it really starts spreading, your chances drop to about one in three.

“Thus, identification of modifiable factors that affect the progression of prostate cancer is [something that deserves study].” So, researchers at Harvard took more than a thousand men with early stage prostate cancer, and followed them for a couple years to see if there was anything in their diet associated with a resurgence of the cancer, such as a spread to the bone.

Compared to men who hardly ate any eggs, men who ate even less than a single egg a day had “a significant 2-fold increased risk of prostate cancer progression.” And, maybe it’s the choline.

“A plausible mechanism that may explain [the]…association between eggs and prostate cancer progression is high dietary choline.” Egg consumption is a determinant of how much choline you have in your blood, and higher blood choline has been associated with “a greater risk” of getting prostate cancer in the first place. So, the choline in eggs may both increase one’s risk of getting it, and then, having it spread, and, also, having it kill you.

“Choline intake and [the] risk of lethal prostate cancer.” Choline consumption is associated not just with getting cancer, and spreading cancer, but also with a significantly increased risk of dying from it. Those who ate the most “had a 70% increased risk of lethal prostate cancer.”

Another recent study found that men who consumed two and a half or more eggs per week—that’s just like one egg every three days—”had an 81% increased risk of lethal prostate cancer.” Now, it could just be the cholesterol in eggs that’s increasing fatal cancer risk, but it could also be that choline.

Maybe that’s why meat, milk, and eggs have all been associated with advanced prostate cancer, because of the choline. In fact, choline is so concentrated in cancer cells, if you follow choline uptake in the body, you can track the spread of cancer throughout your body.

But why may dietary choline increase the risk of lethal prostate cancer? It may be the TMAO, the trimethylamine oxide. The Harvard researchers speculated that the TMAO from the “high dietary choline [intake] may increase inflammation, and this may promote progression of prostate cancer to lethal disease.”

In fact, just yesterday, in the New England Journal of Medicine, that same Cleveland Clinic research team that did the carnitine study repeated the study. But, this time, instead of feeding people a steak, they fed people some hard-boiled eggs. And, just as they suspected, a similar spike in that toxic TMAO. So, it’s not just the red meat. And the link between TMAO levels in the blood and strokes, heart attacks, and death was seen even in low-risk groups like those with low-risk cholesterol levels. So, eating eggs may increase our risk regardless what our cholesterol is, because of the choline. 

It’s ironic that the choline content of eggs is something the egg industry actually boasts about. And, the industry is aware of the cancer data. Through the Freedom of Information Act, I was able to get my hands on an email from the executive director of the industry’s Egg Nutrition Center to an American Egg Board executive talking about how choline may be a culprit in promoting cancer progression: “Certainly worth keeping in mind as we continue to promote choline as another good reason to consume eggs.”

Please consider volunteering to help out on the site.

Image thanks to Nature

Doctor's Note

The TMAO story is such a fascinating twist. It helps explain, for example, Harvard’s Meat & Mortality Studies. The role of the inflammatory “foam” cells (so-called because they’re so packed with cholesterol they look foamy under a microscope) affected by TMAO is explained in my video series that begins with Arterial Acne, and continues in Blocking the First Step of Heart Disease.

When I say we normally make all the carnitine we need, there’s a rare genetic inborn error of metabolism that affects as many as one in 40,000 births, which can result in a need for dietary carnitine. Learn more in When Meat Can Be a Lifesaver.

What does carnitine do? It’s involved in energy production in the mitochondria (“power plants”) in our cells. The enzyme that uses carnitine to help us burn fat (carnitine palmitoyl transferase) is actually upregulated by about 60% in those eating meat-free diets—which may help explain why those eating plant-based diets tend to be slimmer. More details in How to Upregulate Metabolism.

For more on TMAO see:

The prebiotic videos I feature are Fawning over Flora and Boosting Good Bacteria in the Colon without Probiotics, though other videos describing the beneficial products our friendly flora make from the plants we eat include:

And for another behind-the-curtain peek at the egg industry, see Eggs vs. Cigarettes in Atherosclerosis and Egg Industry Blind Spot.

For more context, check out my associated blog posts: Avoid Carnitine & Lethicin Supplements; Why are Eggs Linked to Cancer Progression?; and Top 10 Most Popular Videos of 2013.

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