Transcript: Carnitine, Choline, Cancer, and Cholesterol: The TMAO Connection
Earlier this month, a research team at the Cleveland Clinic offered another explanation as to why meat intake may be related to mortality. "Numerous studies have suggested a decrease in atherosclerotic disease risk—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 they 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 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's there also clipart of white meat, dairy, and eggs?
That's 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 they’d find that same transformation into TMAO, and that's exactly what they found.
Eggs, milk, liver, red meat, poultry, shell fish and fish are 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, 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 modest amounts of 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 8-ounce sirloin (anything in the name of science). Same whopping carnitine load, but basically 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. 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 5-year survival is practically guaranteed, but once it really starts spreading your chances drop to 1 in 3. "Thus, identification of modifiable factors that affect the progression of prostate cancer is something that deserves study. So Harvard researchers 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 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 2 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 the 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 you can track the spread of cancer through the body. But why may dietary choline increase the risk of lethal prostate cancer? It may be 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. Just as they suspected, a similar spike in that toxic TMAO, so it's not just red meat. And the link between TMAO levels in the blood and strokes, heart attack, 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."
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring watch the above video. This is just an approximation of the audio contributed by Jonathan Hodgson.
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