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FLORA LICHTMAN, HOST:

This is SCIENCE FRIDAY, I'm Flora Lichtman, filling in for Ira today. You know the phrase you are what you eat? Well, new research suggests a slight modification: Your gut bacteria are what you eat. And if you eat more red meat, for example, you'll nurture populations of microbes that like to eat red meat, too, which might not seem like a bad thing except that researchers have pinpointed a compound in red meat called L-carnitine that when broken down by gut bacteria might contribute to heart disease.

So the more bugs you have to break it down, the worse off you might be. It's another culprit, like cholesterol and fat, linking red meat to heart disease. Is it time to swear off steak? Dr. Stanley Hazen is chair of the Department of Cellular and Molecular Medicine at the Lerner Research Institute at the Cleveland Clinic in Cleveland, Ohio. He's also lead author on the red meat study in the journal Nature Medicine. Welcome to SCIENCE FRIDAY, Dr. Hazen.

STANLEY HAZEN: Thank you.

LICHTMAN: Tell us a little bit more about this compound L-carnitine.

HAZEN: So carnitine is a form of an amino acid. We make it in our own bodies. All the carnitine that we need we make from our - not from our diet, but we just make it on our own. And it plays an essential role in energy metabolism. It helps to take fatty acids into something called the mitochondria, which is the powerhouse of the cell, and burn fatty acids as fuel.

And while the carnitine is not an essential nutrient, that means that we don't need to have it in our diet. We actually synthesize all the carnitine that we need from protein, and that protein can be either from plant or animal. So even vegetarians or vegans make all the carnitine that they need from their diet.

LICHTMAN: And so what's the problem about getting a little bit extra?

HAZEN: Well, what our studies show is that in our digestive tract, we have many, many bugs, microbes. They can digest carnitine; we can't. We get no calories from carnitine, but the bugs do. A byproduct that the microbes make gets released and converted in our bodies and then detected in the blood into a compound that actually helps promote clogging of the arteries or cholesterol deposition in the artery wall.

It does this by actually changing our metabolism of cholesterol. So this is not independent of cholesterol. It actually works through cholesterol. It changes how our body senses cholesterol and metabolizes cholesterol at the artery wall, in the liver and in the intestines.

LICHTMAN: So let me see if I get this - have this straight. So we eat red meat, it has carnitine it. Microbes in our body break it down, produce another compound, and that's TMAO, is that right?

HAZEN: That's TMA. That then is actually a gas, believe it or not, at body temperature. It smells like rotting fish, but we don't smell like rotting fish when we eat meat. That's because it goes straight to the liver through the portal circulation, and there's a cluster of enzymes in the liver that get rid of that compound and turn it into something called TMAO.

And that compound is the one that actually tracks with cardiovascular risk and promotes atherosclerosis both in animal studies we've - were able to show that if you feed animals carnitine, they got accelerated atherosclerosis, and they did so in a TMAO-dependent fashion. If you gave them antibiotics to suppress their intestinal flora, they no longer made the TMAO, they no longer got accelerate atherosclerosis.

If you give the downstream metabolite, TMAO, you get accelerated atherosclerosis. And then in humans, we went ahead and measured this metabolite of the carnitine, TMAO, and were able to show that blood levels of this metabolite very strongly predict future risks for heart attack, stroke and death.

LICHTMAN: And - but not everybody produces this same amount when they're given the same meal, right?

HAZEN: That was actually some of the more surprising finding of the study. When we look at the metabolism of carnitine, and we compared omnivores as compared to vegetarian or vegans, we saw strikingly different results. The omnivore, that is the individual who eats both animal products, meat, as well as vegetables, they actually metabolized carnitine very readily and formed TMAO that was detected in the blood.

In contrast, the longstanding vegetarian or vegan, and to be enrolled in our study, the subjects had to claim that they had had no animal or no meat product within the last year. So they were longstanding vegetarian or vegan. When they ingested carnitine, they made virtually no TMAO.

And we then subsequently analyzed the microbes in the feces, in the stool, and could show that the composition of the microbes in the - from the gut in the omnivore were very different from what we found in the vegetarian or vegan, and the types of microbes that actually were involved in breaking down carnitine were not found as much in the vegetarian or vegan and were abundant in the omnivore.

LICHTMAN: So you think that if you eat a lot of meat, you've sort of grown a different microbial community that's better adapted or different species that will actually break down the carnitine more efficiently than the other - than if you just eat vegetables?

HAZEN: How you said it is exactly correct. And in fact to test that, what we actually looked at was we took animals we were on a normal chow diet, which is rather vegetarian, and then added carnitine to it and then compared the capacity to make TMAO in the normal chow versus carnitine-supplemented animals, as well as looked at the microbial composition. And what we - in their stool or in their secum, that's a portion of their gut.

And what we found is that the animals that were on the chronic carnitine-containing diet, they made over 10- to 100-fold more TMAO from a carnitine bolus that was given into their stomach compared to the animals that were on the normal chow diet.

LICHTMAN: So they made more of the compound that tracks with cardiovascular risk if they'd been eating meat?

HAZEN: Yes.

LICHTMAN: So when you talk about red meat, is it more than beef?

HAZEN: It is. So carnitine is found in many things. It's - so carnitine comes from the same root word as carnivore. So carnis means flesh. So carnitine was discovered over 100 years ago, and the chemists who discovered it called it carnitine because it was found in animal products, things made of flesh.

And if you look at multiple different types of meat products, you find that the red ones - so beef, lamb, mutton, venison - these have higher levels, even duck and certain types of fish that have red, fleshy meat. They have higher levels of carnitine.

And then the white meats and the poultry and other fish that, you know, the white fish have much, much lower levels of carnitine.

LICHTMAN: Can you - do you have dietary suggestions based on this? Can you maybe still eat red meat but also eat things that encourage bacteria that compete with these TMAO-producing microbes?

HAZEN: Well, we didn't actually - I can make some suggestions, but they're kind of common-sense guesses. They're not based on actual clinical studies yet. Our studies showed that if you cut out all red meat, all meat, and became vegetarian or vegan, after a long time you would actually - that's a sure-fire way to be able to make virtually no TMAO from carnitine because every longstanding vegetarian or vegan who we looked at, who was not on any kind of supplements or anything and was just a longstanding vegetarian, they did not generate TMAO.

Now on the other hand, what we don't know is if you are an omnivore, and you switch to a vegetarian diet, how long before you start seeing this change occur. We know that it's going to be longer than a week, but we don't know if it's actually going to be - it's somewhere between a week and a year. We don't have any information on the - more specific than that.

LICHTMAN: It's amazing to me that you can change the bacteria that live in your gut just by what you eat. I mean, it makes sense, but if you think of it as an ecosystem in there, but it's surprising.

HAZEN: Well, that's exactly what it is, an ecosystem. It's a closed terrarium, if you will, and there's - and there's only so much food. And so if you change the composition of what you're eating, the types of microbes that like what you're eating with proliferate more so than the types that don't. And there's only so much space and oh so much nutrient available.

And so what - the reason why I think it showed up so clearly in this situation is we're talking about a nutrient that we do not - we don't digest ourselves. We get no calories from carnitine. And we're looking at a byproduct of the bacterial metabolism of the carnitine. So this is the waste product of the bacteria.

And then our bodies have developed call it a detoxifying mechanism to get rid of this thing called the gas that stinks called TMA. And so you could see a very dramatic difference in the subjects because the vegan or vegetarian who has very little carnitine in the diet, after a long period of time, the microbes that really critically depend on carnitine for sustenance, their numbers just dwindle, and other microbes that let's say are good at flourishing on leaf litter or, you know, vegetable parts, they increase in number.

LICHTMAN: I have really two minutes left, but I want to go to the phones quickly for a very fast, quick question. Troy(ph) in Iowa City, what's your question?

TROY: Yes, my question is: How much carnitine does a steak have? And did you just raise it to very, very high levels to get that bacteria? So why don't just lions and tigers, like, die at the age of, like, two then?

LICHTMAN: Thanks, Troy.

TROY: Because their bacteria is better than ours?

LICHTMAN: Good question.

HAZEN: OK, it is a good question. So first heart disease or clogging of the arteries, atherosclerosis, is not a disease at least in humans, in big animals, that happens quickly. In us it takes decades to develop, so - most of the time. So that's why thankfully kids, teenagers, even 20- and 30-year-olds usually don't have heart attacks. It happens in middle-aged and older.

So this is not an acute, very fast thing. It takes a long time. And most of the carnivorous animals have a shorter life span. They may get atherosclerotic plaque, I don't know, but they usually don't live more than a 10-year period as far as I can tell.

The second question you said was how much is in a steak. Well, a typical steak is thought to have about 180 milligrams on average of carnitine. And the amount that we were given in a capsule for our studies was 250 milligrams. The amount that you find in some - in, you know, on the grocery store in supplement form varies anywhere from 200, 250 milligrams to 500 milligrams.

LICHTMAN: We're going to have to leave it right there. Thank you, Dr. Hazen, for joining us, really fascinating work.

HAZEN: Thank you.

LICHTMAN: Dr. Hazen is the chair of the Department of Cellular & Molecular Medicine at the Lerner Research Institute at the Cleveland Clinic in Cleveland, Ohio. We'll be right back with Mary Roach. Stay with us.

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LICHTMAN: This is SCIENCE FRIDAY from NPR. Transcript provided by NPR, Copyright NPR.

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