What is carnitine?
Carnitine is a compound our body produces. It helps turn fat into energy. Usually, our bodies make all the carnitine we need. But many of us get more carnitine, a lot more, from sources like red meat, energy drinks, and supplements.
According to the new research, carnitine itself is not clogging up arteries. It’s more like a middleman. Bacteria in the digestive tract get hold of the carnitine we eat and convert it into trimethylamine-N-oxide (TMAO), and it is high levels of TMAO that appear to do the dirty work, enabling cholesterol to burrow into artery walls and build up plaque.
“This is certainly an interesting new area of research in that it suggests yet another plausible mechanism by which a steady diet of red meat or L-carnitine supplements may speed up the development of coronary artery disease,” notes Dr. Jay Kenney, nutrition research specialist and educator at the Pritikin Longevity Center.
But on April 7, when the study came out, much of the media unfortunately went overboard. Several reporters left the public with the impression that high carnitine intake was even more responsible for the clogging up of arteries than high intakes of saturated fat and dietary cholesterol.
One of the biggest exaggerators of the facts was Gina Kolata of The New York Times. She wrote that the study’s authors “suspected that saturated fat and cholesterol made only a minor contribution to the increased amount of heart disease seen in red-meat eaters,” and that the “real culprit” was carnitine turned into TMAO.
But the study’s authors, led by Stanley Hazen, MD, PhD, of the Cleveland Clinic, never stated any such thing.
In response to Gina Kolata’s comments above, Dr. Hazen told Pritikin Perspective: “That was journalistic license. I don’t agree, and would not claim that at this point. And our paper didn’t either.”
More research needed
Concurs Dr. Kenney: “Clearly, the researchers themselves are not saying that TMAO is the real cause of atherosclerosis. Yes, high levels of TMAO may turn out to be a key risk factor, but we need more research.
“It is important to note that we don’t know yet if lowering TMAO would help reduce cardiovascular risk. Remember a few years back when elevated homocysteine levels were associated with heart disease? At first, everyone got excited. But then scientists discovered in several clinical trials that lowering homocysteine with B-vitamin supplements unfortunately failed to reduce heart attacks.
“For now, this new research merely gives us yet another potential health benefit we may accrue from reducing red meat and carnitine intake.”
Agrees Tom Rifai, MD, member of the Pritikin Scientific Advisory Board and Medical Director of Metabolic Nutrition & Weight Management at St Joseph Mercy Oakland Hospital in Michigan:
“The high calories, saturated fat, and heme iron load, which aggravates insulin resistance, have plenty of guilt to explain the toxicity of red meat for many who suffer from being over fat, or have excess body iron load, or high blood levels of cholesterol, or any combination of these problems. TMAO wouldn’t replace this list of cardiovascular risk factors. It would only join it.”
What’s important to know
Here are more key facts and takeaways about the new research on carnitine and TMAO. Just the facts. No media hype. But even without the hype, the data are intriguing.
TMAO does appear troublesome.
A high level of TMAO, studies in mice and humans have found, may not only enable more LDL bad cholesterol to get into artery walls and build up plaque, it may also impair the ability of HDL good cholesterol to remove cholesterol deposits from arteries – “with a net effect of increasing atherosclerosis,” summarizes Dr. Hazen.
And the research implicating TMAO grows. Just this week, a study published in the New England Journal of Medicine found that among 4,007 heart patients followed for three years, higher levels of TMAO meant greater risk for cardiovascular problems.2
Vegetarian and near-vegetarian eating plans like Pritikin may be even healthier than we thought.
When testing the normal daily levels of TMAO of three different groups of people – meat-eaters, vegetarians, and vegans (vegans eat no animal products, including dairy foods) – Dr. Hazen and colleagues found, as they expected, that the meat-eaters had significantly higher levels of TMAO.
But it’s what they discovered next that surprised them. They fed all their subjects, including the vegetarians and vegans, 8-ounce steaks. They anticipated that the carnitine-rich steaks would send the TMAO levels of all three groups soaring.
It didn’t happen. Only the TMAO levels of the regular meat-eaters shot up. It turned out the bacteria community in the guts of vegans and vegetarians was different from that of the meat-eaters, and it made them far less likely than the meat-eaters to convert the steak’s carnitine into artery-damaging TMAO.
The same thing happened when the three groups were given carnitine supplements. Only the TMAO levels of the meat-eaters soared.
It appears we don’t all have the same bacteria in our guts. And what we have is dictated by our dietary patterns, pointed out Dr. Hazen in a Cleveland Clinic news release:
“A diet high in carnitine actually shifts our gut microbe composition to those that like carnitine, making meat eaters even more susceptible to forming TMAO and its artery-clogging effects. Meanwhile, vegans and vegetarians have a significantly reduced capacity to synthesize TMAO from carnitine.”
How much red meat is too much?
An important question this new study does not answer is: Can we eat very small amounts of lean red meat (no more than 4 ounces weekly, as the Pritikin Eating Plan recommends), and still have, like the vegetarians and vegans studied, gut bacteria that keep TMAO production down?
“We just don’t know what amount of red meat is low enough to look like the long-term vegetarian and vegans studied,” Dr. Hazen told Pritikin Perspective. He himself still eats steak “but much less frequently” – no more than twice a month, and in much smaller portions, about 4 to 6 ounces.
“Odds are the bacteria that induce TMOA production from dietary carnitine would largely die off on an eating plan like Pritikin,” surmises Dr. Kenney. “And so the occasional lean red meat meal would likely result in very little TMAO getting produced.
“But clearly, the potential of gut-generated TMAO to promote atherosclerosis warrants further research. For now, the science we have is not compelling enough to change what the Pritikin Eating Plan recommends for lean red meat consumption, which is no more than one 4-ounce serving per week, and preferably grass-fed, free-range game meat like bison.”
To be sure, the Pritikin Program has always encouraged fish and skinless white poultry over red meat. Fish and poultry have far less carnitine, less heme iron, and, in most cases, less saturated fat.
Any supplements of carnitine and/or choline may be too much.
Carnitine is added as a supplement to many popular energy drinks. It’s also available in pill form. The supplement industry has led body builders to believe that carnitine will rev up fat metabolism and build muscle, but the extra carnitine, according to this new research, may actually be building up cholesterol in the arteries.
“Carnitine is not an essential nutrient,” explains Dr. Hazen. “Our body naturally produces all we need. We need to examine the safety of chronically consuming carnitine supplements as we’ve shown that, under some conditions, it can foster the growth of bacteria that produce TMAO and potentially clog arteries.”
There is also evidence that choline supplements, as well as lecithin supplements, are TMAO producers. In 2011, Dr. Hazen and colleagues published data showing that choline intake could also be used by gut bacteria to generate TMAO production.3
All in all, sums up Dr. Tom Rifai, “the possible dangers of TMAO is yet another reason to avoid the allure of hope in a pill, supplement, or energy drink.”
The good news is that the carnitine and choline our bodies naturally produce do not end up in our guts, so they are not converted into TMAO.
Among foods, the richest sources of choline/lecithin are egg yolks and liver, “and so they also increase TMAO production by gut bacteria,” notes Dr. Kenney. But, of course, these two foods, because of their high cholesterol content, have never been recommended on the Pritikin Eating Plan. “Now perhaps we have yet another reason to avoid them.”
A dead fish story
One of the great joys, our alumni know, of coming to the Pritikin Longevity Center is listening to Dr. Jay Kenney’s side stories.
Here’s one about rotting fish, and yes, in its own smelly way, it supports the data that vegetarian-style diets do in fact ward off TMAO production.
When our bodies are in the process of metabolizing carnitine and choline into TMAO, there’s an intermediary chemical that’s produced by gut bacteria called trimethylamine, or TMA, explains Dr. Kenney.
“TMA is responsible for the stench of rotting fish. Our livers contain an enzyme called FMO3 that converts the stinky TMA into TMAO.” TMOA is odor free, but, as we’re now learning, it may not be side-effect-free.
“Interestingly,” continues Dr. Kenney, “there is a rare metabolic defect in which people lack the FMO3 enzyme that converts TMA to TMAO. As a result, they end up smelling like dead fish. But there’s one thing that greatly reduces their gut production of TMA, and largely stops them from smelling like rotting fish, and that’s a vegan diet.”
And now for the Dr. Jay wrap up: “If most people lacked FMO3, there’d be a lot fewer people eating red meat and eggs, which means less TMA, less stink, less TMAO, and likely, less heart disease.”
“I bet,” he smiles that inimitable Dr. Jay smile, chuckling to himself all the while, “that smelling like dead fish would motivate more people to go on Pritikin than fear of a future heart attack.”
The biggest food source of carnitine, by far, is red meat.
There is carnitine in milk products, fish, and chicken, and tiny amounts in some plant foods, but all contain far less than red meat, as the table below shows.
FOOD Milligrams (mg) Beef steak, cooked, 4 ounces 56 – 162 Ground beef, cooked, 4 ounces 87 – 99 Milk, whole, 1 cup 8 Codfish, cooked, 4 ounces 4 – 7 Chicken breast, cooked, 4 ounces 3 – 5 Ice cream, ½ cup 3 Cheese, cheddar, 2 ounces 2 Whole-wheat bread, 2 slices 0.2 Asparagus, cooked, ½ cup 0.1
It could be, surmises Dr. Jay Kenney, that limited TMAO production, the result of eating significantly less red meat, egg yolks, and other TMAO generators, helps explain why the Pritikin Program is more effective at reversing atherosclerosis than statin drugs.
“Statins clearly lower LDL levels significantly, but they do not block TMAO production in the gut or reduce it in the blood. Nor do statins lower blood pressure or halt the absorption of fat and cholesterol from our guts. The Pritikin Program does all the above and more, giving us the best possible protection against atherosclerosis.”
What is carnitine? TMAO? The answers likely spell trouble. This new research on carnitine, TMAO, and potential heart disease risk is yet one more reason people should be leery about eating a lot of red meat as well as egg yolks and organ meat.
And it certainly discourages the use of supplements and energy drinks with carnitine and other TMAO producers like choline.
“But don’t be alarmed by sensationalistic stories in the media,” concludes Dr. Kenney. “A little lean red meat occasionally, as the Pritikin Program recommends, is not likely to cause harm.”
- 1 Nature Medicine, published online 7 April 2013; doi:10.1038/nm.3145
- 2 New England Journal of Medicine, 2013; 368: 1575.
- 3 Nature, 2011; 472: 57.