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L-Carnitine - Good or Bad for Your Heart? Culprit in Heart Disease Goes Beyond Meat's Fat (there are 3 articles in this report)
Published: April 7, 2013
It was breakfast time and the people participating in a study of red meat and its consequences had hot, sizzling sirloin steaks plopped down in front of them. The researcher himself bought a George Foreman grill for the occasion, and the nurse assisting him did the cooking.
In a study, meat eaters who ate steak showed a burst of a chemical that increases risk.
For the sake of science, these six men and women ate every last juicy bite of the 8-ounce steaks. Then they waited to have their blood drawn.
Dr. Stanley Hazen of the Cleveland Clinic, who led the study, and his colleagues had accumulated evidence for a surprising new explanation of why red meat may contribute to heart disease. And they were testing it with this early morning experiment.
The researchers had come to believe that what damaged hearts was not just the thick edge of fat on steaks, or the delectable marbling of their tender interiors. In fact, these scientists suspected that saturated fat and cholesterol made only a minor contribution to the increased amount of heart disease seen in red-meat eaters. The real culprit, they proposed, was a little-studied chemical that is burped out by bacteria in the intestines after people eat red meat. It is quickly converted by the liver into yet another little-studied chemical called TMAO that gets into the blood and increases the risk of heart disease.
That, at least, was the theory. So the question that morning was: Would a burst of TMAO show up in people's blood after they ate steak? And would the same thing happen to a vegan who had not eaten meat for at least a year and who consumed the same meal?
The answers were: yes, there was a TMAO burst in the five meat eaters; and no, the vegan did not have it. And TMAO levels turned out to predict heart attack risk in humans, the researchers found. The researchers also found that TMAO actually caused heart disease in mice. Additional studies with 23 vegetarians and vegans and 51 meat eaters showed that meat eaters normally had more TMAO in their blood and that they, unlike those who spurned meat, readily made TMAO after swallowing pills with carnitine.
"It's really a beautiful combination of mouse studies and human studies to tell a story I find quite plausible," said Dr. Daniel J. Rader, a heart disease researcher at the University of Pennsylvania School of Medicine, who was not involved in the research.
Researchers say the work could lead to new treatments for heart disease - perhaps even an antibiotic to specifically wipe out the bacterial culprit - and also to a new way to assess heart disease risk by looking for TMAO in the blood. Of course, critical questions remain. Would people reduce their heart attack risk if they lowered their blood TMAO levels? An association between TMAO levels in the blood and heart disease risk does not necessarily mean that one causes the other. And which gut bacteria in particular are the culprits?
There also are questions about the safety of supplements, like energy drinks and those used in body building. Such supplements often contain carnitine, a substance found mostly in red meat.
But the investigators' extensive experiments in both humans and animals, published Sunday in Nature Medicine, have persuaded scientists not connected with the study to seriously consider this new theory of why red meat eaten too often might be bad for people.
Dr. Frank Sacks, a professor of cardiovascular disease prevention at the Harvard School of Public Health, called the findings impressive. "I don't have any reason to doubt it," he said, "but it is kind of amazing."
Lora Hooper, an associate professor of immunology and microbiology at the University of Texas Southwestern Medical Center, who follows the Paleo diet, heavy on meat, exclaimed, "Yikes!"
The study does not mean that red meat is entirely bad or that it is best to avoid it entirely, said Dr. Hazen, the lead researcher. Dr. Hazen is the chairman of the department of cellular and molecular medicine at the Lerner Research Institute of the Cleveland Clinic, a nonprofit academic medical center. Meat contains protein, for example, and B vitamins, which are both essential for health. But the study's findings indicated that the often-noticed association between red meat consumption and heart disease risk might be related to more than just the saturated fat and cholesterol in red meats like beef and pork.
Dr. Hazen began his research five years ago with a scientific fishing expedition. He directs a study of patients who come to the Cleveland Clinic for evaluations. Over the years, there have been 10,000. All were at risk for heart disease and agreed to provide blood samples and to be followed so the researchers would know if any patient had a heart attack or died of heart disease in the three years after the first visit. Those samples enabled him to look for small molecules in the blood to see whether any were associated with heart attacks or deaths.
That study and a series of additional experiments led to the discovery that a red meat substance no one had suspected - carnitine - seemed to be a culprit.
Carnitine is found in red meat and gets its name from the Latin word carnis, the root of carnivore, Dr. Hazen said. It is also found in other foods, he noted, including fish and chicken and even dairy products, but in smaller amounts. Red meat, he said, is the major source, and for many people who eat a lot of red meat, it may be a concern.
The researchers found that carnitine was not dangerous by itself. Instead, the problem arose when it was metabolized by bacteria in the intestines and ended up as TMAO in the blood.
That led to the steak-eating study. It turned out that within a couple of hours of a regular meat-eater having a steak, TMAO levels in the blood soared. But the outcome was quite different when a vegan ate a steak. Researchers had hypothesized that vegans would not have as many of the gut bacteria needed to make TMAO, and indeed virtually no TMAO appeared in the vegan's blood after he consumed a steak.
"We did not expect to see such a dramatic difference," Dr. Hazen said. Then researchers gave meat eaters doses of antibiotics to wipe out almost all of their gut bacteria. After that, they no longer had TMAO in their blood either after consuming red meat or carnitine pills. That meant, he said, that the effect really was because of gut bacteria.
Researchers then tried to determine whether people with high blood carnitine or TMAO levels were at higher heart disease risk. They analyzed blood from more than 2,500 people, asking if carnitine or TMAO levels predicted heart attacks independently of traditional risk factors like smoking, high cholesterol and blood pressure. Both carnitine and TMAO did. But upon further analysis, they discovered that the effect was solely because of TMAO.
The researchers' theory, based on their laboratory studies, is that TMAO enables cholesterol to get into artery walls and also prevents the body from excreting excess cholesterol.
But what is it about carnitine that bacteria like? The answer, Dr. Hazen said, is that bacteria use it as a fuel.
He said he worries about carnitine-containing energy drinks. Carnitine often is added to the drinks on the assumption that is will speed fat metabolism and increase a person's energy level, Dr. Hazen said.
Dr. Robert H. Eckel, a professor of medicine at the University of Colorado and a past president of the American Heart Association, worried about how carnitine might be affecting body builders and athletes who often take it because they believe it builds muscle.
Those supplements, Dr. Hazen said, "are scary, especially for our kids." Dr. Hazen, though, has taken his findings to heart. He used to eat red meat several times a week, about 12 ounces at a time. Now, he said, he eats it once every two weeks and has no more than 4 to 6 ounces at a time.
"I am not a vegan," Dr. Hazen said. "I like a good steak."
Study: L-carnitine in red meat, not fats, causes heart disease
By JohnThomas Didymus
Apr 8, 2013
Scientists say they have found that fats and cholesterol are not the main reason why red meat increases susceptibility to heart disease. According to scientists, a substance in red meat called L-carnitine is linked to the risk of heart disease.
In the study published online in the journal Nature on April 7, 2013, titled: "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis," the researchers led by Dr. Stanely Hazen, head of preventive cardiology and chairman of the department of cellular and molecular medicine at the Lerner Research Institute of the Cleveland Clinic, found that the high incidence of heart disease among red meat eaters may be due to a relatively obscure substance called L-carnitine that helps transport fatty acids into the cell's mitochondria where energy is produced.
Although previous studies have linked heart disease with consumption of red meat, it remained uncertain which component of red meat was causing the damage. Researchers had suspected saturated fats and sodium in meat but the evidence was not conclusive. Hazen, investigating the possibly that an unsuspected substance was exposing red meat eaters to risk of cardiovascular disease, soon identified L-carnitine found in high levels in red meat, and a popular additive in energy drinks and supplements.
The discovery followed a previous study Hazen published in the journal Nature that identified a compound in the blood called trimethylamine N-oxide (TMAO) which seemed to be a good predictor of the risk of heart disease. The substance was also found to be linked to heart disease in mice. TMAO is formed when intestinal bacteria breaks down certain substances such as the dietary fat choline in the gut.
Hazen suspected that intestinal gut may also be converting L-carnitine in red meat to TMAO. Choline has a chemical structure similar to L-carnatine.
Hazen and his Ph.D student Robert Koeth, conducted a study in which they fed steak to volunteers, mostly "young, hungry students," who were happy to be used as guinea pigs in the study.
Blood tests administered on the students after a meal of steak found a rise in TMAO levels showing that something in the meat was being converted into TMAO. Further investigation showed that L-carnitine was indeed being converted into TMAO. The researchers were also able to demonstrate that intestinal gut was responsible for converting L-carnitine in TMAO. After giving the meat eaters antibiotics that wiped out their gut bacteria they found that they did not have TMAO in their blood.
According to Nature, the researchers also reported that mice fed a diet supplemented with L-carnitine had much higher levels of TMAO than control animals and that the animals had twice the incidence of atherosclerosis compared to control animals.
The authors reported that the intestine of mice fed L-carnitine was able to adapt by becoming enriched with bacteria that convert L-carnatine to TMAO. The study also found that people who eat a lot of red meat are more efficient at converting L-carnitine to TMAO and that limiting consumption of L-carnitine rich food could lead to reduced ability to convert L-carnitine to TMAO.
Nature reports the study found that vegetarians and vegans have lower levels of bacteria that convert L-carnitine to TMAO.
The study has implications for the use of L-carnatine as an additive in energy drinks. It also has implications for the use of L-carnitine capsules as a supplement used by body builders.
According to The New York Times, the study could also have implications for the treatment of heart disease. Doctors may be prescribing antibiotics that target gut bacteria which produce TMAO from L-carnitine to reduce the risk of strokes, heart attacks and atherosclerosis in high-risk individuals.
The study noted that more research is needed to determine safe levels of L-carnitine in the diet. A portion of red meat may contain up to about 94mg of L-carnitine, while cheese and milk contain only about 3mg per serving.
Nutritionists say that in spite of the study linking L-carnitine and gut microbes to cardiovascular disease, the nutrient plays a vital role in helping the body to convert fat to energy. Thus, rather than recommend abstinence, experts recommend limiting intake of red meat.
According to nutritionists, red meat contributes valuable nutrients such as zinc, iron, B vitamins and vitamin D.
Although biochemists do not yet understand how TMAO causes atherosclerosis, Hazen explains that it is known that long-term ingestion of L-carnitine changes the way the body metabolizes cholesterol, causing more of it to be deposited on artery walls and less being eliminated.
Gut Bacteria To Blame For Red Meat-Heart Disease Link, Study Finds
Gut bacteria turn a compound found in red meat and energy drinks into one that can raise your risk for heart disease, according to a new study.
MONDAY, April 8, 2013 - Red meat is known to increase your risk for heart disease, but according to a new study, it's not just the fat and cholesterol that's the problem. Researchers found that a compound in red meat that's also a common supplement in energy drinks may raise your risk for atherosclerosis - the hardening and clogging of the arteries, according to the study, and gut bacteria may be to blame.
Researchers from the Cleveland Clinic found that when gut bacteria metabolize the compound carnitine, they turn into trimethylamine-N-oxide (TMAO), which has been linked to atherosclerosis and heart disease. In addition, a diet high in carnitine stimulates the growth of more of that type of gut bacteria, creating a loop that can severely raise your risk, researchers said.
"The bacteria living in our digestive tracts are dictated by our long-term dietary patterns," Stanley Hazen, M.D., Ph.D., study author and section head of preventive cardiology and rehabilitation in the Miller Family Heart and Vascular Institute at the Cleveland Clinic, said in a statement. "A diet high in carnitine actually shifts our gut microbe composition to those like carnitine, making meat eaters even more susceptible to forming TMAO and its artery-clogging effects."
This process may explain why a vegetarian diet seems to have heart-health benefits, he added.
"Vegans and vegetarians have a significantly reduced capacity to synthesize TMAO from carnitine, which may explain the cardiovascular health benefits of these diets," he said.
The researchers looked at the levels of carnitine and TMAO in 2,595 patients who were omnivores, vegans and vegetarians, and found that high levels of both carnitine and TMAO were predictors of heart disease and stroke. However, having high levels of only carnitine was not a predictor, indicating that the gut bacteria that metabolize the compound and turn it into TMAO may be to blame. "This process is different in everyone, depending on the gut microbe metabolism of the individual," Hazen said in a statement. "Carnitine metabolism suggests a new way to help explain why a diet rich in red meat promotes atherosclerosis." TMAO acts as an irritant, said Steven Zodkoy, DC, a nutrition specialist with the American Clinical Board of Nutritionist, which causes blood vessels to become inflamed and can lead to heart disease.
"If the blood vessels swell because of an irritiant, such as TMAO, and you combine that with high cholesterol, that's where the heart disease is coming in," he said.
In order to test how gut bacteria influenced heart disease risk, researchers fed carnitine to mice, and found that it doubled their risk of developing atherosclerosis. However, after the mice were given antibiotics designed to clear out their gut bacteria, a diet high in carnitine did not increase their risk.
Ultimately, researchers said the findings make it clear that red meat consumption should be limited, and that people taking carnitine supplements for a boost or drinking energy drinks containing it should stop.
"Carnitine is not an essential nutrient; our body naturally produces all we need," Hazen said in the statement. "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."
Zodkoy said it's important for people to reduce their consumption of red meat in order to ward off heart disease.
"I'm a big fan of reducing red meat," he said. "The proper portion is 4 ounces, but most people when they go out are getting a large 16-ounce steak. Red meat is an important part of the diet, but we overdo it."
The Red Meat Dilemma: Good or Bad for Your Heart?
Two studies released this week came to what seem to be different conclusions about how a red meat protein may affect your heart health - but the results aren't necessarily conflicting.
By Amir Khan, Everyday Health Staff Writer
FRIDAY, April 12, 2013 - A protein commonly found in meat and energy drinks, reported earlier this week to raise your risk for heart disease, may be good for your heart after all, according to a new study published in Mayo Clinic Proceedings.
Researchers found that the protein, l-carnitine, could help reduce the risk of death in people recovering from a heart attack, despite separate reports on Monday indicating that the same protein could contribute to atherosclerosis and heart disease.
L-carnitine is found in in high amounts in red meat, and is naturally produced in the body; it's also a popular energy drink additive and nutritional supplement because of its energy-boosting properties. During a heart attack, the body's level of l-carnitine are depleted. In the new study, researchers from the John Ochsner Heart and Vascular Institute at the University of Queensland School of Medicine found that administering supplements after a heart attack reduced a patient's risk of death.
The Queensland researchers conducted a review of 13 controlled trials on l-carnitine that included a total of 3,629 patients. The found that taking l-carnitine was associated with a 27 percent reduced risk of death, a 65 percent reduced risk of a fatal arrhythmia, and a 40 percent reduction in risk of developing angina.
"It's used as an antioxidant and to produce energy. It's needed by patients who are having a heart attack to reenergize their cells," explained Steven Zodkoy, DC, a nutrition specialist with the American Clinical Board of Nutritionists. However, a recent study in Nature Medicine found that when gut microbes metabolize carnitine, they turn into trimethylamine-N-oxide (TMAO), which has been linked to an increased risk of atherosclerosis and heart disease. And the more carnitine you ingest, they found, the more likely your gut is to produce bacteria that feeds on it, creating a loop that can severely raise your heart risk.
"The bacteria living in our digestive tracts are dictated by our long-term dietary patterns," Stanley Hazen, M.D., Ph.D., study author and section head of preventive cardiology and rehabilitation in the Miller Family Heart and Vascular Institute at the Cleveland Clinic, said in a statement. "A diet high in carnitine actually shifts our gut microbe composition to those like carnitine, making meat eaters even more susceptible to forming TMAO and its artery-clogging effects."
Good for the Heart or Bad for the Heart?
But the two studies aren't necessarily at odds with one another, according to nutritionist Zodkoy. L-carnitine can absolutely cause heart disease - but only if you have the gut microbes needed to break it down, he said.
"The first study found that people who ate a lot of red meat had a certain type of bacteria in their system that broke the compound down into TMAO and raised their risk for heart disease," he explained. "So there's a link between TMAO and heart disease, but that only happened if there was that microbe in your body to breakdown l-carnitine. If you don't have those microbes, you can have all the l-carnitine you want and it won't cause a problem."
For that reason, he added, patients recovering from a heart attack should avoid red meat, especially if their doctor prescribes an l-carnitine supplement. While supplements can also increase the amount of l-carnitine-metabolizing microbes in the body, for heart attack patients, the benefits outweighs the risk, as long as the patients aren't also eating red meat every day.
"If you're eating red meat, it does raise your risk of heart disease," Zodkoy said. "Patients who have had a heart attack need to be on a low red-meat diet."

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