In a new study published April 7 in the journal Nature Medicine, scientists from the Cleveland Clinic reported evidence suggesting that the long-known link between eating red meat and increased risk of heart disease may be explained not just by the cholesterol-inducing fat content of meat, but by a bacteria that red-meat-eating may foster in the gut.

In previous studies, “Consumption of red meat has been found to increase the risk of death from heart disease, even when controlling for levels of fat and cholesterol,” a release issued by Nature, publisher of Nature Medicine, reported.

This and other research led Dr. Stanley Hazen, Head of Cardiovascular Medicine at the Cleveland Clinic in Ohio, and his team to hypothesize that another mechanism besides fat and cholesterol - one involving a chemical-producing bacteria fostered in the gut by eating red meat - may be causing the increased heart risk associated with consuming red meat. To test their hypotheses, they performed the new study.

In the study, published April 7 in the journal Nature Medicine, Dr. Hazen and his colleagues reported that a bacteria apparently found in greater abundance in the intestines of red-meat-eaters appears to feed on the nutrient L-carnitine, contained in red meat. When fed L-carnitine, this bacteria produces a chemical called TMAO which enters the blood and slows the metabolism of cholesterol, causing it to accumulate faster on the walls of arteries.

Dr. Hazen said in the news release issued by Nature, that “the study could signal a new approach to diet and health.”

“In some cases, an individual’s collection of intestinal microbes may be as important to their diet as anything on a nutrition label,” he said. “Bacteria make a whole slew of molecules from food, and those molecules can have a huge effect on our metabolic processes.”

Results of related experiments that the researchers performed on mice suggested that control of the culprit bacteria in the gut – through antibiotics or probiotics – may be able to eliminate the bad effect of consuming L-carnitine. “When the animals were treated with gut-clearing antibiotics, l-carnitine in the diet did not encourage plaques,” the Nature release said. These mouse studies, however, were preliminary, and further study will be required to see if the same results can be achieved in humans, and whether this could lower the heart risk of consuming red meat and other carnitine-containing foods and supplements.

Meanwhile, Dr. Hazen says that as a result of the study findings, he has drastically reduced his own consumption of red meat. He also warns against taking supplements containing carnitine - which, according to the Nature release, “are marketed with the promise that they promote energy, weight loss and athletic performance.”

The Study; Methods and Findings
Phase 1. Findings: Consuming Red Meat Associated with Producing Higher Levels of TMAO in the Blood via a Gut Bacteria Fostered by Meat Consumption.

As part of the study, Hazen and his colleagues had a group of 77 volunteers consume the nutrient l-carnitine - found in red meat and dairy products - along with a capsule that would attach to and label the carnitine for easy detection. The group included 26 people who were vegetarians. One committed vegan (who had not consumed meat in at least one year) agreed to eat a 200-gram sirloin steak, as part of the study.

The researchers tested the participants’ blood levels of the chemical TMAO following their consumption of red meat.

They found that the meat-eating (non-vegan) volunteers showed boosted blood levels of TMAO immediately after they ate an 8-oz. steak. However, the vegans did not show increased TMAO levels in their blood after consuming the carnitine-containing meat.

Additional testing of 23 vegetarians and vegans and 51 meat eaters confirmed that meat eaters had generally higher levels of TMAO in their blood and that, unlike the vegans, they produced boosted blood levels of TMAO after consuming carnitine.

The researchers also found that “The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status.” In other words, the meat-eaters who experienced higher blood levels of TMAO had a certain bacteria in their gut that was not present in the gut of the vegans who did not experience higher blood levels of TMAO after eating meat.

That suggested that eating red meat may foster the growth of a certain intestinal bacteria that converts the carnitine in meat into TMAO in the blood, which in turn leads to more heart-damaging cholesterol in the arteries. Dr. Hazen told Nature that “a regular diet of meat probably encourages the growth of bacteria that can turn l-carnitine into TMAO.”

Phase 2. Findings: High Blood Levels of TMAO Associated with Significantly Higher Levels of Heart Disease, Heart Attack, Stroke, and Death.

To further test their hypotheses, and measure the association between TMAO levels in the blood and heart disease risk, the researchers examined the blood levels of l-carnitine and TMAO in 2,595 of their patients who were having elective heart examinations as part of a larger, on-going study of patients at risk for heart disease.

They found that “Plasma l-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels.”

In other words, the presence of l-carnitine from meat alone was not significantly associated with higher risks of adverse cardiac events. But, the patients who had high levels of both l-carnitine and TMAO in their blood were at significantly greater risk of heart disease, heart attack, stroke and death.

This provided further evidence that the real threat to heart health may derive from the TMAO produced by a carnitine-consuming bacteria found in the gut of regular meat-eaters — not from the l-carnitine alone.

Phase 3. Findings: In mice, a bacteria in the gut was found key to producing higher TMAO levels and plaque in the arteries after consuming L-Carnitine. Suppression of the gut bacteria with antibiotics eliminated the TMAO and plaque build-up, even after consuming L-Carnitine.

“Finally, the researchers found that feeding l-carnitine to mice doubled the animals’ risk of developing arterial plaques, but only when the mice had their usual gut bacteria,” the Nature release reported. “When the animals were treated with gut-clearing antibiotics, l-carnitine in the diet did not encourage plaques.”

In an abstract of their study, the researchers wrote, “Chronic dietary l-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed.”
Conclusions; Implications

The researchers concluded, “Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.”

Daniel Rader, Director of Preventive Cardiovascular Medicine at the University of Pennsylvania in Philadelphia, who was not involved in the research, concluded that “the study makes a ‘fairly compelling’ case that intestinal bacteria feeding on l-carnitine increase the risk of heart disease,” according to the Nature release.

“The finding should give pause not only to meat lovers, but also to people who take l-carnitine supplements, which are marketed with the promise that they promote energy, weight loss and athletic performance,” Dr. Hazen, the principal study author, told Nature.

Dr. Hazen also noted in an interview with CBS News that “besides being found in red meats, carnitine is also added to dietary supplements to boost weight loss, and is commonly found in another item linked to heart risks — energy drinks.”

“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,” Dr. Hazen said in a statement.

“None of [the] claims [of such L-carnitine supplements] have been proven,” he said. “I see no reason why anyone needs to take [L-carnitine supplements].”

“Those supplements are scary, especially for our kids,” Dr. Hazen told the New York Times.

“The study does not mean that red meat is entirely bad or that it is best to avoid it entirely,” Dr. Hazen, told the New York Times. “I am not a vegan,” Dr. Hazen said. “I like a good steak.” In fact, he told the Times that “he used to eat red meat several times a week, about 12 ounces at a time.”

However, Dr. Hazen has taken the findings of his study to heart. Now, he told the Times, he does not eat red meat more than once every two weeks, and he has no more than 4 to 6 ounces at a time.

Victoria Taylor, Senior Dietitian at the British Heart Foundation, told the BBC that “While the findings won’t necessarily mean a change to existing [dietary] recommendations, these scientists have served up a good reminder for us to think about alternative sources of protein if we regularly eat a lot of red or processed meats.”

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