Doctors have long assumed that saturated fat and cholesterol in red meat are what raise the risk of heart disease. But a study in the journal Nature Medicine fingers another culprit: carnitine, a compound abundant in red meat that also is sold as a dietary supplement and found in some energy drinks. (Carnitine is an amino acid)
Carnitine typically helps the body transport fatty acids into cells to be used as energy. But researchers at the Cleveland Clinic found that in both humans and mice, certain bacteria in the digestive tract convert carnitine to another metabolite, called TMAO, that promotes atherosclerosis, or a thickening of the arteries.
The researchers, led by Stanley Hazen, chief of cellular and molecular medicine at the Cleveland Clinic’s Lerner Research Institute, tested the carnitine and TMAO levels of omnivores, vegans and vegetarians, and examined records of 2,595 patients undergoing cardiac evaluations. In patients with high TMAO levels, the more carnitine in their blood, the more likely they were to develop cardiovascular disease, heart attacks, stroke and death.
Many studies have linked consumption of red and processed meat to cardiovascular disease and some cancers. The Harvard School of Public Health reported last year that among 83,000 nurses and 37,000 male health professionals followed since the 1980s, those who consumed the highest levels of red meat had the highest risk of death during the study, and that one additional serving a day of red meat raised the risk of death by 13%.
The new findings don’t mean that red meat is more hazardous than previously thought. But they may help explain the underlying risk of eating red meat, which some researchers have long thought was higher than the saturated fat and cholesterol content alone could explain.
Dr. Hazen speculated that carnitine could be compounding the danger. “Cholesterol is still needed to clog the arteries, but TMAO changes how cholesterol is metabolized—like the dimmer on a light switch,” he said. “It may explain why two people can have the same LDL level [a measure of one type of cholesterol], but one develops cardiovascular disease and the other doesn’t.”
One surprising finding, Dr. Hazen said, was how a long-term diet that includes meat affected the amount of TMAO-producing bacteria in the gut and thus magnified the risk. In the study, when longtime meat-eaters consumed an eight-ounce steak and a carnitine supplement, their bacteria and TMAO levels rose considerably. But when a vegan ate the same combination, he showed no increase in TMAO or bacterial change. (What vegan would consume an eight ounce steak? Not clear on the concept here.) Ed.
“Vegans basically lose their ability to digest carnitine,” said Dr. Hazen.
The study, sponsored by the National Institutes of Health, didn’t assess how little red meat people could consume and still have elevated TMAO. Nor did it look at how long someone had to abstain from red meat to end the process. “We know it will be longer than one week, but shorter than one year,” Dr. Hazen said.
He and his colleagues have been exploring how altering gut bacteria might influence the risk of heart disease. “In the future, maybe there will be a heart-healthy yogurt, or a drug to block the formation of TMAO,” he said.
Consumption of red meat—primarily beef, veal, lamb and pork—has been falling gradually since 1970.
Trade groups for meat producers have questioned the link to cardiovascular disease, saying studies that ask people to recall what they ate over long periods are imprecise.
“Cardiovascular disease…is a complex condition that appears to have a variety of factors associated with it, from genetics to lifestyle,” said Betsy Booren, chief scientist at the American Meat Institute Foundation.
As a dietary supplement, carnitine is designated as “generally regarded as safe” by the Food and Drug Administration, but few studies have looked at its long-term safety. A 2006 risk assessment found no adverse effects when subjects consumed 2,000 milligrams a day for six months. (An eight-ounce steak has roughly 200 mg of carnitine.)
Ads for supplements promote carnitine as helping boost energy levels, particularly in endurance sports, and assisting in recovery after intense exercise; some also claim that it helps shed pounds and improve brain function.
Duffy MacKay, vice president for scientific and regulatory affairs at the Council for Responsible Nutrition, a trade group for the supplement and energy-drink industries, called the study “a new, emerging hypothesis,” but said the researchers were drawing large conclusions from small studies of mice, bacteria and human biomarkers. “The concept that one component of your diet, or one molecule, is responsible for your health woes is questionable,” he said.
Dr. Hazen noted that some energy drinks have more carnitine in a single can than a porterhouse steak. “I worry about what happens in 10, 20 or 30 years of consumption,” he said.
He said humans generally have plenty of carnitine in their diet, which also is found in small amounts in nuts, beans, vegetables and fruit, and don’t need to take it in supplement form.
Write to Melinda Beck at HealthJournal@wsj.com