Red meat boosts gut bugs that raise heart disease risk

Red meat gives a boost to gut bugs that are bad news for your arteries. The discovery may explain why eating lots of meat increases the risk of heart disease.

Stanley Hazen at the Cleveland Clinic Lerner Research Institute in Ohio and colleagues fed mice a diet high in carnitine, a nutrient found in large amounts in red meat and also added to energy drinks. The team found that this increased the incidence of atherosclerosis, a thickening of the artery walls.

However, when the researchers fed the same diet to mice with suppressed gut flora, they saw no increase in atherosclerosis.

A similar effect appears to exist in humans. The team studied a group of people undergoing cardiac evaluation, and found that those who had higher levels of carnitine in their blood also had a higher incidence of previous cardiac problems.

Bacteria boost

Some bacteria in the intestine use carnitine as an energy source, breaking it down and producing a waste product called trimethylamine (TMA). The liver converts this into another substance, trimethylamine-N-oxide (TMAO), which is excreted in urine.

In mice, high levels of dietary carnitine shifted the types of bacteria present in the gut and increased the volume of TMAO produced tenfold. "Imagine a Petri dish full of bacteria," says Hazen. "If you start feeding them carnitine, the ones that like carnitine more will reproduce and those that don't will decrease."

TMAO levels matter because the substance increases the uptake of "bad" cholesterol and prevents its destruction by macrophages ? white blood cells ? in artery walls. This causes a build-up of plaque that can lead to atherosclerosis.

In further tests, Hazen's team found that meat-eaters produced higher levels of TMAO than vegans or vegetarians after they were fed carnitine, suggesting that they had more TMA-producing bacteria in their gut. "I'm not telling people to cut out red meat," Hazens says. "But cut down the frequency and portion sizes."

Too much of a good thing

Carnitine has its good side: it transports fuel into mitochondria, a cell's powerhouses. "A bit like stoking a fire, carnitine shovels fatty acid into the mitochondrial furnace," says Hazen.

As our body makes all of the carnitine it needs, any additional intake ? for example, in energy drinks or commercially available carnitine supplements ? has no significant benefit. Evidence that increasing carnitine intake gives you more energy is weak, Hazen says. He adds that the new work suggests that taking carnitine supplements could in fact alter your metabolism to increase risk of cardiovascular disease.

"This is impressive work that may help to explain the association seen in epidemiological studies between red meat consumption and coronary heart disease," says David Leake at the University of Reading, UK, who studies atherosclerosis. "However it will require a lot more work to prove how important the role of TMAO is in cardiovascular disease in humans."

Hazen hopes to have a diagnostic test for TMAO ready by the end of the year so that doctors could monitor TMAO just like keeping tabs on high cholesterol. This will be useful if TMAO levels in the blood are indeed a precursor for the onset of atherosclerosis.

Journal reference: Nature Medicine, DOI: 10.1038/nm.3145

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