We’ve heard that the saturated fat and cholesterol found in red meat, egg yolks and full-fat dairy products can lead to clogged arteries. But there appears to be an additional danger in how bacteria in our digestive system process these foods.
A team of Cleveland Clinic researchers found that a chemical byproduct created when bacteria digest animal products harms the lining of blood vessels, contributing to the development of atherosclerosis. This byproduct, called trimethylamine (TMA), turns into trimethylamine-N-oxide (TMAO) in the liver. High blood levels of TMAO can more than double the risk of heart attack, stroke and death.
“Blood TMAO levels help explain differences in susceptibility to the development of heart disease through response to diet,” says Stanley Hazen, MD, PhD, who pioneered this exciting research. Dr. Hazen is co-section head of Preventive Cardiology and Rehabilitation, and chair of the Department of Cellular & Molecular Medicine at the Lerner Research Institute.
In addition to clogging arteries, TMAOappears to increase the risk of heart failure and kidney disease. However, the effect is not inevitable: Dr. Hazen’s team has shown the danger can be lowered by changing the composition of the gut bacteria or targeting the TMAO creation process with inhibitors.
How Bacteria Are Involved
Bacteria help break down the food we eat into nutrients we can use. Doctors have known for years that maintaining a healthy colony of bacteria in the gut is important. Yet the role of bacteria in heart health was a surprise.
The relationship appears to be based in how we digest two nutrients: choline and L-carnitine. Choline is found in the membranes of animal cells, egg yolks and high-fat dairy products. L-carnitine is found naturally in red meat and is even found as an additive in energy drinks.
Certain bacteria metabolize choline and L-carnitine into TMA, which is further processed into TMAO. When TMAO hits the bloodstream, it affects how the artery walls take up cholesterol and prevents cholesterol from being removed. The result is a buildup of cholesterol that leads to the creation of unstable plaques.
When Dr. Hazen and his colleague W. H. Wilson Tang, MD, looked at patients with heart failure, they found elevated levels of TMAO. The higher the level, the greater the risk of death within the five-year study period. Other traditional risk factors for heart failure death simply added to this risk.
Drs. Hazen and Tang also found elevated TMAO levels in patients with chronic kidney disease. These levels were associated with poor outcomes and increased risk of death. The finding may explain why patients with end-stage kidney disease tend to die of heart disease, even when they don’t have other risk factors.
Lowering the Risk Naturally
Can altering our gut bacteria, or preventing the bacteria from producing TMA, prevent heart and kidney disease? Such studies will take years to conduct on humans. However, lowering TMAO levels with a natural product called 3,3-dimethyl-1-butanol (DMB) lowered atherosclerosis risk in mice.
“The microbes can dine on many options. We are just dictating that it can’t eat certain things on its plate,” says Dr. Hazen. “The drug blocks TMA and TMAO formation, yet the microbe lives. This is different from an antibiotic, which would kill the microbe.”
Dr. Hazen decided to report on his studies of DMB after his team found it in some grapeseed and cold-pressed extra virgin olive oils, and the animal model studies suggested it was safe.
Whether eliminating animal products from our diet would lower TMAO levels is a harder question to answer. Some vegetarians and vegans have TMAO levels as high as those of meat-eaters.
“The level of TMAO is determined primarily by your gut microbes. Diet impacts our gut microbial community, but the microbes you are exposed to and other aspects of your health, like kidney function and genetics, also play a role in TMAO levels,” says Dr. Hazen.
It has recently become possible to know what your TMAO level is, thanks to a blood test developed by Dr. Hazen. If levels are high, you could try eliminating or reducing your consumption of animal products and increasing your use of extra virgin olive oil. But this may not be enough.
“More aggressive risk reduction efforts across the board may be reasonable, including better weight control, treatment of lipids and blood pressure, diet, exercise, smoking cessation, and other known risk-reducing efforts,” says Dr. Hazen. “There’s good reason to think knowing your TMAO level can help you reduce the odds of developing cardiovascular disease.”