For decades, doctors have known that a diet high in red meat is a risk factor for heart disease. Now, researchers at the Cleveland Clinic have learned more about the mechanisms underlying that connection; they have also identified a role for gut microbes in the process. Research leader Stanley Hazen, MD, Ph.D., has built on previous work by his team that showed that during digestion, gut bacteria generate a chemical called TMAO (trimethylamine N-oxide) when they consume choline, lecithin, and carnitine, which are found at high levels in red meat and other animal products. The scientists showed that TMAO can lead to many cardiovascular problems.
Hazen and other groups have also established that high TMAO levels can be used as a predictor of stroke, heart attack and risk of death. Because of those findings, clinics now check circulating TMAO levels in patients.
A study that Hazen's group reported in the European Heart Journal indicated that diets high in red meat (compared to diets relying on non-meat or white meat sources) increase the levels of circulating TMAO. In people, regular consumption of red meat ramped up the production of TMAO by gut microbes, and the kidneys had to work harder to remove it from the body. That creates a double whammy, resulting in high TMAO levels, and an increased risk of heart disease and atherosclerosis.
For this study, 113 volunteers were given sequential meal plans; 25 percent of the study participants’ daily calories would be provided by one of three protein sources: red meat, white meat or non-meat. In between the different plans, participants had a washout period.
After a month of eating red meat, most study participants had elevated TMAO levels in their urine and blood. The circulating (blood) levels of TMAO in participants eating red meat increased about three-fold on average compared to participants eating diets with white meat or non-meat protein sources. Incredibly, some people had a ten-fold increase in TMAO levels when they ate the red meat diet. When the participants stopped eating the red meat diet, the TMAO levels went down over the next month.
The investigators were surprised to find that chronic consumption of red meat impacted the ability of the kidneys to filter chemicals. The red meat diet lowered TMAO excretion, but it also increased the efficiency of excreting carnitine and metabolites derived from carnitine.
"This is the first study of our knowledge to show that the kidneys can change how effectively they expel different compounds depending on the diet that one eats - other than salts and water," said Dr. Hazen, who also directs Cleveland Clinic Center for Microbiome and Human Health. "We know lifestyle factors are critical for cardiovascular health, and these findings build upon our previous research on TMAO's link with heart disease. They provide further evidence for how dietary interventions may be an effective treatment strategy to reduce TMAO levels and lower subsequent risk of heart disease."