A diet rich in red meat may affect heart disease risk by triggering the production of certain metabolites in the gut.
They found that people who ate red meat as their main source of protein for 1 month had levels of trimethylamine N-oxide (TMAO) that were two to three times higher than those in people who got their protein primarily from white meat or non-meat sources.
Gut bacteria produce TMAO as a byproduct when they feed on certain nutrients during digestion.
Previous studies have implicated high circulating levels of TMAO in the development of artery-blocking plaques and raised risk of heart-related conditions.
In the recent research, scientists at the Cleveland Clinic in Ohio uncovered two mechanisms through which a diet rich in red meat raises TMAO levels.
It appears that not only does frequent consumption of red meat enhance gut bacteria production of TMAO, but it also reduces elimination of the compound through the kidneys.
The European Heart Journal has published a report on the study and its findings.
"This is the first study of our knowledge," says senior study author Dr. Stanley L. Hazen, who chairs the Department of Cellular and Molecular Medicine in the Cleveland Clinic's Lerner Research Institute, "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."
TMAO as a predictor of heart disease risk
In previous work, Dr. Hazen and his team had found that TMAO alters blood platelets to raise the risk of thrombosis, or blood clots.
Their work revealed that TMAO modifies calcium signaling in blood platelets. In addition, it showed that platelets respond differently to blood-clotting triggers when blood levels of TMAO are high.
The team proposed that the compound could be a powerful predictor of the risk of heart attack, stroke, and death — even when cholesterol and blood pressure levels are healthy.
Others have since replicated the findings and, like Dr. Hazen and his team, have continued to investigate TMAO and its impact on health.
Clinical trials are also underway to test TMAO as a predictive marker of heart disease risk.
Red meat diet compared with other diets
The recent study assigned 113 individuals to follow three tightly controlled diets in a random order for 4 weeks each with a "washout diet" preceding the changeover.
The diets differed according to their main source of protein. In the red meat diet, 12 percent of the daily calories came from lean red meat in the form of pork or beef, while in the white meat diet, these calories came from lean white poultry meat.
In the non-meat diet, 12 percent of the daily calorie intake came from "legumes, nuts, grains, [and] isoflavone-free soy products."
In all three diets, protein accounted for 25 percent of the daily calories, and the remaining 13 percent of this protein came from "eggs, dairy, and vegetable sources."
After 4 weeks on the red meat diet, "the majority of" the individuals had raised levels of TMAO in their blood and urine.
On average, compared with levels during the white meat and non-meat diets, blood levels of TMAO during the red meat diet were up to three times higher. For some individuals, the levels were 10 times higher. Urine samples revealed a similar pattern.
Reduced kidney efficiency
The study also yielded an unexpected result. While on the red meat diet, the study participants' kidneys were less efficient at expelling TMAO.
However, in the 4 weeks after ceasing the red meat diet, their blood and urine levels of TMAO fell.
Dr. Hazen says that the findings show that people can reduce their risk of heart-related problems by changing what they eat.
Gut production of TMAO was lower and kidney elimination was higher when the individuals followed the white meat or non-meat protein diet.
This suggests, says Dr. Hazen, that these types of diet are more healthful for the heart and body.
"We know lifestyle factors are critical for cardiovascular health, and these findings build upon our previous research on TMAO's link with heart disease."
Dr. Stanley L. Hazen