Research has pinpointed a potential culprit that could make some people more susceptible to the cardiovascular effects of red meat — and it’s located in the gut. A study published August 1 in the American Heart Association (AHA) journal Arteriosclerosis, Thrombosis, and Vascular Biology zeroed in on a metabolite called trimethylamine N-oxide (TMAO), and the discovery may one day debunk what researchers have believed for decades about how red meat increases the risk of heart disease. According to the study’s lead coauthor, Meng Wang, PhD, a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts University in Somerville, Massachusetts, TMAO has been a new point of focus for researchers in recent years. The metabolite — which is released when gut microbes metabolize phosphatidylcholine (PC), a chemical found in red meat and egg yolks — is known to promote blood clotting and plaque formation in blood vessels in animals. Higher TMAO levels have been linked to a higher risk of death in people who have heart disease. “We also know that TMAO can be produced by our gut microbes during digestion of red meat and other foods that come from animals,” she says, noting that in theory, this could potentially explain why eating red meat increases the risk of cardiovascular disease (CVD). If this was true, the researchers also wanted to measure to what extent increased levels of TMAO were responsible for CVD risk compared with other factors, such as saturated fat and cholesterol, which have been key focal points in red meat and CVD research for decades. The new research included nearly 4,000 Americans older than 65, whose health and diets were tracked over decades as part of the Cardiovascular Health Study (CHS). Almost two-thirds of the participants were female and almost 90 percent were white. The participants were tracked for at least 12 years, while some were followed for more than 20 years. In addition to diet, the study tracked blood biomarkers of TMAO and two related metabolites, gamma-butyrobetaine (GBB), and crotonobetaine, which both come from a chemical in red meat called L-carnitine. They found that the presence of these metabolites — especially TMAO — along with blood sugar and inflammation, appeared to explain the elevated risk of CVD more than blood cholesterol or blood pressure. In the study, a person’s risk of CVD increased by 22 percent for every portion of red meat, especially processed meat, they consumed daily, and about 10 percent of this elevated risk could be explained by increased levels of TMAO, GBB, and crotonobetaine, which gut bacteria produce when they come into contact with nutrients found in red meat. “When making dietary recommendations for animal source foods, it may be less important to focus on saturated fat or cholesterol,” says Dr. Wang. “Other components, like L-carnitine and heme iron, which has been linked to the development of type 2 diabetes, may play a more important role in health.”
Explaining Variability
According to Christopher Gardner, PhD, the director of nutrition studies at the Stanford Prevention Research Center in Stanford, California, who was not involved with the new study, past research has implicated red meat’s high saturated fat content for its role in heart disease. But researchers have always struggled to explain how there could be variability among people who eat the same thing. Since everyone’s gut microbiome is unique, the amount of TMAO a person’s gut microbiota release in the presence of red meat could explain why red meat causes a higher risk of CVD in some people than in others. “It’s not cause and effect. It only shows association, because it’s not an intervention, and there are many other things going on in these peoples’ lives,” says Dr. Gardner. “But it’s another piece of the puzzle showing why TMAO might be important.” According to Gardner, the people in the study who ate the most red meat typically also ate the most saturated fat and the least amount of fiber, two important factors in CVD risk. “There are a lot of other things that could have explained this risk, but TMAO still stood out to be important among these other factors,” he says, emphasizing the need for future research on the metabolite.
Tailored Nutrition
According to Gardner, having more information about how a person’s unique gut microbiome impacts the way their body reacts to different foods could help nutritionists determine the best diet for each individual. “A long-term goal here is precision nutrition. We could one day do a test of your gut microbiome and say what you should eat,” he says, noting that scientists are starting to develop such tests, but they need much more information before precision nutrition based on the gut microbiome will be possible. Gardner says there will likely never be a pill — or a gut microbe — that nullifies the negative health effects of eating things like doughnuts and red meat in excess: “But the more we understand how to explain this variability, the easier it should be to counsel people.” According to Wang, the new research plays an important role in shifting the focus of health research on red meat from saturated fat and its effect on blood cholesterol levels, to a more in-depth look at how different nutrients play a role in CVD risk. “In our study, blood cholesterol levels did not explain the link between meat intake and cardiovascular risk. In fact, there has been growing evidence indicating that dietary saturated fat may not be a major risk factor for CVD,” she says. “Our findings are consistent with these new lines of evidence, and suggest that components in red meat like L-carnitine and heme iron may play a more important role in health than saturated fat.”
