Increased heart disease risk from red meat may stem from gut microbe response to digestion

With one person dying every 34 seconds as a result from cardiovascular disease (CVD) in the US,¹ it’s unsurprising that it’s one of the main focuses of research. Indeed, we’ve seen a lot of science linking red meat to heart disease over the years across the globe, including studies which have related it with certain chemical by-products of food digestion. However, the reason behind the association has remained unclear.

Among these metabolites is TMAO (trimethylamine N-oxide), a chemical produced by gut bacteria to digest red meat that contains high amounts of the chemical L-carnitine.

High blood levels of TMAO in humans may be associated with higher risks of CVD, chronic kidney disease and Type 2 diabetes. However, whether TMAO and related metabolites derived from L-carnitine may help explain the effects of red meat intake on cardiovascular risk, and to what extent they may contribute to cardiovascular risk associated with meat consumption, are still unknown. And this is what the researchers aimed to investigate…

“Most of the focus on red meat intake and health has been around dietary saturated fat and blood cholesterol levels,” said co-lead author of the study Meng Wang, Ph.D., a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts University in Boston. “Based on our findings, novel interventions may be helpful to target the interactions between red meat and the gut microbiome to help us find ways to reduce cardiovascular risk.”

The study explained

To help answer some of the current unknowns, the researchers measured levels of the metabolites in blood samples. They also examined whether blood sugar, inflammation, blood pressure and blood cholesterol may account for the elevated cardiovascular risk associated with red meat consumption.

Study participants included nearly 4,000 of the 5,888 adults initially recruited from 1989 to 1990 for the Cardiovascular Health Study (CHS). The participants selected for the current study were free of clinical CVD at time of enrolment.

The participants were recruited from four communities in the US: Sacramento, California; Hagerstown, Maryland; Winston-Salem, North Carolina; and Pittsburgh, Pennsylvania. The average age of participants at enrolment was 73, with nearly two-thirds of participants female and 88 percent of participants self-identifying as white.

The median follow-up time for participants was 12.5 years, and up to 26 years in some cases. At the follow-up appointment, participants’ medical history, lifestyle, health conditions and sociodemographic characteristics — such as household income, education and age — were assessed.

Several blood biomarkers were measured at the start of the study and again in 1996-1997. The fasting blood samples stored frozen at -80C were tested for levels of several gut microbiome linked to red meat consumption, including TMAO, gamma-butyrobetaine and crotonobetaine.

All participants answered two validated food-frequency questionnaires about their usual dietary habits at the start of the study and again from 1995 to 1996. For the first questionnaire, participants indicated how often, on average in the previous 12 months, they had eaten given amounts of various foods, ranging from ‘never’ to ‘almost every day or at least five times per week’, based on medium portion sizes, which varied depending on the food source.

The second questionnaire used a 10-category frequency of average intake over the past 12 months, ranging from ‘never or less than once per month’ to ‘six+ servings per day’, with defined standard portion sizes.

For the current analyses, the researchers compared the risk of CVD among participants who ate different amounts of animal source foods. They found that eating more meat, especially red meat and processed meat, was linked to a higher risk of atherosclerotic CVD.

According to the authors, the increase in TMAO and related metabolites found in the blood explained roughly one-tenth of this elevated risk. They also noted that blood sugar and general inflammation pathways may help explain the links between red meat intake and CVD.

The researchers also noted that blood sugar and inflammation appeared to be more important in linking red meat intake and CVD, than pathways related to blood cholesterol or blood pressure. Intake of fish, poultry and eggs were not significantly linked to higher risk of CVD.

Study limitations

It is worth noting that the study had several limitations that may have affected its results. Firstly, it was observational, so it could not control for all risk factors for CVD, and may not prove cause and effect between meat consumption and CVD or its mediation by gut microbe-generated chemicals. Additionally, food consumption was self-reported, so errors in reporting are possible. And, as most of the study participants were older, white men and women in the United States, the findings may not apply to the wider population (different races, ages, geographies, etc).

Reference

1. cdc.gov/heartdisease/facts.htm