Research finds link between red meat, gut microbiome and heart disease

02 Aug 2022 --- New research by the Friedman School of Nutrition Science and Policy at Tufts University and Cleveland Clinic Lerner Research Institute has quantified the risk of atherosclerotic cardiovascular disease (ASCVD) associated with meat ingestion and its impact on the gut microbiome.

The chemicals produced in the digestive tract by gut microbes after eating red meat can help explain part of the higher risk of cardiovascular disease associated with red meat consumption, according to the research published in the American Heart Association’s peer-reviewed journal Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

“The interactions between red meat, our gut microbiome, and the bioactive metabolites they generate seem to be an important pathway for risk, which creates a new target for possible interventions to reduce heart disease,” says the paper’s co-first author Meng Wang, postdoctoral fellow, Friedman School. 

Interconnected digestive systems
While scientists have investigated the relationship between heart disease and saturated fat, dietary cholesterol, sodium, nitrites, and high-temperature cooking, the evidence supporting many of these mechanisms has not been robust. 

The Tuft University researchers suggest specialized metabolites are created by the gut bacteria when meat is eaten. 

Understanding the impacts of meat consumption is particularly important in older adults because they are vulnerable to heart disease. At the same time, many benefit from protein to offset age-related loss of muscle mass and strength.High blood levels of TMAO  are associated with higher risks of CVD, chronic kidney disease and Type 2 diabetes.  

The 3,931 study subjects (US men and women over 65 years) were followed for a median of 12.5 years and their average age at baseline was 73. The study adjusted for established risk factors such as age, sex, race/ethnicity, education, smoking, physical activity, other dietary habits, and many additional risk factors. 

The risk of cardiovascular disease was compared among participants who ate different amounts of animal source foods, including red meat, processed meat, fish, chicken and eggs. 

They found that eating more meat, especially red meat and processed meat, was linked to a 22% higher risk of atherosclerotic cardiovascular disease for every 1.1 serving a day, with 10% of this elevated risk explained by increased levels of three metabolites produced by gut bacteria from nutrients abundant in meat. 

“Interestingly, we identified three major pathways that help explain the links between red and processed meat and cardiovascular disease—microbiome-related metabolites like TMAO, blood glucose levels, and general inflammation—and each of these appeared more important than pathways related to blood cholesterol or blood pressure,” says co-senior author, Dariush Mozaffarian, dean for policy at the Friedman School. 

Higher risk and interlinkages with gut bacterial metabolites were found for red meat but not poultry, eggs, or fish. 

The findings were published in “Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.”

Impact of animal-sourced nutrition
The research drew on years of data from the National Institutes of Health’s (NIH’s) Cardiovascular Health Study (CHS), a long-term observational study of risk factors for cardiovascular disease.

Several blood biomarkers were measured at baseline and again during follow-up, including levels of the gut-microbiome generated trimethylamine N-oxide (TMAO) and two of its key intermediates, gamma-butyrobetaine and crotonobetaine, derived from L-carnitine, abundant in red meat. 

In this community-based cohort of older US men and women, higher intakes of unprocessed red meat, total meat (unprocessed red meat plus processed meat), and total animal source foods were prospectively associated with a higher incidence of ASCVD.

“This suggests that, when choosing animal-source foods, it’s less important to focus on differences in total fat, saturated fat, or cholesterol, and more important to better understand the health effects of other components in these foods, like L-carnitine and heme iron,” says Mozaffarian.

More study is needed to determine if the findings are generalizable across ages and nationalities. The authors also noted that while microbiome biomarkers were directly measured in the blood, study participants’ dietary habits were self-reported, and study findings are observational and cannot prove cause-and-effect.Further research is required about red meat consumption and the link to heart disease to be able to generalize the results across ethnicities.  

“While more studies are needed, the current reports provide a potential new target for preventing or treating heart disease in a subgroup of people who consume excessive amounts of red meat,” said Hasan, who was not a part of the study,” says Ahmed Hasan, medical officer and program director, Atherothrombosis & Coronary Artery Disease Branch, National Heart, Lung, and Blood Institute, NIH.

Background leading to current discoveries
Previous research found that specific metabolites – chemical byproducts of food digestion – are associated with a greater risk of cardiovascular disease. One of these metabolites is trimethylamine N-oxide (TMAO), 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. It is still unknown to what extent TMAO and related metabolites derived from L-carnitine can explain the effects of red meat intake on cardiovascular risk.

To understand the dynamic better, researchers measured levels of the metabolites in blood samples. They also examined whether blood sugar, inflammation, blood pressure, and cholesterol accounted for the elevated cardiovascular risk associated with red meat consumption.

Additionally, all study participants answered two validated food-frequency questionnaires about their usual dietary habits, including intake of red meat, processed meat, fish, poultry and eggs, at the start of the study and again from 1995 to 1996. 

According to the authors, the increase in Trimethylamine N-oxide (TMAO) and related metabolites in the blood explained roughly one-tenth of this elevated risk. They noted that blood sugar and general inflammation pathways might help explain the links between red meat intake and cardiovascular disease.

“Research efforts are needed to better understand the potential health effects of L-carnitine and other substances in red meat such as heme iron, which has been associated with Type 2 diabetes, rather than just focusing on saturated fat,” says Wang. 

By Inga de Jong

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