Researchers have for some time linked saturated fat, dietary cholesterol, sodium, nitrites, and even high-temperature cooking, with increased risk of developing atherosclerotic cardiovascular disease (ASCVD). Yet, to date, direct evidence of the mechanisms of these factors has not be clear. Now, a new approach to this question by researchers at the Friedman School of Nutrition Science and Policy at Tufts University and Cleveland Clinic Lerner Research Institute has identified metabolites like TMAO created during digestion of red meat and processed meats as a culprit, identifying the gut microbiome as potential pathway to treatments.
“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, published today in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, is the first to investigate the interrelationships between animal source foods and risk of ASCVD events, and the mediation of this risk by gut microbiota-generated compounds as well as by traditional ASCVD risk pathways such as blood cholesterol, blood pressure, and blood sugar.
Participants in the study were drawn from the Cardiovascular Health Study (CHS) which initially recruited subjects more than 30 years ago. It included nearly 3,931 of the 5,888 adults initially enrolled in the study and participants selected for the current research were free of clinical cardiovascular disease at time of enrollment in the CHS, an observational study of risk factors for cardiovascular disease in adults aged 65 or older. The CHS recruited 5,888 participants from four communities: Sacramento, CA, Hagerstown, MD, Winston-Salem, NC, and Pittsburgh. The average age of participants at enrollment was 73, nearly two-thirds of participants were female and 88% of participants self-identified as white. The median follow-up time for participants was 12.5 years, and up to 26 years in some cases.
At follow-up appointment, participants’ medical history, lifestyle, health conditions and sociodemographic characteristics—such as household income, education and age—were all gathered and assessed. The study participants also answered two validated food-frequency questionnaires to 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.
The researchers found that eating more meat, especially red meat and processed meat, was linked to a higher risk of atherosclerotic cardiovascular disease—a 22% higher risk for about every 1.1 serving per day . The increase in TMAO and related metabolites found in the blood explained roughly one-tenth of this elevated risk.
“These findings help answer long-standing questions on mechanisms linking meats to risk of cardiovascular diseases,” said the paper’s co-first author Meng Wang, a post-doctoral fellow at the Friedman School. “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.”
While 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 investigators noted several limitations that may have affected its results. First, as an observational study it could not control for all risk factors for cardiovascular disease, and may not prove cause and effect between meat consumption and cardiovascular disease or its mediation by gut microbe-generated chemicals. Second, food consumption was self-reported, and, as most of the study participants were older, white men and women in the United States, the findings may not apply to populations that are younger or more racially diverse.
Nevertheless, the research still “links the gut microbial TMAO pathway to animal source foods and heightened atherosclerotic cardiovascular disease risks,” said co-senior author Stanley L. Hazen, section head of preventive cardiology and rehabilitation at Cleveland Clinic. “The study also argues for dietary efforts as a means of reducing that risk, since dietary interventions can significantly lower TMAO.”
