Chemicals produced in the digestive tract by gut microbes after eating red meat may help explain part of the higher risk of cardiovascular disease associated with red meat consumption, according to new research published in the American Heart Association’s peer-reviewed journal Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
 
Cardiovascular disease is the leading cause of death in the U.S. Risk factors include several facets of lifestyle, and high intake of red meat with low intakes of fruits and vegetables are considered a major dietary risk factor.
 
“Most of the focus on red meat intake and health has been around dietary saturated fat and blood cholesterol levels,” said Meng Wang, PhD, co-lead author of the study and 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.”
 
Previous research found that certain metabolites of red meat are associated with greater risk of cardiovascular disease, according to the authors. One of these metabolites is trimethylamine N-oxide (TMAO), which is produced by the gut bacteria to digest red meat that contains high amounts of L-carnitine.
 
High levels in TMAO in humans have previously been linked as a potential risk factor for CVD, chronic kidney disease, and type 2 diabetes. However, whether TMAO and other metabolites derived from L-carnitine may help explain the effect of red meat intake on cardiovascular risk, and to what extent they are involved in the cardiovascular risk of high meat consumption, is still unknown.
 
In the present study, the data group of 4,000 participants of the Cardiovascular Health Study (CHS), an observational study of adults over the age of 65, was used. Participants were selected for the current study because they were free from heart disease at the time of CHS recruitment. CHS followed 5,888 participants from communities in California, Maryland, North Carolina, and Pennsylvania, with an average age of 73, about two-thirds of participants female, and 88% 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 follow-up appointments, participants provided medical history, lifestyle information, health conditions, and sociodemographic characteristics.
 
Several blood biomarkers were measured at the start of the study and again in 1996-1997. The fasting blood samples stored frozen at -80 ˚C were tested for levels of several gut-microbiome linked to red meat consumption including TMAO, gamma-butyrobetaine and crotonobetaine.

Further, the participants took part in two validated food frequency questionnaires at the start of the study and at follow-up. One questionnaire asked participants how often on average in the previous 12 months they had eaten given amounts of food. The second questionnaire used a ten-category frequency of average intake over the past 12 months with defined standard portion sizes.
 
They found that eating more meat, especially red and processed meat, was linked with a higher risk of atherosclerotic cardiovascular disease, with a 22% higher risk for about every 1.1 serving per day.
 
According to the authors, the increase in TMAO and related metabolites found in the blood explained roughly one tenth of the elevated risk. Blood sugar and general inflammation pathways may help explain the links between red meat and cardiovascular disease, and appear to be more important than pathways related to blood cholesterol or blood pressure. Fish, poultry, and eggs were not significantly linked to a higher risk of 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,” Wang said. 
 
The study had several limitations which could have affected its results, according to the authors. The study was observational, meaning that no causal relationship could be established. Further, food consumption was self-reported, so reporting errors were possible. As most of the participants were older, white men and women in the U.S., findings might not apply to populations that are younger or more racially diverse.