Gut Microbes Could Explain Some of Red Meat’s Added Cardiovascular Risk

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Part of the higher risk of cardiovascular disease associated with red meat consumption could be from metabolites produced by gut microbes, suggests new research published in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

“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, PhD. “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 has found that certain metabolites are associated with a greater risk of cardiovascular disease. One of these is trimethylamine N-oxide (TMAO), which is 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 linked to increased risks of CVD, chronic kidney disease and Type 2 diabetes. However, whether TMAO and L-carnitine-derived metabolites was linked to cardiovascular disease and to what extent, are still unknown.

To find out, the study 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 4000 of the 5888 adults initially recruited from 1989 to 1990 for the Cardiovascular Health Study (CHS). The participants selected for the current study were free of clinical cardiovascular disease at time of enrolment in the CHS, an observational study of risk factors for cardiovascular disease in adults aged 65 or older. The CHS follows 5 888 participants, whose average age at enrolment was 73; nearly two-thirds 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 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 -80°C were tested for levels of several gut-microbiome linked to red meat consumption including TMAO, gamma-butyrobetaine and crotonobetaine.

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. 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 based on the food source. The second questionnaire used a ten-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 cardiovascular disease among participants who ate different amounts of animal source foods (ie, red meat, processed meat, fish, chicken and eggs). They found that eating more meat, especially red meat and processed meat, was linked to a higher risk of atherosclerotic cardiovascular disease, an increased risk of 22% for 1.1 serving per day.

The increase in TMAO and related metabolites explained roughly one-tenth of this elevated risk, the authors said. They also noted that blood sugar and general inflammation pathways may help explain the links between red meat intake and cardiovascular disease. Blood sugar and inflammation also appear to be more important in linking red meat intake and cardiovascular disease than pathways related to blood cholesterol or blood pressure. Intake of fish, poultry and eggs were not significantly linked to 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,” Dr Wang said. 

Source: American Heart Association