New research suggests that eating red meat is associated with a 22 percent increased risk of heart disease

In regulating heart disease risk, blood sugar, general inflammation and metabolites associated with microbes such as trimethylamine oxide (TMAO) appear to be more important
than blood pressure or cholesterol levels.

Is eating more meat, especially red and processed meat, linked to an increased risk of cardiovascular disease? If so, why? The effects of food from animals on atherosclerotic cardiovascular disease (ASCVD) are hotly debated, and despite a great deal of research, the mechanism behind any possible effects of animal proteins remains unknown
.
Understanding the impact of meat consumption is critical for older adults, who are at greatest risk of heart disease and can benefit from protein intake to counteract the decline
in muscle mass and strength that occurs as they age.

For years, scientists have been studying the links between heart disease and saturated fat, dietary cholesterol, sodium, nitrites, and even high-temperature cooking, but the evidence for many of these mechanisms is not strong
enough.
Recent data suggest that specific metabolites produced by gut bacteria are potential culprits when we eat meat
.

A recent study led by scientists at the Lerner Institute at the Cleveland Clinic and the Friedman School of Nutritional Sciences and Policy at Tufts University quantified the risks of ASCVD associated with meat consumption and identified potential biological pathways
that may explain this risk 。 The study, of more than 4,000 men and women over the age of 65 in the United States, found that the higher the meat intake, the higher the risk of developing ASCVD — for every 1.
1 servings of meat per day, the risk of developing ASCVD increases by 22 percent — and the increase in levels of three metabolites produced by gut bacteria produced by nutrients ubiquitous in meat explains the increased risk of about 10 percent
.
Red meat is associated with a higher risk of disease and the interconnection of bacterial metabolites in the gut, however, not found in
poultry, eggs or fish.

The study, recently published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, is the first to examine the link between animal-derived foods and the risk of ASCVD events, as well as the regulatory effects
of compounds produced by the gut microbiota and traditional ASCVD risk pathways such as blood cholesterol, blood pressure, and blood sugar.

The study draws on years of data from the National Institutes of Health (NIH) Cardiovascular Health Study (CHS), a long-term observational study
of cardiovascular disease risk factors in Americans 65 years of age and older.
Several blood biomarkers were measured at baseline and during follow-up, including levels of trimethylamine n-oxide (TMAO) produced by the gut microbiome and its two key intermediates γ-butyrobetaine and bartonol betaine, extracted from levocanitin, present
in large amounts in red meat.

• In this community-based cohort of older American men and women, at a median follow-up of 12.
  5 years, higher intake of raw red meat, total meat (raw red meat plus processed meat), and total animal-source foods was prospectively associated
  with higher incidence of ASCVD.
  

• The positive association with ASCVD is partly mediated by plasma TMAO, butyrobetaine and bartonol betaine levels (8-11% risk of excess).
  
  

• The higher risk of ASCVD associated with meat intake is also partly mediated by blood glucose and insulin levels and, for processed meats, by systemic inflammation, but not
  with blood pressure or blood cholesterol levels.
  

• Fish, poultry, and egg intake was not significantly associated with ASCVD
  .
  

These findings help answer long-standing questions about the mechanism of the link between meat and cardiovascular disease risk," said
Wang Meng, a postdoc at Friedman College, co-first author of the paper.
"The interaction between red meat, our gut microbiota and the biologically active metabolites they produce appears to be an important pathway to risk, creating a new goal
for possible interventions to reduce heart disease.
"

The median follow-up of 3931 participants was 12.
5 years, with a mean age of 73 years
at baseline.
The study adjusted for known risk factors such as age, gender, race/ethnicity, education, smoking, physical activity, other dietary habits, and many other risk factors
.

"Interestingly, we identified three main pathways that help explain the link between red and processed meat and cardiovascular disease, such as microbial-related metabolites such as trimethylamine oxide, blood sugar levels, and inflammation in general, each of which appears to be more important than the pathways associated with blood cholesterol or blood pressure," said
Dalish Mozafarian, chair of the Department of Policy at Friedman College and co-senior author 。 "This suggests that when choosing animal foods, it's less important to focus on differences in total fat, saturated fat or cholesterol, and it's more important to better understand the health effects of other ingredients in these foods, such as L-Carnitine and Heme Iron
.
"

Stanley L.
Hazen, director of the Department of Preventive Cardiology and Rehabilitation at the Cleveland Clinic, said that by leveraging extensive clinical and dietary data from a large elderly community, the study "links the gut microbiome trimethylamine pathway to animal-derived foods and an increased risk of atherosclerotic cardiovascular disease
.
" The study also advocates reducing this risk through diet, as dietary interventions can significantly reduce trimethylamine
oxide.
”

More research is needed to determine whether these findings apply to people of different ages and nationalities
.
The authors also note that while microbiome biomarkers were measured directly in the blood, the study participants' eating habits were self-reported and the findings were observational and could not prove causality
.

Ahmed Hasan, a medical officer and program director of the Division of Atherosium Thrombosis and Coronary Artery Disease at the National Institutes of Health, agrees
.
"While more research is needed, the current report offers a potential new target for preventing or treating heart disease in people who consume excessive amounts of red meat," said Hassan, who was not involved in the study
.

Currently, NHLBI's Hasan says consumers are encouraged to follow current heart-healthy lifestyle recommendations, including adopting a healthy diet
rich in vegetables, fruits, whole grains and other heart-healthy foods.
Other lifestyle changes that benefit heart health include targeting a healthy weight, managing stress, controlling blood pressure, exercising more, getting enough sleep and quitting smoking
, he added.

The ATVB study is part of an ongoing collaboration between scientists at Friedman College and the Cleveland Clinic to shed light on the role
the gut microbiota plays in human health, particularly cardiovascular health.
In a paper published May in the journal JAMA Network Open, many of the same researchers reported that trimethylamine oxide and related metabolites in older adults were positively associated with a higher risk of death, regardless of whether death was linked
to cardiovascular disease or other diseases.
Participants with the highest levels of plasma trimethylamine oxide and its biomarkers had a 20 to 30 percent
higher risk of death than those with the lowest plasma trimethylamine oxide levels.

The study included more than 5,000 participants
from CHS.
The findings are noteworthy because there are few studies on trimethylamine oxide and the risk of death in the general population; Previous studies have typically looked at clinical patients
with underlying conditions such as diabetes, kidney disease and heart disease.
While the identified risk factors are worrying, the good news is that trimethylamine oxide levels can be altered
.
"Now that we know more about the severity of the risks associated with trimethylamine oxide, we can explore effective ways to alter trimethylamine oxide levels in the body," said Amanda Frets of the University of Washington's Department of Epidemiology,
co-first author of the paper.

References

“Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study” by Meng Wang, Zeneng Wang, Yujin Lee, Heidi T.
M.
Lai, Marcia C.
de Oliveira Otto, Rozenn N.
Lemaitre, Amanda Fretts, Nona Sotoodehnia, Matthew Budoff, Joseph A.
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H.
Wilson Tang, Bruce M.
Psaty, David S.
Siscovick, Stanley L.
Hazen and Dariush Mozaffarian, 1 August 2022, Arteriosclerosis Thrombosis and Vascular Biology.

“Association of Trimethylamine N-Oxide and Metabolites With Mortality in Older Adults” by Amanda M.
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