Earlier this month, researchers reported in Nature Medicine how they found L-carnitine, a compound found in red meat and added to energy drinks, can increase heart risk because gut bacteria digest it to produce trimethylamine-N-oxide (TMAO), a metabolite already suspected of helping to clog up arteries.
Now in another study, published this week in the New England Journal of Medicine, Stanley Hazen, of the Cleveland Clinic in Ohio, and colleagues, add more evidence to the growing pile that shows at least where heart disease is concerned, gut bacteria play an important role in the link between diet and health.
Hazen, who is section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at the Cleveland Clinic, says in a statement:
"We need to find new pathways to attack heart disease, and these findings strongly suggest that further research into the involvement of gut microbiome in the development of cardiovascular disease could lead to new avenues of prevention and treatment of heart disease."
TMAO Could Serve as an Accurate Screening Tool for Future Heart RiskIn this latest clinical study involving over 4,000 participants, Hazen and colleagues found blood TMAO levels linked to increased risk of heart disease, even in the absence of known cardiovascular risks.
They suggest TMAO could serve as an accurate marker for predicting future risk of heart attack, stroke and death in people not otherwise identified through current screening tools.
The study extends Hazen's previous work where he found TMAO is produced when gut bacteria digest the nutrient phosphatidylcholine, commonly known as lecithin. He showed then that blood levels of TMAO were linked to heart disease.
Gut Bacteria Essential for TMAO Production and TMAO Independently Linked to Future Heart RiskNow in this study the team confirms first that gut bacteria are key to producing TMAO in humans, and secondly, that there are links between TMAO levels and future cardiac events like heart attack, stroke and death, even in people with no earlier signs of heart disease.
For the first part of the study, the researchers asked a group of participants to eat two hard-boiled eggs, a known source of dietary lecithin. This raised their blood TMAO. But when these same participants took a course of antibiotics (to wipe out their gut bacteria), their blood TMAO went down, and even eating eggs again did not raise it back up. This showed gut bacteria are essential for producing TMAO.
For the second part of the study, the researchers measured TMAO levels in 4,007 patients having cardiac evaluations at the Cleveland Clinic and followed them for three years. They found that the ones with higher blood levels of TMAO were more likely to have a heart attack or stroke in the follow up, regardless of other risk factors and blood test results.
Results Complement Earlier Carnitine StudyThe results complement those of the earlier Nature Medicine study linking carnitine, a compound abundant in red meat and added to popular energy drinks, to TMAO production and heart risk. Lecithin and carnitine have similar chemical structures.
Hazen, who is also Vice Chair of Translational Research and Chair of the Department of Cellular and Molecular Medicine for the Lerner Research Institute, says:
"Heart disease remains the No. 1 killer, and while we know how to reduce cholesterol, treat blood pressure, and reduce cardiac risks through diet and other interventions, a substantial residual risk still remains."
"These studies show that measuring blood levels of TMAO could serve as a powerful tool for predicting future cardiovascular risk, even for those without known risk factors."
He and his colleagues suggest more studies should now be done to confirm that TMAO testing, like testing cholesterol, triglyceride or glucose levels, could help doctors give patients more personalized dietary advice on how to prevent heart disease.
Hazen also emphasizes that:
"Our goal is not to suggest dietary restrictions of entire food groups. Eggs, meat and other animal products are an integral part of most individuals' diets."
"Our work shows, however, that when digesting these foods, gut flora can generate a chemical mediator, TMAO, that may contribute to cardiovascular disease," he adds.
Grants from the National Institutes of Health helped to finance the research.