Researchers show dietary choline and TMAO linked with increased blood clotting

April 24, 2017, Cleveland Clinic

Cleveland Clinic researchers have shown, for the first time in humans, that choline is directly linked to increased production of a gut bacteria byproduct that increases the risk of blood-clotting events like heart attack and stroke. However, the research also showed that adding a low dose of aspirin may reduce that risk.

In a small interventional study, the researchers provided oral supplements to groups of healthy vegans/vegetarians (eight patients) and omnivores (10 patients). Both groups showed at least a 10-fold increase in plasma levels of trimethylamine N-oxide (TMAO) - a metabolite generated by gut microbes ¬- after choline supplementation, as well as an increase in platelet responsiveness, a risk factor for thrombotic events (blood clotting) like and stroke.

In a separate study, omnivores not taking supplements initially had tested at baseline, and then after taking a daily regimen of for at least a month. They then were followed for another two months while continuing to take aspirin and a daily supplement of choline. The researchers found that while elevated TMAO levels and enhanced susceptibility for platelet activation still occurred, the TMAO levels were attenuated by aspirin. These new findings suggest two things - that a low dose of aspirin may partially counter the pro-thrombotic effects of a high TMAO plasma level associated with a Western diet rich in choline, commonly found in egg yolk and meats; and that a high TMAO level can partially overcome the beneficial anti-platelet effects of taking low dose aspirin.

The research team was led by Stanley Hazen, M.D., Ph.D., chair of the Department of Cellular & Molecular Medicine for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic, and Dr Wilson Tang, cardiologist and transplant specialist at the Miller Family Heart and Vascular Institute at Cleveland Clinic. The research will be published April 24 in Circulation, the American Heart Association's journal, with Weifei Zhu, Ph.D., of Dr. Hazen's laboratory as lead author.

"This is the first study in humans to directly demonstrate that dietary choline substantially elevates TMAO production by gut bacteria, impacting platelet function. It provides direct evidence of a mechanistic link between TMAO levels and risk for blood clotting events like attack and stroke, the major culprit for the development of cardiovascular events," Dr. Hazen said. "Further research is necessary to confirm these findings, but these studies suggest patients without known cardiovascular disease but with elevated TMAO levels may benefit from aspirin and diet modification in preventing blood clotting, which can lead to heart attack and stroke. They also suggest that a high TMAO level in a patient with known cardiovascular disease should be considered for more aggressive anti-platelet therapy."

Dr. Hazen, who also holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis, has previously linked TMAO to an increased risk of cardiovascular disease and has shown it can be a powerful tool for predicting future heart attacks, stroke and death in multiple patient populations.

TMAO is a byproduct of bacterial digestion of choline, lecithin and carnitine, nutrients that are especially abundant in animal products such as red meat, processed meats and liver. In 2016, his team discovered in animal models that gut microbes alter platelet function and thrombosis risks, and that microbial transplantation studies could be used to demonstrate the TMAO pathway plays a role in thrombosis potential in a stroke model in mice. Findings from this new study shows that dietary choline in humans raises TMAO levels, which may directly alter platelet function, increasing thrombosis (blood clot) potential. These studies help explain the strong association between plasma TMAO levels and heart attack and stroke risk observed in a study of over 4000 patients.

Explore further: Study shows gut microbes influence platelet function, risk of thrombosis

More information: Circulation (2017). dx.doi.org/10.1161/CIRCULATIONAHA.116.025338

Related Stories

Study shows gut microbes influence platelet function, risk of thrombosis

March 10, 2016
Cleveland: In a combination of both clinical studies of over 4,000 patients and animal model studies, Cleveland Clinic researchers have demonstrated—for the first time—that gut microbes alter platelet function and risk ...

Gut bacteria byproduct linked to chronic kidney disease for the first time

January 29, 2015
Cleveland Clinic researchers have, for the first time, linked trimethylamine N-oxide (TMAO) - a gut metabolite formed during the digestion of egg-, red meat- or dairy-derived nutrients choline and carnitine - to chronic kidney ...

Study shows gut bacteria byproduct impacts heart failure

October 27, 2014
A chemical byproduct of intestinal bacteria-dependent digestion, TMAO (trimethylamine N-oxide) – already proven to contribute to heart disease and to be an accurate tool for predicting future heart attacks, stroke and death ...

Researchers identify potential approach to treat heart disease through the gut

December 17, 2015
Cleveland Clinic researchers have demonstrated - for the first time—that targeting microbes in the gut may prevent heart disease brought on by nutrients contained in a diet rich in red meat, eggs and high-fat dairy products.

Study shows gut bacteria byproduct predicts heart attack and stroke

April 24, 2013
A microbial byproduct of intestinal bacteria contributes to heart disease and serves as an accurate screening tool for predicting future risks of heart attack, stroke and death in persons not otherwise identified by traditional ...

Byproduct of intestinal bacteria may jeopardize heart health in kidney disease patients

July 30, 2015
In patients with chronic kidney disease (CKD), atherosclerosis is exceedingly common and contributes to the development of heart disease, which is the leading cause of death in this group. New research suggests that an organic ...

Recommended for you

The molecular mechanism underlying hypertrophic cardiomyopathy

August 20, 2018
A study led by Stanford Medicine researchers shows why so many mutations associated with hypertrophic cardiomyopathy, a heart disorder, alter a key constituent of muscle cells in a way that makes it work overtime.

Chagas disease, caused by a parasite, has spread outside of Latin America and carries a high risk of heart disease

August 20, 2018
Chagas disease, caused by infection with a parasite called Trypanosoma cruzi (T cruzi), causes chronic heart disease in about one third of those infected. Over the past 40 years, Chagas disease has spread to areas where it ...

As body mass index increases, blood pressure may as well

August 17, 2018
Body mass index is positively associated with blood pressure, according to the ongoing study of 1.7 million Chinese men and women being conducted by researchers at the Yale Center for Outcomes Research and Evaluation (CORE) ...

Gout could increase heart disease risk

August 17, 2018
Having a type of inflammatory arthritis called gout may worsen heart-related outcomes for people being treated for coronary artery disease, according to new research.

Stroke patients treated at a teaching hospital are less likely to be readmitted

August 17, 2018
Stroke patients appear to receive better care at teaching hospitals with less of a chance of landing back in a hospital during the early stages of recovery, according to new research from The University of Texas Health Science ...

Cardiovascular disease related to type 2 diabetes can be reduced significantly

August 16, 2018
Properly composed treatment and refraining from cigarette consumption can significantly reduce the risk of cardiovascular disease resulting from type 2 diabetes, according to a study published in the New England Journal of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.