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1 6 C L E V E L A N D C L I N I C R E S E A R C H E R S 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. I n a s m a l l i nt er vent ion a l s t udy, t he r e s e a r c h e r s p r o v i d e d o r a l c h o l i n e supplements to g roups of hea lthy vega ns/ veget a r ia n s (ei g ht pat ient s) a nd om n i- vores (10 patients). Bot h g roups showed at least a 10-fold increase in plasma levels of trimet hyla mine N-oxide (TM AO) — a metabolite generated by g ut microbes — a f ter choline supplementation, a s well a s a n increa se in platelet responsiveness, a risk factor for t hrombotic events ( blood clotting) like hea r t attack a nd stroke. In a separate study, omnivores not taking supplements initially had platelet function tested at baseline, a nd then a f ter ta king a daily regimen of low-dose aspirin 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 e"ects 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 e"ects of taking low-dose aspirin. The resea rch tea m was led by Sta nley Hazen, MD, PhD, 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 was published April 24 in Circulation, the American Heart Association's journal, with Weifei Zhu, PhD, of Dr. Hazen's laboratory as lead author. D r. H a z e n , w h o a l s o h o l d s t h e Ja n 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 bacteria l diges - t ion of chol i ne, lecit h i n a nd ca r n it i ne, nutrients that a re especia lly abunda nt in animal products such as red meat, processed meats and liver. In 2016, his team discovered in a nima l models that g ut microbes a lter platelet function and thrombosis risks, and that microbial transplantation studies could be used to demonstrate the TMAO pathway plays a role in thrombosis potentia l in a stroke model in mice. Findings from this new study shows that dieta r y choline in huma ns ra ises TM AO levels, which may directly a lter platelet function, increasing thrombosis ( blood clot) potentia l. These studies help explain the strong association bet ween pla sma TM AO levels a nd hea r t attack and stroke risk obser ved in a study of over 4,000 patients. This research was supported by grants from the National Institutes of Health and the O¬ce of Dietary Supplements (R01HL103866, R01DK106000, R01HL126827). ■ 1 6R E C E N T R E S E A R C H Dietary Choline and Gut Bacteria Byproduct Linked with Increased Blood Clotting Risk, Heart Disease Low-dose Aspirin May Reduce Risk