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New heart disease-red meat link also involves popular supplement

April 7, 2013
Courtesy of the Cleveland Clinic
and World Science staff

A com­pound plenti­ful in red meat and added as a sup­ple­ment to pop­u­lar en­er­gy drinks has been found to pro­mote ath­er­o­scle­rosis, the hard­en­ing or clog­ging of the ar­ter­ies.

The find­ings from re­search­ers at the Cleve­land Clin­ic are pub­lished on­line this week in the jour­nal Na­ture Med­i­cine.

Their study found that bac­te­ria in the hu­man di­ges­tive tract break down a com­pound called car­ni­tine, turn­ing it in­to an­oth­er chem­i­cal called tri­methyl­amine-N-oxide, or TMAO. The re­search­ers had linked that sub­stance in a 2011 study to the pro­mo­tion of ath­er­o­scle­rosis. 

Com­pound­ing the prob­lem, the study al­so found that a di­et high in car­ni­tine pro­motes the growth of the bac­te­ria that me­tab­o­lize car­ni­tine. “A di­et high in car­ni­tine ac­tu­ally shifts our gut mi­crobe com­po­si­tion to those that like car­ni­tine, mak­ing meat eaters even more sus­cep­ti­ble to form­ing TMAO and its artery-clog­ging ef­fects,” said re­search team lead­er Stan­ley Ha­zen.

The sci­en­tists tested the car­ni­tine and TMAO lev­els of meat-eaters, ve­g­ans and veg­e­tar­i­an, and ex­am­ined the clin­i­cal da­ta of 2,595 pa­tients un­der­go­ing elec­tive heart evalua­t­ions. They al­so ex­am­ined the car­di­ac ef­fects of a car­ni­tine-enhanced di­et in nor­mal mice com­pared to mice with sup­pressed lev­els of gut mi­crobes.

The re­search­ers found that in­creased car­ni­tine lev­els in pa­tients pre­dicted in­creased risks for car­di­o­vas­cu­lar dis­ease and ma­jor car­di­ac inci­dents like heart at­tack, stroke and death—but only in peo­ple with high TMAO lev­els at the time. 

They al­so found that TMAO lev­els at the start of the study were sig­nif­i­cantly low­er among ve­g­ans and veg­e­tar­i­ans. Re­mark­ably, they said, these people, even af­ter eat­ing lots of car­ni­tine, did­n’t pro­duce much of the mi­crobe prod­uct TMAO, where­as peo­ple who eat meat and who ate the same amount of car­ni­tine did.

Pri­or re­search had found that a red meat-rich di­et is as­so­ci­at­ed with in­creased car­di­o­vas­cu­lar dis­ease risk, but that the cho­les­ter­ol and sat­u­rat­ed fat con­tent in red meat does­n’t seem to be enough to ex­plain the in­creased risks. This dis­crep­an­cy had been at­trib­ut­ed to ge­net­ic dif­fer­ences, a high salt di­et that is of­ten as­so­ci­at­ed with red meat con­sump­tion, and even pos­sibly the cook­ing pro­cess. Ha­zen said the new work sug­gests an­other ex­plana­t­ion.

“Car­ni­tine me­tab­o­lism sug­gests a new way to help ex­plain why a di­et rich in red meat pro­motes ath­er­o­scle­rosis,” he said. But “this pro­cess is dif­fer­ent in eve­ry­one, de­pend­ing on the gut mi­crobe me­tab­o­lism of the in­di­vid­u­al.” 

While car­ni­tine nat­u­rally oc­curs in red meats, in­clud­ing beef, ven­i­son, lamb, mut­ton, duck, and pork, it’s al­so a di­etary sup­ple­ment avail­a­ble in pill form and a com­mon in­gre­di­ent in en­er­gy drinks. Ha­zen said more re­search is needed to ex­am­ine the safe­ty of fre­quent car­ni­tine sup­ple­menta­t­ion.

“Car­ni­tine is not an es­sen­tial nu­tri­ent; our body nat­u­rally pro­duces all we need,” he said. “We need to ex­am­ine the safe­ty of chron­ic­ally con­sum­ing car­ni­tine sup­ple­ments as we’ve shown that, un­der some con­di­tions, it can fos­ter the growth of bac­te­ria that pro­duce TMAO and po­ten­tially clog ar­ter­ies.”


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A compound abundant in red meat and added as a supplement to popular energy drinks has been found to promote atherosclerosis, the hardening or clogging of the arteries. The findings from researchers at the Cleveland Clinic are published online this week in the journal Nature Medicine. Their study found that bacteria in the human digestive tract break down a compound called carnitine, turning it into another chemical called trimethylamine-N-oxide, or TMAO. The researchers had previously linked that substance linked in a 2011 study to the promotion of atherosclerosis. Compounding the problem, the study also found that a diet high in carnitine promotes the growth of the bacteria that metabolize carnitine. “A diet high in carnitine actually shifts our gut microbe composition to those that like carnitine, making meat eaters even more susceptible to forming TMAO and its artery-clogging effects,” said research team leader Stanley Hazen. The scientists tested the carnitine and TMAO levels of meat-eaters, vegans and vegetarians, and examined the clinical data of 2,595 patients undergoing elective heart evaluations. They also examined the cardiac effects of a carnitine-enhanced diet in normal mice compared to mice with suppressed levels of gut microbes. The researchers found that increased carnitine levels in patients predicted increased risks for cardiovascular disease and major cardiac events like heart attack, stroke and death, but only in subjects with high TMAO levels at the time. They also found specific gut microbe types in subjects associated with both blood TMAO levels and dietary patterns, and that TMAO levels at the start of the study were significantly lower among vegans and vegetarians. Remarkably, they said, vegans and vegetarians, even after consuming a large amount of carnitine, didn’t produce much of the microbe product TMAO, whereas people who eat meat and who consumed the same amount of carnitine did. Prior research had found that a red meat-rich diet is associated with increased cardiovascular disease risk, but that the cholesterol and saturated fat content in red meat doesn’t seem to be enough to explain the increased risks. This discrepancy had been attributed to genetic differences, a high salt diet that is often associated with red meat consumption, and even possibly the cooking process. But Hazen said the new work suggests an alternative explanation. “Carnitine metabolism suggests a new way to help explain why a diet rich in red meat promotes atherosclerosis,” he said. But “this process is different in everyone, depending on the gut microbe metabolism of the individual.” While carnitine naturally occurs in red meats, including beef, venison, lamb, mutton, duck, and pork, it’s also a dietary supplement available in pill form and a common ingredient in energy drinks. Hazen said more research is needed to examine the safety of frequent carnitine supplementation. “Carnitine is not an essential nutrient; our body naturally produces all we need,” he said. “We need to examine the safety of chronically consuming carnitine supplements as we’ve shown that, under some conditions, it can foster the growth of bacteria that produce TMAO and potentially clog arteries.” compound in energy drinks