"But what is it about carnitine that bacteria like? The answer, Dr. Hazen said, is that bacteria use it as a fuel."
By GINA KOLATA Published: April 7, 2013
It was breakfast time and the people participating in a study of red meat and its consequences had hot, sizzling sirloin steaks plopped down in front of them. The researcher himself bought a George Foreman grill for the occasion and the nurse assisting him did the cooking.
For the sake of science, these six men and women ate every last juicy bite of the 8-ounce steaks. Then they waited to have their blood drawn.
Dr. Stanley Hazen of the Cleveland Clinic, who led the study, and his colleagues had accumulated evidence for a surprising new explanation of why red meat may contribute to heart disease. And they were testing it with this early morning experiment.
The researchers had come to believe that what damaged hearts was not just the thick edge of fat on steaks, or the delectable marbling of their tender interiors. In fact, these scientists suspected that saturated fat and cholesterol made only a minor contribution to the increased amount of heart disease seen in red-meat eaters. The real culprit, they proposed, was a little-studied chemical that is burped out by bacteria in the stomach after people eat red meat. It is quickly converted by the liver into yet another little-studied chemical called TMAO that gets into the blood and increases the risk of heart disease.
That, at least, was the theory. So the question that morning was: Would a burst of TMAO show up in peoples’ blood after they ate steak? And would the same thing happen to a vegan who had not had meat for at least a year and who consumed the same meal?
The answers were: yes, there was a TMAO burst in the five meat eaters and no, the vegan did not have it. And TMAO levels turned out to predict heart attack risk in humans, the researchers found. The researchers also found that TMAO actually caused heart disease in mice. Additional studies with 23 vegetarians and vegans and 51 meat eaters showed that meat eaters normally had more TMAO in their blood and that they, unlike those who spurned meat, readily made TMAO after swallowing pills with carnitine.
Of course, critical questions remain. Would people reduce their heart attack risk if they lowered their blood TMAO levels? An association between TMAO levels in the blood and heart disease risk does not necessarily mean that one causes the other. And which gut bacteria in particular are the culprits?
There also are questions about the safety of supplements, like energy drinks and those used in body building. Such supplements often contain carnitine, a substance found mostly in red meat.
The researchers’ theory, based on their laboratory studies, is that TMAO enables cholesterol to get into artery walls and also prevents the body from excreting excess cholesterol.
But what is it about carnitine that bacteria like? The answer, Dr. Hazen said, is that bacteria use it as a fuel.
He said he worries about carnitine-containing energy drinks. Carnitine often is added to the drinks on the assumption that is will speed fat metabolism and increase a person’s energy level, Dr. Hazen said.
Dr. Robert H. Eckel, a professor of medicine at the University of Colorado and a past president of the American Heart Association, worried about how carnitine might be affecting body builders and athletes who often take it because they believe it builds muscle.
Those supplements, Dr. Hazen said, “are scary, especially for our kids.”
Entire article at: nytimes.com/2013/04/08/he...nted=1&_r=0&hp
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Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis
Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.
nature.com/nm/journal/vaop/ncurrent/full/nm.3145.html
By GINA KOLATA Published: April 7, 2013
It was breakfast time and the people participating in a study of red meat and its consequences had hot, sizzling sirloin steaks plopped down in front of them. The researcher himself bought a George Foreman grill for the occasion and the nurse assisting him did the cooking.
For the sake of science, these six men and women ate every last juicy bite of the 8-ounce steaks. Then they waited to have their blood drawn.
Dr. Stanley Hazen of the Cleveland Clinic, who led the study, and his colleagues had accumulated evidence for a surprising new explanation of why red meat may contribute to heart disease. And they were testing it with this early morning experiment.
The researchers had come to believe that what damaged hearts was not just the thick edge of fat on steaks, or the delectable marbling of their tender interiors. In fact, these scientists suspected that saturated fat and cholesterol made only a minor contribution to the increased amount of heart disease seen in red-meat eaters. The real culprit, they proposed, was a little-studied chemical that is burped out by bacteria in the stomach after people eat red meat. It is quickly converted by the liver into yet another little-studied chemical called TMAO that gets into the blood and increases the risk of heart disease.
That, at least, was the theory. So the question that morning was: Would a burst of TMAO show up in peoples’ blood after they ate steak? And would the same thing happen to a vegan who had not had meat for at least a year and who consumed the same meal?
The answers were: yes, there was a TMAO burst in the five meat eaters and no, the vegan did not have it. And TMAO levels turned out to predict heart attack risk in humans, the researchers found. The researchers also found that TMAO actually caused heart disease in mice. Additional studies with 23 vegetarians and vegans and 51 meat eaters showed that meat eaters normally had more TMAO in their blood and that they, unlike those who spurned meat, readily made TMAO after swallowing pills with carnitine.
Of course, critical questions remain. Would people reduce their heart attack risk if they lowered their blood TMAO levels? An association between TMAO levels in the blood and heart disease risk does not necessarily mean that one causes the other. And which gut bacteria in particular are the culprits?
There also are questions about the safety of supplements, like energy drinks and those used in body building. Such supplements often contain carnitine, a substance found mostly in red meat.
The researchers’ theory, based on their laboratory studies, is that TMAO enables cholesterol to get into artery walls and also prevents the body from excreting excess cholesterol.
But what is it about carnitine that bacteria like? The answer, Dr. Hazen said, is that bacteria use it as a fuel.
He said he worries about carnitine-containing energy drinks. Carnitine often is added to the drinks on the assumption that is will speed fat metabolism and increase a person’s energy level, Dr. Hazen said.
Dr. Robert H. Eckel, a professor of medicine at the University of Colorado and a past president of the American Heart Association, worried about how carnitine might be affecting body builders and athletes who often take it because they believe it builds muscle.
Those supplements, Dr. Hazen said, “are scary, especially for our kids.”
Entire article at: nytimes.com/2013/04/08/he...nted=1&_r=0&hp
----------------------------------------------------------------------------------------------------------------------------------------------------
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis
Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.
nature.com/nm/journal/vaop/ncurrent/full/nm.3145.html