By
GINA KOLATA
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.
“It’s really a beautiful combination
of mouse studies and human studies to tell a story I find quite plausible,”
said Dr.
Daniel J. Rader, a heart disease researcher at the University of
Pennsylvania School of Medicine, who was not involved in the research.
Researchers say the work could lead
to new treatments for heart disease — perhaps even an antibiotic to
specifically wipe out the bacterial culprit — and also to a new way to assess
heart disease risk by looking for TMAO in the blood.
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.
But the investigators’ extensive
experiments in both humans and animals, published Sunday in Nature Medicine, have persuaded
scientists not connected with the study to seriously consider this new theory
of why red meat eaten too often might be bad for people.
Dr. Frank Sacks, a
professor of cardiovascular disease prevention at the Harvard School of Public
Health, called the findings impressive. “I don’t have any reason to doubt it,
but it is kind of amazing.”
And Lora
Hooper, an associate professor of immunology and microbiology at the
University of Texas Southwestern Medical Center, who follows the Paleo
diet, heavy on meat, exclaimed, “Yikes!”
The study does not mean that red
meat is entirely bad or that it is best to avoid it entirely, said Dr. Stanley
Hazen, the lead researcher. Dr. Hazen is the chairman of the department of
cellular and molecular medicine at the Lerner Research Institute of the
Cleveland Clinic, a nonprofit academic medical center. Meat contains protein,
for example, and B vitamins, which are both essential for health. But the
study’s findings indicated that the often-noticed association between red meat
consumption and heart disease risk might be related to more than just the saturated
fat and cholesterol in red meats like beef and pork.
Dr. Hazen began his research five years ago with a scientific fishing
expedition. He directs a study of patients who come to the Cleveland Clinic for
evaluations. Over the years, there have been 10,000. All were at risk for heart
disease and agreed to provide blood samples and to be followed so the
researchers would know if any patient had a heart attack or died of heart
disease in the three years after the first visit. Those samples enabled him to
look for small molecules in the blood to see whether any were associated with
heart attacks or deaths.
That study and a series of additional experiments led
to the discovery that a red meat substance no one had suspected — carnitine —
seemed to be a culprit. Carnitine is found in red meat and gets its name from
the Latin word carnis, the root of carnivore, Dr. Hazen said. It is also found in
other foods, he noted, including fish and chicken and even dairy products, but
in smaller amounts. Red meat, he said, is the major source, and for many people
who eat a lot of red meat, it may be a concern.
The researchers found that carnitine was not dangerous
by itself. Instead, the problem arose when it was metabolized by bacteria in
the intestines and ended up as TMAO in the blood.
That led to the steak-eating study. It turned out that
within a couple of hours of a regular meat-eater having a steak, TMAO levels in
the blood soared.
But the outcome was quite different when a vegan ate a
steak. Researchers had hypothesized that vegans would not have as many of the
gut bacteria needed to make TMAO, and indeed virtually no TMAO appeared in the
vegan’s blood after he consumed a steak.
“We did not expect to see such a dramatic difference,”
Dr. Hazen said.
Then researchers gave meat eaters doses of antibiotics
to wipe out almost all of their gut bacteria. After that, they no longer had
TMAO in their blood either after consuming red meat or carnitine pills. That
meant, he said, that the effect really was because of gut bacteria.
Researchers then tried to determine whether people with
high blood carnitine or TMAO levels were at higher heart disease risk. They
analyzed blood from more than 2,500 people, asking if carnitine or TMAO levels
predicted heart attacks independently of traditional risk factors like smoking,
high cholesterol and blood pressure. Both carnitine and TMAO did. But upon
further analysis, they discovered that the effect was solely because of TMAO.
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.”
Dr. Hazen, though, has taken his findings to heart. He
used to eat red meat several times a week, about 12 ounces at a time. Now, he
said, he eats it once every two weeks and has no more than 4 to 6 ounces at a
time.
“I am not a vegan,” Dr. Hazen said. “I like a good
steak.”
New York Times
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