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 intestines
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 people’s blood after they ate steak? And would
the same thing happen to a vegan who had not eaten 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,” he said, “but it is kind of amazing.”
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. 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.”
