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Food, Health, and Eco-news
The Real Heart-Attacker in Red Meat?
Finding further discredits the always-dubious link between saturated fat and heart disease 04/08/2013
By Craig Weatherby
We just reported on additional evidence linking processed red meats to cardiovascular risks … see “Processed Meat May Speed Death”.
But we had second thoughts about the meaning of that news, expressed in a follow up … see “Processed Meats … Really so Risky?”.
Coincidentally, scientists just uncovered a surprising reason why diets rich in red meat can raise heart risks.
Prior research has linked diets rich in red meat to greater cardiovascular risks … yet, the abundance of cholesterol and saturated fat in red meat doesn't explain much of the increased risk.
This discrepancy has been attributed to genetic differences, the high-salt diets, smoking, and sedentary habits often associated with red meat consumption, and even various cooking methods.
But new clinical and epidemiological research from the Cleveland Clinic suggests a previously unsuspected reason for the link between red meat and cardiovascular disease (Koeth R et al. 2013).
The results further debunk the idea that saturated fat is a key cardiovascular culprit … and help explain the cardiovascular benefits of diets relatively low in red meat.
Heart risk tied to a gut bacteria's favorite, meat-derived food
It turns out that a compound that's unusually abundant in red meat promotes atherosclerosis (hardening/clogging of the arteries).
The Cleveland Clinic group found that certain gut bacteria feed on an essential natural metabolic compound called carnitine … and break it down into a metabolite previously linked to atherosclerosis in people (Koeth R et al. 2013).
Further, the Cleveland researchers found that a diet high in carnitine – mostly obtained from red meat – promotes the growth of bacteria that metabolize carnitine into an artery-clogging compound.
Carnitine is essential for transporting fatty acids within our cells to generate metabolic energy, and our bodies make carnitine from the amino acids lysine and methionine.
The carnitine metabolite or breakdown product that's making headlines is called TMAO (trimethylamine-N-oxide).
And it looks like TMAO may soon supplant saturated fat as the real reason to avoid diets excessively rich in red meat.
Seafood is low in carnitine
Red meats are the richest food sources of carnitine by far ... especially beef, which contains more than 10 times the carnitine content of fish.
Beef steak and hamburger contain 16 times more carnitine than cod fish, and 12 times more than salmon.
Finding challenges conventional wisdom
The research team – led by Stanley Hazen, M.D., Ph.D., and medical student Robert Koeth – tested the carnitine and TMAO blood levels of omnivores, vegans and vegetarians.
In addition, they compared clinical data from 2,595 patients undergoing elective cardiac evaluations to their carnitine and TMAO blood levels.
The researchers found that patients with higher carnitine and TMAO levels also had higher risks for cardiovascular disease, cardiovascular death, and adverse cardiac events like heart attack and stroke.
Additionally, they linked specific gut microbe types to high blood TMAO levels and dietary patterns, and found that TMAO levels were significantly lower among vegans and vegetarians than omnivores.
Remarkably, even after consuming a large amount of carnitine, vegans and vegetarians did not produce significant levels of TMAOwhereas omnivores consuming the same amount of carnitine did.
“The bacteria living in our digestive tracts are dictated by our long-term dietary patterns,” Hazen said.
He went on the make the key point:
“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. Meanwhile, vegans and vegetarians have a significantly reduced capacity to synthesize TMAO from carnitine, which may explain the cardiovascular health benefits of these diets.” (CC 2013)
While carnitine occurs naturally in all meats and poultry it's especially abundant in beef, lamb, and pork. But it's also available in pill form and is a common ingredient in energy drinks.
We presume that diets in which fish and chicken – both lower in carnitine – replace red meats are safer: and that hypothesis is supported by the epidemiological evidence.
How does TMAO harm arteries?
The researchers' theory, based on earlier laboratory studies in animals, is twofold. First, TMAO facilitates the infiltration of oxidized cholesterol into artery walls … an essential part of the atherosclerosis process and cardiovascular disease.
And TMAO prevents the body from excreting excess cholesterol.
Dr. Hazen worries about energy drinks with carnitine, which is added on the assumption that is will speed fat metabolism and increase a person's energy level.
The Cleveland team also looked at the cardiac effects of a carnitine-enhanced diet in normal mice compared to mice with suppressed levels of gut microbes.
And they found that TMAO alters cholesterol metabolism at multiple levels, explaining how it enhances atherosclerosis.
“This process is different in everyone, depending on the gut microbe metabolism of the individual,” said Hazen. “Carnitine metabolism suggests a new way to help explain why a diet rich in red meat promotes atherosclerosis.” (CC 2013)
With this new research in mind, Hazen cautions that more research needs to be done to examine the safety of routine carnitine supplementation via pills or energy drinks.
“Our body naturally produces all [the carnitine] we need,” he says. “We need to examine the safety of chronically consuming carnitine supplements [which] can foster the growth of bacteria that produce TMAO and potentially clog arteries.” (CC 2013)
In a 2011 study, Dr. Hazen and his colleagues reported finding that people are also predisposed to cardiovascular disease based on how the micro-organisms in their digestive tracts metabolize lecithin … a very commonly used natural food ingredient (emulsifier) with a structure similar to carnitine.
  • Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards PA, Hazen SL, Lusis AJ. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013 Jan 8;17(1):49-60. doi: 10.1016/j.cmet.2012.12.011.
  • Cleveland Clinic (CC). Cleveland Clinic researchers discover new link between heart disease and red meat. April 7, 2013. Accessed at
  • Graham M, Crooke R, Edwards PA, Hazen SL, Lusis AJ. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013 Jan 8;17(1):49-60. doi: 10.1016/j.cmet.2012.12.011.
  • Koeth R et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine. Published online April 7, 2013. doi: 10.1038/nm.3145.
  • Wang Z et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, Vol. 472, April 7, 2011, p. 57 doi:10.1038/nature09922