Carnitine, Choline, Cancer and Cholesterol: The TMAO Connection

“Carnitine, Choline, Cancer and Cholesterol:
The TMAO Connection” Earlier this month, a research team at the Cleveland Clinic offered a novel explanation as to why meat intake may
be related to mortality. “Numerous studies have suggested a
decrease in atherosclerotic disease risk — heart disease our #1 killer –” “in vegan and vegetarian individuals
compared to omnivores,” but we’ve just assumed that
this was due to reduced intake of dietary cholesterol
and saturated fat. But what these researchers found was that within
24 hours of carnitine consumption -eating a sirloin steak,
taking a carnitine supplement- certain gut bacteria
metabolize the carnitine to a toxic substance
called trimethylamine, which then gets oxidized in our liver
to TMAO, trimethylamine-n-oxide, which then circulates
throughout our bloodstream. The way we know it’s the
gut bacteria that’s doing it, is that if you give people
antibiotics to wipe out gut bacteria, you can apparently eat all the steak
you want without making any TMAO, but then if you wait a couple of weeks
until your gut bacteria grows back, you’re back to the
same problem. So what’s so bad about
this TMAO stuff? Well, it may increase the risk
of buildup of cholesterol in the inflammatory cells in the
atherosclerotic plaques in our arteries, increasing the risk of
heart attack, stroke, death, and if that isn’t enough,
cardiac surgery as well. So how do you stay
away from carnitine? Well there’s zero dietary requirement;
our body normally makes all that we need. The problem is that the
bodies of other animals also make all that they
need so when we eat them, their carnitine can end up
in our gut for those bacteria to feast upon,
resulting in TMAO. Some animals make more than others;
carnitine is concentrated in red meat, so then why’s there also clipart
of white meat, dairy, and eggs? That’s what most media reports missed —
even though it’s the very first sentence of the paper. How do you think the researchers
even thought to look into carnitine? Because gut bacteria can turn
choline into TMAO too! Given the similarity in structure
between carnitine and choline, they figured that the same kind of
transformation would occur into TMAO.,, and that’s exactly
what they found. Eggs, milk, liver, red meat, poultry,
shellfish, and fish all believed to be major dietary sources of choline,
and hence TMAO production. So it’s not just
red meat. The good news is that this
may mean a new approach to prevent or treat
heart disease, the most obvious of which would
be to limit dietary choline intake. But if that means decreasing egg,
meat, and dairy consumption, then the new approach sounds
an awful lot like the old approach. Unlike carnitine, we do need
to take in some choline. So should vegans be worried
about the choline they’re getting from beans,
veggies, grains, and fruit? And same question
with carnitine. There’s a small amount of carnitine
found in fruits, veggies, and grains as well. Of course, it’s not the carnitine itself
we’re worried about, but the toxic TMAO. And you can feed a
vegan a steak – literally, an 8-ounce sirloin (anything
in the name of science), same whopping carnitine load, but
essentially no TMAO was produced! Apparently, the vegans don’t develop those
TMAO–producing bacteria in their gut. And why should they? It’s like the whole
prebiotic story. You eat a lot of fiber and you select
for fiber-consuming bacteria. And some of the compounds they
make with fiber are beneficial, like that propionate
I’ve talked about, that appears to have an
anti-obesity effect. So eat fiber, select for
fiber–eating bacteria. Well, if we eat a lot of animal
products we may instead be selecting for animal
product-digesting bacteria, and it appears some of
those waste products, like the trymethylamine
may be harmful. Even if you eat vegan, though,
you’re not necessarily out of the woods. If you regularly drink
carnitine–containing energy drinks, or take carnitine
supplements, or lecithin supplements,
which contain choline, presumably you’d foster and maintain those same kinds
of TMAO-producing bacteria in your gut and increase your risk of
heart disease and, perhaps cancer. About 2 million men in the U.S.
are living with prostate cancer, but that’s better than
dying from prostate cancer. Catch it when it’s localized and your
5-year survival is practically guaranteed, but once it really starts spreading
your chances drop to about 1 in 3. “Thus, identification of modifiable
factors that affect the progression of prostate cancer” is
something that deserves study. So researchers at Harvard took more than
1,000 men with early-stage prostate cancer, followed them for
a couple years to see if there’s anything in
their diet associated with a resurgence of the cancer,
such as spread to the bone. Compared to men who
hardly ate any eggs, men who ate even less
than a single egg a day had a significant 2-fold increased
risk of prostate cancer progression. And maybe it’s
the choline. “A plausible mechanism that may
explain the association between eggs and prostate cancer
progression is high dietary choline.” “Egg consumption is a determinant of how
much choline you have in your blood,” and higher blood choline has
been associated with greater risk of getting prostate
cancer in the first place. So the choline in eggs may both
increase one’s risk of getting it and then having it spread,
and also having it kill you. Choline intake and the risk
of lethal prostate cancer. Choline consumption, associated with not
just getting cancer and spreading cancer, but also significantly increased
risk of dying from it. Those that ate the most had a 70%
increase risk of lethal prostate cancer. Another recent study found that men
who consumed 2 1/2 or more eggs per week — that’s just
like one egg every 3 days — had an 81% increase risk
of lethal prostate cancer. Now it could just be the cholesterol in
eggs that’s increasing fatal cancer risk, but it could also
be that choline. Maybe that’s why meat,
milk, and eggs have all been associated
with advanced prostate cancer, because of the choline. In fact, choline is so
concentrated in cancer cells, if you follow choline uptake
in the body you can track the spread of cancer
throughout your body. But why may dietary choline increase
the risk of lethal prostate cancer? It may be the TMAO, the
trimethylamine oxide. The Harvard researcher
speculated that the TMAO from the high dietary
choline intake may increase inflammation
and this may promote progression of prostate
cancer to lethal disease. In fact just yesterday in the
New England Journal of Medicine, that same Cleveland Clinic research team that
did the carnitine study repeated the study, but this time instead of
feeding people a steak, they fed people some
hard-boiled eggs. And just as they suspected,
a similar spike in that toxic TMAO. So it’s not just
the red meat. And the link between TMAO levels in the
blood and strokes, heart attack, and death was seen even in low-risk groups like those with low-risk cholesterol levels. So eating eggs may increase our risk
regardless what our cholesterol is, because of
the choline. It’s ironic that the choline content of eggs is
something the egg industry actually boasts about. And the industry is aware
of the cancer data. Through the Freedom of Information Act,
I was able to get my hands on an email from the executive director of the
industry’s Egg Nutrition Center to an American Egg
Board executive, talking about how choline may be a
culprit in promoting cancer progression, “Certainly worth keeping in
mind as we continue to promote choline as another good
reason to consume eggs.”