"Egg Industry Response to Choline and TMAO"
Metabolomics is a term used to describe the measurement
of multiple metabolites in biological specimens
like bodily fluids with the goal of identifying molecular signatures.
For example, if you compared the metabolic profile
of those with severe heart disease to those with clean arteries
maybe we could come up with a cheap, simple, noninvasive way to screen people.
If heart patients happened to have something in their blood
that healthy people didn't, we could test for that.
And maybe it would even help us understand the mechanisms of disease.
To refer to metabolomics as a new field, though, is to do injustice
to ancient doctors who used ants to diagnose people with diabetes,
because the ants could detect the sugar in their urine.
The first modern foray discovered hundreds of substances
in a single breath, for example, thanks to the development of computer technology
that made it possible to handle large amounts of information.
And that was in 1971, a time when computers looked like this.
New technologies have allowed researchers to measure hundreds
or even thousands of metabolites at a time, which is good since more
than 25,000 compounds may be entering our body through our diet alone.
The data comes out looking like this, which computers can turn into maps
that allow researchers to try to piece together connections.
Metabolomics is where the story of TMAO started.
Everyone knows that a bad diet can lead to heart disease,
but which dietary components are the most harmful?
So researchers at the Cleveland Clinic screened blood from patients
who had experienced a heart attack or stroke
and compare the results with those from blood of people who had not.
Using all sorts of fancy technology,
they identified a compound called TMAO, which stands for trimethylamine oxide.
The more of this TMAO stuff people had in their blood,
the greater the odds they had heart disease,
and the worse their heart disease was.
Where does this TMAO stuff come from?
Our liver turns TMA into TMAO.
OK, where does TMA come from?
Certain bacteria in our gut turn something in our diet
called choline into TMA.
Where is the highest concentration of choline found?
Eggs, milk, and meats, including poultry and fish.
So when we eat these foods, our gut bacteria may make TMA,
which is absorbed into our system and oxidized by our liver into TMAO,
which may then increase our risk of heart attack, stroke, and death.
But just because at a snapshot in time people with heart disease
tend to have higher TMAO levels doesn't mean
having high TMAO necessarily leads to bad outcomes.
We'd really want to follow people over time, which is what they did next.
4,000 people followed for 3 years, and those with the highest TMAO levels
went on to have significantly more heart attacks, stroke, or death.
Wait a second though...
If high TMAO levels come from eating lots of meat, dairy, and eggs,
then maybe the only reason people with high TMAO levels
have lots of heart attacks is they're eating lots of meat, dairy, and eggs.
Maybe having high TMAO levels is just a marker of a diet
high in red meat, eggs, milk, and chicken that's killing people
by raising cholesterol levels or something, and has nothing to do with TMAO at all.
Conversely, the reason a low TMAO level seems so protective
may just be because it's indicative of a more plant-based diet.
One of the reasons we think TMAO is directly responsible
is that TMAO levels predict the risk of heart attack, stroke, and death
independently of other traditional cardiovascular risk factors,
meaning whether or not you have high cholesterol or low cholesterol,
high blood pressure or low blood pressure,
having high TMAO levels appeared to be bad news.
This has since been replicated in other studies;
up to 9 times the odds of heart disease at high TMAO blood levels
even after controlling for meat, fish,
and cholesterol intake, which is a surrogate for egg intake.
But what about the rest of this sequence?
How can we be certain that our gut bacteria can take the choline we eat
and turn it into trimethylamine in the first place?
Easily. They'd just have to administer a simple dietary choline challenge.
How do you do that? Just give them some eggs.
Have people eat two hard boiled eggs and you get a bump of TMAO
in their blood within an hour of consumption.
Ah, but what if you then gave them antibiotics to wipe out their gut flora?
Then you can give them eggs and nothing happens.
In fact, their TMAO levels are down at zero,
showing gut bacteria plays a critical role.
But if you wait a month, give their gut some time to recover from the antibiotics,
TMAO levels come creeping back up.
These findings did not thrill the egg industry.
Imagine you work for the American Egg Board, tasked with designing a study
to show no effect of eating nearly an egg a day.
How could you rig it to show no difference?
Well, if you look at the effect of an egg meal, you get a bump in TMAO levels,
but your kidneys are so good at getting rid of this nasty stuff,
that by hours 4, 6, 8, you're back to baseline.
So all you have to do is just make sure they hadn't eaten those eggs
in the last 12 hours and you can show no effect and get your study published
in the Journal of the Academy of Nutrition and Dietetics, and collect your paycheck.