Matt Palazzolo says, "Hello Chris, question regarding choline, I eat three to four eggs a day,
three to four ounces of fish two to three times a week, and three to four ounces of red meat two to
three times a week. I also supplement 300 to 600 milligrams of alpha-GPC a couple of times a week,
as I feel it helps me with the cognition. I've come across some conflicting info regarding TMAO
and high choline consumption. I know the upper limit is somewhere around 1200 milligrams with
the GPC supplement. Should I be concerned? What biomarkers would you look for on a blood panel?"
It's funny, just before I came on I did a really quick YouTube live
on this exact topic, so I was just looking at the data.
I might as well just show the data real quick and I can do it more quickly now since I
already spent time trying to figure out and oriented myself to it before.
Before I share my screen, let me close off the panelist names. Let me make sure I don't have any
data out from clients. Okay. All right. I'm going to share my screen.
And come over here. So, first of all,
this was a study where the Cleveland Clinic, who are in the leading camp of the sort of choline
and carnitine from red meat and eggs cause TMAO to rise, which causes heart disease camp
and this was a study where they tested, I believe it was 500 milligrams twice daily,
so 1000 milligrams... No sorry, 500 milligrams of choline bisulfate,
which equals 450 milligrams of total choline per day. And the graph is a little confusing
because the TMAO is printed in numbers on the bottom. Let me see if I can make this bigger.
Okay, so the TMAO is printed on numbers in the bottom. And what they did was they took the
blood from the subjects and in vitro they dumped ADP on it as a stimulus of clotting to see
the aggregation of the blood as a percent of maximal response. And so
plotted in the bars and on this axis of 40 to 60% is the percent of maximal aggregation response,
and so it's basically the degree of clotting potential. This is not clotting. This is
clotting potential. And you have to realize that you wouldn't necessarily observe this in vivo
because the factors that cause clotting could be altered by the supplementation, in addition to the
potential of the blood to clot in response to those signals.
So this does not show that choline bisulfate causes clotting,
but it does support the hypothesis that it could increase clotting.
And so on a scale of one to 10, this increases my concern that high levels of TMAO in the blood
cause clotting up to a 3 out of 10. So, I'm still not too worried about it.
Nevertheless, what they showed here is, on the left is baseline, in the middle is one month,
and on the right... This is all in the left panel, panel A, so the red and green Christmas
bars on the left are baseline, in the middle they are one month of consuming choline bisulfate,
500 milligrams of choline a day, and on the right they are two months of consuming the choline.
And then the green bars are vegetarians and vegans, the red bars are omnivores, and the vegans
have a microbiome that is less likely to generate TMAO. The omnivores have a microbiome
that is more likely to generate TMAO. They've shown this previously in a different study.
Now, while the size of the bars indicates the degree of clotting risk, keep in mind this is not
a zero to 100 Y-axis, this is a 40 to 60 Y-axis. So your visual perception of the difference in the
bars is dramatically exaggerating the difference between the treatments compared to what it would
be on a zero to 100 basis. But on the bottom is where you see the plasma TMAO. So it's two
and a half is baseline, micromolar, and then in vegetarians and vegans that goes up to 27.2 mean.
I guess I should note the variation in this response.
Well, the variation is too much.
Let me look at it quickly. I don't remember whether this is standard error or standard...
If its standard error, it's going to be really difficult to get a sense of the variation
because I'm going to have to do calculations and stuff. So, this is standard error. Okay, I'm not
doing that calculation. Let's just take the means because that gives us most of the information.
So the mean TMAO is going up to 27.2 in the vegans and vegetarians at one month and it's going to
28.9 at two months. In the omnivores, it's going up to 36.4 at one month and to 36.8 at two months.
So it looks like there's a teeny tiny increase from the one month to two month mark,
but basically the one month TMAO is the maximal TMAO response to the choline supplementation.
And you can see here that basically it's going up into the high 20s in the vegetarians and vegans,
and it's going up to the mid 30s in the omnivores
and the aggregation response in the blood is going from
low 40% let's say at baseline to 48% in the vegetarians and vegans
at one month and 50% at two months in the vegetarians and vegans, and going up to about
55% in omnivores and 57% or so at two months. And then in the middle graph, you can see
what they're plotting here is the aggregation response in individual people against their
plasma TMAO. And you basically see, these are mostly baseline values plotted as a vertical here.
So there's basically no correlation at low levels of TMAO and if you want to visually inspect this,
you can kind of say somewhere around 20 micromolar is where you're starting
to see a correlation emerge. Let's see, what's the... our value is 0.66. And so
let's see, 0.66, if we're going to square this. That's not what I wanted. Six, six times six, six,
so it's 43% of the variation in the clotting risk is explained by the TMAO, but that correlation is
kicking into gear basically at the 20 micromolar point and it's lasting to maybe say the 60
micromolar point. So that's the range where the TMAO is actually correlated with this response.
So, based on the group means getting up at least to 27 where you're seeing the response
and the correlation seeming to kick in at least around 20, with most of it taking
place in the 30 to 60 range, I'm going to say if you don't get up to 20 micromolar TMAO,
you're probably not getting this clotting potential response. I emphasize again that
they didn't show clotting was increased and this doesn't mean that clotting is increased in vivo.
Okay, so now let's go to the egg data. This is where they gave people zero eggs,
one egg, two eggs, four eggs or six eggs. One egg has 136 milligrams of choline in it.
So, to do the math here, four eggs has 544 milligrams of choline in it.
Two eggs has a 272 milligrams of choline in it. And six eggs has 816 milligrams of choline in it.
Most of this choline is phosphatidylcholine. Not all of it, but most of it. If you go to
Masterjohn choline database, search that on Google, and you can get the breakdown
of different forms of choline in eggs, but it's predominantly phosphatidylcholine.
And so remember the Cleveland Clinic studies, looking at 450 milligrams of total choline per day
to increase TMAO up to 27 or 28, or 29 in vegans, and up into the high 30s in omnivores.
450 milligrams of choline per day is less than four eggs and it's more than two eggs.
So that's probably around three eggs per day is probably what's going to give you that
dose of choline. Now, look at this. So here the vertical axis of TMAO from zero to 20.
The only person who hit... And remember the vegans and vegetarians went to 26 on 450 milligrams of
choline. The omnivores went to high 30s. Okay? So the only person that even makes it up to 20
is subject four eating six eggs per day, which is giving 816 milligrams of choline. So clearly
the person with maximal TMAO potential, presumably based on their gut microbiome, is not getting
anywhere near the vegans or vegetarians when consuming almost twice as much choline from eggs.
Now, the general response is to be able to eat six eggs,
half the people, so subject one, subject two, and subject five, half these people
ate six eggs, providing 816 milligrams of choline and didn't get anywhere near 10,
which is less than half, almost down to a third as much TMAO as the vegetarians and vegans had
on 450 milligrams of choline. And 10 is less than a third of what the omnivores had.
So half of subjects can eat six eggs at one time and not hit half of what it takes to increase ex
vivo clotting risk potential, but even in subject four, who has the greatest TMAO generation,
they're getting basically a non-response to one and two eggs a day. So even worst case scenario,
if you're eating two eggs, you're not really generating TMAO. So, that's the data.
Now, let me give my... Okay, how do I get back to Zoom here?
Stop share. Okay. Now, let me give my sort of summary of this.
If you really want to know what eggs are doing to your TMAO, then I'm pretty sure Cleveland Clinic
has a TMAO blood test, and that would be the best way to do it. Yeah, the Cleveland heart lab has a
TMAO blood test, so you could test your response to this. If you didn't want to test, then if you
assumed the worst case scenario, I would say you could probably just eat two eggs at a time
and you would not raise your TMAO that much, but if you do test TMAO, you can probably show
that you might be able to get away with eating six eggs at a time and not raise your TMAO that much.
But the thing is, I don't think you're going to get the same response from
six eggs at a time as in that study, as you would get from eating two eggs separated and
spread out from the day. And the reason is I think the TMAO is mostly generated from
the choline that does not get absorbed in the small intestine, going to the colon,
being available to the microbiome. So if you lower the dose of eggs and spread them out,
then you should be able to kind of totally head off significant TMAO generation.
So on a guesswork basis I would say... ...say worst case scenario is you should
limit eggs to two at a time, but if you want to test TMAO, you may be able to show that
you're in the clear eating six eggs at a time. And on a scale of 1 to 10, how bothered am I
enough to justify testing my TMAO? I would put 3 out of 10 and I've never tested my TMAO.
Because 3 out of a 10 has not motivated me to test my TMAO. So hope that helps. Matt follows up,
"On a side note I know you mentioned on your podcast with Peter Attia, choline supplements
being somewhere around 30% of the list of choline on the bottle. Is that the same for GPC?"
So Alpha-GPC actually, this is... I put this in the Cliff Notes, which as Masterpass members,
you have access to. It's somewhere around 40% for Alpha-GPC but let me just pull up the numbers
because I know I have them in the Cliff Notes. Looking at the label, if you're using Alpha-GPC,
where did it go? Oh, multiply it by 0.4 and then phosphatidylcholine, you want to multiply by 0.13
to get the dose. And if you ever want to know yourself, so I guess
I'm going to answer my own... So thank you, Matt, for your question. I hope that helped.