Chris: Have you put any thought into why that happens?
Because my thought right now is that that pathway is how you make niacin from tryptophan.
So I think that it's basically the body trying to make sure that the baby has enough niacin
because chronic estrogen exposure would occur during pregnancy.
When I was doing my niacin research, one thing that I found is that women seem to need more
total niacin than men, but they seem to be better at making niacin from protein.
What's really interesting is that the studies that were done that were used to make the
RDA, there weren't comparisons in men and women, but two of the studies were men and
two studies were in women.
The standard deviations, meaning how much variation there was person to person, in how
much niacin that they needed to normalize what they were looking at was way bigger in
men than it was in women.
One of the interesting things is that it seems like, and this is not a strong conclusion,
but it's one worth talking about, it seems like in men, the ability to make niacin from
tryptophan is not regulated at all.
It's largely because if you have too much tryptophan, you need to get rid of it down
that pathway.
If your ability to completely burn it for energy is topped off, then quinolinate, which
is neurotoxic, will build up unless you convert it to niacin.
Carrie: Same with kynurenic, right, and xanthurenic?
Chris: Well, yeah, everything that goes into that.
Once you start going down that pathway, you can build -- well, yeah, like if you had a
backup in that.
Kynurenic and xanthurenic are spilling off from higher parts of the pathway.
Carrie: Right, that's true.
Chris: If you have block in one of those parts, then if you have too much tryptophan coming
in, they will build up.
But if the block is not in those parts and tryptophan goes down, what it's ultimately
doing is it's going to be burned for energy or it's going to go into quinolinate, which
is neurotoxic, and then into niacin.
In men, imagine that most of that pathway is working fine, so you're not getting buildup
of xanthurenate and kynurenate.
If you get down to completely burn the tryptophan for energy and suddenly your capacity to do
that is blocked up, then at the very end of the pathway is where you have the quinolinate,
which is a potential neurotoxic risk.
It's not that quinolinate is poisonous.
It's like glutamate, like too much is bad.
Making niacin for quinolinate is a way of making sure that you don't have neurotoxic
levels of quinolinate building up.
It's like a safety valve.
But estrogen dramatically increases this pathway, and it increases the steps at the end that
generate quinolinate even more than it increases the beginning of the pathway.
As a result, women have much better ability on average than men to make niacin from tryptophan.
But also, they seem to have a much more consistent ability.
In other words, in men, there's no regulation to it at all.
One man versus another man is really, really random.
Whereas for women, there's variation, but it's in a much tighter range.
That variation is probably, if you accounted for their estrogen levels, probably that would
really narrow the range down.
Carrie: Yeah, absolutely.
Chris: It can be really, really, really tightly regulated by estrogen.
But if your estrogen levels are really, really high and they're consistently high and you're
not pregnant and you're not using the niacin for the baby and you're just exceeding the
capacity to deal with that quinolinate, it seems like that's the condition where you
have the potential for that quinolinate building up as a result of estrogen that's going to
do dirty nasty things in the brain that it shouldn't be doing.
Carrie: Think about the men too who overaromatize.
They're on unregulated testosterone.
By unregulated, I mean they're just on testosterone.
Their doctor just ran a testosterone, just gave them testosterone.
Maybe it's an injection.
It's high dose.
Here you go.
All of a sudden, they're like, "I felt good initially and now I feel worse.
I brain fog.
I'm moody.
I have this breast development.
What's going on?"
It's like, you're just aromatizing all the estrogen and then if you have that same pathway.
Chris: Right.
Yeah, that's a really great point.
In fact, in one of these AMAs a couple months ago, one of the first ones I did, there was
a man who was asking why his B6 deficiency markers were so high.
The B6 deficiency markers in the urine are the things we're talking about right here
that's filling up the pathway.
I was asking him a few different questions.
Maybe you're eating too much protein, this and that.
Then I mentioned something about estrogen regulating.
He said, "Oh, by the way, my estrogen is pretty high."
I was like, "Oh, wow."
I was inappropriately excluding that because of the sex issue.
But yeah, estrogen is not just a female thing.
Carrie: For sure, for sure, yeah.
And then that whole cycle just keeps going round and round.
The one marker, the xanthurenate which is a B6 dependent, it will complex with insulin
and then it will make somebody have higher glucose.
Right now they're on the track to developing insulin resistance and diabetes which further
increases estrogen especially in men.
Then now you're back on the same circle.