What should people with glucose-6-phosphate
dehydrogenase deficiency be doing not just
about glutathione, but about folate, vitamin
K, fatty acids, and neurotransmitters?
Philippa says, “At the last AMA, you mentioned
that G6PD deficiency would have trouble recycling
other things such as folate and vitamin K.
Could you expand on these problems and how
to manage them?
Also, do you recommend glutathione supplementation
for those with G6PD deficiency?”
Sure, I can expand a little bit.
At some point, we hit up against the wall
here because there are certain things that
you just can’t do to fix the root cause.
But basically, to expand means to go into
G6PD, glucose-6-phosphate dehydrogenase deficiency
is an inborn error of metabolism.
It’s the most common one in the world.
About 8% globally have some impairment in
The reason that it’s important is because
glucose-6-phosphate dehydrogenase is the enzyme
that allows you to make NADPH.
NADPH is a specific derivative of niacin that’s
involved in antioxidant defense, detoxification,
synthesis of neurotransmitters, synthesis
of nucleotides, which are needed for cell
division because they’re parts of DNA, needed
to produce every protein in your body.
That plays a role in everything in your body
because they’re needed to produce RNA, affects
every aspect of energy metabolism because
every energy carrier in your body has nucleotides,
and then synthesis of cholesterol, synthesis
of fatty acids, and recycling of vitamin K,
folate, and glutathione.
You basically have your NADPH production has
taken a hit and your body is going to engage
in many compensations to try to make up for
One of the problems and the problem that is
most well-studied because it’s the problem
that is most obviously manifest in someone
with glucose-6-phosphate dehydrogenase deficiency,
this is also called favism because there’s
a toxin in fava beans that most people can
But someone with an impairment in this enzyme,
when they eat the fava beans, they can’t tolerate
that toxin because they don’t have the glutathione
needed or they don’t have enough glutathione
to protect the membranes in their red blood
cells from being destroyed basically.
They’re vulnerable to hemolysis which is when
the red blood cells fall apart.
One of the problems of hemolysis is that you
essentially become anemic.
We usually think of anemia as iron deficiency
where you have fewer red blood cells or they
have less hemoglobin and they’re less able
to carry oxygen.
Well, if you’re just destroying your red blood
cells, you’re going to have very similar problems
coming out of that.
The most obvious and manifest problem, and
therefore the most studied one, focuses on
glutathione because glutathione is the specific
thing that can’t be recycled in the red blood
cells that is specifically causing the vulnerability
What I said in the last episode was glutathione
reductase is the enzyme that uses NADPH, the
thing that you can’t make here.
Glutathione reductase uses that energy to
It does so using riboflavin, or vitamin B2,
as an intermediate.
One of the adaptations that someone with this
impairment has to try to protect themselves
is for the glutathione reductase enzyme to
hog all the riboflavin so that it says, “Look,
I don’t have enough of the raw material I
need to make this happen, so I’m just going
to make myself get way, way, way, way, way
better at using what I do have.”
That’s an adaptation to compensate for not
being able to make NADPH is just to get way
better at using NADPH to recycle glutathione.
Now, obviously, it’s not good enough when
the system is taxed.
Otherwise, you wouldn’t get hemolysis, for
example, eating fava beans.
But it is a partial compensation, and so if
you can minimize the stresses on your body,
then your ability to partially compensate
is very good.
The thing is when you ask, “What else can
I do about this?” the thing is we’re talking
here about your neurotransmitters, your cholesterol,
your fatty acids, the entirety of your system
of energy metabolism, your glutathione, your
detoxification, your antioxidant defense,
your folate, your vitamin K. There’s no way
you can possibly come up with the hundreds
of different specific things to fix all those
Supplementing glutathione, it’s not necessarily
a bad idea.
You just have to be conscious of, at a certain
point you just can’t solve every one of the
dozens of problems that are happening.
I think that you should measure your glutathione
Probably the best test available, not because
it’s the best we could have available but
because there’s nothing better right now,
is LabCorp’s test for glutathione.
If that looks low, then I would supplement
with glutathione to try to bring that up to
I would do that.
For the folate recycling and the vitamin K
recycling, for folate, you have to consider
this basically as if you had a really bad
The reason is that in this case, what’s happening
is G6PD is needed to make the NADPH that MTHFR
uses, again, with the help of riboflavin to
make the methyl group on methylfolate.
You can take some methylfolate, but as I’ve
made the point in my MTHFR protocol at chrismasterjohnphd.com/methylation,
as I’ve made the point there, you have to
take 18,000 times the RDA to compensate for
the 18,000 times a day that you add a methyl
group to the folate molecule using that enzyme,
using the NADPH that you’re less good at making
because of this impairment.
It’s not safe to take anywhere near that much
I don’t know what happens when you do.
But I wouldn’t do that, it’s not safe, and
it makes no sense.
What I would do is I would just very strictly
follow the MTHFR protocol that I have at chrismasterjohnphd.com/methylation,
and that involves doubling your choline intake
because you don’t need NADPH to use choline
to support methylation.
Just as if MTHFR didn’t work because of genetics
and not enzyme, what you would do is you double
your choline utilization for methylation because
you’re not good at using folate.
Well, presumably, that’s also what happens
It also involves compensating for low methylfolate
effects that deplete glycine, and so you put
some glycine into the system and it also involves
creatine synthesis to lower your methylation
I would do that.
On recycling vitamin K, it probably just means
that you need a high amount of vitamin K in
I think it’s probably similar as if you had
a bad VKOR polymorphism.
VKOR is the enzyme that recycles vitamin K
using NADPH that you got from this pathway
that’s not working right when you have G6PD
But I have a bad VKOR enzyme, and so I don’t
recycle vitamin K well.
I think that’s why I get mad tooth decay when
my diet is not that good.
When I was vegan, I had over 15 cavities,
and I needed two root canals.
I found out about all of them in one sitting
at the dentist.
I think part of that is that I didn’t have
that vitamin K2 in my diet.
Vitamin K2 protects against tooth decay, protects
against cardiovascular calcification.
Because my vitamin K recycling enzyme wasn’t
very good, I needed way higher vitamin K.
Well, if you have G6PD deficiency, your vitamin
K recycling enzyme genetically might be fine,
but you can’t make the NADPH it needs, and
so it’s as if it wasn’t good at recycling
In that case, there’s no alternative like
there is with methylfolate.
There’s nothing you can do except add more
K2 into the system.
My tooth decay went away when I just started
hardcore eating Weston Price.
I’m not talking about I took the most palatable
things about Weston Price like the raw milk
and the bone broth and ignored the organ meats.
I’m talking hardcore.
I’m talking of eating a pound of bison liver
a week for a very long time, just every single
thing that Weston Price said, just tripling
down on it.
My tooth decay went away.
I don’t know exactly what the dose is, but
maybe you would want to put in a milligram
or two or three or four of MK-4.
But you have to test this against symptoms
basically because there’s no good test of
vitamin K status.
In terms of all this stuff that you are not
good at synthesizing, because remember, NADPH
from the pathway that uses G6PD which is the
one that’s impaired here is responsible for
synthesizing cholesterol, fatty acids, nucleotides,
I think the only thing that you can do for
that is to try to eat a lot of these things
Now, I’m not saying eat dopamine, a neurotransmitter.
But I think what you can do is probably you
want to eat a diet that is high in animal
foods because animal foods have a lot more
of these things preformed in them and animal
foods have cholesterol, for example, that
plant foods don’t have, but also just the
nucleotides and all that kind of stuff.
You probably want to eat a diet that is fairly
low in fat and fairly low in starch.
What I mean by that is even though I said
rich in animal foods, all that preformed stuff,
not much of it is in the fat.
It’s really in the flesh, for example.
When you’re looking at plants, you’re basically
going after all the stuff that’s in the cells.
If you look at plants, some plants don’t store
a lot of energy.
The low-calorie plants are mostly cells.
It’s mostly all that preformed stuff that
you’re not as good at making in that plant.
Whereas if you have a potato, that potato
has cells in it, but it also has a ton of
extra storage starch that it’s put into it.
Same thing with the fat; adipose tissue is
your extra storage.
You have like one adipose cell has got one
giant lipid droplet in it.
When you’re looking at fatty tissues, the
ratios of all the cellular meat, so to speak,
to the extra energy are fairly low.
But you don’t want to go extremely low-fat
because you’re not as good at synthesizing
How much fat would you synthesize?
Actually, let me take that back.
It’s not that important to eat much fat because
even when you’re healthy, you only synthesize
about one to two grams per day of fat, except
for a woman in I believe it’s the luteal phase
of the menstrual cycle will make up to 10
grams of fat per day.
But who eats less than 10 grams of fat per
I think if you eat a diet fairly rich in animal
foods, you’re going to get a lot of the specific
fatty acids that you can’t make.
In other words, a high-fat diet is mostly
giving you just a bunch of fat that you could
have made yourself.
But if you eat organ meats and you eat different
types of meats and you diversify across animal
foods, you’re getting a lot of fatty acids
that maybe are in small amounts but are really
For example, arachidonic acid is found in
milligram amounts in foods.
In the foods that are really rich in it, liver
and egg yolks, you’re getting a few hundred
milligrams of arachidonic acid.
It’s way more important.
If you can’t synthesize fatty acids, it’s
not that important for you to get a high volume
It is important for you to get those specific
fatty acids such as arachidonic acid in small
amounts by eating liver and egg yolks.
I think I went into probably more depth than
maybe you were looking for, but I hope that
answers your question, Philippa.
Thank you for your question.