[Rhonda]: You mentioned when you were talking about gluconeogenesis, you triggered something
in my mind.
I wanted to ask you, I forgot.
So when you're in nutritional ketosis or fasting-induced ketosis, you need to make glucose you still
need glucose, your red blood cells have no mitochondria and your red blood cells are
important, right?
So you're making glucose through this process that you mentioned called gluconeogenesis.
[Dom]: Glucose does not bottom out.
It's not like one or the other.
You're pulling fuel source from...
[Rhonda]: So I wanted to ask you about, like, how...
Has anyone looked at where...so if you are on a pretty strict ketogenic diet or whatever
it is you're doing to get into ketosis, what...so does the liver use, like, glycerol, lactate,
like, both as a primary source to make glucose?
Is that glucose predominantly going to red blood cells or does it go has that been looked
at to see, like, where, you know...?
So red blood cells, like, are they getting enough of their glucose or they, you know?
[Dom]: I think so.
I mean, you'd probably have to severely calorie restrict.
In those cases, you could become anemic or impair...your immune system is also, too,
highly dependent to some extent on glucose and glutamate.
So, yeah, you have lactate, you have the glycerol backbone, the fats...
[Rhonda]: But they always have mitochondria.
[Dom]: Yes, yes.
So glycerol backbone of fatty acids or of triglycerides, for sure, lactate, yes, and
amino acids, gluconeogenic amino acids in your diet also are a source of glucose.
So gluconeogenic amino acids in your skeletal muscle your muscles constantly breaking down
or remodeling especially in athletes.
So they're all sources.
The contribution of each of these gluconeogenic sources in each individual probably varies
tremendously, but I would say that...
So glucose is always going to be there, and the body ensures through very powerful homeostatic
mechanisms that your glucose is going to stay, rarely go below three, maybe 2.5 millimolar,
mine will drop two, go to four and stay within a very tight range, but what does change considerably
from a glucose regulation standpoint is the insulin.
Insulin bottoms out to the point where I've seen enough blood work to show that in many
cases, insulin and IGF-1 is below the reference range.
So insulin signaling goes down.
So if insulin's down, all those insulin pathways that you see on your flowcharts are all going
to be suppressed and IGF-1, obviously, it's going to be lower and I think that's a really
important consideration to factor in as it relates to cancer therapeutics, cancer biology,
cancer prevention, even.
But also from the perspective of muscle metabolism.
And I think by keeping insulin signaling sort of low, you upregulate factors that make you
more responsive to insulin.
So I think, and ketones can kind of compensate for a deficiency in insulin, and that was,
a lot of the reviews by Richard Veech talked about that.
And the ketones themselves are anti-catabolic for protein sparing.
So if you're in a state of ketosis, you're protecting gluconeogenic amino acids and skeletal
muscle from being degraded.
So you are as a metabolic fuel, but you're also, there's evidence that you're inhibiting
proteolytic enzymes and pathways that would otherwise be chewing up your muscle tissue
over time.
[Rhonda]: That's super-cool.
[Dom]: So it's anti-catabolic, yeah, so ketones are anti-catabolic in that part.
[Rhonda]: So then you're probably not using, I mean, the gluconeogenic amino acids as much...
[Dom]: From skeletal muscle, yeah, not as much.
So the idea is that you want to keep pumping in the fat, too, if you're on a ketogenic
diet.
If it's not sufficient with ample amounts of fat, you're probably much more catabolic.
So you want to ensure that you're using the fatty acids, go to the mitochondria that uses
fuel, they keep the mitochondria happy as do the ketones.
Then the glycerol is kind of,shuttled and it's a very nice kind of an elegant pathway
to ensure that we have that flux of glucose for vital functions like the red blood cells
and making...there's an number of neurotransmitters and hormones that require a baseline level
of insulin or glucose to be used.