Anonymous says, "You recommend high-glycemic carbs to help tryptophan get into the brain.
What is the maximum level that your blood glucose can spike to after a meal without
causing any damage?
Some say 140 is the limit.
Is there any evidence to support this?"
Anonymous, what the evidence is, is that people who, in a controlled test have their blood
glucose spike over 140, are at a higher risk of developing diabetes.
That's really what the evidence is.
Now, does it cause damage?
It's tough to say.
I'll come out and say it.
I don't believe that hyperglycemia is harmful because it is hyperglycemia.
I will clarify that there are levels of hyperglycemia that can kill you.
That's definitely true.
But what I mean is that outside the context of someone with diabetic ketoacidosis or hyperglycemia
that is causing osmotic stress to the level that can kill the person that winds them up
in the emergency room, even in diabetes, I think that it's not really about the glucose.
Let's start with diabetes as the model where we really have the evidence of what is causing
harm.
The harm of actually damaging your tissues and actually producing the cardiovascular
and retinal, eye and other neurological complications of diabetes, that's caused primarily by advanced
glycation end products.
Advanced glycation end products are partly caused by glucose reacting with proteins,
but they are mainly caused by methylglyoxal reacting with proteins.
The reason that methylglyoxal, which I did my doctoral dissertation on, the reason that
methylglyoxal, which is quantitatively the most important form of advanced glycation
end products in diabetics, the reason that it is elevated is not because of hyperglycemia.
It's because of deficient insulin signaling.
That is for two reasons.
One is that you can derive methylglyoxal from glycolysis.
You can derive methylglyoxal from ketogenesis.
You can derive methylglyoxal from protein, specifically from the amino acid threonine.
Insulin prevents you from making methylglyoxal in the glycolytic pathway no matter how high
the glucose level is.
Insulin, what it does in glycolysis is at the step where the intermediates spill out
to generate methylglyoxal, insulin stimulates that enzyme that sucks the intermediates down.
Diabetes, you have lower expression of that enzyme, and you have greater spillover out
of glycolysis into forming methylglyoxal.
In untreated diabetes, you can have blood glucose that goes up five times normal.
That will be a factor that is influencing you to make not just five, maybe ten or far
more times methylglyoxal on glycolysis.
But the reason the glucose is elevated is because of deficient insulin signaling.
No matter how much glucose you have or don't have, once the glucose gets into the glycolytic
pathway, insulin is protecting against methylglyoxal by clearing the glucose down.
The high glucose is an influence, but it's a minor influence compared to the effect of
insulin.
Besides this, insulin stops ketogenesis and suppresses the generation of methylglyoxal
from ketogenesis.
Insulin also stops the generation of methylglyoxal from threonine, which is an amino acid found
in protein.
Insulin also makes you make more glutathione, and glutathione is what detoxifies methylglyoxal.
Insulin also stimulates the enzymes that use glutathione to clear out methylglyoxal.
Insulin is way more important to the formation of advanced glycation end products than glucose
is.
Specifically, the problem is not too much insulin.
The problem is not enough insulin signaling.
Even in type 2 diabetes where insulin levels are high, you don't have enough insulin to
normalize the protective pathways because you're resistant to that function of insulin.
A great example, totally irrelevant to how you treat diabetes, but a great mechanistic
demonstration of this is a study where they—
First of all, type 2 diabetics have bad glutathione status.
If you put them in a normoglycemic hyperinsulinemic clamp, which is a situation where you pump
them full of glucose and you pump them full of insulin, and you try to pump them with
as much insulin as you want, but you pump them with enough glucose to prevent that insulin
from dropping their blood sugar.
It's a way to mechanistically intervene by raising insulin levels and keeping glucose
levels normal.
In type 2 diabetics who have high insulin levels already, as long as you keep their
blood sugar normal, raising their insulin levels even further will take their bad glutathione
status and make it the glutathione status of a normal healthy person.
Real world practical implications, nothing.
In other words, I'm not saying that the treatment for diabetes is that people inject you continuously
with glucose and insulin.
What I am saying is that this is proof of principle that the problem in diabetes, especially
with respect to advanced glycation end products, is low insulin signaling.
It isn't high glucose.
High glucose plays a role but a very minor role compared to low insulin signaling.
The role of methylglyoxal starts at the first instance of hyperglycemia to cause the development
from an acute first ever instance of hyperglycemia through the pathway of developing diabetes.
Then in diabetes, methylglyoxal is overwhelmingly responsible for causing the cardiovascular
complications, the complications in the eyes, and the neurological complications of diabetes,
cataracts, all of these things.
And so I think it's a huge mistake to think that the spiking glucose is the thing going
on rather than the deficient insulin signaling.
With that said, at some point, your blood glucose spiking will spill glucose into what's
called the polyol pathway.
The polyol pathway is a way of metabolizing glucose that you can't put into the normal
pathways.
When that happens, you start sucking up NADPH, and NADPH happens to be very important for
glutathione recycling.
Glutathione recycling is very important for getting rid of methylglyoxal.
Here is a way that a normal spike in blood glucose, maybe to 140, depending on your metabolism,
could zap your glutathione status and contribute to advanced glycation end products.
There's a way to test for that.
There is a test called 1,5-anhydroglucitol I think is what it's called.
Let me look that up to make sure.
This test is called the GlycoMark.
I'll put a link to it in the show notes, but it's 1,5-anhydroglucitol.
This is a marker of whether your glucose spikes are on average
generating consumption of glucose in the polyol pathway.
I think the best thing to do is to individualize the question of what's too high of a glucose
spike.
Too high of a glucose spike is whatever gives you a bad mark on the GlycoMark test.
That I think is the real true answer to your question.
Now, if you want to use a rule of thumb that is not individually tailored to you, then
the answer that is not a long rant is yeah, use the 140 limit.
But you follow that up with, is there evidence to support this?
No, I think the evidence says that this is a mediocre approximation of how to identify
whether there's a problem.
But a good way to try to identify whether you're having a problem with glucose spikes
is the GlycoMark test.
All right.
Thanks, Anonymous, for your question.