Heather Chandler says, "Are you aware of any mechanism by which methylated vitamins such as
methylfolate and methylcobalamin could increase pain in the form of central sensitization?
Increase in BDNF, TNF-alpha, and VEGF, vascular endothelial growth factor
are well-established ways to increase central sensitization,
but I'm not sure if methylated vitamins have any relation to those."
So, first of all, my general default position, if people have problems with methylated vitamins
that they don't have from other vitamins is that their methylation system is
kind of unstable and it needs to be stabilized. And so my first thoughts without getting into
specifics on mechanisms or symptoms is that for someone who has a very specific reaction
to the methylated B vitamins they probably need two things. Number one, they need to make sure
that their glycine levels are middle of the range normal. And number two, they need to start with
very low doses and equilibrate to those very low doses, and then titrate up very slowly over time.
Now, as to whether I can speculate anything about pain or central sensitization of pain?
I'm not sure. Just to throw out some random... I can't offer an answer to that.
It's possible if I spent more time thinking about it, I could. But just to throw out some
random threads that may or may not be of use. I think methylation in some people is going to
lead to increase synthesis of dopamine. But in general, the effect is going to be to decrease
the tonic pool of dopamine. There's going to be some degree to which it decreases other
neuro-transmitters. And it's possible that if, particularly, if glycine is not stabilized,
that you're going to lose the inhibitory effect of glycine and that you might also lose the
effect of ambient glycine in coactivating NMDA receptors.
Now off the top of my head, I would think that you would want
the glycine there to support... Excuse me. I would think that if you lost glycine,
that I would think that NMDA receptor hypofunction would not lead to central sensitization of pain.
Because I think in general, glutamate neurotransmission is going to promote
chronic pain. Generally, NMDA receptors are going to promote maybe not as much the pain itself as
long-term potentiation and strengthening of synaptic connections that solidify
the sensitization. But to the extent that glycine is a inhibitory neurotransmitter at many nerves
where glutamate transmission could be involved in the pain,
then I think it's possible that glycine depletion could play a role in why those
methylated metabolites would lead to more of that pain, neurotransmission that results in pain.
And that would fit in with what I was saying before, which is my default based cases to assume
that there is instability in the methylation flux that is driven in part by low glycine
levels. And so, I guess I would look there first as a possible explanation, but I'm speculating.
All right. Thank you, Heather, for your question.