Hi, all.
I'd like to bounce something off you.
As some of you know, when people start doing the methylation block treatment, many of them experience an increase in symptoms that appear to be associated with excitotoxicity ("wired" feeling, insomnia, anxiety, hypersensitivity to light, sound and touch). This is associated with more rapid firing of action potentials by neurons that incorporate NMDA receptors. I've wondered for a long time why this gets worse when a person starts to lift the partial methylation cycle block.
O.K., here's what I suggest as the cause:
When a person has a partial methylation cycle block, they experience draining of their sulfur metabolites excessively down the transsulfuration pathway, because homocysteine is not being recycled back to methionine as rapidly as normal. Over the course of time, this depletes methionine somewhat, and PWCs tend to be low in methionine.
But even though this has occurred, there is still some draining down the transsulfuration pathway, and some of this serves to supply cysteine to make some glutathione. Glutathione is somewhat depleted, but some is still being made. If it weren't, the person would not survive.
O.K., now consider what happens when the activity of methionine synthase is increased by raising the availability of methylcobalamin and 5-methyl THF to this enzyme. All of a sudden, more of the homocysteine is recycled back to methionine, and therefore, less is available to the transsulfuration pathway. I suggest that this results in temporarily lowering glutathione even further! Over time, this situation will improve, and we have observed in lab tests that glutathione does come up to normal over a period of some months, on the average. However, initially, I suspect that it goes down, worsening the glutathione depletion temporarily.
Now here's how I think this impacts the excitotoxicity. Further glutathione depletion would increase the state of oxidative stress in the mitochondria of the neurons. This would intensify the partial blocks in the Krebs cycle and the respiratory chain, and that would further lower the rate of production of ATP. ATP is needed to power the membrane ion pumps in the neurons, and they normally maintain the electrical potential across the cell membranes.
This potential in turn determines the firing threshold for action potentials (nerve impulses). When the potential is lowered, the neurons become more sensitive and fire more readily. Thus, this results in increased excitotoxicity.
If this is actually what is going on, there may be some benefit to supporting the glutathione during treatment to lift the methylation cycle block, at least early on.
I would be very interested to know what you think about the theoretical aspects of this, as well as whether any of you have experience in boosting glutathione more directly while lifting the methylation cycle block, and if so, whether it seems to have helped calm down the excitotoxicity.
Thanks.
Best regards,
Rich
I'd like to bounce something off you.
As some of you know, when people start doing the methylation block treatment, many of them experience an increase in symptoms that appear to be associated with excitotoxicity ("wired" feeling, insomnia, anxiety, hypersensitivity to light, sound and touch). This is associated with more rapid firing of action potentials by neurons that incorporate NMDA receptors. I've wondered for a long time why this gets worse when a person starts to lift the partial methylation cycle block.
O.K., here's what I suggest as the cause:
When a person has a partial methylation cycle block, they experience draining of their sulfur metabolites excessively down the transsulfuration pathway, because homocysteine is not being recycled back to methionine as rapidly as normal. Over the course of time, this depletes methionine somewhat, and PWCs tend to be low in methionine.
But even though this has occurred, there is still some draining down the transsulfuration pathway, and some of this serves to supply cysteine to make some glutathione. Glutathione is somewhat depleted, but some is still being made. If it weren't, the person would not survive.
O.K., now consider what happens when the activity of methionine synthase is increased by raising the availability of methylcobalamin and 5-methyl THF to this enzyme. All of a sudden, more of the homocysteine is recycled back to methionine, and therefore, less is available to the transsulfuration pathway. I suggest that this results in temporarily lowering glutathione even further! Over time, this situation will improve, and we have observed in lab tests that glutathione does come up to normal over a period of some months, on the average. However, initially, I suspect that it goes down, worsening the glutathione depletion temporarily.
Now here's how I think this impacts the excitotoxicity. Further glutathione depletion would increase the state of oxidative stress in the mitochondria of the neurons. This would intensify the partial blocks in the Krebs cycle and the respiratory chain, and that would further lower the rate of production of ATP. ATP is needed to power the membrane ion pumps in the neurons, and they normally maintain the electrical potential across the cell membranes.
This potential in turn determines the firing threshold for action potentials (nerve impulses). When the potential is lowered, the neurons become more sensitive and fire more readily. Thus, this results in increased excitotoxicity.
If this is actually what is going on, there may be some benefit to supporting the glutathione during treatment to lift the methylation cycle block, at least early on.
I would be very interested to know what you think about the theoretical aspects of this, as well as whether any of you have experience in boosting glutathione more directly while lifting the methylation cycle block, and if so, whether it seems to have helped calm down the excitotoxicity.
Thanks.
Best regards,
Rich