arx:
Thanks for the links.
I tried a day with no folinic acid and to be honest the results were mixed. I think most of my body was better in terms of calmness, clarity of thought, basic energy, etc. but to be honest my low dopamine symptoms started to set in at night which was not fun. I am also hypokalemic (3.2 serum) so I have to be careful as I know methylation support can affect that (I take a lot of extended release KCL and other potassium per day for a total of 3000 mg / day). But then again I have been borderline hypokalemic for a decade or more. Reduction of folate for other biological purposes beyond methylation will lower biopterin levels indirectly through folate intermediates and lower catecholamine production, while increased methylation will metabolize catecholamines faster via the COMT enzyme. So it is a sticky situation.
I read the post you attached from Freddd in reply to another forum post.
I agree with some his points. Namely that taking glutathione exogenously is a fad and a waste of money.
But not for the same reasons.
Glutathione is notorious for breaking down into glutamine and cysteine and glycine. In fact to get through the cellular membrane it must disassemble and be re-assembled inside the cell. Period. When taking glutathione exogenously even via IV at most some gets uptaken by the liver and maybe a little in the kidneys, the rest is broken down.
But glutathione is a key cofactor in multiple parts of the Krebs cycle. You never want to down-regulate the Krebs cycle. Second of all glutathione is a major anti-oxidant and a major component of immune function. Low glutathione also greatly exacerbates autoimmune conditions. These things are all well known in the scientific literature having nothing to do with the quacks and charlatans like Suzanne Sommers who are pushing glutathione itself.
Ironically Freddd puts vitamin C and D-ribose both into his basic protocol. Vitamin C is the main way to break the GSSG complex and recycle glutathione. D-ribose and L-carnitine fumarate all lead to increased ATP through different mechanisms (as does magnesium and CoQ10 for example). ATP is a major rate limiting step in making glutathione from glutamine and cysteine. ATP is the energy currency of the body. So on hand he blasts glutathione,
says no precursors and then includes supplements that will increase glutathione. I think we would all agree ATP is extremely important to health.
Also as I pointed out in the earlier post, your body makes hundreds of grams of glutamine a day. That is fact. Glutamine is a major indirect branch off the Krebs cycle and is the backbone of glutamate and GABA. Low levels
of glutamine in the body or the brain have all sorts of nasty consequnces, which is why it is so hard to achieve unless someone is on a starvation diet or has zero Krebs cycle activity. So taking an extra 5 grams of glutamine a day, is like 2-3% of your bodies budget and somehow that extinguishes all benefits of the methylation protocol as seen in a 10 patient unpublished trial?? I don't get that.
Many people with CFS, may confuse problems with the NMDA glutamate receptor as being due to other problems.
Excess glutamate is a problem. If conversion of GABA is limited by low P-5-P, magnesium, etc. then a build up of glutamate is bad, and extra glutamine is not helpful. Trust me over-activation of the NMDA receptors = neurological pain that cannot be reduced by any medicine including opiates. The only answers are taurine, magnesium, glycine and GABA for different reasons (too long to discuss here). Trust me I have lived this nightmare, since my autoimmune disease is in fact Stiff Person Syndrome. Personally IV glutathione was a disaster for me, since prior to my real diagnosis, I was getting infused with large amounts of glutamate that I could not process and my NMDA receptors went wild making my muscles cramp like crazy.
NAC is another matter. NAC has a lot of nasty side effects. Most notably in the brain. The side effects have exactly zilch to do with glutathione production. But what is hilarioius (ignoring NAC) is if the methylation protocol works
(whoever's you use) then you will increase cysteine production and ultimately some amount of glutathione (unless you are blocked with ATP like I was). So more methylation = more cysteine production which with the high intrinsic amounts of glutamine in most people = more glutathione provided ATP is present.
So there is a circular logic here that simply makes no sense to me.
I suspect Freddd was dealt a particularly bad genotype with active B12 processing and thus walks a razor's edge not being able to convert from any of the inactive forms.
Don't get me wrong I respect the heck out of his research and passion and his obviously difficult health story, but the like I said your body will make glutathione if you are healthy and have methyl groups and ATP and there is nothing you can do to stop that ...