Thanks Fredd for the explanations. I will get the pottassium supplement. Even though you and Rich have explained it all I am embarrassed and have to confess that after reading and reading about the methylation trap as apart from the methylation block, my poor old foggy brain simply will not co-operate and make me understand what the difference is. So I will just continue with the protocol and deal with symptoms as they arise.
Hi, Anne P.
Since I think I'm the one who introduced the partial methylation cycle block and the methyl trap to the discussion here, I will try to describe what they are.
I invented the term "partial methylation cycle block." What I mean by it is that the methionine synthase reaction that links the methylation cycle to the folate metabolism is chronically operating more slowly than is normal. This is usually caused by an insufficiency of methylcobalamin (methyl B12), which serves as a coenzyme for this reaction, but it can also be caused by an insufficiency of methylfolate (Metafolin, FolaPro, MethylMate B or Deplin), which is one of the reactants in this reaction, and which leaks out of the cells via the "methyl trap" mechanism (see below). That's why both a B12 and a folate are necessary to lift this partial block. In my hypothesis for ME/CFS, the reason for the insufficiency of methyl B12 is that B12 is lost to reactions with toxins because there is insufficient glutathione in the cells to protect the B12 from this hijacking by toxins. The reason such a high B12 dosage is needed, compared to the usual RDA requirement for B12, is this hijacking. Enough B12 needs to be put in so that some is left over to do its normal jobs, and it can require large dosages to do this.
The "methyl trap," on the other hand, is not something I invented. It is discussed in the published research on folate metabolism. What it means is that when the methionine synthase reaction is running more slowly than normal (i.e. a partial methylation cycle block is present), the cells will produce more methylfolate than is being used in this reaction, which is essentially the only reaction that makes use of methylfolate (except that it has been found to react with peroxynitrite). Methylfolate, unlike other folate forms in the cells, does not have a glutamate tail (which is negatively charged because glutamate ionizes under the pH condition in the cells). The absence of this charge enables methylfolate to diffuse through the cell membrane into the blood. As this process continues, other forms of folate in the cells decrease, and methylfolate rises in the blood serum. Because of the methyl trap mechanism, it is necessary to take a folate supplement as part of the treatment to lift the partial methylation cycle block. Once the methionine synthase reaction gets going at a normal rate again, the requirement for B12 should drop back down, and probably the folate requirement will come down some, too.
Best regards,
Rich