I'm interested in learning more about B-12 but don't dare try to read the 1628 (!
) posts in the "B-12 - The Hidden Story" thread. Can someone who has been following it give a synoposis of B-12 and how it's significant to those suffering from ME/CFS? I realize it's a lot of material to summarize, but I would like the abbreviated cliff notes version please
I'll try to give you my perspective on B12 and ME/CFS. I, of course, think it's an accurate perspective, but I must note that there are some differing views on this subject. I'll try to separate hypothesis from what is currently viewed as scientifically established.
First, vitamin B12 is normally used in the human body to form two coenzymes that do different jobs in the biochemistry of each cell. These are adenosylcobalamin and methylcobalamin. Adenosylcobalamin is formed and used in the mitochondria (little power plants) of the cells. It is involved in helping to metabolize certain amino acids and other substances so that they can be used in the Krebs cycle to produce ATP, which powers many of the biochemical reactions in the cells. So adenosylcobalamin is involved directly in energy production.
The more vital form is methylcobalamin. This form of B12 is used as a coenzyme by the enzyme methionine synthase, which is in the methylation cycle. The methylation cycle plays some vital roles in the cells. One is that it makes methyl (CH3) groups, which are needed by a large number of reactions in the cell, some of which make various needed substances, and some of which involve methylating DNA. The latter is important for controlling the expression of genes, and has wide-ranging effects on the overall operation of the cells. The methylation cycle is also located at the beginning of the overall sulfur metabolism in the cells, and thus controls the formation of several other sulfur-containing species, including cysteine, glutathione, taurine, and sulfate. These in turn play important roles in controlling oxidative stress, removing toxins from the cells, and supporting the immune system. So when there is a problem with vitamin B12, it ends up affecting many important functions in the body.
So far, what I've written is considered to be scientifically established. Now I'm going to talk about my hypothesis for ME/CFS. I have hypothesized, that in ME/CFS, as appears to be true in autism as well, there is a partial block of the enzyme methionine synthase, and this partial block is associated with depletion of glutathione in a vicious circle interaction mechanism, which makes ME/CFS a chronic condition. We have lab test evidence that supports this, but it is not yet considered to be scientifically proven by the ME/CFS community.
I have suggested that this situation comes about in most cases of ME/CFS when glutathione becomes depleted as a result of the action of some combination of a variety of physical, chemical, biological and/or psychological/emotional stressors, the combination being different for each case. For a person who is genomically predisposed by having inherited an appropriate combination of polymorphisms, this leads to the partial block of methionine synthase.
I have suggested that the mechanism by which this occurs is that depletion of glutathione removes the normal protection from vitamin B12 in the cells, and also allows buildup of toxins within the cells. The toxins then react with the B12, hijacking it, so that it cannot be used to make the two coenzymes. The results are that the fuel supply to the Krebs cycle is decreased, and more importantly, methionine synthase becomes partially blocked, and the methylation cycle thus becomes dysfunctional, reflecting dysfunction on the rest of the sulfur metabolism, including the synthesis of glutathione, and producing all the symptoms of ME/CFS.
When methionine synthase becomes partially blocked, it also disrupts the folate metabolism, because one form of folate is a reactant of methionine synthase. Since it is not being used by this reaction, it leaks out of the cells into the blood, by a process called the methyl trap mechanism, and this ends up depleting the folate in the cells.
When it comes to treating this condition, there are differences of opinion about how this should be done. I think that all those involved agree that both B12 and folate must be taken simultaneously, but the exact forms and dosages are debated. I have proposed what I have called the Simplified Treatment Approach, so named because it was extracted from the much more comprehensive treatment program developed by Dr. Amy Yasko, mainly for autism, but also used for other neurological diseases as well as for CFS. This treatment uses sublingual hydroxocobalamin as the B12 form, and uses mainly 5-methyl tetrahydrofolate (aka FolaPro, Metafolin, or Deplin) as the folate form, as well as some folinic acid and some ordinary folic acid. There is also a special multi and a phospholipid supplement included.
Most of the long B12 thread to which you referred describes the treatment advocated by freddd for the whole variety of B12 deficiency conditions, as well as for ME/CFS. He recommends relatively large dosages of both methylcobalamin and adenosylcobalamin, as well as 5-methyl tetrahydrofolate and some other supporting nutrients.
There is also the Vinitsky protocol, which uses sublingual hydroxocobalamin together with relatively large dosages of sublingual ordinary folic acid. There are also some additional nutrients used.
The DAN! project for treating autism has used subcutaneously injected methylcobalamin together with oral folinic acid, primarily, and other supplements are also added.
The protocol recommended by Prof. Martin Pall uses hydroxocobalamin and a form of folate also. Initially he recommended folic acid, but more recently seems to be moving to 5-methyl tetrahydrofolate. His rationale for using them is different, being based on his NO-ONOO model for CFS. He believes that the main role of the hydroxocobalamin in CFS treatment is to scavenge nitric oxide, and the role of the 5-methyl tetrahydrofolate is to scavenge peroxynitrite.
I hope this gives you a place to start. It's probably a little more detailed that Cliff notes, but that's about the best I can do!