Hi Rich,
I just checked the sheet again. It is definitely reported as 312.
O.K., globalpilot, then here goes!
It looks to me as though your methylation cycle is being overdriven, so that the SAMe level is very high, and the ratio of SAMe to SAH is also high, but the glutathione is not being restored to normal.
There appears to be a pathogen (or, I think less likely in view of your history, a tumor) present that is able to produce nagalase and suppress the response of the immune system.
This may be a retrovirus. There also appears to be a state of oxidative stress, perhaps also caused by infection with a pathogen. The oxidative stress is indicated by the elevated oxidized glutathione and the low RBC folic acid, the latter suggesting damage to cell membranes by oxidative stress.
With this high level of SAMe., I would expect that the glycine N-methyltransferase reaction is running at high activity to prevent the ratio of SAMe to SAH from becoming too high, though it is still running at about 6.4, well above the mean normal value of 5.48. This will be lowering glycine and raising sarcosine. (We don't have values for these, but I am inferring them here from your other results, the way the biochemistry works, and what I have seen in other cases.) The (inferred) low glycine may be hindering the synthesis of glutathione. Normally, cysteine is the rate-limiting amino acid for glutathione synthesis, but if glycine goes too low, it can become rate limiting.
The effect of taking folinic acid as the source of folate can be seen in the relatively high levels of 5-formyl tetrahydrofolate and folinic acid (which are the same substance, just measured in different places), compared to the levels that were achieved in our clinical study. Judging from your fairly high level of 5-CH3-THF, I would say that your cells are capable of using folinic acid well. As you may know, Freddd has argued from his experience and that of others that folinic acid is not used well in some cases. This does not seem to be a problem in your case.
The elevated level of FIGLU results from the low-normal level of THF. I suspect that what is happening is that sarcosine is being produced at a high rate, and it is reacting with THF at a high rate to give it a methyl group, producing 5,10-methylene tetrahydrofolate, which in turn is being converted to 5-CH3-THF pretty well. This is holding THF down, so that FIGLU stays elevated.
This glycine-sarcosine reaction normally serves the double purpose of limiting the SAME to SAH ratio, which controls the rate of numerous methyltransferase reactions in the body, and also conserving and recycling methyl groups when they are abundant, so that they can be provided when they are scarce. However, when methylcobalamin is continuously supplied sublingually or by injection, there is an abundance of methyl groups on a continuous basis, and if the flow into the transsulfuration pathway is not fast enough, the system sort of gets swamped with methyl groups.
I think that the elevated adenosine is indicating that the SAHH reaction is proceeding faster than normal, which I think agrees with the high SAMe level and the inferred high rate of reaction of glycine N-methyltransferase, converting SAMe to SAH at a higher than normal rate.
So what can be done? Well, I think that it would be good to make sure that there is enough B6 and magnesium available to support the enzymes of the transsulfuration pathway, so that the flow of homocysteine in that direction can be increased, hopefully draining more of the metabolites from the methylation cycle and lowering SAMe to a normal level.
Also, it may be necessary to switch from methylcobalamin to hydroxocobalamin so that the cells can control how much methylcobalamin is made, also (I realize that this is heresy to Freddd, but thats what your lab results appear to be saying. I think this varies between cases, depending on genetics.).
In addition, I suspect that you will have to try to figure out what is making nagalase and go after it, because it is probably contributing to oxidative stress and hindering the normalization of the glutathione levels. As you probably know, Drs. de Meirleir and Cheney believe that the retroviruses are the cause of the elevated nagalase in ME/CFS, and they are currently treating it with GcMAF and other additional things.
As you may also know, some of the CFS/ME old-timers on the methylation treatment are now reporting that it has not done the whole job for them, though it does seem to help, and they are having to treat other issues in addition, including exposure to mold toxins, Lyme disease and its coinfections, and high body burdens of heavy metals. I suspect that these are preventing the recovery of glutathione in various PWCs, and they may have been what brought it down in the first place. So, while this methylation--glutathione issue may be the central core of the pathogenesis and pathophysiology (and I still think it is), it may not be possible to fix it in many cases unless whatever is holding down glutathione is also addressed specifically. I think this agrees with what we saw in the clinical study, in which the women had previously been treated for a number of other issues, and some received subsequent treatment for other issues and were found to benefit. I think it also agrees with anecdotal reports from those who have experienced recovery or near-recovery on the methylation treatment. They reported that they had also done other prior treatments.
I hope this helps.
Best regards,
Rich