Hi, Sasha.
The main reasons I encourage people to run the methylation pathways panel are (1) to find out if they do have the vicious circle mechanism going on in their biochemistry that involves glutathione depletion, a functional B12 deficiency, a partial block in the methylation cycle, and loss of folates, and (2) to obtain baseline data for levels of the parameters in the methylation cycle and the folate metabolism, and the levels of reduced and oxidized glutathione. Having the baseline data is helpful later on in treatment, to gauge the progress. It isn't always clear from symptoms alone how the treatment is doing, because the treatment can make symptoms worse for a while. By repeating the panel later on, a person can find out if the treatment is actually helping, and how much more things need to be improved.
There are also some other things that can be learned. In a small subset of PWMEs, the glutathione level comes out normal, but there is still a partial block in the methylation cycle. These people may have low activity or genomic polymorphisms in the enzymes that normally use the glutathione, i.e. glutathione peroxidase and/or glutathione transferases. It is helpful to know whether this is the case, because it can indicate that more selenium might be needed for the glutathione peroxidases, or it can alert a person to the need to focus special attention on heavy metal toxicity, which may require chelation.
As harrycat noted, this panel can also indicate whether the main issue causing a partial methylation cycle block is the B12 functional deficiency or lack of enough active folate.
This panel can also indicate the severity of oxidative stress. When this is severe, it can be helpful to add some once-through antioxidants to help to control it.
If the initial panel shows very low reduced glutathione and S-adenosylmethionine, I think it indicates that methylcobalamin would be the preferable form of B12 to use, rather than hydroxocobalamin, because these two are needed to convert hydroxocobalamin to methylcobalamin.
(As you probably know, Freddd favors use of methylcbbalamin and adenosylcobalamin in all cases, and finds hydroxocobalamin unhelpful. I think this results from his inheritance of a mutation in the Cblc complementation group, which is coded by the MMACHC gene. Some of the mutations that can occur in this complementation group will hinder the formation of both methylcobalamin and adenosylcobalamin from hydroxocobalamin, and they will also cause glutathione to interfere with, rather than to help, as is normal, with formation of these coenzyme forms of B12, which Freddd also experiences. I don't know what fraction of the ME/CFS population has one of these mutations. Freddd is also intolerant of folinic acid, and I suspect that the reason is that he has also inherited a polymorphism in the MTHFS enzyme, which is the only enzyme that can convert folinic acid to be used to form other forms of folate. I also don't know how widespread this polymorphism is.)
In my opinion, the advantage of using hydroxocobalamin, when it is possible, is that it leaves control of the amounts of methylcobalamin and adenosylcobalamin that are produced to the cells themselves. When large amounts of methylcobalamin and 5-methyltetrahydrofolate are taken together, the methylation cycle can be overdriven, and it appears that this will slow the recovery of glutathione, because too much of the homocysteine is converted to methionine, leaving too little to feed synthesis of cysteine, which is the rate-limiting amino acid for the synthesis of glutathione.
Dr. Amy Yasko uses different criteria to decide which form of B12 is best in a particular case, looking at the polymorphisms in COMT and VDR.
Depending on the various polymorphisms that people have in genes associated with the methylation cycle, they may need more or less B12 support, according to Dr. Yasko's approach.
As harrycat mentioned, it is also very helpful to run some other tests, including urine organic acids and plasma amino acids (urine amino acids panels can also be used). When these are run together with the methylation pathways panel, it is possible to get a more complete picture of the status of the metabolism, and to identify particular deficiencies. If there are problems with the digestive system, running a comprehensive stool analysis panel is helpful to identify what the particular issues are, to guide treatment.
Best regards,
Rich