This sounds good to me. But what is the difference btwn folinic acid and methyl folate? They are both active forms of folate--right? SO how do you know which is best/better for you?
This is from Rich. He says that folinic serves other useful purposes besides just converting to methylfolate. He also explains what happens when taking too much methylfolate with a high dose of b12
I actually prefer including both folinic acid and 5-MTHF. 5-MTHF is the form needed by methionine synthase, which is the enzyme with the partial block. Many people's cells are able to convert folinic acid to 5-MTHF well, but many others have inherited genetic polymorphisms that slow this conversion down considerably. The polymorphisms in the MTHFR enzyme are a good example, and these are very prevalent in the population.
Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.
[The reason] I don't recommend [a high dose of] Methylfolate when it is combined with several milligrams of methyl B12 is that this combination takes control of the rate of the methionine synthase enzyme away from the cells and drives it too fast. The result is that too much of the homocysteine is converted to methionine, and there is not enough left to flow into the transsulfuration pathway to support synthesis of glutathione and other sulfur-containing substances that the cells need.
The result is that the methylation cycle gets going well, but glutathione does not come up, as it needs to do for full recovery. There are excess methyl groups produced because of overdriving the methylation cycle. These are shunted off to the folate metabolism by sarcosine, which is produced by the glycine N-methyltransferase reaction, and then they come back to the methylation cycle via methylfolate. It's sort of like a futile cycle, like a squirrel in a rotating cage.
This is not just based on biochemical theory, though it is supported by that. It is based on lab tests that people who have been on this regimen have sent me.
For most PWMEs, this does not work very well in the long run. In Freddd's own case, because of the genetic variations that he apparently has in the CblC complementation group and in MTHFS (not to be confused with MTHFR), it is necessary for him to use a high dosage of methyl B12 to overcome the CblC problem, and it is necessary for him to use a high dosage of methylfolate to feed his folate metabolism, since he cannot use folinic acid or folic acid. (I'm not sure why he cannot use folic acid. Perhaps he has a polymorphism in the DHFR enzyme, also). Freddd cannot tolerate raising glutathione, because it binds cobalamin to form glutathionylcobalamin, and his version of the CblC complementation group is not able to retrieve cobalamin from glutathionylcobalamin. As far as I can tell, this is a rare genetic variation. Most PWMEs are depleted in glutathione, and this is responsible for a large number of the symptoms.
There may be other PWMEs who have one or more of these genetic issues as well, since Freddd reports that there are some others who respond to these supplements in the same way he does, but most do not seem to have them, based on our clinical study and anecdotal reports from quite a few PWMEs.
He also has explained this to Freddd (on multiple occasions) why he has a problem with folinic acid, but says that this is rare
Hi, Freddd.
As I've suggested, I suspect that you have what appears to be a rare deficiency in the enzyme MTHFS (methenyltrahydrofolate synthetase) which is the enzyme that normally converts folinic acid to methenyltetrahydrofolate, from which it can normally be converted to other forms of folate, including 5L-methyltetrahydrofolate. I think that explains why your body is not able to use folinic acid, and in fact why it blocks your folate metabolism, as folinic acid is known to inhibit the SHMT reaction, which is the main reaction that converts THF to 5,10-methylene tetrahydrofolate, which in turn can be converted to 5L-methyltetrahydrofolate.
