Hi, Rachel.
To convert folic acid to methylfolate, four sequential reactions are required. The first two require NADPH, which is based on vitamin B3, and it requires some additional metabolism to form NADPH, including burning of glucose via the pentose phosphate shunt on the glycolysis chain. Magnesium is also needed. These two reactions convert folic acid to tetrahydrofolate (THF).
Next, a reaction is needed to convert THF to methylene THF, and that is usually done using serine via the SHMT reaction. Then methylene THF must be converted to methylfolate via the MTHFR reaction, which requires vitamin B2 and NADPH.
I don't favor using folic acid to treat ME/CFS, because some people have genetic issues that slow these various reactions, and NADPH is found to be low in many PWMEs. It's preferable to use methylfolate, which avoids this reaction pathway.
Best regards,
Rich
Hi, Rachel.
To convert folic acid to methylfolate, four sequential reactions are required. The first two require NADPH, which is based on vitamin B3, and it requires some additional metabolism to form NADPH, including burning of glucose via the pentose phosphate shunt on the glycolysis chain. Magnesium is also needed. These two reactions convert folic acid to tetrahydrofolate (THF).
Next, a reaction is needed to convert THF to methylene THF, and that is usually done using serine via the SHMT reaction. Then methylene THF must be converted to methylfolate via the MTHFR reaction, which requires vitamin B2 and NADPH.
I don't favor using folic acid to treat ME/CFS, because some people have genetic issues that slow these various reactions, and NADPH is found to be low in many PWMEs. It's preferable to use methylfolate, which avoids this reaction pathway.
Best regards,
Rich
What are the possible symptoms of not converting folic acid to active folate?
On the topic of a conversion problem:
After having taken 5-MTHF since Sept. 2010, I stopped taking it a few months ago. I also, had not taken any other supplemental folates since that time. For some reason, I recently decided to take a couple tabs of 800 mcg folinic acid just to see what would happen. This proved to be a big mistake as I promptly developed a very severe mood fluctuation in a matter of hours. It was not pretty, in fact it was one of the worst days I can ever recall. While I had taken folinic in the past as part of the SMP, it was always or nearly always concurrently with MTHF. Perhaps this having never taken folinic acid independently along with the 2 months without MTHF explains why I have never experienced such a reaction. In this case, I have to wonder about the problems caused by the inefficient conversion of 5-formyltetrahydrofolate.
Rich, I remember you wrote about the possible involvement of MTHFS, which catalyzes the conversion of formyl to methyltetrhydrofolate, but I wonder about the involvement of formyltetrathydrofolate dehydrogenase, which I believe catalyzes excess formyltetrahydrofolate back to tetrahydrofolate. Have you already discussed the possibility that some have not only difficulty making methyl, but recycling formyl back to tetrahydrofolate via the dehydrogenase enzyme. Could chronic deficiency of some of the nutrients here result in changes in gene expression that would in effect prioritize or bias the other reactions?
P.S. Speaking of formyltetrathydrofolate dehydrogenase,I know a Co-A/phosphopantethine prosthetic group is involved with this particular reaction. I only mention it because I have always derived so much benefit from pantethine.