How exactly does folic acid block methylfolate?
Hi, arx.
In people in general, folic acid competes with the active, chemically reduced forms of folate for absorption by the gut and for transport into the cells.
In people who have ME/CFS, lab testing has shown that NADPH is low. A folic acid molecule requires two NADPH molecules for its conversion to tetrahydrofolate, which is chemically reduced, is the "hub" of the folate metabolism and can be converted to other useful, chemically reduced forms of folate. NADPH is also needed for other important reactions, including MTHFR (which is used to make methylfolate) and glutathione reductase. So taking folic acid will use a substrate that is already low and is needed elsewhere in the biochemistry.
Some people are genetically not able to convert folic acid very rapidly. Then it builds up in the blood, and there is some evidence that it inhibits the action of natural killer cells and can increase cancer risk, though there is not a consensus on this.
Since the natural forms of folate (methylfolate and folinic acid) are now available over-the-counter as supplements, it is best to use them. Some people do not tolerate folinic acid well, and in that case, methylfolate is the one to use. Most do tolerate folinic acid, and it offers benefit in supplying other forms of folate in the early part of treatment, when methylfolate is not being converted to tetrahydrofolate very rapidly.
Best regards,
Rich
