Question from a Member:
Do you have any experience using leucovorin instead of L-methylfolate (Deplin) in patients with MTHFR mutations?
Why even consider L-methylfolate supplementation?
As discussed in another article on this website, we noted that the folates we take in our diet or the folic acid we take as a supplement are metabolized in four steps:
Step 1: folate/folic acid → dihydrofolate
Step 2: dihydrofolate → tetrahydrofolate
Step 3: tetrahydrofolate → methylene tetrahydrofolate
Step 4: methylene tetrahydrofolate→ L-methylfolate.
In step 4, methylene tetrahydrofolate is metabolized by the enzyme methylene tetrahydrofolate reductase (MTHFR). In only some people with polymorphisms (variations) in the gene that codes for the enzyme (MTHFR), there may be lower activity of MTHFR, which may lead to lower conversion of methylene tetrahydrofolate to L-methylfolate.
If this is a problem, L-methylfolate can be given orally, making the enzyme MTHFR irrelevant.
Please note that it is NOT true that all patients with polymorphisms of the gene that codes for the enzyme methylene tetrahydrofolate reductase (MTHFR) should be given L-methylfolate (Deplin®). Elsewhere on this website, we have discussed the clinical circumstances under which L-methylfolate supplementation may be appropriate (see Related Pages below).
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