Folate part 2: MTHFR and genetic testing

The last post about folate deficiency got me thinking.  Absolute absence of folic acid is a risk for non-response to antidepressants, but suppose you have adequate intake of folic acid.  Is that good enough?  In most cases, yes.  In some cases, no.  Lets look at some chemistry so you have a better understanding of why we need to be concerned about this.  Folic acid is a synthetic form of the vitamin folate, and is the form found in enriched wheat products.  The form of folate found in nature is dihydrofolate.  This is the form found in green vegetables, egg yolk, beans and some organ meats such as liver and kidney.  One of the key steps in activation of folate is by an enzyme called methylene tetrahydrofolate reductase (MTHFR).  This enzyme converts folic acid and dihydrofolate to the form used by the body:  L-methylfolate.  It is this form that can cross the blood-brain barrier and support the enzymatic processes that result in the formation of the neurotransmitters serotonin, norepinephreine and dopamine.

There are now available tests to determine how well your body produces MTHFR.  If your genetic code includes one of the variants that results in diminshed production of MTHFR, you have a limited ability to turn folat or dihydrofolate into L-methylfolate.  It will be as if you are folate deficient!  This will, in turn, make it less likely that you will respond to antidepressant medications.  This is easily remedied by supplementation with L-methylfolate.  This was marketed as a “nutraceutical” under the names Deplin and Enlyte.  These were a bit expensive and insurance did not pay for them.  This limited people’s willingness to give it a try.  There are now many L-methylfolate products available on Amazon and in the nutritional sections of some supermarkets and pharmacies.

Absence of folate or limited functioning of MTHFR is an infrequent reason for lack of response to antidepressants.  It is, however, one that is easily remedied and should not be forgotten.

–Dan Hartman, MD


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