Dr. Lisa Rankin


This article was written on 14 Apr 2015, and is filled under LisaRankin.

MTHFR and COMT…..What do all these letters mean?

MTHFR and COMT what do all these letters mean?

MTHFR and COMT what do all these letters mean?

By now many of you have become familiar with the Methyltetrahydrofolate Reductase Mutation MTHFR and may have even been tested to see if you have an altered copy of this gene which affects the function of a chemical pathway of metabolism involving folate one of the B vitamins. In a VERY simplified explanation MTHFR is a key enzyme involved in serotonin and catecholamine (dopamine,epinephrine, norepinephrine) production. They act as neurotransmitters/ chemical messengers in our body including the brain and play a significant role in mood,behavior and cognition. Currently the main classes of meds for Depression, Anxiety and Mood swings target/affect one or more of these neurotransmitters. If you have a mutation in the MTHFR pathway you would then expect to have a defeciency in the prodcution of these neurotransmitters which would affect your mood. In many cases this is true and for years this knowledge has been used to suggest high dose Methyl-folate ( One Rx form is Deplin) as a way to “bypass” the problem pathway and make sure the body has enough of the necessary form of this B vitamin to make adequate supply of these “mood chemicals”. Utilizing folic acid, the more familiar and synthetic form willl not work and the natural form found in foods, folate, is needed. Nice and simple, test for MTHFR status and if there is a altered copy or copies of the genes give the patient high dose folate in prescription or over the counter form.

Of course it is not so simple. There are two main copies of the altered gene 677 and 1298 and there are different combinations of abnormalities that can be seen. One mutation has a more significant impact on production of the Neurotransmitters than the other which should then alter the clinical effect also. Just to make things more complicated we cannot forget about Catechol-O-Methyltransferase (COMT) which is one of several enzymes that breakdown catecholamines (dopamine,epinephrine, norepinephrine). Just as with the MTHFR there are several combinations of altered genes one can have that will effect the level of these neurotransmitters in your body and consequently have impact on mood, behavior and cognition. If you happen to have a combination that slows the breakdown of these catecholamines AND you start taking high dose of methyl- folate or other substances that have the ability to donate methyl groups, like methyl b12, you can end up with excess of these neurotransmitters and worsening of anxiety, irritibility and anger. METHYLATION is a whole other topic very important to this one but needs its own post and you do not need to understand methylation to understand this concept. This is why things like Deplin or similar products help some but seem to aggrevate others.

So what can you do to prevent this problem? First things is to be informed. Genetic testing to provide this information is now available fairly inexpensively and can be done at home. 23 and me has home kits and then you can upload the results to another site that will provide you with useful information. You should then bring that to your medical provider so they can help you pick the best supplement regimen for you.