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COMT and reaction to methylation and b vitamins


Senior Member
it seems that COMT mutations are critical to neurological health, to adrenal health and in many cases they can define in a percentage the personality of a person.

There are people that have COMT status especially when they are homozygous in both COMT mutations that trigger a severe reaction when they are supplementing with methyl donors and/or other b vitamins as b6.

The picture gets more complicated if you add MAOA in to the mix, as having COMT status means higher concentration of dopamine in the brain and MAOA means higher reuptake of serotonin in the brain by the receptors resulting in even larger amounts of dopamine and low serotonin resulting in high anxiety and adrenal exhaustion.

Also we often meet this pattern status of mutations to people that are trying to supplement with methylfolate and they do get severe side effects from it.

And then there is also the Gaba/glutamine balance to consider. When glutamine is much higher in concentration than gaba it is causing excitotoxicity in the brain that damages the nerves and maybe this is a reason that supplementation could get you worse if you try it.

Various "Expert" doctors say that in these cases where supplementation gets you worse even though you are giving to your body what it is actually inadequate and especially when this has to do with b vitamins you have to consider dealing with underlying problems first that has to do with nerves before starting supplementation.

I am looking for opinions about my views, also I am looking with people that have this pattern of snps (both COMT homozygous also MAOA homozygous and possibly the MTHFR C667) and they are doing good with the treatment they receive.
I know you posted this a few weeks ago, but I'm assuming having all these mutations is a bit of a rarity so...I have all 4 of the homozygous mutations you refer to (both COMT, MAOA, and MTHFR C677T) I'm just starting to look at methylation issues so I don't have a lot to report but this: I can take high doses of B2, B6, and any form of B12 other than methyl without problems. I tried taking methylcobalamin a year or two ago, before I knew about any of this, and it made me jittery/borderline anxious - nothing terrible, but enough that I stopped taking it.

I'd love to hear more about your theory and if you're interested, once I start methylfolate I'm happy to keep you updated on my reactions to see if they fit with your views.


Senior Member
Front Range Colorado
I'm going to chime in on this because I have those mutations, but not as severe. I am homo for MAO A and hetero for two COMTS (negative for two others) and hetero for c667. A month or so into Freddd's protocol, I am struggling with anxiety, exercise intolerance (fatigue and palpitations upon even mild exertion, better as the day goes on).

I've worked up to 4g mfolate, and I don't feel like that creates anxiety when I take it. I do think mb12 might be a trigger, as I experience an increase in anxiety after taking my morning mb12/adb12 combo. I may try just adb12 for a few days and see how that goes. I also feel like L carnitine fumarate is causing me anxiety. I've started titrating down from 500mg to maybe 50-75 to little effect so far.

I should try hydroxocobalamin, but Freddd was so down on it, as I interpreted his comments, that it's seemed like a waste of money to buy some.