Very confused about metylation

[uriraha8]

Hey

I did the 23andme test a few months ago.
I thought i have some MTHFR issues because of my depression and CFS.
The results showed no MTHFR mutations, but some other mutations:
COMT V158M +/-
COMT H62H +/- VDR Taq +/+
MAO-A R297R +/+ MTR A2756G +/-
MTRR K350A +/- CBS A360A +/-

I started taking MB12 but in small quantities 500 mcg usually so it wont cause agitation.
I tried adding Folinic acid as my ND told me to take them both i tried Folacal by Thorne. but the folinic caused me to be very nervous and agitated so as the methyl folate (metafolin) caused the same issue.
I tried taking methyl folate in the form of (6S)-5-Methyltetrahydrofolic acid, glucosamine salt in small amount of 500 mcg and found that i can tolerate it. i felt a bit anxiety but my depression was better.
My question is why can i tolerate this form better than folonic although i don't have MTHFR issues?
Can anyone make suggestions to what supplements I should take? Would hydroxycobalamin be effective in this scenario?
Should i keep taking (6S)-5-Methyltetrahydrofolic?
I will appreciate your help

Thanks

 

[Critterina]

(1) My question is why can i tolerate this form better than folonic although i don't have MTHFR issues?
(2) Can anyone make suggestions to what supplements I should take?
(3) Would hydroxycobalamin be effective in this scenario?
(4) Should i keep taking (6S)-5-Methyltetrahydrofolic?

Hey @uriraha ,

I'm no expert, but let me attempt some of your questions:

1. The folinic acid/methylfolate is an equilibrium reaction. Whatever there is more of gets converted into whatever there is less of. If you had MTHFR mutations, one of those conversions wouldn't work very well. But it's a case of the "other part of the reaction" that affects your anxiety and depression. Oversimplifying it:

Folinic acid + BH4 <--- ---> methylfolate + BH2 (that's a double arrow showing it goes both directions.)

BH4 is used to make neurotransmitters, both serotonin (which relieves depression) and dopamine (which in excess can cause anxiety). I think the key is in how they balance out, which is beyond my understanding. (But I guess that your body tends to make more dopamine than serotonin, just naturally.)

So, back to our story: When you take folinic acid, the reaction proceeds in a way that it uses up the BH4 that would other wise have been used to make neurotransmitters. If you take the methylfolate, the reaction proceeds in a way that it makes BH4, so you have plenty for making the neurotransmitters. (My guess: it's enough for both dopamine and serotonin, so your depression lifts a little.) Clear as mud?

2. Yep, anybody can make suggestions. Who is going to make good ones, though? I think that there is nothing else I would add based on what you've said. I agree with your ND about B12 being good, and you seem to have worked out the folate issue. Maybe an active B complex? I just started one that I really like. Brand name is Emerald Laboratories, but you'd have to check out the form and amount of folate in it. If you want a comprehensive set of suggestions, see what the NutrEval test by Genova Diagnostics turns up. (It now costs $799 for Blue Cross patients, but tells you a LOT!)

3. Hydroxycobalamin probably wouldn't be too bad, since you don't show mutations that keep you from converting it to methylcobalamin. But if you tolerate methylcobalamin, why would you switch? Is it a lot cheaper?

4. I'm not sure. I think your depression could worsen without it, since taking the B12 will lower methylfolate levels. The question in my mind is how to get your biopterin cycle to preferentially make serotonin instead of dopamine . Sorry, I don't know enough. Perhaps if you can slowly increase the type of folate you're taking, you'll have enough biopterin to make appropriate quantities of both.

Best of health to you!