COMT says don't take methyl MTRR says DO take.....

[Critterina]

My husband is having the same confusion about taking methyl-whatever....QUESTION: With those MTHFR snps (and MTRR), would you think he might need either some methylfolate or some methylB12 occasionally? Or should he stop experimenting with those?

My guess is that he will (eventually) want to take methylfolate and the hydroxyB12 plus the adenosylB12 that he was taking, but the question will be dose and proportions of the three. (if I understand what you said above, he has both MTHFR C667T and MTHFR A1298C, both +/+, right?)

When he raised his dose, my guess is that his methylfolate reserve went down, BH4 went down, his SAMe went up and somehow got stuck there, leading to the crash. Whatever imbalance was not completely corrected with the first niacin dose, so when he went back to his old B12 doses, so it didn't take too long before the imbalance worked it's way back to a crash. Not sure, but thinking that the adenosyl is not the culprit, but the hydroxy here. And that he will end up with either a lower dose of hydroxyB12, or that he'll spread it out into smaller doses during the day.

Does he have a B complex with niacin/niacinamide in it, so that he gets a little of it and other B vitamins daily?

 

[picante]

(if I understand what you said above, he has both MTHFR C667T and MTHFR A1298C, both +/+, right?)

No, C677T is -/-.

When he raised his dose, my guess is that his methylfolate reserve went down,

When he raised his doses, he raised all three at once: MeB12, AdB12, and mefolate. In other words, he doubled everything.

Whatever imbalance was not completely corrected with the first niacin dose

That imbalance was corrected with 2-3 niacin doses, and ...

so when he went back to his old B12 doses,

He didn't. Then he stopped the methylfolate and the MeB12, and switched to the HydroxyB12, which I'm assuming mopped up the excess methyl groups that he wasn't using due to the COMT mutations.

HydroxyB12 wasn't the culprit in today's crash. After he took the niacin to try and reverse the harm he did by taking MeB12, about an hour later, he took a half-dose of HydroxyB12 (Perque), and it helped even more. He seems completely recovered from his crash now. He's planning on increasing the HydroxyB12 because he's convinced he needs more, and that's what made him crash in the first place -- not taking enough.

One tab of Perque B12 Guard is 2000 mcg, and he plans on increasing to 1 1/2 tabs tomorrow, since that's what he ended up taking today.

My best guess is that either he's right about needing more HydroxyB12 now, or he's taking too much AdB12 (1/4 tab of Dibencozide). Or he's missing a co-factor.

 

[Critterina]

@picante ,
Sorry, when you said the SNPs were like AlKlein's, I assumed that the ones you didn't write were the same, the C677T being the more important one... I could never have guessed this additional info from your first post, sorry.

It is clear that he needs the B12, whether hydroxy or methyl depends on things that are hinted at my SNPs, but there's not enough consistency to predict - either it's an SNP or haplotype we are not testing or it's a lifestyle/environment issue. Although A1298C is associated with a lot of symptoms, if he doesn't have them, it wouldn't be necessary to take methylfolate.

It is also NOT clear that upping all doses would NOT have the effect I spoke of, the B12 contributing to an enzyme function, and the methylfolate being a substrate of a reaction - you don't use up one B12 for each methylfolate.

I'm sure you know the signs of folate deficiency, so as long as increasing the B12 makes him feel better and he doesn't get deficiency symptoms, he'll be good.

 

[picante]

Although A1298C is associated with a lot of symptoms, if he doesn't have them, it wouldn't be necessary to take methylfolate.

Is there a list somewhere? His symptoms are so different from mine, I'm not sure I would associate them with A1298C (and I'm compound heterozygous, anyway).

It is also NOT clear that upping all doses would NOT have the effect I spoke of, the B12 contributing to an enzyme function, and the methylfolate being a substrate of a reaction - you don't use up one B12 for each methylfolate.

Oh, that's interesting.

I'm sure you know the signs of folate deficiency, so as long as increasing the B12 makes him feel better and he doesn't get deficiency symptoms, he'll be good.

I know the signs for me, but I find it trickier than identifying potassium deficiency. I'm working from the list in "A Guide to Freddd's Protocol", and it's a long, varied list. So far he hasn't had potassium deficiency on any of these doses.

He's quite athletic (mid-fifties), but has always had the mental crashes and becomes rather inert until the neurotransmitters balance out.

I assumed that the ones you didn't write were the same, the C677T being the more important one...

Woops, I thought Al said he didn't have MTHFR.

 

[Critterina]

Hi @picante ,

The list of A1298C symptoms - oh, everyone seems to have a different one - includes CFS, Fibromyalgia, anxiety, depression, biopolar, autism, ADHD, schizophrenia, OCD, migraines, Parkinson's, and on one list "biopterin disorders", whatever that means. And I would look for trends over a person's lifetime, not just a single episode. For example, I'm hetero for the A1298C only, but still was a melancholy child, have had a couple mild episodes of depression, one major one (associated with brain chemistry, not circumstance), and ocular migraines.

Someone figured out that one methylB12 will convert 200-2000 methylfolate molecules (or some such). I had my doubts about that number, but I know that it does activate an enzyme, so it does convert multiple methylfolate molecules.

Good that your DH is doing so well most of the time. The crashes, like something that only goes wrong intermittently in your car, is so hard to diagnose and correct. I wish you both the best.

Did Al say she didn't have C677T? I must have been reading in my sleep! Let me re-look at that one. Edit: Yep, you were right - she doesn't.