1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
The Mighty Egg: New Life Springs Forth Despite ME/CFS
Jody Smith finds that even with ME/CFS, new life as symbolized by the mighty egg, can still spring forth ...
Discuss the article on the Forums.

Need for folates at all MTHRF +/- and MTR+ MTRR++?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by sregan, Aug 19, 2013.

  1. sregan

    sregan Senior Member

    Messages:
    259
    Likes:
    87
    Southeast
    My recent downfall after stopping SMP supps from what I can tell has been remedied by taking Cobalamin. I had an initial great reaction to a small amount (100-200 mcg) of Hcbl but there are some side effects I'm having with. I switched to MCbl and feeling more like a normal person again. Mentally better (depression gone), gut is much much better. This leaves me with a couple of questions.

    1. What is it about the HCbl that doesn't seem to be as effective (making me feel as good) as MCbl? I'm tempted to think it might be doing something good (generating ACbl?) that I need and I should "tough out" trying it.

    2. I am MTR+/- and 2 MTRR++ (corrected), while only MTHFR +/- (see tag line for specifics). So from my genetics is it possible I only need to supplement with MCbl and NOT folates? If folates are eating up MCbl then if I already have enough in my system and my MTHFR mutations aren't blocking them then if I supplement folates can that deplete my MCbl and end up where I have been the last 6 weeks (feeling awful) MethylTrapped with a MCbl deficiency? I know I have seen suggestions to start SMP with just MCbl (or HCbl). Maybe that is prudent especially for those with my genetics?
  2. Critterina

    Critterina Senior Member

    Messages:
    518
    Likes:
    184
    Arizona, USA
    Your MTRR A66G +/+ indicates to me that you have trouble making MCbl to fuel the MTR gene in the folate cycle. Hcbl won't do this because you can't methylate it. When you supply the mb12, your MTR reaction will be a little overambitious (overexpressed) because of your +/- status, using up methylfolate to regenerate methionine from homocysteine. This is your best bet for regenerating methionine, since your BHMT +/+, the alternate route, is very inefficient.

    I don't know how far along you were on the SMP, but I'm guessing that with HCbl and folate (MTHF) (and maybe folinic acid), yes, you're right, you probably were taking a lot of methyl groups and not able to process them, because of the MTRR A66G +/+, so it seems likely you may have been methyltrapped. (I've never heard what exactly that feels like).
    I think I understand where you're going with the folates depleting the MCbl and it all ending up a wash. But having the right levels of folate and MCbl is not an end in itself. You need both of them to rotate the folate cycle to recycle homocysteine. And I'm not sure what HCbl does for people with our type of genetics.
    And you may also need some extra MTHF to push the back reaction of MTHF to folinic acid - it's the backwards conversion that creates BH4. It won't work as well in you, since you're MTHFR A1298C +/- (like me!). And BH4 is used to make serotonin and dopamine, as well as some other important things. Talk about feeling awful - try doing without those!
    So, the way I think of it, is take MCbl, but take MTHF too. And if you start getting sores at the sides of your mouth, acne-like lesions on your face and scalp, and gut issues, it may mean you need more MTHF. I hear this is common. It took me 4 months of 1 mg MTHF and 5 mg MCbl per day to develop these symptoms, and two more months to figure out what to do. I've been upping my MTHF, at first by 1 mg every 3 days, then every day. Now, after 3 weeks, I'm at 8 mg MTHF today, and my scalp is clear, my face is almost clear.
    Another thing you might consider is supplementing with TMG to encourage the BHMT reaction for recycling homocysteine to methionine. I plan to try that once I get my MTHF, folinic acid (since I'm SHMT +/+), MCbl, and AdCbl adjusted. And once I figure out where AdCbl fits into the whole cycle. Anyway, that would be down the line. My methionine has tested low a couple of times, so the more I recycle it, the better, as far as I'm concerned.
    sregan likes this.
  3. Crux

    Crux Senior Member

    Messages:
    577
    Likes:
    201
    USA
    Hi sregan;

    I'm not sure whether HCbl or MCbl is better for you. I think a trial is a good idea. ( I take both, seems to be good.)

    I'm also MTHFR A1298C, hetero., apparently it's common, and it may only mildly affect folate metabolism, if at all. Most of what I've read has shown that people with this snp have normal and even elevated serum or RBC folate.

    I've only had serum folate checked a few times, and the last time, it was very elevated. I was not taking a folate supp., and, I was avoiding fortified foods. ( I believe I'm an extreme case, because I've had very painful side effects from folate supps. lately, even 100 mcg.)

    I see you are homo for 2 MTRR's, and hetero for an MTR. ( There are also more snps for B12 metabolism that could be involved.) ( I'm only hetero for an MTR and a couple of MTRR's.)

    Personally, I'm needing alot of B12, 15mg. or more daily, and I'm avoiding folate supps.
    I hope you won't have the extreme problem I have, but I would guess that maybe folate supps. aren't necessary, at least for now.

    It may be a good idea to have serum or RBC folate checked. From what I've read about it, it's OK for it to be in the high normal range, but could be problematic if elevated.

    Here's an article that only briefly discusses MTHFR A1298C, near the end.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696357/
    sregan likes this.
  4. sregan

    sregan Senior Member

    Messages:
    259
    Likes:
    87
    Southeast
    Critterina thank you so much, your response was exactly what I needed... It took me a few days to digest this and put it to the test. And yes it seems I need some MFolate. Taking the MCbl alone helped for a few days but then I started to get out of balance again. The trick for now, I think, is going to be finding the right balance of Mfolate and MB12. I've written a blog entry that has more detail. And where you mention "Talk about feeling awful - try doing without those!". I think I did for a while and it's about the worst I've ever felt and it's all in my head. The body doesn't feel bad, a little fatigued but the mind is in a very bad place :(

    I also would like to know where AdCbl and LCF fit into the picture if at all for me. And P5P (sulfation pathway in general) I did try a small amount of P5P which brought a reduced version of my depression back for one morning. I need to try that again to see if opening the CBS door is causing me issues.

    Thank you again!
    Critterina likes this.
  5. sregan

    sregan Senior Member

    Messages:
    259
    Likes:
    87
    Southeast
    Crux likes this.
  6. Critterina

    Critterina Senior Member

    Messages:
    518
    Likes:
    184
    Arizona, USA
    @sreagan
    Amen, sister! :D
    I think you got to this understanding before I did. Last night I posted my mutations and Valentijn kindly commented on my results. See what she said:
    http://forums.phoenixrising.me/inde...in-with-my-23andme-results-for-comment.24913/
    I've been trying to get out of Level 1 folate deficiency with more folate, and perhaps it's the MB12 that I need to increase. Balance is really it! We will journey together.


    I just had someone answer that for me about AdB12 Here is the post on ADB12: http://forums.phoenixrising.me/inde...min-the-very-large-gorilla-in-the-room.20229/
    Here's a good article on L-carnitine: http://umm.edu/health/medical/altmed/supplement/carnitine-lcarnitine For me the LCF was part of getting out of the sleepiness that seemed to be brought on by folinic acid.
    B6 is everywhere. It's used (with BH4) in converting tryptophan to serotonin. It helps convert glutamic acid and ammonia to glutamine. I think it helps make threonine into something (I forget what). It helps several places in getting rid of homocysteine through the various steps. And more, but those were the easy ones to pick out.

    So, it causes you some mild depression, you think. :( Perhaps it could be operating in the BH4 cycle, using the BH4 to make more dopamine (instead of the many other things BH4 can do, including serotonin and NO production or clearing homo cysteine). It seems there's a lot of competition for both B6 (P5P) and BH4. I think your plan to wait a while and try it again once you get your MB12 and MTHF balanced is a good one.:)

See more popular forum discussions.

Share This Page