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S.O.S. Macrocytic Anemia and Methylation SNP's help

Discussion in 'Genetic Testing and SNPs' started by Bead Dog, Jan 18, 2013.

  1. Bead Dog

    Bead Dog

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    Hi all. New here and glad to have found this place:)
    Short run down: I've been treating macrocytic anemia since July. Numbers are improving, but have neurological symptoms. I decided to get 23andme testing since having a long wait to get neuro appointment and internet sleuthing. Now waiting on MRI scheduling. Neuro just said to keep taking b12 and that he did not know anything about methylation or genetic variances related to it. Last blood work showed off the charts high b12 serum (1923) and also high serum folic acid > 19.9 but still macrocytic.
    The results of my SNP's for methylation are as follows:
    MAO A R297R +-
    MTHFR C667T ++
    MTRR A66G ++
    MTRR A664A +-
    BHMT-02 ++
    BHMT-04 ++
    BHMT-08 ++
    CBS A360A ++
    Any ideas for a better approach to handling supplementation? I feel as if my body and muscles are always "electrically charged", seem to get system overload from too much going on, lack of focus, and also big fatigue. The strange thing is, the fatigue is quite variable, sometimes awful, and other days I manage really well.
    As an aside, I've been Paleo (meats, veggies and smae amounts of fruits and nuts), sugar and caffeine free since September.
    Thanks in advance for any thoughts shared.
     
    Patrick* and merylg like this.
  2. kday

    kday Senior Member

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    Since you seem to tolerate B12, have you tried about 25-30 mg of B12 in one dose? Do you take methyl form or hydroxy? I've had macrocytic anemia before and I can relate to the electrically charged feeling.
     
  3. kday

    kday Senior Member

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    Forget the serum levels. Probably a functional problem. Mine are >1999 and still feel so much better after each dose of B12.
     
    Crux likes this.
  4. Bead Dog

    Bead Dog

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    Started loading with injections of cyano and then switched to sublingual mb12 5000 mcg. MD advised to cut to 1000mcg since level was high. I think you are right on about forgetting about serum levels. I just feel like I'm missing a link in the process. Tried taking folic acid and that about sent me over the edge. I eat 3 cups of greens a day, so diet is not lacking. Thanks for taking the time to comment.
     
  5. merylg

    merylg Senior Member

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    Hi Bead Dog,
    Have you considered the macrocytic anemia may have another cause?

    http://en.wikipedia.org/wiki/Macrocytic_anemia

    I had a similar response taking B12 & methylfolate as part of trying methylation protocols, in that I just built up huge levels of serum B12, serum folate & red cell folate. In the end I had difficulty tolerating any tiny dose of any kind of B12. As for Methylfolate, I can again tolerate about 1/4 Solgar Metafolin, but at the moment am having a rest from supplements in general.
    You may find that B12 is overstimulating you??? Only way to find out is to stop taking it, then challenge with tiny dose like a crumb/or drop diluted in water.

    I have SOME similar snp results to you.
     
  6. kday

    kday Senior Member

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    Do you notice a difference from B12, and if so, positive or negative?
     
  7. Bead Dog

    Bead Dog

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    Mostly positive on the b12. Palpitations, fatigue and L'hermittes improved. Also less pain in feet and calves. But, still have buzzing, zaps, tingles and some gastro symptoms. Had my last injection around the holidays and tried to cut back on sublingual. But buzzing and neuro symptoms increased. So I am back to 1000 mcg daily. It does baffle me.
     
  8. LaurieL

    LaurieL Senior Member

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    Bead Dog,

    You have a +/+ CBS mutation, so you need to address that first. This is the transulfuration pathway, and CBS is an upregulation. So basically the supplements you take will drain straight down this pathway. BHMT is the shortcut through the pathway from methionine to homocystiene. You need to support this shortcut after you address CBS with TMG. Then the MTRR with the methyl B12, and serum levels are not accurate as well as the MTHFR +/+ with methylfolate not folic or folinic acid at this time.

    Your serum levels make me curious as to whether you have the methyl donors and folate to address your condition. Are you also trying adenosylcobalamin?

    But prior to any of this, you will want the supportives on board first, so when you kick start the cycle, it doesn't run out of the adjuncts it needs to keep going.

    Lauriel
     
  9. Bead Dog

    Bead Dog

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    I have been trying to read and understand Yasko's report. Let's see if I understand ...so I will need to test for sulfites and sulfurs and get that handled if it is an issue (likely), then proceed with the mb12 and methyl folate in this order? I have not tried the adenosylcobalamin. When you mention supportives, what do you mean? This is all so new for me. I'm trying to figure out what I'll need to purchase.
    Thanks for the direction and explaining in layperson terms. Really appreciate it very helpful.
     
  10. Aileen

    Aileen Senior Member

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    I have problems in both pathways too. Exactly how does the TMG help with the CBS problem? I'm having a hard time understanding what to do about this snp. And what do you then do to support the BHMT shortcut?

    What do you consider to be the key supportive adjuncts that one needs to be taking? I've seen potassium frequently mentioned and magnesium. I'm trying to start on some fish oil capsules to make sure I have enough fatty acids. This stuff is just so complicated! Thanks.
     
  11. Bead Dog

    Bead Dog

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    Are we to be looking at Yasko's recommendations on page 79-80 in Pathways To Recovery? I do take some of these basics already. My diet is Paleo, so assume I need to look at that and especially the crucifers as they relate to the CBS++. Perhaps consider becoming a "breath-a-tarian" :)
     
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  12. LaurieL

    LaurieL Senior Member

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    Bead Dog,

    To clarify, are you talking about Autism: Pathways to Recovery by Dr. Amy Yasko? If so, then chapter 6 would be a good read for many, in explaining the pathways relevant to your mutations, and some additional info on what their function is. You can also do internet searches cross referencing Dr. Amy Yasko, with XXXX (for example SHMT) and you will get specific information as well. I think many here, including myself start supplementing the methylation pathway specifically with the methylfolate and active b's too soon and experience awful symptomology, sometimes as disabling as CFS/ME itself.

    After doing it the wrong way, and becoming more familiar, I completely agree with her recommendations concerning her first priority mutational targets. CBS mutations are one of them. Specifically the third of three first priority mutations. Although the 360A mutation (CBS) is not considered as significant a mutation as the C699T (40 something increase in upregulation), it is still an upregulation. And this upregulation is what contributes to the swing of supportive intermediates to be drained down this pathway and shunted to either Taurine or depending on further mutations, excess sulfite (SOUX downregulation), or excess sulfate (SOUX upregulation). I see nothing in your post about SOUX. The strips would be helpful in determining whether you have a SOUX problem by identifying whether you have excess sulfite or excess sulfate, but remember, deficiencies can mimic other conditions even though a mutation may not exist. So the strips would not offer a definitive evaluation. Also in this cycle, you would have to consider ACHY mutations as well. I also see that mutation not listed in your post, but it would have an impact on Hcy.

    Another impact on Hcy (homocystiene), is your BHMT mutations. This is the shortcut through the transsulfuration pathways to convert homocystiene to methionine. These are down regulations, and would affect your levels of SAMe, and also affect your ability to methylate DNA and RNA.

    So the long way around the beginning of the cycle has MTRR mutation, and then you have the CBS mutation, and the BHMT mutation which has downregulation the short cut through the cycle as well. The long way and the short way are downregulated and the CBS is upregulated.

    In this context, you will also need to consider ammonia, and its relation to sulfate, hence the SOUX again. Diet, especially protein can produce sulfur metabolites, of which your CBS mutation contributes and excaberates. Diet didn't "fix" my problem, although it did help.

    Another consideration when evaluating your sulfur problem, is chronic bacterial and viral infections. These steal tryptophan, and lead to sulfur and ammonia problems as well as heavy metal accumulations. The kind of bacterial or viral infections, will affect which metals are correlated as problematic. Example, most chronic bacterial infections will sequester aluminum. So this then can affect your MAOA status, and serotonin levels, and could manifest as the wired but tired, buzzy neuro problems, and sleep cycle problems should you have this as well. Addtionally, BHMT 08 +/+ can also lead to nor-epi, also contributing to a wired but tired, buzzy neuro issue. I don't have the BHMT mutations, but I did have a big problem with nor-epi. Dr. Yasko states high levels of stress and cortisol production as inducers of nor-epi as well.

    To support your BHMT shortcut, TMG supports it, DMG shuts it down and shifts the metabolites through the long way of the cycle, but your long way has an MTRR mutation. Molybdenum is also recommended for both (CBS and sulfur metabolism, ammonia, and the BHMT)

    Molybdenum as a caution, was a biggie for me. Makes you downright fluey for about a week, and then it seems to clear. I have done experiments with moly three times, and each time I experience the same thing, no matter how far along I have come.

    So by addressing CBS and then the BHMT and MTRR, you will level out your SAMe, Methionine, Hcy, sulfur, and ammonia. Then the long way around the folate cycle in which the forward reaction, MTHFR 677 is also of concern to you and another possible roadblock.

    All this is just going off the possibilities of mutational aspects, and not off of specific metabolites showing in your urine, by testing. That is what I lack, and so recommendations made by anybody will be refined to your own symptoms. Those of which I am unfamiliar and I am certainly not an expert, just trying to help.

    The supportives I will address in another post.

    I did want to provide a link for those interested for the Autism: Pathways to Recovery book, should one not possess the book. The entire book is available at this link.

    http://www.scribd.com/doc/81963801/113/BHMT-Status

    I apologize I wasn't able to respond earlier, I do work two jobs, and it is why I must reply in two parts.

    Lauriel
     
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  13. Bead Dog

    Bead Dog

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    Lauriel, Thank you for the detailed reply. I greatly appreciate your time and information shared.
    I work two jobs as well and some days the gas gauge is runnin' on empty:)


    My plan based on input and research is:
    Eliminate sulfur rich veggies ( I was eating three cups of greens and three cups of sulfur rich veggies daily), and get some sulfur and sulfite testing strips.
    Reduce protein.

    I have started on TMG and Molybdenum. Next in line is to get homocysteine level tested. I have been doing mb12 for the anemia, but may try cutting back or eliminating. I have noticed that I do seem to be sensitive to it. I just didn't know the signs or symptoms that I had experienced could be attributed to that.
    You really nailed it for the relation to the BHMT and the " tired but wired- buzzy feeling". That is exactly how I feel.
    Perhaps down the line, heavy metals testing and detox.

    The only mutations in the methylation cycle are those listed above. so, I know I have methylation challenges.
     
  14. Bead Dog

    Bead Dog

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    Just got the testing strips in and looks like somewhere between 400-800. I will continue to lay off the sulfur foods and meat and monitor. I did a blood draw for homocysteine and H.Pylori the other day and I'm waiting on results. MRI of brain and C- spine next week ( after waiting months for neuro referral.) I think I'll get the Vit D level checked next.
     
    merylg likes this.
  15. triffid113

    triffid113 Day of the Square Peg

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    My food for your thought is not genetic. But whenever I heard people complaining of buzzing I want to tell you that you should check your thyroid. And be aware that you can have a SERIOUS thyroid problem and still be diagnosed 'normal' because the range of thyroid values is NOT based on science. Look here: http://www.lef.org/protocols/appendix/blood_testing_02.htm?source=search&key=TSH reference range

    When I had buzzing, it was HYPERthyroid (buzzing), due to taking Iodoral (I am sensitive to iodine...which is not natural but I haven't figured that one out yet). Allergies (low zinc) also drive me clinically HYPOthyroid (tinnitus). Your TSH should be < 2.0 or else you are hypothyroid despite what the bogus reference range says.

    My father had 13 genetic mutations and his fingers were positively BLUE at MCV of only 101. I believe that was due to taking a PPI (stmoach acid inhibitor). Unfortunately you can't do alot with someone who is in hospital and on kidney dialysis. When he was home we gave him Thorne Basic B. Getting someone off a PPI is a long haul since it causes hyper acidity.

    Regarding gut issues (if you mean dysbiosis) I take 1 g/day Olive Leaf Extract and it kills all gut pathogens even though I have low-ish stomach acidity.
     
  16. Branston

    Branston

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    I have Macrocytosis ( MCV 107 ) also, and low RBC and Platelets. I have the same MTHFR/MTRR/BHMT's as you do. Also have 2 CBS +/-'s. I started with the CBS.... I was taking N-Acetyl Cysteine as a supplement, and tesing with the sulphite strips was >1200, so I stopped the NAC and the level is now 400.
    I started the Simplified Methylation Protocol and got what I presumed was a heavy detox reaction, because i have a very, very strong metallic taste. I know i have high Lead levels.
    Even after 6 months of active Folate ( 5MTHF ) and B12 ( AdB12 and MeB12 ) my MCV is still very high......so I guess I must need much higher doses.
     
  17. Bead Dog

    Bead Dog

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    I had thought about thyroid. Had it tested in the fall. TSH was 1.36, and everything was in normal range.
     
  18. Bead Dog

    Bead Dog

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    Hi Branston,
    My MCV was 107 about six months ago. Last time I had it tested it had dipped down to 99. My platelets were also low and those have improved too. I still have some rough days, but do feel some improvement. Better energy, don't get fatigued as easily, easier time breathing. I do still have some visual issues, still get tingling and pulsing in the feet and lower legs, muscle spasms and gut issues. Tired but wired feeling still. I've adjusted my diet to reduce sulfur, eliminated dairy, grains. eating mostly vegetables small amounts of meat, nuts and fruit. Switched to the recommended brands of supplements for Fredd's protocol. Hoping to see more improvement soon.
     
  19. Bead Dog

    Bead Dog

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    A little update, almost a year later...recently had an MRI of brain and neck. Neck a bit of a mess from c4-c7, disc bulge at c5, two bone spurs, with one touching the cord. I was already aware of all that stuff.

    The brain showed one lesion in the periventricular area with location and orientation suspect of MS ( so said radiologist report.) The chuckle head neurologist said one lesion is not enough to cause symptoms and has stated that all neurological problems are from the neck. Recommends physical therapy for neck. I teach a very gentle hatha yoga class to seniors, so I laughed at his suggestion.

    No recommendations for this (at times) crushing fatigue, heat intolerance, PEM, or lingering macrocyctic anemia. My MCV and MCH just popped back up into the high range again. I have also lost 25 pounds since this all started. That is okay as I am probably very close to an ideal weight for me. But, I have no appetite and my digestion sucks.

    I did just get the results from an amino acids plasma profile:

    isoleucine - low
    Glutamine - low
    Tyrosine - low

    Taurine - high
    Glutamic acid - high
    Serene - high
    1- methyl histidine -high
    3-methyl histidine - high
    Phosphoethanolamine- high

    Anyone have any ideas on what to test next or what to supplement?
     

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