The 12th Invest in ME Conference, Part 1
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Completely stuck: Methylation Protocol vs. Lab Results vs. Systemic Response

Discussion in 'Genetic Testing and SNPs' started by frchli, Aug 7, 2015.

  1. frchli

    frchli Cutaneous mastocytosis, IBS, Intolerances, MCS,...

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    Germany
    Hello everyone,

    I received my 23andme results 2 months ago and have tried to work out a treatment myself by reading posts in the forum, http://mthfrliving.com/ and on http://www.heartfixer.com/.

    I have had some success:

    Low sulfur/vegan diet:
    => ALAT/ASAT back to normal range of 30 U/l after being as high as around 300 U/l for 1.5 years on a high protein/SCD type diet for curing SIBO (which is now cured :))[falling to an average of about 80 U/L and 120 U/L after quitting oral cromolyn sodium, which is a mast cell stabilizer to the surprise of my mastocytosis specialist who thought something "as harmless as cromolyn sodium could not raise liver transaminases...];
    =>chronic gastritis that painfully persisted for years vanished;
    =>food is finally digested in stool and uncontrolled scary weight loss (low point of 49.5 kg/176cm) with inability to gain weight despite eating up massive amounts has stopped (56kg without much effort);
    =>waking up feeling completely hungover from intestinal gases has become a lot less severe;
    =>MCS less severe

    I also take molybdenum (100-200µg) whenever I do get bloating and a hungover feeling. Gases probably arise for the following reason: I have a severe gut dysbiosis, which 3 independent flora tests over the past 2.5 years have shown. Despite taking probiotics, the last one in February came out as NO(!) Lactobacilli, Bifido Bacteria and other good ones, normal-low candida, while HIGH Clostridium species(which live off protein which is probably why I suffer so much when ingesting protein/have had a protein aversion pretty much all my life without declaring is as a certain diet but just following my instincts before I got ill).

    I am very excited about the fact that some symptoms have vanished/improved and would recommend for others to try it as I didn't even expect the results...

    Before I received my results from geneticgenie, which are as follows:
    COMT V158M (+/-)
    COMT H62H (+/-)
    [COMT P199P (-/-)]

    VDR Bsm (+/-)
    VDR Taq (+/-)

    MAO A R297R (+/-)

    [ACAT1-02 (-/-)]

    [MTHFR C677T (-/-)]
    MTHFR 03 P39P (+/-)
    MTHFR A1298C (+/-)

    **MTR A2756G (+/+)**

    MTRR A66G (+/-)
    [MTRR K350A (-/-)]
    MTRR A664A (+/-)

    BHMT-02 (+/-)
    BHMT-08 (+/-)

    [AHCY-01 and -19 (-/-)]

    [CBS C699T (-/-)]
    **CBS A360A (+/+)**

    {0. I would LOVE for someone, who has a deeper understanding than me on the results, to comment on them/suggest a suitable methylation protocol for me by the way... Or recommend a knowledgeable health practitioner near Berlin, Germany.=P}

    The reason I went for the low sulfur CBS protocol first is not only because I have **CBS A360A (+/+)**, which seems to be the less important CBS mutation and CBS C699T is (-/-) so should work, but also because I have severe Mast Cell Activation Syndrome (and cutaneous mastocytosis) and a lack in BH4 is apparently linked to mast cell degranulation
    (http://mthfrliving.com/health-conditions/mast-cell-activation-disorder-histamine-intolerance/).

    However, some things do puzzle me: After starting my protocol, my lab results changed quite dramatically {showing abnormal results only mainly}:

    *BEFORE / AFTER ABOUT 2 MONTHS* [RANGE]
    Erythrocytes 13.40 / 11.7- [12-16 g/dl]
    Leucocytes 2.83- / 3.55- [3.98-10.04bc/nl]
    *MCV 97.4+ /105.6+ [79.4-94.8 fl]
    MCHC 32.6 / 29.5- [32.2-35.5 g/dl]
    ASAT 55+ / 30 [10-35 U/l]
    ALAT 103+ / 31 [10-35 U/l]
    Creatinine 0,59 / 0,49- [0.5-0.9 mg/dl]

    *Serotonin - / 264+ [40/200 µg/l] despite low tryptophan diet before
    Vit B12 476 / 425 [191-663 pg/ml]
    Methylmalonic acid 158++(pathologically high) [9-32 µg/l]
    i.e. 1340 nmol/L [<243 nmol/L]
    Active-B12 (Holotranscobalamin) >128+ (path. high) [0-50 pmol/l]

    Some other typical results include:
    Folic acid above measurable;
    elevated basophils and eosinophils;
    leucopenia;
    normal ferritin but low coeruloplasmin;
    low CRP;
    high triglycerides;
    low to low-normal FT3 and FT4; high normal-high TSH;
    low-normal copper in serum;
    low-normal 25 OH Vit D (substituted);
    without substitution no estradiol, lh;
    low testosterone;
    normal blood histamine;
    normal DAO;
    very low B-lymphocytes (CD19)

    1.) I thought that by
    http://www.heartfixer.com/AMRI-Nutrigenomics.htm ,
    "low BH4 [causing mast cell activation], leading to insufficient dopamine and serotonin production" but my serotonin is always high... though this is peripheral serotonin... does the source talk about brain serotonin only? Hm! I'm not usually the depressed type unless I'm heavily inflamed or have a really bad histamine reaction (which is also inflammation...)

    2.) No matter how much I research, I do not get the fact that my Vit B12 always seems in normal range [or even slightly above maybe due to substitution at the time though], while my Methylmalonic acid 158++(pathologically high) value suggests immense B12 deficiency (having been a vegetarian/meat averse for all my life and having gastritis and bowel inflammation, this would make sense) while the Active-B12 (Holotranscobalamin) >128+ (path. high) value suggests no deficiency AT ALL! Apparently if creatinine is high, this can explain false values but it's absolutely not. But then MCV 105.6 suggests macrocytic anemia I guess?

    So if anyone could give me an explanation of this/tell me whether I should supplement B12 and which kind, that'd be AMAZING!! (The endocrinologists don't comment on the results, sadly/tell me I have weird results but don't do anything about it...)

    3.) I have tried taking pure encapsulations b-complex plus

    http://www.pureencapsulations.com/b-complex-plus.html

    which has l-methylfolate and methylcobalamine in it. However, I seem to be getting ADHD like symptoms and a huge urge to move (too much for my current strength) and mast cell activation when taking it. The symptoms increase the longer I take it but vanish after taking it for a little while.

    I would love to hear any thoughts on this and suggestions on what to supplement instead. (I tried injecting B12 as cyanocobalamine some time ago which didn't seem to make much of a difference neither negatively or positively...)

    4.) Should I avoid Methylfolate due to my Folate levels always being above measurable even without substitution? Do you have an explanation for this?


    As you can see, I am very much stuck despite trying very had. My main symptoms are gastrointestinal (bloating linked with fatigue and muscle cramps/stiffness and difficulty to focus, constipation, sometimes diarrhea, inflammation/mucus when eating dairy, soy, medications, other stuff I cannot handle, difficulty ingesting proteins), mast cell degranulation/cutaneous mastocytosis (flush, edema, increase heart rate, coordination problems, brain fog, diarrhea, skin rash, headaches, mucus,...), MCS, fatigue, osteopenia, amenorrhea. It got really bad 3 years ago. I spent the most of 1.5 years in bed and inflamed. The only thing that helped for a little while back then was a course of Rifaximin, which made me feel amazing until I started "just eating whatever" like the doctors had recommended and the symptoms came back/got much worse after a course of then-prescribed Metronidazole.
    Back on my legs now most days after figuring out a more suitable diet/dropping supplements/medication i cannot handle/taking it easy whenever I can/avoiding triggers and chemicals but I am still nowhere fit and would like to be able to have a job/good social life again etc. especially as I am only 26 years old.

    I would REALLY appreciate ANY advice even to parts of my mystery and I am of course happy to help out where I can. Also, I have tons of results here so if you would need anything else to clarify my case, just let me know.

    Thanks so so much for taking the time to read this! :)

    Have a nice weekend!
     
    Last edited: Aug 8, 2015
    AndyPandy likes this.
  2. ahmo

    ahmo Senior Member

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    Northcoast NSW, Australia
    I can only offer a couple suggestions. In my signature are 2 links for Martin Pall. At the centre of his theory about the role of the nitric oxide cycle (NO/ONOO) is BH4. It's possible by using some of his recommendations for antioxidants you might improve your BH4 levels, as well as calm mast cells.

    Lab results for B12 are notoriously unreliable. With your MTHFR snps it's very likely you need B12/folate. And I eventually found that eating green vegetables blocked folate uptake with their folinic form of folate, so I had to quit green veg. mthfr.net; mthfrsupport.com; beyondmthfr.com

    Have you tried gluten-free? Checked thyroid?
    I've found low dose naltrexone (LDN) marvelous for reducing inflammation. there's a long thread on pr.

    http://www.lowdosenaltrexone.org/index.htm

    https://sites.google.com/site/dudleyslowdosenaltrexonesites/
     
    frchli likes this.
  3. frchli

    frchli Cutaneous mastocytosis, IBS, Intolerances, MCS,...

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    Germany
    Dear ahmo,

    Thanks a lot for your helpful reply!

    I have had a look at Martin Pall's page at some point in the past but I shall have a closer look again.
    What puzzles me with the supposed lack of BH4, however, is the fact that I have read in various sources that it is supposed to deplete serotonin due to a lack of conversion. However, my serotonin serum levels are always high: 264+ [40/200 µg/l] despite low tryptophan diet before; another time when I was not paying attention to the diet before testing them, they were as high as 600 µg/l... Is this contradictory/should I assume BH4 is not depleted after all? I suppose serotonin could be raised for other reasons but it does seem strange to me...

    Would it be ok to just substitute hydroxocolabamine acetate 1000 microgram as an injection and methylfolate orally? If so, what dose would you recommend?
    As described above, I tried pure encapsulations b-complex (even splitting the content of a capsule over days), which benefitted me in some ways (less edema, more energy, pallor gone, looked healthy) but has caused problems (restlessness, urge to move, nervousness, feeling "hyper" but not in a good way..., lower histamine tolerance, quicker mast cell degranulation) as well.

    I do eat a lot of green vege which could maybe explain the folic acid results that are always above measurable, should I have a conversion problem, right?

    I've been strictly gluten-free for 3.5 yrs. It helped me but didn't solve things at all! An AIP type of diet seems to work best for me but as I really struggle with protein digestion—due to Clostridium sp overgrowth which causes major gas leading to me feeling like I have the worst hangover ever/cannot think straight—I am feeling better on a vegan diet (as the liver enzymes show but then the macrocytic anemia really kicked in with that...)

    My thyroid levels are currently (end of May):

    TSH basal mIU/l [0,27-2,5] 2,41 (though has been as high as 8 but then gone back down within days)

    FT3 pg/ml [2-4,4] 2,20

    FT4 pg/ml [9,3-17] 8,50—

    TPO AK IU/ml [0-34] 20,40

    PTH pmol/l [1,3-6,8] 4,10

    Anti-Thyreoglob. lU/ml [0-115] 723.2+ (this is from April 2013 but it has been over 800 but with a downwards tendency towards 600 last time taken)

    My endocrinologist seems to think that nothing should be done about them (they have been like this for 2 years) because she thinks they are like this because I am ill. So speeding up metabolic processes without correcting the underlying illness could make things worse according to her. Would you agree?
    But then the search for the underlying illness (apart from cutaneous mastocytosis and extreme dysbiosis/clostridium overgrowth) isn't really going anywhere... also, this is the same doctor that seems to think the Methylmalonic acid 158++(pathologically high) [9-32 µg/l]
    i.e. 1340 nmol/L [<243 nmol/L] can be ignored. Though she might just be clueless what to do because the Active-B12 (Holotranscobalamin) >128+ (path. high) [0-50 pmol/l] contradicts the B12 deficiency result...
    Do you have any idea, why this could be the case? Would HoloTC for example increase quite quickly when substituting MethylB12 whereas MMA doesn't? (I'm unsure whether I was on B-Complex at the time as the doctor did not inform me that she was taking MMA and HoloTC, which I only found out 2 weeks ago...)

    Also, I forgot to mention in my first post that I have bleeding gum every day despite professional cleaning and good hygiene as well as super easy bruising...

    I've thought about LDN quite a bit but then decided to leave it for now because people seem to react pretty differently to it and in quite a lot it seems to affect mast cell degranulation quite a bit...
    I don't usually feel too inflamed anymore now that I found out what foods/chemicals I can't tolerate. Hm... tough decision but thanks for bringing the thought back to my mind! :)

    Thanks again for your thoughts on this, ahmo. I appreciate it! =)
     
  4. ahmo

    ahmo Senior Member

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    Northcoast NSW, Australia
    [​IMG]

    [​IMG]You've used B12 as cyanocobalamine. I don't think this is a preferred form. You might need to start w/ smaller doses of folate, maybe try just a 1/4 of your capsule, see if it gives you restlessness. Ben Lynch advises B3 to dampen excess folate, with the symptoms of restlessness, histamine. I, instead, took Enzymatics Therapies sublingual B12, which also halted the restless symptoms.

    I don't know. I just mentioned it as something to be aware of. I'd been increasing my folate endlessly, until I worked out that my veg intake was blocking it.

    [​IMG] sorry, I don't know lab values.

    ] [​IMG]sorry, I don't know lab values.
     
  5. frchli

    frchli Cutaneous mastocytosis, IBS, Intolerances, MCS,...

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    Germany
    Thanks for your reply, ahmo! :)

    May I ask if you know whether the LDN can be taken sporadically only i.e. when inflammation occurs?

    Have a nice Sunday!!
     

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