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Transsulfuration pathway - help with interpretation required

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by BiancaS, Jul 21, 2011.

  1. BiancaS

    BiancaS

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    Hi, I received yesterday my amino acid urine panel back and would really appreciate some help with the interpretation. For clarification, this amino acid panel was taken just before the switch from HDXCBL and Folate to MTHCBL/ADCBL and 5-MTHF.

    As far as I can see, there did not seem to be much of an issue with Folate. However, given that I had positive MMA on another test, I think that switching to the active forms of B12 was a good idea.

    From serine/cystathinine levels, I guess there is a problem with the transsulfuration process (high serine/low cystathionine). I was deficient on Molyb, so that might be a cause. What is puzzeling though is the high level of Glycine and the fact that my intracellular glutathione levels have gone up significantlly. Since I used to supplment with iv Glutathione, I am not sure if this actally means that my methylition cycle is now producin glutathione, or if these are inflated results due to supplementation. My ATP level is still low, which means there is still a problem somewhere in the chain.

    I am borderline KPU/HPU positive and it looks like I might have a heavy metal issue (aluminium, cadmium and plumb). Since detox is important, I am wondering if chelation is possible with DMPS or DMSA when there is an issue wh the transsulfuration pathway.

    Thanks foryour help!

    GABA 7 (5-12)
    Alanin 97 (95-277)
    Asparagin 83 (25-71) +
    Cystein 47 (35-81)
    Cystathionin 6 (<196)
    Glutaminc acid 16 (1-14) +
    Glutamin 402 (252-614)
    Glycin 2839 (388-1179)+
    Taurin 400.8 (90-800)
    Histidin 481 (121-541)
    Lysin 121 (36-96) +
    Laucin 40 (18-39) +
    Methionin 27 (3-38)
    1-Methyl Histidin 150 (104-263)
    3-Methyl Histidin 294 (<1022)
    Phenylalanin 36 (9-42)
    Serin 516 (124-246) +
    Threonin 87 (37-114)
    Tyrosin 61 (59-132)
    Valin 31 (13-34)
    Cirtullin 1,9 (<2,9)
     
  2. richvank

    richvank Senior Member

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    Hi, Bianca.

    I've looked over your test results and your earlier posts. It looks as though you had some good testing done. I can't say that I understand all the results, though. The broad supplementation you have had makes it difficult to interpret your test results, because some things that might be expected to be low have been raised artificially by supplementation.

    Since your recent results showed elevated MMA and leucine, I think that you must have low adenosyl B12, even though your blood serum B12 was high. Usually when adenosyl B12 is low, methyl B12 is also low. However, your results of normal methionine, SAMe, and homocysteine suggest that your methionine synthase reaction is operating normally, which suggests that there is enough methyl B12. However, your high MCV and low erythrocyte count indicate that the erythropoietic cells in the bone marrow do not have enough active folate. That would suggest that your reduced folate is low, which in turn would suggest that your methionine synthase reaction is not running at up to a normal rate. So this is puzzling to me. You also have a high ratio of phenylalanine to tyrosine, and that suggests low tetrahydrobiopterin (BH4), which also suggests that there might be a problem in the folate metabolism, since the biopterin cycle is linked to the folate metabolism.

    You do appear to have low flow in your transsulfuration pathway, based on the high serine and low cystathionine, as you suggested. I realize that you are supplementing B6 and magnesium, and that B6 has tested normal, but there may still be insufficient B6 (or its active form, P5P, which requires B2 for its formation).

    I suspect that you might be a person who has inherited a slow version of the DHFR enzyme, which converts folic acid to tetrahydrofolate, and also completes the thymidine synthesis pathway by converting dihydrofolate to tetrahydrofolate. It is also involved in the biopterin cycle. I think that could explain some of your results. Now that you have switched from folic acid to 5MTHF, that should help with the folate issues (high MCV, low erythrocyte count), and maybe the BH4 deficiency, also. (I think that the Thorne product is a racemic mixture of the active and inactive forms of methylfolate, so your effective dosage will be half of the nominal dosage of the supplement. Merck in Switzerlad and Germany have a patent on making Metafolin, which is the pure active form, but I don't know if it is sold there.) By taking adenosyl B12 directly, you should experience a lowering of the MMA level.

    You initially had some indicators of low glutathione (measured low in immune cells, Hashimoto's hypothyroidism, poor cell-mediated immunity, buildup of toxic metals), but it seems that that has been corrected by the I.V.s and the oral acetyl glutathione.

    It sounds as though the heavy antibiotics have knocked out the friendly flora in your gut, and these will need to be built back up with probiotics.

    You appear to have mitochondrial dysfunction, based on the low ATP and the fatigue. It may be caused by toxin buildup.

    As I say, I don't completely understand all your results. I guess these are all the comments I can make. So I guess you still have not found the prince. :D I hope that your switch to the different forms of B12 and folate will help you.

    Best regards,

    Rich
     
  3. BiancaS

    BiancaS

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    Hi RIch,

    Thanks so much for taking the time to reply.

    I am expecting my BH4 levels today, but I would also suspect them to be rather low. Am also waiting for the Yasko test to check for polymorphisms and NutrEVal should bring me further towards understanding the problem. How many day before taking the NutrEval would you suggest stopping all supplements to get realistic results?

    Doctors suspect that my low erythrocyte count is due to intracellular pathogens (Bartonella), so that might be an explanation. I am taking 100mg a day of the active B6, but given that I have KPU, I am not sure this is enough. I think I might also be low on B2, so will add additional supplement of the active B2, plus moly. Have to check in Germany if the Merck 5-MTHF is sold here.

    Until all test results are back, my main priority seems to be detox and pathogen killing ;-) Detox does not seem to be that simple. I had 2 months worth of iv ALA and Glutathione, which should have helped with Detox, but it doe not seem to do the trick. Maybe it's because I have a Val105 polymorphism in my GST-P1 enzyme. Therefore, I am looking into either DMSA or DMPS, but not sure if this can be taken if there is an issue with sulfuration? As an alternative, I am considering Apherese (plasma washing) that is used here to clean the plasma of toxins, pathogens, etc.

    As far as I understand, as long as the methyliation cycle is not fully restored, it is very likely my glutathione will be depleted quickly if supplementation is stopped, so I guess the new intracellular levels do not relect actual glutathione production of the body, but reflect supplementation only?

    Thanks again!
     
  4. richvank

    richvank Senior Member

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    ***You're welcome.

    ***Best regards,

    ***Rich
     
  5. aquariusgirl

    aquariusgirl Senior Member

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    hi bianca
    if you go ahead with the apharesis...could you please post about it here?
    thanks!
     
  6. BiancaS

    BiancaS

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    Hi,

    Will do. It's called cellabsorptionapheresis or so. They are running your plasma through specialised filters, depending on what they re treating for (apheresis is indicated in various conditions), but in the case of lyme, cfs, mcs, I understand they are using a filter called Cellsorption if I am not wrong. They are following the guidelines of international apheresis organisation (not the german one - thank god). He also said that after the apheresis, you get ivs with mitochondiral support, liver support, etc and they are also tesing what would be the best therapeutical way to balance out Th1/Th2. The doctor running the center is an environmental doctor, who specialises in immunology and immunotoxicology.
    After your first session, they remove your sludge and will do an indepth analysis of what is going on in your body, based on what they have found there. Sessions are done with 14 days inbetween and th number you need depends on what they find in your blood after your fist session. OK, that's the theory, let me see how it works in practice.

    Rich, I will be looking at the methylation pathway panel in Europe and will run that as well. I tested positive for slight oxidative stress, so there might be an issue with theredused vs oxidated glutathione. I currently take 150 mg of benfotiamine and 100mg of thiamine. B3 is 100mg per day. B2 is certainly my current weak spot and will get the active form as soon as possible.
     
  7. richvank

    richvank Senior Member

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    Hi, Bianca.

    This all sounds really good: the apheresis, the methylation pathways panel, and the B vitamins.

    This use of apheresis sounds really innovative. I wonder if they have published any results on this approach. I'll have to look in PubMed. It sounds as though it could be helpful to many people, especially those whose immune system and detox system are not able to clear toxins from the blood adequately.

    Best regards,

    Rich
     
  8. BiancaS

    BiancaS

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    I looked at their website and the mention something about collecting data on what they find in the plasma and publishing it. The website is unfortunately in German. http://www.inus-world.de/de/privates-apherese-und-dialysezentrum Will ask the doctor if they have their material in English as well, as I would think this might be interesting for people outside of Germany as well. Will keep you posted.
     
  9. lucyhem

    lucyhem

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    Montague, MA
    Help with interpretatin of Methylation Panel

    Hi all
    I am up and running with the protocol and the Health Diagnostic's test.
    I would like some help with interpretation.


    Glutathione (oxidised) .54 [/B] (.16-.500)
    Glutathione (reduced) 3.0 (3.8-5.5)
    S-Adenosylmethionine (RBC) 239 (221-256)
    S-adenosylhomocysteine (RBC) 56.6 (38-49)

    FOLIC ACID DERIVIATIVES
    5-CH3-THF 9.0 (8.4-72.6)
    10 Formyl-THF 1.2 (1.5-8.2)
    5-Formyl-THF 1.9 (1.2-11.7)
    THF 1.04 (.60-6.80)
    Folic Acid 10.2 (8.9-24.6)
    Folinic Acid (WB) 9.7 (9-35.5)
    Folic Acid (RBC) 312 (400-1500)

    Adenosine 24.9 (16.8-21.4)

    These are the preliminary results faxed to my doctor. I don't know if the final results will be more detailed or complete.

    I am happy to find a test the finally confirms some of what i have been experiencing!
    How often do people retest to track progress?
    My doctor who treats autistic children had some recommendations based on his experience. I would like some feedback on that.
    He suggested raising Glutathione w NAC.
    He also recommended B6, TMG and DMG.

    I am up to almost a full dose of the Simplified Methylation Protocol for about a week. I am still not on a full dose of the neurological health formula but I am with the methylmate, folinic acid and B12. Have not got the Lecithin yet but will soon. I am not having any significant NEW reactions, but i have constant fluctuations of symptoms so it is a little hard to track. My first day on the almost full protocol I had one of those I Feel-Like-MySelf-Again days, preceded by a full uneventful, restful nights sleep, which is rare. But that has not occurred again.

    My sense about the methylfolate is that my body loves it. But I am not sure about the B12. I am know there is talk about trying other forms of B12 and I will look back at Fredd's posts. Any thoughts about the welcomed.

    Thank you for your help,

    Lucy H.
     
  10. lucyhem

    lucyhem

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    Montague, MA
    PS I have the double 677T gene variant. That is the only one I have tested.
     
  11. richvank

    richvank Senior Member

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    ***Hi, Lucy.

     
  12. richvank

    richvank Senior Member

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    Thanks, Bianca. I see that there are some published papers on this. Looks like most of them are involved with using this technique to lower cholesterol. I think that analyzing what is pulled out of the blood by this method is a very good idea.

    Best regards,

    Rich
     
  13. lucyhem

    lucyhem

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    Montague, MA
    a few more questions

    Rich
    Thank you so much for your quick and thorough response. A few more questions.
    Do you recommend a dosage and kind of B6 and B2? Is it P5P plus B6 or just P5P? I can buy supplements wholesale as I am a healthcare provider. The B6 seems to come in 50 mg capsules.

    I think think that the folinic acid is fine for me. Does one ever raise that dose?

    Re B12, I can get the injectable. Do you think it would be worth trying injecting again now that i have the methylfolate, which I did not last time I tried the injections. IF so, what dosage do you recommend?

    What is the BMHT pathway? I am a bit confused by the last bit about stimulating and also slowing the BMHT pathway.

    You refer to a study already completed. Are there published results from that?
    Have people had the experience of feeling more symptoms at first, then better, on this protocol?
     
  14. richvank

    richvank Senior Member

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    ***Hi, Lucy.

    ***Yes, most do have that experience. I think it is due to mobilization of toxins, as the improving function of the sulfur metabolism brings the detox system and the immune system back up to more normal operation. They go to work on the backlog of toxins and pathogens that have accumulated during the illness.

    ***Best regards,

    ***Rich
     
  15. rydra_wong

    rydra_wong Guest

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    TMG protects against postprandial (after meal) homocysteine (neurotoxin) surges. So your average SAMe/homocysteine may be normal, but after meals homocysteine can go high causing damage still. The people who get the highest doses of TMG by diet get 2g/day. Unless you eat a lot of fruits and veggies you probably dont get that much. Keeping homocysteine low is an important key to longevity.

    P5P protects the kidneys from glycation by blood suagr, whereas B6 does not. This has been proven. Also B6 in a dose as low as 100mg can cause neuropathy, whereas P5P does not. P5P is the active form. I dont know about how it is digested, only the study results from its consumption vs B6.

    I did not know that P5P was important in PKU...that is BH4 deficiency, is it not? (Which I have). I cant pin it down for sure but I seem to need an extra 50mg P5P tablet besides what is in my Thorne Basic B. I did verify that for my genes, there is no difference in homocysteine between 50mg and 200mg P5P. This may be because I take 1g TMG and that route runs faster than any other route for homocysteine as it involves only 1 enzyme. Or it may have something to do with my AHCY genes slowing down the cycle in som eway (idk what the AHCY defects do to me, actually). I have a problem becomeing anemic post menopause...it seems like if I run out of my extra P5P pill I am gasping for air. But I cant tell for sure because times when I've tested I have been found to be low ferritin (but not low hemoglobin) and iron fixes it.

    Very interesting. Thanks!
    Rydra
     
  16. greenshots

    greenshots Senior Member

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    California
    I can't say why exactly but I know that Yasko always recommends NADH with any glutathione since it often becomes oxidized & somehow drains a critical area, the MTR/MTRR. If the MTR goes down, you get into big trouble and don't make methyl B 12 or recycle it properly.

    I also remember that just the leucine being elevated can mean clostridia but its been years since I understand that whole pathway and the results.

    Angela
     

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