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Methylation a problem but protocol doesn't help - what to do?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Nina, Jul 20, 2011.

  1. Nina

    Nina Senior Member

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    Hi all,

    although various lab results suggest that methylation and mitochondrial function are at least part of the problem (I'm at the very severe end, 100% beridden), the protocol doesn't seem to help.

    I had been on the Myhill protocol for a couple of months, then on the SMP and lately I've been implementing most of Dr. Yasko's suggestions as well.

    For quite some time I thought I was going somewhere (not literally ;) ), but a slight stabilisation seems to have been due to resting more.

    The past couple of weeks have seen me decline again with more flu-like symptoms and extreme weakness.

    Can anybody advise what else might be needed to make progress?

    Due to my very fragile condition and lack of medical supervision I'm unable to do much chelation or ABx.

    Thanks
    Nina
  2. richvank

    richvank Senior Member

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    Hi, Nina.

    I'm very sorry that this has not worked for you. What I can do is to discuss some possible causes of this, based on the biochemistry and analysis of a very small number of the cases in which this treatment has not worked.

    If you have a partially blocked methylation cycle, and it is not restored to a normal rate of operation by this treatment (and by that I mean restoring the level of SAMe and the ratio of SAMe to SAH up to normal levels on the methylation pathways panel), then here are some possible causes:

    1. Your body is lacking enough of one or more of the cofactor vitamins and minerals, or enough of the amino acids needed by this cycle. The main cofactor vitamins and minerals needed (in addition to B12 and folate, which are the primary ones needed to lift the partial block in methionine synthase) are B2, and B3 (best taken as B-complex), and zinc. The main amino acids needed are methionine and serine.

    2. Your genomic makeup makes it necessary for you to use a higher dosage of B12, or a different form, than is suggested in the simplified treatment approach. As you may know, Freddd, on these forums, recommends use of methylcobalamin and adenosylcobalamin, and at higher dosages.

    3. One or more of the enzymes in the methylation cycle is blocked by a high level of one or more toxic metals, such as mercury.

    On the other hand, if the methylation cycle does come up, but there is insufficient flow down the transsulfuration pathway, as indicated by low cystathionine, so that glutathione will not come up, then I think the likely possibilities are deficiencies in magnesium or vitamin B6.

    If the methylation cycle and the transsulfuration pathway are restored, but glutathione still remains low, then I would suggest these possibilities:

    1. Something is placing a large demand on glutathione. This could be a high body burden of one or more toxins, or a pathogen that is able to suppress glutathione. The latter could include viruses, bacteria such as Borrelia burgdorferi or its coinfections (Lyme disease), or sensitivity to biotoxins combined with exposure to them, such as in a water-damaged building.
    If the other parts of the antioxidant enzyme system are not working well, this can also place a large load on glutathione. This could be caused by deficiencies in selenium, manganese, copper or zinc.

    2. There could be a deficiency of one of the amino acids needed for synthesizing glutathione. They are cysteine, glycine and glutamate (or glutamine).

    I think those are all the possibilities that occur to me. I hope this is helpful.

    Best regards,

    Rich
  3. determined

    determined Senior Member

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    Nina,
    How long have you been this sick? Is there anything that has helped you to a significant degree?

    I hate to hear this!
  4. BiancaS

    BiancaS

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    Nina,

    I am currently doing a lot of reasearch accross Germany on doctors and found one who is working with Genova Diagnostics and will run the NutrEval panel for me. Will get him to interpret once results are available and see if he's any good at this and gives the correct interpretation (me, as newbie, will of course double check with this forum first). If he's any good, will let you know, maybe he might be an option for you? He also does heavy metal detox as he is an environmental medicine doctor, as well as orthomolecular, so this could well go hand in hand (caveat: if he is indeed any good, have kissed a lot of frogs recently, still waiting for the prince). I am not sure how intensive your diagnosis has been so far, but given the time you have been ill, I assume very intensive. So fingers crossed this NutrEval doc is good and is able to determine the blocks AND knows how to treat.
    Currently doing IPT to (try to) kill those buggers pestering me, so will see how that goes.

    Rich, you mentioned that serine is an important amino acid for the methylation cycle. I had my amino acid panel run both on blood, as well as in urine and in both, my serine levels are actually too high. Does that mean that the body has either an oversupply, or that it cannot use the serine and is just excreted. SAMe is notmal though, methionine as well. Given higher MMS, I have now introduced AD12 and MB12 (and 5-MTHF), as per Freddd' recommendation.

    Interestingly, Cystathionin is very low (6 ref <190), so I assume a problem with the transsulfuration pathway (isn't that normal for people with KPU/HPU?) I am supplementing with Vit B6 and Magnesium. Vit B is 100mg a day in the active form and mag is 800mg a day. Since in KPU Vit B6 is lost, what would be a safe daily dose for me to take, maybe Vit B6 isnot enough? Similarily, does Molybd also play a big role? Similar, what is the current recommendation on B2 and B3 and in which form?

    Glycine is very high, glutamine is normal ad cystein is low. I assume I can supplement cystein without a problem, even if there is an issue with the transsulfuration pathway?
  5. Freddd

    Freddd Senior Member

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    HI Nina,

    Maybe it's time to try plan B based on a different set of assumptions; ie all the basics, adb12, 5 star mb12, metafolin, poatassium, NO FOLIC ACID, NO FOLINIC ACID, no gltuathione or precursoprs, no whey or NAC. Then considering several other possible critical cofacors is enough to get going almost everybody who could benefit.
  6. Nina

    Nina Senior Member

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    Thank you so much for your help and suggestions!

    rich: Thanks, as always, for sharing your knowledge and time so generously. It is very much appreciated. I will add my thoughts to some of the points you raised below (*****):

    To find out if the methylation cycle is still blocked, what other tests would you suggest?
    - SAMe (whole blood?)
    - Cystathionine (Urine, Blood?) (The last UAE in 11/10 showed low cystathionine (9 ?mol/g creatinine, ref: <196)

    My KPU test was also highly positive (64,4 mg/g Creatinine, ref: < 6). Maybe 6 months of supplementing P-5-P (~ 25mg/day) wasn't enough to bring levels up to a normal range? A recent test showed low urinary BH4.

    The above mentioned UAE also showed very high levels of GABA, Alanine, Asparagine, Glutamine, Glycine, Histidine, Lysine, Leucine, Serine and Threonine and very low creatinine. I will get a recent one and will update here on what has changed, maybe that could also give some more clues.

    determined: Thanks for your concern. I've been completely bedridden for well over 8 months now and haven't been able to leave my bedroom except for short trips to the bathroom since December 2009 before that. Cyanocobalamine used to give me a real boost about 1 year into the illness but the effects faded after a couple of weeks and nothing has been of any noticeable help since then.

    @Bianca, thanks, I hope this doctor will be able to help you. As I said, I wouldn't be able to see him or even have a phone consult, so I doubt there would be much he could do for me. I'll be interested to hear what your impression of him was!

    Freddd, I've pretty much implemented all of your suggestions for a while. I didn't notice any change, so I added the folinic acid back as it was suggested when BH4 is low. I was on the very conservative side for potassium though, that's certainly something I could increase further. From your experience, do you think it can take more than 6-9- months before any effects are noticed?

    Again, thank you all for your input. If you have any other ideas, I'd be grateful to hear them.

    Nina
  7. BiancaS

    BiancaS

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    Hi Nina,

    By the sound have similar problems that I do. Adrenal fatigue, KPU and sulfuration issue (high serine, low cystathione), low BH4

    Adrenal fatigue: This is very important to consider, as it can impact immune system function. Good guidline on how to treat it can be found on www.adrenal-fatigue.de . Important is high level of B5 (around 1000mg-1500mg daily), magnesium. I also take the Cytozyme AD 3x2 Tabletts as day, for adrenal support. Will retest soon to see if it is enough. Don't forget digestive enzymes, as people with adrenal fatigue have difficulty digesting protein. How is your thyroid? Neurotransmitter would also be important to check.

    Low BH4: If you are low on BH4 and might have issues with protein, then you might have an issue with amonia, which further reduces BH4. Besides the folate, you might want to consider everything that is recycling your BH4, such as vitamin C, little to no protein, NADH (Fairvital, 12mg Tabl.), "Leberextrakte" (organoprparat, you should get it on ebay UK.) Riboflavine-5-Phosphat, Raw Thyroid (Bigvits.co.uk).

    If you have massive KPU, then the amount of B6 you are taking might not be enough, Rich pointed out to the biopure Europe website, which is showing how much Klinghardts tablets do contain. http://www.biopureeurope.com/core-mineral.html However, pls note that the amounts indicated there are already the daily dose (ie for all 4 tablets). He uses 75mg per day day of B6. The products also contains other important ingredients required for transsulfuration, such as molybdaenum and zink (!) Maybe it might be an idea to start with a KPU product and add on the other vitamins from there. I might actually do the same. There are also other KPU products in Grmany on the market, so you might want to look around.
    http://www.symptome.ch/vbboard/kryp...eise-guenstige-medikamente-bezugsquellen.html

    Let me know what the NL lab is saying. The best other alternative in Germany is Ganzimmun. I did the "Aminosaeren im Urin" panel (including cystathione), BH4, oxidative stress, nitrostess (includes MMA - a good guide on where you are), SAMe, etc, KPU and Vitamins in full blood. The best digestive test panel you can can get at Vitatest and the best neurotransmitter is at Lab4more. I know that Ganzimmun now also offers some other panels (split into a few tests), which should come probably close to the methylation panels, it is a bit of puzzeling however. IMD in Berlin offers intracellular glutathione in the immunce cells, plus ATP, NK zytotoxicity tests, as well as the most recognised LTT panels for infectious activity,

    And, I cannot believe your doctor is seriously only coming out to see you every 6 months or so! You should have regular check ups much more often then that! Given that all the tests are quite pricey, have you considered getting in touch with Dr Mayhill in the UK and ordering the tests that she would suggest for you? It comes with recommendation on treatment and further tests, so maybe that can move your doctor a bit.
  8. Freddd

    Freddd Senior Member

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    Hi Nina,

    When the mb12 and/or adb12 work you will generally know rather quickly. Even if there are no apparant startup responses one of the biggest typical tipoffs is suddenly lower potassium and the symptoms that occur which are then almost immediately relieved with a 500mg (495mg) dose of potassium. In 10 days epithelial healing is often apparant. In 3 months neurological healing becomes obvious. However, it is very sensitive to misteps. If you look a the BASICS thread there is a list of the main reasons mb12/adb12/metafolin doesn't work. Check that out and tell me which conditions you don't meet.
  9. richvank

    richvank Senior Member

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    ***Hi, Nina.

    Rich: Thanks, as always, for sharing your knowledge and time so generously. It is very much appreciated.

    ***You're very welcome.

    I will add my thoughts to some of the points you raised below (*****):

    ***O.K.

    If you have a partially blocked methylation cycle, and it is not restored to a normal rate of operation by this treatment (and by that I mean restoring the level of SAMe and the ratio of SAMe to SAH up to normal levels on the methylation pathways panel), then here are some possible causes:

    ***** I do not know wether my SAMe levels have been restored. Being bedridden it is extremely difficult to get lab tests done, simply because I don't have anyone to draw blood. My doctor willl make her semi-annual home visit in August and I hope that will give me the opportunity to get a couple of tests, including SAMe. I'm not sure if the European Lab for Nutrients is still offering the methylation pathway panel but I just sent them an email asking if they do.

    ***I understand the difficulty in getting tests run. The Health Diagnostics and Research Institute in New Jersey (formerly called Vitamin Diagnostics, Inc.) is still offering the methylation pathways panel. It costs $295, including the mailer to send the blood samples back to the lab, and requires an order from a physician or a chiropracter. This panel has proven to be very helpful for determining the status of the methylation cycle, the folate metabolism and glutathione by direct measurements.

    1. Your body is lacking enough of one or more of the cofactor vitamins and minerals, or enough of the amino acids needed by this cycle. The main cofactor vitamins and minerals needed (in addition to B12 and folate, which are the primary ones needed to lift the partial block in methionine synthase) are B2, and B3 (best taken as B-complex), and zinc. The main amino acids needed are methionine and serine.

    **** After supplementing with all the different B12 forms for over a year, I don't think there's any way I am still lacking B12. I'm at 200mcg of each folinic acid and MTHF.

    ***I don't know what your folate status currently is, but you might need more MTHF. The methylation pathways panel will tell.

    I've been very careful adding in sulfur-containing supplements and have therefore not taken methionine for any length of time, it might be worth a shot?

    ***Maybe so. Methionine is commonly found to be low in M.E., as first reported by Lord and Bralley of Metametrix several years ago. It is the feed material for the methylation cycle, so if it is depleted, the flow in the cycle is not going to be able to come up, even though methionine synthase has the nutrients it needs.

    Likewise, I've not added the phosphatidyl-serine because of its cortisol-lowering properties. My adrenal hormones are very low. Do you think this alone could be a stumbling block and if so, is there any other form or serine that I could take?

    ***In the latest revision of the simplified protocol, I have added the option of taking lecithin instead of phos. serine, for those who have low cortisol. This won't help with serine, but serine is available as a supplement (L-serine).

    2. Your genomic makeup makes it necessary for you to use a higher dosage of B12, or a different form, than is suggested in the simplified treatment approach. As you may know, Freddd, on these forums, recommends use of methylcobalamin and adenosylcobalamin, and at higher dosages.

    ***** See above, I have been taking both MB12 and ADB12 for quite some time in high doses, with no effect.

    ***O.K.

    To find out if the methylation cycle is still blocked, what other tests would you suggest?
    - SAMe (whole blood?)
    - Cystathionine (Urine, Blood?) (The last UAE in 11/10 showed low cystathionine (9 ?mol/g creatinine, ref: <196)

    ***I favor the methylation pathways panel and the Metametrix plasma 40-amino acid panel, as is available from www.directlabs.com:
    https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx This combination will tell the story pretty well.

    My KPU test was also highly positive (64,4 mg/g Creatinine, ref: < 6). Maybe 6 months of supplementing P-5-P (~ 25mg/day) wasn't enough to bring levels up to a normal range? A recent test showed low urinary BH4.

    ***As you may know, Dr. Klinghardt uses the "Core" suppleent for KPU, and its composition is as follows:

    Vitamin B-6 75 mg (3,750% DV) (as Pyridoxine HCl and Pyridoxal-5-Phosphate.
    Biotin 8,000 mcg (2,667% DV.)
    Elemental Zinc 40 mg (267% DV) ( from Opti-Zinc, Zinc Monomethionine,) Zinc Glycinate, Zinc Gluconate, Zine-Picolinate.
    Manganese (from Manganese Glycinate) 7 mg (350% DV).
    Chromium (as Chromium Chelate) 500 mcg (417% DV).
    Molybdenum ( as Molybdenum Krebst) 400 mcg (533% DV).
    Boron (as Boron/Aspartate/Citrate/Glycinate complex) 3 mg (* DV).
    L-Taurine 85 mg (* DV).
    Magnesium Glycinate (providing less than 2 mg magnesium) 10 mg (* DV).

    ***Dr. Klinghardt has emphasized that when KPU is present, it must be corrected in order for the methylation cycle to be restored.

    ***Low BH4, as I think you know, suggests a problem with the folate metabolism, which is intimately linked with the methylation cycle.

    The above mentioned UAE also showed very high levels of GABA, Alanine, Asparagine, Glutamine, Glycine, Histidine, Lysine, Leucine, Serine and Threonine and very low creatinine. I will get a recent one and will update here on what has changed, maybe that could also give some more clues.

    ***When several amino acids are high, it suggests that the transamination reactions that are necessary to feed them into the Krebs cycle are not working well. These reactions require P5P, so maybe that is the issue. Low creatinine suggests low creatine production, and that points back to a methylation cycle deficit.

    ***Best regards,

    ***Rich
  10. Nina

    Nina Senior Member

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    Sorry for taking some time to update this thread but I have been really unwell.

    I will try to answer each of the suggestions you made and also post my latest lab work as it comes in, but will need to break it into several short posts. So please bear with me, I will get there :)

    Re: Freddd's protocol: The most likely block might be potassium for me. I like to stay on the safe side since I also have pronounced adrenal fatigue issues and this can cause your potassium to be high (and also, often makes you feel worse with increased intake). I ordered a blood test now to know for sure, and indeed it's on the lower end:

    Potassium: 1581 mg/l (1545-1857)

    I'll carefully increase this now and see how that works out.

    Methylation:

    The results I have received so far are:

    UAA Panel: Pretty much unchanged. if I can get a scan, I will try to post this here.
    KPU: Went down from ~65 to ~10 (<6)
    Q10: 0,52 (0,55-2,5)
    SAM-e: 0,1 (0,8-1,8)
    reduced glutathione: 476 (639-1146)
    oxidized glutathione: 334 (<72)

    So I guess there's still some room for improvement ;)

    After supplementing ubiquinol with 100-300mg a day for about a year, it's beyond me why the levels won't go up.

    To be continued...
  11. therron

    therron

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    Hi Nina, Freddd, and Rich,
    While I have made some progress on the methylation protocol (a bit more energy, more focused thinking, less muscle issues), I know that I have not yet opened the methylation block since histamine and sulfite sensitivity are increasing. I think that Nina and others, like myself, who have adrenal issues, find moving forward very challenging.
    I can't take potassium (it makes me extremely weak), but sodium seems quite beneficial. From what I have read, adrenal problems raise potassium and lower sodium....so this makes sense in how my body reacts to potassium. I haven't been good about taking daily doses of sodium, but I discovered last night how critical this might be for me. I took my nightly dose of magnesium and calcium, adding some sea salt. I believe the sodium helped make my cells more permeable, causing an overdosed reaction to the magnesium (weird heart thumping). Now............may I apply this to all of my supplements......meaning that I will actually receive all of the intended doses when accompanied with sodium? Also, would it be beneficial to increase B6 since it helps regulate sodium/potassium balance? Is adrenal treatment necessary also.....or will my adrenals eventually catch up with the protocol?
    How does histamine fit into this picture?
  12. Nina

    Nina Senior Member

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    Hi Therron,

    histamine is a huge issue for me, too.

    Some sources list vitamine B1 and folates as contra-indicated but I know at least regarding the folates Rich doesn't quite agree so I have continued taking it. I may try and go without it for a while to see if that changes anything.

    Sea salt seems beneficial for me as well but not to a great extent (though little does when you're so ill it seems).
  13. richvank

    richvank Senior Member

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    Hi, Nina.

    This is really helpful information. Looks like you've made good progress on correcting the KPU. The methylation cycle is still partially blocked, and glutathione is not really depleted in terms of the total amount, but there is too much oxidized glutathione relative to the reduced glutathione, which is the active form. The Co Q10 is low, probably because of the methylation deficit, even though you have been supplementing it.

    Since your reduced glutathione and SAMe are so low, I don't think your cells will be able to convert hydroxo B12 to methyl B12 very well, so I think that taking methyl B12, as Freddd recommends, will work better for you. How does the methionine level look in your UAA panel? If it's low, that might at least partially explain why SAMe is so low. Bringing potassium up also looks like a good idea.

    Hope this helps.

    Rich
  14. Nina

    Nina Senior Member

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    Hi Rich,

    I have been taking the active forms of B12 for a long time now, including at least 1ml MB12 a day, so I guess this is unlikely to be the bottle neck.

    I'm not sure if Methionine got tested on the UAA panel but will look that up as soon as I can.

    I've been thinking about injecting glutathione directly in the hope of feeling better, but I'm not sure if that would help considering that my total glutathione isn't even low? I used to tolerate it well but it's been almost 2 years since I last got it and I was still doing a lot better back then. Do you reckon it's worth a shot?

    Thanks, as always,
    Nina
  15. richvank

    richvank Senior Member

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    Hi, therron.

    I think it's interesting that raising sodium helped you. As you've suggested, several substances needed by the cells are cotransported in with sodium. The sodium provides the driving force to carry them in, because the concentration of sodium is normally maintained lower inside the cells than outside. I note that the Blasi protocol from Spain, which has helped a lot of people, is a mixture of electrolytes called Recuperation. Dr. Enlander uses his own solution, called Lectrolyte. Perhaps at least part of the benefit of these solutions is what you have alluded to.

    I don't know if B6 will help you or not. I do find that many PWME's are low in B6 from the lab tests I've seen. I think it gets depleted by being cycled back and forth as a coenzyme for the transamination reactions, which convert one amino acid to another. I think PWME's use these reactions more than normal, because they are needed to feed amino acids into the Krebs cycle to be burned to make ATP. I think PWME's do this more than normal because the glutathione depletion partially blocks the normal use of carbs and fats for fuel by the Krebs cycle.

    In most cases of ME, I don't think the adrenal glands themselves are at fault for the "adrenal fatigue." I think the problem is higher up in the HPA axis, at the pituitary and hypothalamus. I think they have difficulty secreting enough CRH and ACTH and doing it with the correct regulation, because of glutathione depletion in them. There may also be damage to the hippocampus in the brain, which affects the HPA axis. As the methylation cycle, glutathione and folate are restored, I'm hopeful that the function of the HPA axis will be normalized.
    Note that the hippocampus is the one part of the brain that has been found to be able to make new neurons. Note also that this requires new DNA and that folate is important for making new DNA.

    My view of the histamine problem in ME is as follows: Histamine is made from the amino acids histidine. Normally histidine is broken down by a pathway that requires folate. If this pathway is not working well, Figlu rises in the urine organic acids test, and this is commonly seen in ME. I think that the excess histidine may drive synthesis of more histamine.

    At the other end of histamine metabolism, there are two enzymes that normally break down histamine. One is a methyltransferase that uses SAMe. If there is a partial methylation cycle block, this reaction will not work as well as normal. The other is diamine oxidase. It requires copper and B6. B6 is low in many people with ME.

    So the combination of all of this is that histamine may be made at a higher rate and may be broken down at a slower rate, resulting in a higher level of histamine. There were studies early on after CFS was identified that indicated that people with ME/CFS don't have more Type 1 allergies (not to be confused with delayed food allergies), but it appears that they do have more issues with histamine. So it's not that there are more allergies to provoke histamine secretion, but rather, the problem is in the synthesis and breakdown of histamine itself, becuase of the vicious circle mechanism involving the methylation cycle, folate, and glutathione depletion.

    Best regards,

    Rich
  16. Mary

    Mary Senior Member

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    Nina - potassium can make a huge difference doing Freddd's protocol. If I had not upped my dose significantly, I would be bedridden too. After an initial burst of energy on his protocol, I was completely exhausted until I added in potassium. Your number is quite low, so I think you might be very surprised if you take enough. I titrated up slowly to 1000 mg. a day, and now have cut back to around 600. I used to have adrenal issues too.

    Re your adrenal fatigue - have you ever taken an adrenal glandular product? I had very good results with Drenatrophin PMG by Standard Process and a couple of other products, I forget the names right now. Also, extra pantothenic acid, in addition to a good B complex, helped a lot. I had to start with a high dose of the Drenatrophin, but it was great stuff, within a couple of days my energy started coming back. I got it from my chiropractor who does muscle testing - he helped me a lot.

    Mary
    Nina likes this.
  17. Vegas

    Vegas Senior Member

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    Sorry, I don't have time to read the thread to see what has been recommended, but I would be concerned that some of the many supplements you are taking through Yasko or Myhill are making you worse. I'm not talking about sensitivities, but rather supplements that are possibility counterproductive. I know Coq-10 and D-Ribose are recommended by Myhill as part of her utilization of a modified Sinatra protocol. I found that these were very problematic and exacerbated the mito dysfunction. Also, I certainly hope you are not using Myhill's chelation protocol, from what I have heard of that, this will certainly set you back.

    You might want to consider some of the key cofactors, particularly zinc.

    Also, as I'm sure you have read, for many doing the SMP it gets worse before it gets better. The flu-like symptoms and weakness sounds like worsening oxidative stress/mito dysfunction. This can certainly happen when you are mobilizing toxins. Your precious endogenous antioxidant resources are limited, and flushing that stuff out of your cells, intestinal tract, and other tissues exacerbates things. If you are continuing to get worse, you really need to re-examine the supplements you are taking.


    Sorry if I'm repeating what has been said.
  18. therron

    therron

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    Hi Rich,
    Thank you for the detailed explanation of histamine reactions and the scapegoat nature of blaming adrenals for body malfunctions. I am trying to utilize this information, along with my own anecdotal records, in moving forward with the methylation protocol. Since starting the protocol about 3 months ago, my histamine reactions and sulfite sensitivity have gotten much worse..........so...........based on your explanation of histamine which cofactor might be a next step? It may also be helpful to know that my lab tests do show low B6, and I have compound heterozygous MTHFR gene mutations (1298 and 677). I currently take 500 mcg Mb12, 2 mg adb12, 400 mcg Solgar Metafolin. I haven't found a b complex that I can tolerate yet (I did try Pure Encapsulation a couple of months ago...might give it another go now that excitotoxicty has calmed). I take separate B6, B5, B2, Biotin, Vit C, D3, E, A, magnesium, calcium, zinc, and molybdenum for sulfite issues after increasing folate. I would love to hear from Freddd and you both on next steps.
  19. Nina

    Nina Senior Member

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    I have now uploaded my recent UAA test. The left column contains the latest results, the column right of the diagram contains my previous results. Reference ranges on the far right.


    UAA August.jpg
  20. richvank

    richvank Senior Member

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    Hi, Nina.

    Your methionine is in the normal range, but SAMe is low. That means that the MAT1A reaction is not going fast enough. Either there is a polymorphism in it that slows it down, or ATP is low. I suspect the latter, because the low glutathione and low Co Q10 will be hindering the production of ATP by the mitochondria.

    The demand for methionine will likely rise as flow through cystathionine and the transsulfuration pathway is improved (see below).

    The combination of high serine and low cystathionine means that the CBS reaction and flow through the transsulfuration pathway are not running fast enough. That could be due to low B6 (or low B2, which is needed to produce the active form P5P from B6), or low magnesium, or both.

    The combination of high glutamate and very high glycine with low glutathione suggests that cysteine is low, which would be consistent with low flow through cystathionine. Taking some N-acetylcysteine may help the production of glutathione. Dr. David Quig has emphasized that the NAC dosage should be no higher than 300 mg per day if it is likely that there is a high mercury body burden, because NAC can move mercury into the brain.

    The combination of low reduced glutathione and high oxidized glutathione means that the glutathione reductase reaction is not able to keep up with the demand on glutathione from oxidative stress. This reaction benefits from B1, B2, and B3.

    The observation that several amino acids are high suggests that they are not being fed into the Krebs cycle at high enough rates, and that is likely due to low B6 (or low B2, which is needed to convert B6 to its active form, P5P). This is needed for the transamination reactions which convert one amino acid into another. This is necessary to feed them into the Krebs cycle.

    I hope this helps.

    Rich

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