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Methylation panel: to diagnose block or to tailor treatment?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Sasha, Jan 7, 2012.

  1. Sasha

    Sasha Fine, thank you

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    I've been asking on another thread about how to get the methylation panel because I thought that people were getting advice based on their results about how to tailor their supplements according to their specific problems. It just occurred to me that I might have misunderstood this and that the purpose of getting the test is simply to establish whether one has a partial methylation block and should just go on the standard protocol and then try to adjust it by trial and error.

    I'm already convinced I've got a partial methylation block problem because when I started Fred's protocol, I immediately got an energy surge (within half a minute) from ab12 which was sustained for several days; plus I had reproducible start-up symptoms (weird sensations and twitching in my face and sacro-iliac joints) and then a huge need for potassium and then extreme exhaustion and muscle soreness as what was presumably some sort of induced deficiency got beyond my ability to deal with. Fred has said that if you don't have b12 deficiencies you don't get any symptoms and I certainly had a load.

    So, do I actually need to do the methylation panel? I've been on Rich's SMP now for 10 weeks with no apparent effects (good or bad) and am thinking that if I need to tailor it, should I be getting the panel done to guide me? But would it?
     
  2. harrycat

    harrycat

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    Unless you have loads of cash I probably wouldn't bother - it can tell you if b12 or folate is the more limiting factor ... But if you are sure you have the block it's probably not that helpful. It gave me confidence that I needed to address this area but not much more.

    I'd have the amino acid plasma and organic acid test (urine) instead which gives loads of info including indirectly b12/folate status.
     
  3. Sasha

    Sasha Fine, thank you

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    Hi Harry - I think it's clear from my response to Fred's protocol that I've got methylation problems so if all the panel does is diagnose that, it's not worth me having.

    Do the amino acid plasma & organic acid test yield info that guides treatment? I'm assuming my b12/folate status must be poor anyway.
     
  4. harrycat

    harrycat

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    Hi Sasha. Yes it does. Rich kindly interpreted mine. They give information on amino acid levels, essential vit and mineral status, krebs cycle function, sulphur metabolism, and more. Stuff can be inferred about b12 and folate too. The upshot for me was I needed more vit a, e, magnesium, vit b2 and b3. Also general amino acid supplement, methionine, digestive enzymes and betaine hcl. Probably some other stuff i have forgotten! I also had a digestive function test done (stool sample) at the same time.
     
  5. Freddd

    Freddd Senior Member

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    Hi Sasha,

    I immediately got an energy surge (within half a minute) from ab12

    Adb12 doesn't do methylation and isn't connected with it. The energy surge with adb12 is very fundamental, it is ATP generation in the mithochondria.

    On the other hand if you take mb12 then you will feel neurology startup and methylation startup as methylb12 os a methyl donor and generates SAM-e as the body's "universal methyl donor". However, some adb12 will convert to mb12 but not instantly. Adb12 is not a methyl donor. It competes for methy groups and is an uphill energy conversion to methylb12. There is a lag time. There is some crossover in both direction but most find that they have separate primary reactions to both. As with other forms of cobalamin, about 99% of a dose is excreted by the next day, some a little faster than others, but just as inevitably.

    And you are correct. I had a lot of people sample mb12 and adb12, separately and together. Both together increased total response about 10% for those with symptoms. For those without symptoms it had all the effects of a pleasent flavored candy. I trialed about 1000 people this way. Sitiing around in a group the people with no symptoms wondered if those having huge reactions were making it up or something. Those with big response found it almost unbeliveable that some people, about half, had no response at all.

    That half the people at a recreational resort or a medical conference had enough symptoms of this type to respond was kind of shocking to me. I thought that most of them were healthy. I kept repeating it at other places with other similar groups.
     
  6. Sasha

    Sasha Fine, thank you

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    Thanks, Fred - I didn't realise the ab12 didn't mean anything in terms of methylation but the neuro & induced deficiency symptoms I got when I introduced mb12 presumably mean I've got a partial methylation block.

    That's interesting about how many people get a reaction.
     
  7. richvank

    richvank Senior Member

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    Hi, Sasha.

    The main reasons I encourage people to run the methylation pathways panel are (1) to find out if they do have the vicious circle mechanism going on in their biochemistry that involves glutathione depletion, a functional B12 deficiency, a partial block in the methylation cycle, and loss of folates, and (2) to obtain baseline data for levels of the parameters in the methylation cycle and the folate metabolism, and the levels of reduced and oxidized glutathione. Having the baseline data is helpful later on in treatment, to gauge the progress. It isn't always clear from symptoms alone how the treatment is doing, because the treatment can make symptoms worse for a while. By repeating the panel later on, a person can find out if the treatment is actually helping, and how much more things need to be improved.

    There are also some other things that can be learned. In a small subset of PWMEs, the glutathione level comes out normal, but there is still a partial block in the methylation cycle. These people may have low activity or genomic polymorphisms in the enzymes that normally use the glutathione, i.e. glutathione peroxidase and/or glutathione transferases. It is helpful to know whether this is the case, because it can indicate that more selenium might be needed for the glutathione peroxidases, or it can alert a person to the need to focus special attention on heavy metal toxicity, which may require chelation.

    As harrycat noted, this panel can also indicate whether the main issue causing a partial methylation cycle block is the B12 functional deficiency or lack of enough active folate.

    This panel can also indicate the severity of oxidative stress. When this is severe, it can be helpful to add some once-through antioxidants to help to control it.

    If the initial panel shows very low reduced glutathione and S-adenosylmethionine, I think it indicates that methylcobalamin would be the preferable form of B12 to use, rather than hydroxocobalamin, because these two are needed to convert hydroxocobalamin to methylcobalamin.

    (As you probably know, Freddd favors use of methylcbbalamin and adenosylcobalamin in all cases, and finds hydroxocobalamin unhelpful. I think this results from his inheritance of a mutation in the Cblc complementation group, which is coded by the MMACHC gene. Some of the mutations that can occur in this complementation group will hinder the formation of both methylcobalamin and adenosylcobalamin from hydroxocobalamin, and they will also cause glutathione to interfere with, rather than to help, as is normal, with formation of these coenzyme forms of B12, which Freddd also experiences. I don't know what fraction of the ME/CFS population has one of these mutations. Freddd is also intolerant of folinic acid, and I suspect that the reason is that he has also inherited a polymorphism in the MTHFS enzyme, which is the only enzyme that can convert folinic acid to be used to form other forms of folate. I also don't know how widespread this polymorphism is.)

    In my opinion, the advantage of using hydroxocobalamin, when it is possible, is that it leaves control of the amounts of methylcobalamin and adenosylcobalamin that are produced to the cells themselves. When large amounts of methylcobalamin and 5-methyltetrahydrofolate are taken together, the methylation cycle can be overdriven, and it appears that this will slow the recovery of glutathione, because too much of the homocysteine is converted to methionine, leaving too little to feed synthesis of cysteine, which is the rate-limiting amino acid for the synthesis of glutathione.

    Dr. Amy Yasko uses different criteria to decide which form of B12 is best in a particular case, looking at the polymorphisms in COMT and VDR.
    Depending on the various polymorphisms that people have in genes associated with the methylation cycle, they may need more or less B12 support, according to Dr. Yasko's approach.

    As harrycat mentioned, it is also very helpful to run some other tests, including urine organic acids and plasma amino acids (urine amino acids panels can also be used). When these are run together with the methylation pathways panel, it is possible to get a more complete picture of the status of the metabolism, and to identify particular deficiencies. If there are problems with the digestive system, running a comprehensive stool analysis panel is helpful to identify what the particular issues are, to guide treatment.

    Best regards,

    Rich
     
  8. Jenny

    Jenny Senior Member

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    Hi Freddd, what symptoms are you referring to? I've taken sublingual 5000mcg of mb12 a day for months, and I agree, it tastes like candy. (A bit too sweet for my liking though.) It seems to do nothing whatsoever for my ME, good or bad. No reaction at all. I'm taking it with metafolin.

    I have all the symptoms of ME, sometimes moderate, sometimes quite severe.

    Jenny
     
  9. Sasha

    Sasha Fine, thank you

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    Hi rich - thanks very much indeed for the detailed reply. It sounds as though I should go ahead with the meth panel test, at least! And hold off switching from hb12 to ab12 and mb12 until I get the results.
     
  10. anniekim

    anniekim Senior Member

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    Hi Harrycat, do you mind me asking how you are faring on the methylation protocol? Many thanks
     
  11. Freddd

    Freddd Senior Member

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    Hi Jenny,

    I have a daughter of the same name. Could you list ALL the symptoms you have from the master list and any others as well as each and every supplement you are taking. The symptoms I am referring to are those that ended up on that list. A pure ME might not respond to 5mg for any number of reasons. There are additional critical cofactors and complicating supplements and medications. Let's work through this.
     
  12. Jenny

    Jenny Senior Member

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    Not sure what the master list is but my symptoms are:

    Extreme weakness and exhaustion
    Flu-like symptoms (sweating, shivering, headaches, painful lymph nodes in back of skull, groin, armpits)
    Stabbing pain at back of eyes
    Electric shock sensations up right arm
    Malaise
    Very sensitive to cold
    Dizziness
    Vertigo
    Sore soles of feet
    Tingling in face
    Painful joints, particularly knees, elbows and base of thumb (can't hold a pen for long)
    Pain at site of previous injuries
    Back pain
    Fast and irregular heartbeat
    Shortness of breath
    Nausea
    I rarely have any cognitive problems

    All these symptoms come and go, fortunately I rarely have them all at once. I am often bed-bound for months, but also have had periods of virtual remission.

    Supplements:

    Hydro B12 injections 1000mcg once a week
    Methyl B12 5000mcg daily
    Metafolin 800mcg daily
    Vit C
    Acetyl-l-carnitine
    D-ribose
    Creatine
    Vit D3
    Niacinamide
    Zinc
    Potassium iodide
    Magnesium citrate
    TMG
    Selenium
    Alpha lipoic acid 50mg every 3 hours, 3 days a week (Cutler protocol)
    Jarro-dophilius
    Omega 3
    Nutrient 950 (multivitamin with vit K)

    I've taken most of these for years.


    Medications:

    Valacyclovir 2gms daily (taken this for one year)
    Amytriptyline 10mg at night
    Nexavir 2mls twice a week

    Thanks in advance!

    Jenny
     
  13. Freddd

    Freddd Senior Member

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    Hi Jenny,

    Thankyou for the information. I would like to have some clarification on several things. Sometimes the devil is in the small details, the "fine print". First I want to say that the Nutrient 950 with K is the best multivitamin I have ever seen. I'm going to be able to suggest it to others looking for something to make their life easier with fewer pills. Also, as I have said about a good multi vitamin, it requires 6 caps per day for the full dosage.

    Why are you taking the one with vitamin K? Have you had bleeding problems?

    Could you go through the separates and specifiy how much of each and what brands?

    With the 5mg b2 how are you taking it?

    Also when you have remissions what symptoms back off and how far?

    What symptoms get worse and leave you bed-bound. I've been there by the way. When I had my crash. I could barely walk to the car to go to the doc and my wife had to drive me. I was barely able to function at all and was bed-bound or rocking chair bound for 6 months and yet the doc could find NOTHING wrong. I stayed almost that bad for 16 years. I have now recovered. I had most all of your symptoms or minor variations of them.

    Tell me about your sense of taste. Are strawberries as good as they used to be?

    Do you eat white flour products?
    What breakfast cerials
    what fortified drinks or protein drinks, instant breakfast, etc?
    how much meat
    how much genuine dairy, milk and cheese etc -
    how much fruit
    how much veggies not incluing potatoes
    how much junk food
    how much nuts and seeds
    how much whole grain products, wheat, rye, corn

    Is there anything at all you suspect causes the crashes? Tell me about your diet. Do you have somebody preparing food for you when bed-bound?

    Does your diet change before bed-bound happens
    Change after bed bound
    change back before recovery?
    change back after recovery?

    Also, do you have some basic blood count info like numbers from a CBC or any results from other tests that might be relevant if you have had nutritional or hormonal tezsting done.


    I know I'm asking for a lot but I'm looking for all sorts of clues that may not be obvious enough to ask about directly. What I am looking for might be various combos that I recognize when I see them but couylsn't ask about directly. Thankyou
     
  14. Jenny

    Jenny Senior Member

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    Thanks very much for this Freddd - my responses are below.

     
  15. Freddd

    Freddd Senior Member

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    Hi Jenny,

    Why are you taking the one with vitamin K? Have you had bleeding problems? It was the one my doc recommended, not sure why

    What I wanted to see in the CBC was the platelet info. Low platelet count is a common occurance in these deficiencies.


    Flu-like symptoms diminish, have more energy, pain is better, dizziness gone, no headaches. I never feel 100% but I do have periods of 3-5 months where these symptoms are much less severe and I'm at around 90%. These good periods have been much less frequent in the last 10 years though

    Very severe malaise, aching pain all over, can't get warm, yet have frequent night sweats. Can't walk more than a few steps without total exhaustion

    I have periods where I feel so ill and nauseous I can hardly eat anything



    SO "flu-like symptoms, especially body ache and pain? Would that be muscles and/or joint pain? Does it respond to asprin or ibuprofen or naproxin as in inflmmatory pain? Does that include fevers, or feeling feverish with the skin feel of fever? Just keep going, we are almost there.

    I would like to mention that those were my exact symptoms during the bed-bound periods intially and on several flairups during the years.


    Not linked to overdoing things or infections. But always crash in Sept/Oct


    THAT timing is very suggestive.

    Do you go on holiday in July or August? Are you out in the sun a lot more? Do you get more exercise? Do you take advantage of harvest season to enjoy more fresh veggies. I have a nice organic garden and really enjoy eating all those fresh produce items with the fantastic fresh out of the garden flavor. Even though I don't think of myself as eating a lot more porduce at that time of year I do because it is there in abundence, I do. For instance I make a summer squash with tomatos, carrots and onions and with wheat germ and cheese topping dish and variations thereon. And maybe a side of chard and some fresh salad. Do you find yourself doing that or something like it in July-September or October? How does your diet change during harvest season whether from local produce or your own garden?
     
  16. Jenny

    Jenny Senior Member

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    Hi again Freddd - see responses below, in italics:

    Thanks, Jenny
     
  17. greenshots

    greenshots Senior Member

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    Personally, I don't think having the panel done is that expensive. If you consider that I've paid out thousands over the years to help my daughter, and none of it helped, spending $500 on the panel gave us a tailored regimen. I don't think you need to be on every supplement or herb or whatever, for every defect, and neither did my doctor, but it sure helped us. My daughter is back and even better than she ever was. I thank God every day we could take advantage of cutting-edge medicine to do this.
    Angela
     
  18. Freddd

    Freddd Senior Member

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    Hi Jenny,

    What other symptoms if any coordinate with your crashes, ie angular cheilitis? Skin problems? Cold feet or hands? Increased allergies? Increased asthma? Increased chemical sensitivity?
     
  19. Jenny

    Jenny Senior Member

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    The only one of these I have is cold hands and feet, also cold nose! They are all worse in a crash. No angular cheilitis. Don't seem to have any allergies, except mild hayfever in early summer, no asthma, no chemical sensitivity.

    Jenny
     
  20. Freddd

    Freddd Senior Member

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    "The last question was asked for the first time, half in jest, on May 21, 2061..."

    Can Entropy be reversed?

    There is as yet insufficient data for a meaniful answer.

    However, there are some possibilites of an answer to your situation.

    I would say that the information presented provide a strong argument for paradoxical folate deficiency. If that is the case some larger doses of Methylfolate, perhaps 8mg to 16mg perhaps in a single dose or maybe across several doses per day. Also a 50mg Jarrow Mb12 dose and a 50mg ADb12 dose, sublingual held for 2-3 hours, maybe 4 hours depending upon how many tablets you can fit at a time. This could correct it pretty quickly. Then titration of substances to find what maintains it. Metafolin in large doses and timed before the food and at the same time to try ot out-compete the veggie folate may help. Problems is that the veggie folate builds up over time until it appears to completely block Metafolin. Learn the early symptoms so you can stop the veggies when trouble starts before it gets serious. This is all bleeding edge experimental so no pat abswers.

    In the fall you qwould be having a decrease in Vit D. A supplemnt of 4000-5000 per day might help.

    adenosylb12, Source Naturals could be a HUGE help.

    For some people Acetyl l- carnitine interfers with l-carnitine fumarate and prevents it from working. In even more people acetyl l-carnitne doesn't work at all with adenosylb12 to activate mitochondria. Changing to l-carnitine fumarate might help anywhere from a little to HUGE differences.

    Increased vitamin C, to 4000 to 6000mg or more might help.
     

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