Rich Van K: Methylation and MSH

Discussion in 'Fibromyalgia Main Forum' started by Forebearance, Jun 29, 2008.

  1. Forebearance

    Forebearance Member

    Hi Rich,

    I have a question for you. Or maybe it's an observation.

    I clearly have mold poisoning, and I fit into Dr. Shoemaker's theory very well, except for one thing.

    Dr. Shoemaker says: "Nearly 100% of the patients who have Chronic Fatigue Syndrome (CFS) will have MSH deficiency."

    I even have one genotype that makes a person susceptible to low MSH. So you would think that I, of all people, would have low MSH. And yet my test results showed my MSH is in the normal range.

    So I'm trying to figure out what could be causing this anomaly.

    People who have been taking the methylation supplements you recommend have been finding that their endocrine systems seem to be healthier. I recall several people who were able to reduce or discontinue various hormone supplements after they began to methylate better (including me).

    Is is possible that the simplified methylation protocol could raise a person's level of MSH?

    If it could, maybe that would make Dr. Shoemaker sit up and pay more attention to it. He's always talking about trying to find a way to raise MSH levels in his patients.

    I just wonder.

    Now you'll probably tell me it all comes down to glutathione. As everything does in the end. Hee hee

    But I would honestly like to hear your thoughts about this issue, if you have any.

    The number of people with CFS who have both tried methylation supplements and have had their MSH level tested must be pretty small. So how could one tell if this was going to be a trend?

    I wish I had had my MSH level tested before starting the methylation supplements.

    [This Message was Edited on 06/29/2008]
  2. Slayadragon

    Slayadragon New Member

    What was your level of MSH compared to the reference range?

    Interesting hypothesis.

    [This Message was Edited on 06/29/2008]
  3. richvank

    richvank New Member

    Hi, Forebearance.

    Fascinating! I, too, wish you had before and after measurements of MSH, but just for the heck of it, I'm going to suppose that the methylation cycle block treatment did in fact raise your MSH to normal.

    Now, I must warn you that Dr. Shoemaker currently is not buying the following explanation, but I'm hopeful that that will change if we can ever get enough data to check it out!

    Yes, you guessed it! Glutathione! The answer to every question! Well, almost. Once in a while I invoke the methylation deficit or the folate problem, just to keep people guessing! (;-)

    Here's the story: MSH is made from part of the molecule called POMC (proopiomelanocortin), which is formed in the pituitary. Other parts of this same molecule are used to form ACTH (which signals the adrenals to secrete cortisol) and an endorphin (which makes us feel better).

    If the cells in the pituitary that make POMC are low in glutathione, they will not be able to make as much POMC as normal, and they will not be able to route it to the so-called regulated secretory pathway.

    The reason is that there is normally a hook on the POMC molecule that contains four cysteine residues that have to be connected together properly to form the hook, which is used to route the molecule to the right pathway. If there isn't enough glutathione present when amino acids are strung together to make the protein, this hook will not be formed properly, because the cysteines will bind together with each other too soon, forming cystine molecules with the wrong partners, and this will mess up the process. A lot of the bogus molecules will be sent to the recycling bin (the proteosome), and others will be routed to the unregulated secretory pathway.

    Well, that's the hypothesis. It would really be cool to be able to test it, but as you noted, we don't have a before and after, and of course one case sure won't convince my friend Dr. Shoemaker. I'm sure of that!

    Thanks for posting this.

  4. Slayadragon

    Slayadragon New Member

    Hi Rich,

    Well, that's encouraging.

    Dr. S seems to be at a loss with regard to some people, and that makes me wonder if I'll ever get well just following his approach (or mold detox in general).

    Before I was wondering if maybe just getting the other "gunk" out of the body through methylation might be enough to help to give big improvements, though I wasn't persuaded of that.

    The idea that this might help MSH (which seems to be hugely important in his mind) is a cool idea though.

    I'm going to be getting all those Shoemaker tests run within the next week or two, and so it will be interesting to see how they come out.

    On another note.....this isn't really your area, but do you have any idea how human growth hormone and MSH tie into one another?

    It seems to me that they must be pretty closely related, even though I've not seen anything on this.

    Do you think that supplementing hgh might help to improve MSH? I'd be much more inclined to spend the $10-20 per day if it did.

    Thanks for checking the board!

    Best, Lisa
  5. richvank

    richvank New Member

    Hi, Lisa.

    Same problem. The human growth hormone molecule has two cystine disulfide bridges in it. If those are not formed properly, the molecule won't do its job properly. Glutathione depletion is the problem here, too.

    By the way, this same argument holds for antidiuretic hormone, oxytoxin, ACTH, and perforin in NK cells. It may apply to some other secretory proteins in CFS also, but I haven't checked them all out.

    The reason I'm fond of this part of the hypothesis is that it can explain the oddball collection of several symptoms and several corresponding known biochemical abnormalities in CFS.

    By the way, Dr. Cheney tried supplementing hGH in some of his patients a few years ago, and it started out looking good for some of them, and then they really crashed. He doesn't advocate that anymore, as far as I know.

  6. Forebearance

    Forebearance Member

    Thank you Rich. That is very interesting.

    Well, Lisa, my MSH level was 29. The test report said the Limits are 0-40. Limits sound like a different thing than normal range. But I was about in the middle of the limits.

    Maybe I need a doctor to interpret the test results for me, since they don't actually say what the normal range is.

    I can say that before I began the methylation supplements, I was definitely having symptoms of low MSH. I had put on 100 pounds in ten years without changing my eating habits, and I had unrefreshing sleep. Even now I still have slightly high Leptin.

    And it's possible that my MSH level should be higher in order to be normal for me. I don't know.

    But I can tell you that when I began the methylation supplements, I began to have more restorative sleep and I began to get thinner.

    Those effects were gradual and subtle. Now that I am away from mycotoxins and detoxing faster, those effects are more pronounced. I'm getting thinner faster and am sleeping more deeply.

    I wonder how Dr. Shoemaker would explain a person who has had CFS for 18 years, has mold poisoning and a low MSH genotype, had low MSH symptoms and now has an MSH level of 29? Could he explain me?

    And Dr. S. says he has quite a few low MSH patients who are feeling desperate. If I were one of them, I'd be motivated to at least try the simplified methylation protocol, because it's pretty cheap and easy to take. And it's harmless if you don't need it, I'm assuming.

    Yes, thanks for checking the board, Rich!

    I'm trying to be a good guinea pig.
    [This Message was Edited on 07/01/2008]
  7. ETN

    ETN New Member

    What is MSH?
  8. Slayadragon

    Slayadragon New Member

    Hi Rich,

    I'm pasting your comment here so that I can look at it while I'm writing:

    "Same problem. The human growth hormone molecule has two cystine disulfide bridges in it. If those are not formed properly, the molecule won't do its job properly. Glutathione depletion is the problem here, too.

    "By the way, this same argument holds for antidiuretic hormone, oxytoxin, ACTH, and perforin in NK cells. It may apply to some other secretory proteins in CFS also, but I haven't checked them all out."

    So if your system isn't working properly, can we say that we only have so many "cystine bridges" to go around?

    If that's the case, then it seems like all the things you mention (MSH, antidiuretic hormone, oxytocin, ACTH, perforin in NKC cells, human growth hormone) all would suffer.

    My thought then is that by supplementing some of these things, there would be more of the "cystine bridges" stuff to go around to the others.

    (Impressive use of the technical jargon here, no?!? lol)

    If that's the case, then supplementing with things like oxytocin and HGH seems like it might be more likely to allow MSH and NKC cells to form.

    My own experiences with HGH:

    This stuff worked marvels when I was on Famvir, allowing me to increase my dosage of the drug from 250 mg to 1000 mg without huge die-off. This always perplexed me. But if indeed this was allowing me to use "cystine bridges" to form more NKC's, this would make sense.

    (It happened super-fast though. Like within 24-48 hours.)

    I didn't crash when I was using HGH for that purpose.

    What I've found when using HGH and not on antivirals is that it makes me very sleepy. When I first tried it years and years ago (just before Cheney released his comments), I thought this was a bad thing and discontinued it after just a few days.

    I'm more suspicious that this is a bad thing now. I believe that the HGH allows/forces my body to go into "repair mode," channeling my energy into fixing the structural problems that have resulted from my CFS over the years.

    (For instance, without enough Vitamin C, structural problems are going to be rampant. Did you say something about Vitamin C not recycling itself in PWC's recently? That seems to have been the case for me, though my deficiency seems to be finally lessening now.)

    A while back, cuts and bruises were taking me months to heal. With HGH, they heal up very fast.

    I have to presume there's a lot of healing not going on inside my body rather than just on my skin as a result of too little HGH as well. This could be a cause of leaky gut symptom, for instance.

    I don't take this stuff as often as my doctor suggests, mostly because I can't really afford it. And I always would take it kind of scattershot, because it's better if your own body doesn't forget how to make it.

    (Not that my own body is making much to begin with, but maybe that will change.)

    My experience is that the sleepiness (if that's what we call a "crash") is worse when I've not taken the HGH for a month or more. After I've used it several times, the sleepiness on the following days starts to get less....suggesting to me that my body is getting caught up in its repairs.

    So I think it's a good thing for me. I just wish it weren't so hard to get insurance reimbursement for. I'm going to give it one more try though.

    If indeed it might be allowing me to increase MSH production, that would be even more of an incentive to keep using it. I don't know if that makes theoretical sense though.

    I'm not sure what Cheney meant by crashing. I do know that if you're not functioning pretty well with regard to adrenals, HGH is not a good thing to take. (I'm not sure what the mechanism is.) I'm also not sure if (like me) the patients might have started to feel better if they'd pursued it longer and gotten "caught up" on their repairs.

    It may be that only certain CFS patients benefit from it. I've had immensely positive reactions to every hormone I've tried, and it's no surprise that this one would be helpful too.

    Best, Lisa

    [This Message was Edited on 06/30/2008]
  9. acer2000

    acer2000 New Member

    FWIW someone asked the question of what is a desirable level of MSH on shoemakers "message board" recently:

    Also, I tried the methylation protocol for a month or so and it did nothing for me. I also had a test through Dr. Myhill a while back and it measured glutathione. It said:

    GSX-Px 59 U/gHb (67-90)
    GSH 1.57 mmol/l (1.7-2.6)

    Which I guess seems kind of low, but not crazy low. Her suggestion was to take a "reduced glutathione" supplement. My understanding is that taking it orally does nothing. It didn't do anything for me as far as I can tell symptoms wise. But then again, neither did the CoQ10 she recommended.

    So maybe the Methylation block doesn't apply to me? I think the vitamin I take has the activated folate in it, so maybe I already had that base covered?

    Also, Lisa, have you considered just going to see Dr. Shoemaker? From reading the presentations on his web site etc... he sounds like he has a pretty structured procotol he does. Also, are you getting the nasal swab as part of the group of tests?[This Message was Edited on 06/30/2008]
  10. Forebearance

    Forebearance Member

    Hi etn,

    MSH stands for melanocyte-stimulating hormone. According to Dr. Shoemaker, it is a master hormone that controls all the other hormones.

    Hi A,

    Thank you so much for that link! So Dr. Shoemaker says
    "With respect to biotoxin or neurotoxin illness(es), any level less than 35 is too low."

    Wow, so that makes my observation less significant.
    But you could still say that my MSH is not as low as it could be. Maybe it is in the process of coming up.

    That scale for MSH is kind of odd.

    So the methylation cycle block supplements and CoQ-10 did nothing for you. Amazing. Something else is going on with you, apparently.

    [This Message was Edited on 06/30/2008]
  11. Slayadragon

    Slayadragon New Member

    I'm not sure that Dr. S even sees patients who don't have those tests done. You're supposed to get them done with your PCP and then bring them with you.

    Then you meet with him during one appointment and he prescribes his protocol (as described on the Web site). One visit it supposed to be enough, though I think he keeps track of the follow-up progress.

    (I actually ordered all of his new patient stuff last fall, though I threw it away after realizing that it had been contaminated with mold poison in my house.)

    Anyway, I'm not sure that seeing Dr. S would help me that much. Between Dr. B and Dr. G, I will get the tests run soon. It's good that Dr. S is available for a consultation though. (He really should get my data on his files anyway. He's got 6500 cases in his database of test info already, but the more the better.)

    I also think that Dr. S is pretty tied to his own protocol, even as he admits that it doesn't work very well for patients who are more likely to be defined as "CFS." Getting better is seeming to require a lot more tinkering than just using his tools.

    Which is not to say that I'm not really really grateful to him for putting together the toolbox!

    P.S. Dr. B keeps being perplexed with regard to where to get these tests, and I keep reminding him that the LabCorp rep would be so delighted to get his call that s/he would find out all the test info immediately so that he wouldn't have to think about them any more. Hopefully he will do that soon. I might as well have the nasal swab, I think. I had some terrible fast-spreading skin infections, apparently staph, after getting some moles removed last winter. So it would be really good for me to look into this. (Though my hope is that I eventually can wipe out that stuff with high-dose vitamin C IV's rather than drugs!)
    [This Message was Edited on 06/30/2008]
  12. acer2000

    acer2000 New Member

    I had no problem getting the tests done. Labcorp had the MSH as a routine test, and Quest had no problem with any of the ones on his list except for MMP-9, which they had to call the central office and get a different code for. Apparently the code on his website isn't updated, and they have to freeze and send out the tube to a specialty lab. My Dr. just wrote out on a perscription pad the tests and the labcorp or quest catalog numbers and DX codes and they accepted it.

    Getting the nasal swab done is proving to be a real challange. I got my Dr. to phone an ENT who can do the swab no problem, but no labs around here use the API-staph culture technique. Dr. Shoemakers office suggested calling the University of Maryland where they send their cultures and navigating through their system to get to the person who does that test has been not very straightforward. Dr. shoemakers secretary said to just come to MD and have it done... I am trying to avoid that...
  13. richvank

    richvank New Member

    Hi, Lisa.

    It sounds from your experience that supplementing hGH is indeed beneficial for you, and maybe it's because you fixed your adrenals first, I don't know.

    With regard to the cystine thing, I don't think that by supplementing one of the substances that has cystine double bonds one can help out the others.

    The reason is that these substances are made in different cells, so the production of one is independent of the production of another.

    It's not that there is a limited number of cystine double bonds that have to go around. It's that the cells need to have enough glutathione in them to hold the cysteines in their reduced (unpartnered) state during the process of building the protein molecules until the proper time to hook them together in the correct pairs to form cystine disulfide bonds. They are all going to become cystine ultimately, but it's important which partner each one has in the molecule, because that will determine the physical shape of the molecule, which in turn determines how it will mate up with its receptors and other molecules in lock-and-key arrangements.

    So the point is that to fix all of this, it's necessary to get the glutathione levels up in all the cells that make these various secretory proteins. And to do that, it's necessary to lift the partial methylation cycle block.

  14. Forebearance

    Forebearance Member

    Hey, wait a minute!

    I was looking at Dr. Shoemaker's downloadable document called labrefrangesheet. It contains the reference ranges for the lab tests he orders.

    On it, he says the Normal Range for MSH is:
    "35-81 pg/mL "

    On my MSH test, it says the "Limits" are:

    Why aren't these reference ranges matching up?
    I think I'll call LabCorp on Monday and try to find out what is going on. They have a customer service line.

  15. redhummingbird

    redhummingbird New Member

    Well, I had my MSH tested last week prior to starting the simplified methylation protocal.

    It will be interesting to see if it affects it.

    I'll keep you posted.

    Any suggestions on how long to wait before retesting?

    I think someone needs to write a book on the simplified methylation protocol for people with cfs/mold/lyme, etc...

    I have so many questions about it and would love to have a reference guide...
  16. Forebearance

    Forebearance Member

    That is way cool, redhummingbird. It will be interesting to see what your MSH does. Especially if you turn out to have some kind of neurotoxin poisoning.

    Well, my doctor wants me to retest MSH and everything else in 3-6 months. She's not an expert on this stuff, though.

  17. Forebearance

    Forebearance Member

    Well, the LabCorp customer service couldn't tell me why the reference range they use is different from the one Dr. Shoemaker uses.

    So I finally called Dr. Shoemaker's office. The receptionist there (who was not the one in his book), told me that LabCorp has changed their reference range, but that Dr. Shoemaker still uses the same range. He still considers 35-81 to be the normal range for MSH. Then we were disconnected. (Now I think it may have been my Skype that did it.)

    So I guess there is a difference of opinion on what is normal and healthy for MSH.


    It's hard, being a mere patient, to get answers out of anybody. And my doctor doesn't have time to go chasing down questions like this. Sigh.


    [This Message was Edited on 07/19/2008]
  18. Slayadragon

    Slayadragon New Member

    So at 29, your level was a little below what Dr. S would like to see.

    So it sounds like you did get your answer, no? Just that the receptionist was not very polite.

    Based on everything I've heard of Dr. S, that sounds like what I'd expect. I'm not sure that he's much nicer to other doctors than his office is to patients, which could be why he doesn't have more adherents. No wonder he and Erik have such a bond....both brilliant but with no marketing skills whatsoever.

    Considering that you're obviously suffering from mold poisoning (in addition to high mold sensitivity), I would be surprised if your MSH were perfectly normal. How much better it would be without methylation, I'm not sure.

    It will be interesting to see how the level changes over time. Now I wish I had the info to see that myself.
  19. Forebearance

    Forebearance Member

    Yeah, I did get the most basic answer, which at least lets me know that my MSH is low.

    Lol about your comment about Erik and Dr. Shoemaker. I get the impression that his small town medical practice must be overwhelmed by the demand on him.

    Did you mean that you wonder how much worse my MSH would be without the methylation supps? I wonder that, too.

    Yes, it will be interesting to see what my result is on the next MSH test.

    I forgot to add one other thing. Dr. Shoemaker's receptionist brushed off my question "So some people could have an MSH level that is higher than LabCorp's range?" by saying "We never see that."

    Don't some of Dr. S's patients recover and have a normal MSH level? So using Dr. S's range, an MSH level of between 35 and 81? I guess that is a question that Dr. S. would have to answer, not the poor receptionist. I was probably annoying her.

    But I thought I'd share what I found out so others of us don't have to annoy her as well.

    If you do have to call, don't ask her if she's Shannon, because that seems to really tick her off. lol

    The thing that still puzzles me is LabCorp's use of the word "Limits" on their test results. What in the heck is that supposed to mean? It doesn't sound like "Reference Range" or "Normal Range". It is confusing. Have you run into the use of that word on lab tests, Rich?

    [This Message was Edited on 07/19/2008]
  20. richvank

    richvank New Member

    Hi, Forebearance.

    Usually I see "reference range" on lab test results, but I imagine that "limits" probably means the same thing. I think the usual practice is to test a bunch of people and fit the results with a bell-shaped curve. Then the reference range extends from two standard deviations below the mean value to two standard deviations above it. Thus, about 95% of the people would fall within the reference range.

    The important thing is which group of people did they use to set the reference range? You might expect that they would look for "normal, healthy" people. Some do, but some labs just use the population that orders their test, which would seem a little shaky, because people who order it probably are not normal, healthy people. Why would a healthy person plunk down the money? I guess it's a convenient, no-cost way for them to get a reference range, and they probably figure that many of the people will be normal for each particular parameter.

    In the case of the Vitamin Diagnostics methylation panel, I specifically asked Dr. Audhya, the lab director, who he used to determine the reference ranges. He had a good answer. He uses NYU medical student volunteers, ages 20 to 40, nonsmoking, no known chronic illnesses, no fewer than 120 of them.