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Methylation protocol and glutathione

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

  1. Vegas

    Vegas Senior Member

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    Correct me if I am wrong, but doesn't this study just suggest that the caffeine

    is doing just what other stimulants do, they increase dopamine and stimulate methylation on a temporary basis. Does this really result in any net gains, and does this apply to a human with low glutathione. Obviously improvement in lipid peroxidation, SOD activity etc., is desirable; however, I wonder how well this translates to someone who has abnormal methylation capacity. In someone with low glutathione would this have any lasting consequence if they are not correcting the limiting factors. I would have to speculate that there is a consequence to this binge since glutathione resources are finite, and a temporary rise in brain concentration could result in deficits later. At least that is how I have always looked at it; everyone has finite resources, but ours are much more susceptible to the effects of stimulating energy.

  2. Waverunner

    Waverunner Senior Member

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    Well, that's an interesting question. In my eyes 90 days are pretty long for a short term effect but this cannot be excluded of course. Moreover I don't know how long after the last caffeine intake, they measured glutathione. And last but not least we have to ask ourselves if human brains react accordingly.
  3. Dreambirdie

    Dreambirdie work in progress

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    Thanks for this explanation, Rich. The methylB12 has been an ongoing problem for me, even with using the TD-glutathione to assist the flood of toxicity that results when I take more than a smidge. I wish I had the funds to do a lab test to see if it actually causes over-methylation, but since I don't, I am going to opt for the hydroxo for my next round of this protocol.

    This is what I appreciate most about your approach. Being open to what works for each individual is the best way to go.
  4. mellster

    mellster Marco

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    I think this depends on the individual and if it is otherwise well tolerated - if my stomach permits I do drink coffee/espresso in moderation (recommend it on a full stomach) and energy-wise it makes me feel better without crashing later. It could be very well some of the additional supplements for some people in a modified methylation protocol.
  5. Richard Lee

    Richard Lee

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    Thank you, Rich, for patiently explaining the ideas behind your protocol. It's given me much food for thought.

    I'm not sure how many people would be taking "both methylfolate and methylcobalamin at dosages in the several milligrams per day range". I myself am taking 800mcg methylfolate and 10mg sublingual (i.e. perhaps 1.5mg absorbed) methylcobalamin, and I would be curious to know if my testing reveals "futile cycles". Which test is it that would define this?

    I know that Freddd himself is taking doses in the higher range, but he has also titrated it to find the minimum that works for him, and therefore satisfies your "smallest dosage that will do the job". I would be very curious to see Freddd's test results.

    It is true that cancer cells have a voracious appetite for B12. But surely they will get a disproportionate share of B12 even if they are fed conventionally by holoTC instead of by diffusion, due to their higher number of TC-receptors. Perhaps diffusion might even distribute B12 more equitably.

    Also the chain of causation might be the other way around: someone's B12 might have become low BECAUSE his cancer-cells were stealing the lion's share, or because his body ran low levels of B12 deliberately to frustrate the cancer cells.
    William S Beck 1995: "In cancer patients, values of holoTC and RBC-Cbl were subnormal."

    The risk of methyl-mercury is of concern to me. I wish that there were some conclusive research. I would like to experiment with hydroxocbl as an alternative, but I am not sure that I can switch with impunity. Once started on these B12 protocols, it often seems to be a case of "crash through or crash".

    The other concern that I have about B12 therapy, which applies equally to hydroxo- as well as to methyl-cobalamin, is the possibility of an immune-reaction to B12 itself. If high supplementation is likely to saturate the body's TC and HC, there is a risk to someone (like me) who is prone to allergies that he will eventually develop an IgG-IgM-B12 immune-complex. I refer to two recent papers:
    2006 Markedly Increased Vitamin B12 Concentrations Attributable to IgG-IgMVitamin B12 Immune Complexes
    2010 An IgG-complexed form of vitamin B12 is a common cause of elevated serum concentrations

    The immune-complex shows up on conventional B12 tests as an elevated (and misleading) level for serum B12. The long-term implications are unknown. Even the saturation of haptocorrin is problematic, because the consequent proliferation of inactive B12 analogs might interfere with B12 metabolism and cause "setbacks".

    Altogether there is a daunting number of unknowns with B12 therapy. Yet inaction is not an option. I'd rather take my chances with a shark-infested ocean than remain on a burning boat. I appreciate that you and Freddd are helping us navigate treacherous waters.
  6. richvank

    richvank Senior Member

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    ***Hi, Richard.

    ***Yes, I guess we all have to do risk-benefit analyses in the light of our own situations. I hope you will be able to successfully dodge the sharks as well as the fire!

    ***Best regards,

    ***Rich
  7. Freddd

    Freddd Senior Member

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    Hi Rich and Richard,

    A few comments on the things said here. The research that speaks of "B12" without specifying what cobalamin is being considered is speaking of cyanocbl by definition. Methylb12 and adenosylb12 are both "b12 analogs"

    Methylb12 is being researched for it's anti-cancer properties. Methylb12 is being researched for it's lack playing a role in the cause of a dozen or so cancers.

    B12 deficiency is known to cause at least two autoimmune diseases and is suspected as a cause of others.

    I am not against testing. I spent out of pocket (not insured) approximate US$200,000 over 20 years in the dollars of the time for testing and treatment based on that testing. It was 100% a total waste of time and money. Testing and treatment based on studies done on cyanocbl and hydroxycbl don't have relevant interpretations and lead the physicians to wrong and ineffective conclusions.
  8. L'engle

    L'engle moderate ME

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    Hi Freddd,

    Which autoimmune diseases are linked with B12 deficiency? Thanks!
  9. Freddd

    Freddd Senior Member

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    Hi L'engle,

    Hashimoto's thyroiditis. If it is still in active phase there is a little evidence that it can reverse with the mb12. The other one is the process that develops antibodies to intrinsic factor. Some others are suspected. Mb12 (and Metafolin) deficiency causes hyper-responsiveness in multiple ways (MCS, allergies, asthma, neurological, smell, taste, sensation, pain, startlement) and causes havoc with the immune system.
  10. richvank

    richvank Senior Member

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    Hi, Freddd and the group.

    For what it's worth, my hypothesis for Hashimoto's thyroiditis in ME/CFS is that glutathione becomes depleted in the thyroid gland. Normally, the thyroid makes hydrogen peroxide for use in oxidizing iodide ions in the pathway for making the thyroid hormones. Normally, the thyroid cells themselves are protected from damage due to this self-produced hydrogen peroxide by glutathione. When it becomes depleted, the hydrogen peroxide is able to oxidize proteins in the thyroid, and the immune system views them as foreign substances and mounts an autoimmune attack against them. The basic model for this is due to Duthoit, et al.

    Glutathione depletion can result from B12 deficiency because methylcobalamin is needed as a cofactor for methionine synthase. If it becomes depleted, the methylation cycle drains metabolites into the transsulfuration pathway, and the entire sulfur metabolism becomes dysfunctional, including the synthesis of glutathione, and this precipitates Hashimoto's thyroiditis in the thyroid gland.

    Best regards,

    Rich
  11. Freddd

    Freddd Senior Member

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    Hi Rich,

    Thank you for the insight into possible mechanisms. A hydrogen peroxide mechanism appears to be at work in the whitening of hair from b12 deficiency as we have previously discussed. Would this basically be the same or similar mechanism with the H2O2? Could there be a similar mechanism at work in other autoimmune responses including parietal cell and IF antibody production? I'm thinking of Lupus too among other things.
  12. redo

    redo Senior Member

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    Interesting thread. I have heard of several people whom have had great effects from glutathione (I.V. not oral, because of the hardship of getting high doses orally). Many feel it within the day, if not hour. Anyone who knows someone who's done glutathione IV? I think K. De Meirleir gives suppositories with it.
  13. leela

    leela Slow But Hopeful

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    Redo,
    I have done IV GSH. I get equally good results (if not better, due to being able to administer as needed) from the TD GSH available from Lee Silsby compounding pharmacy. You need someone to Rx it, but the pharmacists are very helpful in assisting the prescribing physician who may not be familiar with it (most aren't.)
  14. redo

    redo Senior Member

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    What's TD GSH? Are they tablets or suppositories?
  15. richvank

    richvank Senior Member

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    Hi, redo.

    The "TD" stands for transdermal. It is applied to the skin.

    Rich
  16. lucyhem

    lucyhem

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    how to assess what kind of B12 will be best for me

    I don't think that the HydroxyB12 is working for me in the SMP. I might have a slight adverse reaction to it or the fillers. I have had that reaction in the past to sublingual B12 as well. I have also had a months trial on methylB12 injections several years ago for neuropathy from Wellness Pharmacy, before SMP, without much response either way. I do suspect that B12 is important for me as I have many nervous system symptoms and have this feeling at times that my cells are starving that the methylfolate seems to address. How do I assess, make some trials about what kind of B12 to try? I will be getting the Great Plains OAT test. Will that tell me more about B12 use? Does it make sense to do that while I am a month into the SMP protocol? Or should I go off of the protocol for a short time so I have a baseline?
  17. hixxy

    hixxy Woof woof

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    I've tried TD glutathione in the past and found it was hard to get a decent amount into your system this way. Has anyone tried liposomal glutathione as an alternative?
  18. richvank

    richvank Senior Member

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    Hi, Lucy.

    It is difficult to sort out whether there is a reaction to the supplements or whether the detox system is mobilizing toxins because it has started to function better as a result of the supplements. I am currently suggesting that people stick with the SMP for three months before deciding whether it's helping or not. If it doesn't seem to be producing positive results by three months, then I think something needs to be changed.

    When you had the trial on methyl B12 injections, were you also supplementing active folate, such as methylfolate? If not, this may be the reason you did not experience a response. It's necessary to supplement B12 and folate together to lift the partial methylation cycle block. From what you've reported, it does seem that you receive a positive response to methylfolate.

    The easiest thing to do to try to determine which B12 is best for you is to try one for 3 months, and if it isn't helping, try the other.

    If you are planning to run a urine organic acids test, I would recommend the Genova Diagnostics Metabolic Analysis Profile, because it has both Figlu and MMA on it. It will give indirect information about the status of your methylation cycle, folate metabolism, and glutathione. However, it will not tell you which B12 form would be best.

    Dr. Amy Yasko offers a nutrigenomic panel, and from the results for the COMT and VDR Bsm SNPs, she determines whether hydroxo B12 or methyl B12 is better for the person. I don't know of published experimental support for this approach. She bases it on her experience.

    Best regards,

    Rich
  19. lampkld2

    lampkld2

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    Rich,

    Do you know or know where I can find the guidelines she uses with regards to this? Choosing MB12 vs HXB12 based on Snps? I have 23 and me, COMT ++, Still trying to figure out VDR.

    Thanks
  20. Freddd

    Freddd Senior Member

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    Hi Lucyhem,

    I have also had a months trial on methylB12 injections several years ago for neuropathy from Wellness Pharmacy, before SMP, without much response either way.

    A large percentage of injectable mb12 is worthless or near worthless. Many pharmacies expose it to too much light while mixing so that what you get is photolytically decomposed mb12 otherwise known as hydroxcbl. Furthyer moast people then further degrade it by exposing it to light. It should be kept in the frig wrapped in foil so it can be drawn without exposing it to light. Further the syringe must be wrapped in foil. Even if it is well protected from light about 80% of the original crystal is such that it is zero to 2 stars just like the sublingual mb12. Further if there is a missing cofactor, Metafolin about 80% of the time and including zinc, magnesium, Vit D, adb12, l-carnitine fumarate, SAM-e, TMG and maybe some others, the mb12 may be a complete non-starter. All of these may need to be in place along with A, D, E, C, POATASSIUM and others in order for mb12 to actually work. The only 2 brands of sublingual mb12 that can be counted on to work well are Jarrow and Enzymatixc Therapy and they need to be kept in tissue contact (unter tongue or lip) for 45-120 minutes or more. And one more set of things can prevent mb12/adb12/Metafolin from working; glutathione, glutathione precursors, whey (especially undenatuered), folic acid, folinic acid and for a few, vegetable food source folate. So it is a little more complicated than merely figuring out "which" b12 you need. That is a question that will almost always give you a wrong or incomplete answer just based on how it is phrased and the assumptions behind that. Most people have separate responses to each of mb12 and adb12.

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