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THE STAGES OF METHYLATION AND HEALING

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Freddd, Feb 7, 2013.

  1. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    1) Look at Rich's latest revised protocol: http://forums.phoenixrising.me/inde...ation-protocol-august-25-2012-revision.19050/ He made very minor changes and he wrote this just a few weeks before he died.

    2) As far as patients healed by using hydroxycobalamin, note Dr. Neil Nathan's report of his trial with Rich--86% inproved: (http://www.prohealth.com/fibromyalgia/library/showarticle.cfm?libid=16138)

    3) And working in the industry yourself? I believe you have stated that you worked in computer data analysis in the health insurance industry. My request would be that you differentiate between personal research on yourself and those you are in contact with and public research that has been vetted and that we can read for ourselves.

    Sushi
     
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  2. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Here is a post from Rich suggesting why Freddd may respond differently to forms of B12 and methylation protocols and thus differ in his recommendations. I am reposting this just to highlight that our differences (genetic and otherwise) make a huge difference in our responses and thus the treatment appropriate for us:

    richvankSenior Member




     
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  3. Freddd

    Freddd Senior Member

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    And I actually took those things that were correct to heart and modified and revised and filled in holes. I filled in a lot of empty spots. All in all, I'm just trying to get this out. People will have to make what they want of it. There are tremendous variations because a whole lot of different problems are lumped together under a a few names and not understood precisely because of the blindness induced by decades of research based on a serious laboratory mistake. Some of Rich's specific objections were very helpful. I never expected that Paradoxical folate deficiency would be at the heart of the problem for me and sizable percentage of people here. I learned more than half of these things listening to Rich and a lot of helpful people here who asked the questions and presented details that lead to understanding. Rich never answered most of my direct questions that questioned his interpretations in writing for publication. We did share data and discuss the implications. For instance he kept insisting that I must have a rare genetic situation based on an early misunderstanding despite confirming without a doubt that the area of difficulties were becasue of folate problems shared with 20%+ of the population, and my CyCbl and HyCbl responses were normal. I would much prefer he were here speaking for himself.

    I'm trying to do something no one else is doing or has done, describing this family of diseases as a system. What I am working towards is a questionaire that can detect each of the variations, whatever they are. I very much hope that a whole lot of people find it understandable and useful in understanding things, I've tried to keep it simple. but it can't be explained linearly. It's structure isn't linear. It isn't filled with answers. I would very much suggest printing out the whole thing and put it in front of their doctors. And it will be revised and the kinks worked out.

    I worked in the group health business from about 1980 onwards and supervised and evaluated doctors, in an insurance context (financial, fraud, questionable practices, lack of hand washing, patient complaints and so on) and am well aware of the many problems in finding a knowlegable doctor and so a major function was education. I don't know that any doctors will pay attention, but then I would be surprised if anybody here has ever been allowed to tell ALL their symptoms to a doctor before being cut off. If someone has then that is a most unusual doctor, just for being willing to pay attention long enough to get the whole story. I was fortunate in the end. I found a doctor that was willing to talk to me an hour at a time and get the whole story, instead of play "blame the patient" and monitored me to keep me out of trouble which he never had to do except for alerting me to potassium problems. The big story in all this is the corruption (in a technical way, like a corrupt database, not anything crooked) of the medical-industrial-research industry, which I will get to. And I bet lots of others here have found that and said that in their own ways. Much of the "missing money" we were hired to find had ended up in the insurance comnpany's pockets via lack of data validation and flawed reporting requirments which were written by the very people who were supposed to be auditing them and caused the data to be missed. The system was unintentionally corrupt. Millions are sick because of this corruption I am writing about. Be in good health.
     
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  4. Freddd

    Freddd Senior Member

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    Hi Suchi,

    I designed and wrote HMO software systems. In that I worked every area including provider rating for 2nd opinions, aberrant treament patterns that need to be checked out, fraud detection, consulting in plan design, patient dissatisfaction, office audits, evaluation of in office infection problems and lack of hand washing, patient medical advocate (I worked for the Plan trustees, for the insureds), questionaires, claims forms redesign to minimize errors, databases, organization of data for easier understanding (meaniful reports) and a whole of of things. Data analyst was a small part of what I did. I did a lot of private research becasue I would be long dead if I had waited for it to happen. So would my kids. I did a lot of private research, and lots of reading of everything I could get my hands on. Shortly I will post a summary of all the private research I did do over the past decade, as I get a chance. I didn't have time to do a lot of things the way I would have preferred. I went on as soon as I had the answers I needed for healing. As Edison said it "99% persperation". I got the answers and looked for the next set. The order was dictated by whatever stopped healing, a bottom up appoach. I hope you enjoy them when I get them posted. Be In Good Health.
     
  5. Freddd

    Freddd Senior Member

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    Hi Sushi,

    One problem with that whole business. Rich was 100% wrong as regards my handling of inactive cobalamins. The do correct my MCV IF I have l-methyfolate. I have normal range inactive cobalamin processing. This re-evaluation occurred when when I found my folate problems, with Rich's suggestions. Every piece of logic and reasonaing based on my having faulty cobalamin processing with a rare genetic condition is itself completely flawed. I have a common folate polymorphism. It was the shortage of usable folatge that caused my MCV and other problems. The b12 was unusable because of too little active folate. You can believe what you wish but if you believe anything based on that idea of my having faulty Cbl procssing it is assurredly incorrect. I tried to tell Rich that over and over, both posting and by personal email. He never chose to change his statements or his understanding to account for that. It was data he refused to incorporate. I was incorrect ever think that might be a possibilty based on ignorance of the folate situation. Be in good health.
     
  6. dbkita

    dbkita Senior Member

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    Thank you for clarifying this. I reverse-engineered the 40% number from your post since it was no clear in your text that you meant 1000 mcg absorbed across both Meb12 and Adb12. I interpreted as each 1000 mcg absorbed.

    Yes I am certain it is not induced paradoxical folate deficiency as you put it. Folinic acid has similar effect to 5mthf for me though maybe not quite 1:1 ratio. I have only have the MTHFR A1298C deficiency heterozygote. I take plenty of P5p to saturate the THF to methylene intermediate conversion and plenty of R5p to saturate the methylene intermediate to 5mthf production. Besides I have not taken folinic acid in 7 months and had the same potassium issues to differing degrees even after 2.5 years on the methylation protocol. I also fastidiously avoid folic acid in all ways (no fortified foods, or supplements that contain it, paleolithic diet, no grains, etc.) and have been observing that restriction for 3+ years now. I hope we can agree "startup effects" are not an appropriate term 30+ months into treatment.

    Personally I look back now and realize that being on 800 mcg 5mthf / 800 mcg folinic acid and then later 1600 mcg 5mthf combined with TMG, and lots of P5p and (especially) r5p along with 5000 mcg of sublingual b12 (Jarrow's before it changed in Aug 2012, then Enzymatic therapy) was in some ways useful and in other ways counterproductive. Adding Source Natural adb12 nine months ago only complicated things at that time.Things were out of control when I added SAME 400 and even 200 mg on top of the above list for six months. That is when my potassium need went from strong to absolutely bonkers.

    The reductions in homocysteine were not very significant for me whereas the abnormally high levels of catecholamine production, the insomnia, the high potassium requirement, etc. should have been obvious warning signs but I pushed through like a trooper thinking things would normalize ... they did not. Also at no time did small variations of the protocol ever increase muscle capacity or reverse my catabolic state into an anabolic one (though I grant maybe carnitine is a missing issue for that aspect). My MCV has never budged below 95-96 even when I went to 10 mg mb12 for a long stretch. My B12 levels are beyond the measurement range and I take zero cyano or hydoxy b12 only methyl.

    I did see positive signs with energy levels, some neurotransmitter support, lower histamine levels, etc.

    Fortunately when recognizing that I was taking too much (sorry you don't like the word overmethylation though I don't know what you would call such effects since startup effects is ludicrous in my own case history) and removing SAMe, removing TMG, going to 800 mcg of 5mthf from 1600, cutting my R5p and P5p to more normal amounts, and going to 2000 mcg meb12 sublingual and 2.5 grams adb12 sublingual ... things got MUCH better. I still had energy but it was not destroying my sleep, my personality, and was far more controllable .... and my hypokalemia went away. It is ironic that the way I discovered this was by accident. I simply took vitamin C at some point with my Folapro tablets and since ascorbic acid destabilizes 5mthf in the gut within a 20 minute window, suddenly a number of long standing negative symptoms eased up.

    I do no think the explanation for the clinical need of high potassium with high methylation support is well explained by the proposed cell growth argument put forth by Rich Vank. The basic accounting of high potassium required over a long period of time does not fit with what in reality is at most a small fractional amount of net cellular turnover. And besides I would strongly argue that most cell growth need not have anything to do with real healing. On top of this apoptosis also occurs with regularity when growth is high ... hence a steady state more or less.

    That being said for me personally for my case history the argument is hopelessly flawed. I base this simply on excretion data and intracellular RBC values. When I had to supplement 4 grams a day and eat 6-7 grams a day and was excreting 250 mEQ per day I could not reverse the hypokalemia and my intracellular numbers stunk. I lived like that for over six months at my worst and to various degrees of that for an additional 2 years before that. It was so bad I literally chose my daily diet based on how much potassium I could ingest since using time released KCL was causing a lot of GI damage and reflux.

    After backing off the aforementioned levels, I have reversed hypokalemia, my intracellular rbc numbers are marginally up, I take 1200 mg a day in supplement form and eat 5-5.5 grams a day (which I think is reasonable).
    And lo and behold my 24 hour excretion numbers dropped 30-40%. I only mention this since the cell growth theory cannot explain the excretion numbers since I was (a) absorbing potassium, (b) it was not going into my cells, and (c) I was dumping it in the toilet as urine which means it hit my bloodstream. Net cell growth would retain potassium in the body That is not consistent with my data. Hence I think the theory is flawed. I suspect that activity of the renal Na-ATpase pumps or even reduction of 11 beta HSD1 activity allowing cortisol to exert mineralcorticoid effects are more likely candidates. But that is a separate discussion.

    I will choose to disagree on this point but based on your other posts I don't think I will convince you otherwise :)

    I have not supplemented hyCbl or Cycbl in any fashion. My only source has been Meb12 which 5 years ago brought me from low normal to above measurement range in 3 months for serum B12. Since then I am saturated in the bloodstream with B12 so deficiency is not relevant.

    TMG made the neurotransmitter effects worse which is consistent with the property that BHMT stimulation results (for unknown reasons) in preferentially more norepinephrine vs dopamine based on metabolite studies. AdoCbl supplementation induced temporary fatigue spells when I was at the higher methylation level, now at reduced levels the exact same amount of adob12 gives me positive energy. I have been on 600 mg Alpha Lipoic acid for eight year, though ironically I have benefited of late switching to 300 mg R-ALA but that has been only in the last two weeks so is not relevant to the aforementioned longer term issues.

    I have yet to experiment with L-carnitine fumarate. I will try it soon though I have been reluctant since at high doses acetyl-l-carnitine is one of the best natural agents to block nuclear hormone receptor binding of T3, setting up a vicious cycle for hypothyroid patients (a fact which is well known and verified multiple times over in the research community).

    Please remember one of the primary effects of methylation is not merely energy production, neurotransmitter production and regulation, protein synthesis or its bridge to other biochemical cycles ... but what is often overlooked is its direct impact on gene expression and gene regulatory networks. High enough concentrations of SAMe for example can silence signaling for many expression products. This is standard molecular biochemistry. That is both the promise and price paid when using methylation treatments since such a mechanism gives direct access to a an unbelievable number of reactions.

    So while you may not like the term overmethylation, I would argue the term "startup effects" is of limited application for some of us. So at least for me overmethylation is as good a term as any to use when the amount of methylation is excessive in terms of its impact on many facets of a person's life. Sadly it took me 2+ years to learn this the hard way. Fortunately my inadvertent accident with vitamin C and further confirmation with extra supplementation of niacinamide confirmed what was transpiring. I will try the carnitine though. That could be a missing link of great importance to me.

    That being said I want to thank you for your empirical treatment guidelines since trying to get a handle on the clinical impact for some of the different protocol variants is very difficult when aimlessly experimenting on yourself only. Why I liked your staged guidelines is it is pretty clear different people need different treatment regimes. God bless :)
     
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  7. EastWest

    EastWest

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    Thanks to all who have posted as I have learned a ton over the past months. I have great respect for Rich and learned a great deal from his video, powerpoint and his posts. I regret a lot not being able to discuss my case with him. Also, I agree with doing these protocols under medical supervision (which I am doing) and that every case is unique.

    Yet the approach that is working extremely well for me so far is Freddd's. Thank you, Freddd! (And I am not a family member or friend, nor have I corresponded directly with Freddd at all so far.)

    I am needing 35-40 mg per day of injected MB12 which I divide into three injections. This fits exactly with Freddd's post above. I need 60 mg a day of ADB12 or more right now, and am experimenting with how to try to get my absorption higher. I take 15 mg deplin which I split into 4 doses. I do need high amounts of potassium at times, and use prescription strength powder. I also take acetyl carnitine (LCF stopped agreeing with me), a few other amino acids, extra B2, magnesium glycinate, and some other vitamins and minerals.

    I'm celiac (probably since childhood but diagnosed 6 years ago) Hashi's, and have chronic lyme. So while I fit the criteria for CFS, maybe I am not a typical case. The carnitine has not had a noticeable effect on thyroid for me.
     
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  8. Freddd

    Freddd Senior Member

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    Hi Eastwest,

    I just have time for a short reply here. I would be interested in hearing how LCF stopped agreeing with you. Stomach upset? Another of the mysteries in all this is why so many people don't find ALCAR effective. As the body is supposed to be able to change the carnitines around for various purposes, and the mitochondria specificaly use the LC fumarate. I glad that the ALCAR works for you. It is more easily available. Some people swear by the tartrate and The liquid freebase carnitine has worked for everybody that has tried it and told me. All the best reports come from brands derived from the Sigma Tau made carnitine. The liquid freebase form seems to wrok well for microtitration. If anybody has answers about the hows and whys of carnitne I would be very interested in hearing them.

    How do you take the AdoCbl and what brand?

    As far as typical goes, for those doses you clearly have the problem of getting the cobalamin into the CSF/CNS sufficiently. How long have you been at it? Do you take alpha lipoic acid? That can increase efficiency in the AdoCbl/carnitine area according to some studies. Good helath to you.
     
  9. EastWest

    EastWest

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    Its hard for me to explain about the LCF. I had a strong response to it initially. Then I started struggling with symptoms but I don't recall specifics. It seemed to be the LCF, so I dropped it for awhile. I then started the ALCAR in a powder form and had major start-up, now that is stabilizing and I am hopeful that I can stay on this powder form just fine.

    I have tried both the Source Naturals and Anabol ADB12. Both work the same for me. My current experiment at the suggestion of my doctor is to take an ADB12 with a drop of DMSO liquid. My first impression is that it is more than doubling my absorption.

    I started working on this last June approximately. Finally got my doses up into the current range in December.

    I take R-lipoic acid, 300 mg a day in 3 doses.
     
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  10. Linda828

    Linda828

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    You first post expressed almost exactly my sense, East West, much better than I could have. It is good to know all the pitfalls and benefits people can experience on this protocol. It helps me to be watchful of danger signs. So far, though, Freddds protocol has worked for me where nothing else has. I’ve tried most everything over the last 20 years.

    The basic supplements in my daily regimen are 7.5 mg MeCbl injection (preservative Free), 10 mg of dibencoplex SL under the lower lip, 5 mg of Thorne MTHF, 500 mg/2Xday L-Carn-Fum or ALCarn pure powder form, and potassium gluconate as needed. What has really amazed me, besides the many cognitive and physical improvements, has been the lack of any negative reactions to these substances at such high doses. I’m normally hyper reactive to everything. Other supplements come and go due to this.

    I suppose I’m not the typical CFS profile either. I was diagnosed with autoimmune pernicious anemia last fall. That causal route of B12 deficiency probably largely accounts for a life of spiraling down into progressive chronic illness. It became manifest with IBS at 12, turned to CFS at 19, and finally developed into MCS at 29. What predominately remains after 8 months of high dose B12 is the MCS. I heard you, Freddd, that this could indicate a need for more MTHF. I’m starting to titrate that up.

    I came across Rich’s videos shortly after his death. They helped me to put together many pieces of the health puzzle and I could also see what a gold mine of information and human compassion he was. I felt much grief for the loss of his presence here. I’m glad for all the wisdom he has left in his various posts.

    Blessings
    Linda
     
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  11. LisaGoddard

    LisaGoddard Senior Member

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    Hi, Just to add my bit. I have been doing Fredd's protocol and have had results. The methlyb12 and folate deal with the terrible inflammation symptoms that I have had for so many years. I have to say that I am taking 30mg or more of the folate (MTHF). I always know when the hour is up and I need my next dose because my throat starts hurting, ears itch and nose runs. After taking the folate, the symptoms quickly subside again.
     
  12. Freddd

    Freddd Senior Member

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    Hi Eastwest,

    A lot of people have expressed an interest in finding out about the effects of DMSO in this way and have performed several experiements. You are the first with such a positive success that I have heard of. I had a similar doubling of effect when I went to Anabol and a lot of folks have reported that and speculated that it is the Boron, which I am still trying to chase down. That was the first differential effect AdoCbl experience I have had other than the first two doses and the first 50mg dose after the glutathione, all different brands. Finding the working balance is difficult. Keep following the clues. As I have mentioned before I am ALWAYS doing trials to see how things work, comparing brands, doses, timing and order. I have found that a 4000mcg Metafolin dose 1 hour before starting absorbing the MeCbl and AdoCbl increases retention substantially.
     
  13. Freddd

    Freddd Senior Member

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    Hi Linda,

    Good to hear you are doing so well. I would assume, by your normal response to LCF or ALCAR instead of hypersensitive that you don't have chronic anxiety as a symptom. When that is present is typically when people have the most intolerable reactions to any of the Dealock quartet, but especially AdoCbl and LCF. It was Rich's answers, advice and videos that lead me to think that you and I and others like us with childhood symptoms as you decribe are suffering from paradoxical folate deficiency and that it is the folate deficiency that leads to b12 deficiency which then combined leads to hyperreactions of many kinds including autoimmune and MCS. Be in good health. I am about to post another reply with a lot of folate insufficiency details in it.
    .
     
  14. Freddd

    Freddd Senior Member

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    Hi Lisa,

    With the pulblication of Carmen Wheatley's GIANT GORILLA ... ADENOSYLCOMALMIN paper, link elsewhere on the thread, Perhaps AdoCbl could make a big difference for you. I hope you can find some more clues in all this. Also, I am about to post more detail on the paradoxical folate deficiency and the TIMING of L-methylfolate that allows me to use a total lower dose by taking into account the short serum half life.
     
  15. Freddd

    Freddd Senior Member

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    Hi Dbkita



    I find that I need to respond to a piece at a time to do it right. It’s good of you to participate in a stimulating dialog. Thank you. Perhaps a change of understanding will give the clues you need to work it out for yourself the desired balance with healing. Just give this the possibility of a willing suspension of disbelief until this whole thing can be laid out.



    Yes I am certain it is not induced paradoxical folate deficiency as you put it. Folinic acid has similar effect to 5mthf for me though maybe not quite 1:1 ratio. I have only have the MTHFR A1298C deficiency heterozygote



    The only reason I mentioned that is that there is kind of donut hole induced folate insufficiency. It occurs usually in the startup phase when a person has taken doses of a folate effective for them that are enough to start up a whole lot healing but not enough to maintain it. Then a person develops any number of the folate insufficiency specific things, often angular cheilitis, acne type lesions on scalp and face especially, IBS, mood changes, and such. It is not severe like a methyltrap shutoff or glutathione induced methyltrap. A certain number of symptoms overlap with the hypokalemia. When more effective folate is added then those things heal, promptly.



    Then usually the need for potassium goes up in a spiral with the folate. One of the things I have found is that unless a person actually trials L-methylfolate they don’t know if it will actually work better for them. It is very clear that the various polymorphisms are only weakly linked to the effects I’m speaking of. There is a big gap in the interpretation. People that rely on those tests for choosing folate don’t generally have the effectiveness that a person who has trialed theme. They are poor predictors of response. These tests are done in a population which chronic deficiency conditions and the meaning is obscured by that. In at least some of the testing the corruption of the system is evident, the norming population is suffering the effects caused by the lesser activity of the inactive vitamirs and more of the inactive vitamirs are given trying to adjust the test results. As a result a very simple test has had the range of alert for MCV and other measures move in to abnormal territory and that is now “normal”. About 30 years ago > 92 or 93 was alerted. About 15 years ago it moved to > 96 or so. Now it is as high as > 102 depending upon the lab. I talked to a lab rep (labs are, from where I worked, a provider of services). I was told that with the average having moved up to > 96, they adjusted the upper limit to > 100 (2 standard deviations?) so they wouldn’t have to “alert all the tests and have the doctors ignore us”. That is a system corruption. That establishes these deficiency diseases as “normal”.





    Another factor, at least with L-methylfolate is a short serum halflife, about 3 hours. I normally take 4 doses a day. Distributed across 4 doses, first thing, last thing and 2 meals I get by on 16 mg. At two doses a day I need 30mg daily to have the same effect.





    With folic acid plenty of research has indicated that approximately 20% of USA population can’t convert folic acid to L-methylfolate at all, 30% can do so to more limited degree and 50% to the biological capacity limit of approximately 800mcg/day. I don’t know what the comparable



    What can apparently happen, according to many researchers, though I have seen no research supporting it directly, is that folic acid can block the folate absorption and distribution mechanism. That appears to be supported empirically. Many a person taking 400 mcg of folic acid and HyCbl or CyCbl has no folate insufficiency symptoms.



    1. Then the person increases to 800 or 1200 or 2500mcg of folic acid. They start getting folate insufficiency symptoms.

    2. The switch to MeCbl/AdoCbl and start getting folate insufficiency symptoms.

    3. The add 200-800mcg of L-methylfolate and all sorts of epithelial tissues start visibly healing, potassium need goes up and “donut hole” folate insufficiency starts as the Metafolin starts more healing than it can maintain and folate is directed away from some of the epithelial tissues.

    4. Folic acid appears to compete directly with L-methylfolate in the absorption and transport systems. L-methylfolate must be taken at a high enough dose with each meal as well as other times per day in order to compete. If Metafolin not taken with meals then the folates in the meal or other supplements taken with food dominate all day and can trigger a person in folate insufficiency. Folic acid appears to clear sufficiently in 24-48 hours for l-methylfolate to have an effect again.

    5. Folic acid appears to be most effective at lower doses and effectiveness turns negative as doses increase. This causes all sorts of unreliable, unrepeatable, frustrating, conundrums etc related to interpreting folic acid research. See other post for the reasons folic acid doses is a poor predictor of effects. The results of adding folic acid to food supply (white flour) for neural tube defects was “disappointing”. It is unknown how many additional cases it caused, bringing the returns well below the expected reduction.

    6. Folic acid is dependent (enzyme and ATP and methyl groups) upon the Deadlock Quartet being present to be converted to l-methylfolate.

    7. Folinic acid competes for absorption.

    8. Folinic acid in veggies or supplements, above the level that can be converted to l-methylfolate by the body appears to be able to block the system same as folic acid does causing folate insufficiency symptoms. This appears to be quantity related at least. It appears to take folinic acid about 48-96 hours to clear sufficiently after blockade has been established for l-methylfolate to be effective again.

    9. Folinic acid is dependent (enzyme and ATP and methyl groups) upon the Deadlock Quartet being present to be converted to l-methylfolate.

    10. Folinic acid and folic acid both only can produce as much l-methylfolate as the keyhole will let them. When more l-methylfolate is required than the body can produce from folic and/or folinic acid, folate insufficiency symptoms appear





    The only place where the various polymorphisms come into play in these terms is at what level is the body maxed out for conversion. People that become depleted methylators, those who have been taking methyl competing vitamirs instead of methyl donating vitamirs can watch effectiveness wear off over time and folate insufficiency symptoms appear in many cases. This is the Deadlock Quartet again. Again, it is quite unknown if polymorphisms matter at all in this. It is this “wearing out of response” that was so common in research that what should be GOOD results were viewed as placebo effect, leading to incorrect conclusions.



    Folate insufficiency symptoms can be caused by any number of medications. They can be caused by some herbs.



    Glutathione, NAC and sometimes Whey can cause sudden onset of the most severe folate deficiency symptoms if they are not already present, as a result of the “methyl trap”. It typically starts with inflammation and rapidly add other symptoms. If you are feeling good methyltrap onset feels like that mysterious severe flu like or “viral” disease that starts or worsens FMS, CFS and ME. If a person already has these symptoms severely there is no noticeable change





    Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with cyanocobalamin it is very common with methylb12 and adensosylb12 and less so with hydroxycobalamin..

    IBS – Steady constipation , Nausea, Vomiting, Paralyzed Ileum, Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness, Abnormal heart rhythms (dysrhythmias), Increased pulse rate, Increased blood pressure, Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.

    Group 2a - Both

    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation

    Group 2b – Either or both

    Headache, Increased malaise, Fatigue

    Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency

    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.



    Group 4 - Hydroxycbl onset, degraded methylcbl onset, methylcbl after photolytic breakdown onset.

    Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.



    Group 3 symptoms, induced paradoxical folate deficiency or insufficiency are corrected quickly with titrated doses of Metafolin, methylb12 and adenosylb12. If glutathione (precursors) are the cause then larger doses of Metafolin, 7.5-15mg,or maybe more are needed. Different tissues are affected at different levels of methylfolate, it comes or goes in stages. Very strong dose proportionate characteristics are present. Serum folate levels may be high or even very high despite Metafolin responsive deficiency/insufficiency symptoms.

    Group 1 symptoms respond readily to potassium. The symptoms and response to potassium may occur at a serum level of 4.3 or less.





    INDUCED HYPOKALEMIA AND FOLATE INSUFFICIENCY DECISION TREE

    Note: ATP startup is not yet in this tree.

    IF taking Glutathione, NAC, Cerefolin-NAC, whey, all glutathione or glutathione precursors

    AND often sudden onset of several group 3 symptoms (“Detox”) maybe in a sequence, ie pain and inflammation the first day, cheilitis occurs on day 2-3 and IBS on day 5-6, plus any group 2 symptoms. Symptoms increase for weeks or months and can vary from mild to extreme.

    THEN Induced Paradoxical Folate Deficiency onset. B12 deficiencies follow in a week for methylb12 deficiency symptoms and several weeks for adenosylb12 deficiency symptoms. None of the other supplements can overcome the effects of glutathione or NAC.

    ELSE - all other conditions

    IF injecting b12

    AND itchy bumps and acne type lesions appear mostly on scalp and face but not exclusive

    THEN B12 was hydroxycbl OR photolytically deteriorated methylcbl OR cyanocbl, Lesions can be reversed in days with methylcbl injections not exposed to light at all.



    IF starting or adding methylb12, adenposylb12 or hydroxycbl, AND OR Metafolin (perhaps 80%)

    AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2

    THEN this can be the onset of Hypokalemia triggered by sudden widespread healing onset. This usually occurs as soon as methylation therapy starts widespread healing process by allowing DNA replications with methylb12 and methylfolate.



    IF adding adenosylcobalamin AND OR L-carnitine fumarate AND OR SAM-e to program (perhaps 50%)

    AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2

    THEN this can be the onset of Hypokalemia triggered by sudden healing and /or muscle growth. This usually occurs when the person has experienced muscle shrinkage perhaps from decades of inactivity, as soon as these supplements step up mitochondria functioning.



    IF adding or increasing any of Vitamins D, A, E, or C, magnesium, zinc (perhaps 10%)

    AND on the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2

    THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folinic acid is the primary form found in vegetable source. In some unknown percentage of people who appear unable to convert folinic acid adequately to methylfolate the accumulating unconverted folinic acid can actually block the methylfolate.



    IF starting or increasing folic acid

    AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2

    THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folic acid is the most oxidized form of folate that anybody can use. In some unknown percentage of people who appear unable to convert folic acid adequately to methylfolate the accumulating unconverted folic acid can actually block the methylfolate.



    IF starting or increasing folinic acid

    AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2

    THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folinic acid is a less oxidized form of folate than folic acid.. In some unknown percentage of people who appear unable to convert folinic acid adequately to methylfolate the accumulating unconverted folinic acid can actually block the methylfolate.



    IF an increase in dietary vegetable folate, “green drinks”, a garden feast

    AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2

    THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folinic acid is the primary form found in vegetable source. In some unknown percentage of people who appear unable to convert folinic acid adequately to methylfolate the accumulating unconverted folinic acid can actually block the methylfolate.



    IF starting or increasing folic acid AND OR starting or increasing folinic acid AND OR an increase in dietary vegetable folate

    AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2

    AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2

    THEN this can be the onset of Paradoxical Folate Insufficiency AND this can be the onset of Hypokalemia triggered by sudden healing



    IF starting or Methylfolate – Metafolin starting low and titrating

    AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2

    AND OR usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2

    THEN this can be the onset of Paradoxical Folate Insufficiency, a “donut hole” deficiency. The effects of folate deficiency/insufficiency comes in layers. Several tissue groups can be healing at the same time as other tissue groups are deteriorating. IBS and angular cheilitis can be worsening at the same time as muscles are healing or growing. There is a dose of Metafolin that can start more tissue formation than the same dose can sustain causing a Paradoxical Folate Insufficiency at the same time. In some people at least as they increase Metafolin the need for potassium increases approximately proportionately. The donut hole can be closed with total daily doses of Metafolin of about 15mg for many people.









    HOW TO INDUCE SUBACUTE COMBINED DEGENERATION and enlarged MCV in humans in 3 months or less.



    Causing SCD and macrocytic anemia was NEVER our intention, our intention was to induce health benefits from glutathione or precursors as claimed these days amongst certain practitioners. This is just how it turned out, 180 degrees from what we expected.



    Individual results will vary but in an N=10 trial, 100% of subjects had the results to varying degrees, perhaps as they used several different precursor combos or infusions. The subjects were all successful with adb12, mb12 and Metafolin. Those not in this group that had never relieved the deficiency symptoms claimed pain relief from the glutathione as their nerves were damaged further into numbness. I experienced this myself in the glutathione trial as my neurological damage was increased.

    Method 1 - feed subjects 1 gram of l-glutamine and 600mg of time release NAC twice a day for duration (or frequent glutathione infusions, or NAC or whey in some). In 3 hours after first dose most of available b12 in the body will be flushed out in the urine. Then within the next few hours methylfolate is expelled from the cells via the "methyl trap". Widespread body, muscle and joint, inflammation and pain start within hours and gets worse by the day. This is responsive to NSAIDS generally. Folate deficiency symptoms appear the first day, mb12 deficiency symptoms in several days and adb12 deficiency symptoms - 3 months or so.

    Over the next days and weeks, CPR heads for the roof. Hypersensitivity of all sorts starts, MCS, hyper-immune response, hypersensitivity in nerves, etc. In 3 days angular cheilitis starts up in those who are prone to it. In 2 more days IBS starts. At about the same time acne type lesions start up on scalp and face and often infected follicles in other body areas. Oral lesions usually follow. By six weeks centrally mediated numbness and pain of feet and legs, hands, arms, shoulders etc are all spreading and worsening.

    Dr Jeckyl leaves the house and is replaced with Mr Hyde for the duration. Sleep disorders increase. In 3 months macrocytosis is obvious, MCV > 100. MS will be dramatically worsened. If the person is also extremely low on l-carnitine and/or adb12 Parkinson's like symptoms may worsen explosively. Then if l-carnitine is given the subject may go absolutely nuts and a walkthrough of the extreme FFF characteristics of the limbic system will be demonstrated in usually the same order each time, dependent upon rising or falling l-carnitine level.

    Reversal, if SCD is not allowed to go too far is multiple 15mg doses of Metafolin (Deplin) and three 50mg mb12 doses or 10mg SC injections of SUITABLE 5 star mecbl until healed for at least a year, and of adcbl the first few days. On day 3, the need for potassium will often increase by 2000-3000mg to avoid dramatic sudden onset of Hypokalemia symptoms when backlogged healing starts up. Also on day 3 Metafolin dosage needs increase. In about a month inflammation will be largely gone if all cofactors are present that are needed, CRP <=1.0, multitudes of pains will be fading. MCV corrects when folate deficiency doesn’t exist for several months. Maintaining folate sufficiency for 3 months straight can be extremely difficult for those with paradoxical folate deficiency. Only the remyelization takes about 9 months to correct to the extent that it can but trails on for years as it is an ongoing equilibrium that is either getting better or worse. By careful active management one can approximately tread water otherwise it gets worse.

     
  16. Valentijn

    Valentijn Activity Level: 3

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    This whole introduction stinks. You're implying that Rich supports your "new" hypothesis (which really looks the same as the old one), even though publicly he disagreed with it on a general basis, only agreeing that yourself and a very few others might need the active B12 approach.

    Are you serious? Rich was constantly analyzing new information and exploring different theories and reconsidering his own. You're the one that has consistently insisted that you are right and your way is the only way things should be done.

    Personally I find hydroxyB12 to be quite effective, and lacking the methlyB12 side-effect of requiring potassium supplementation. If one form works without side-effects, and the other requires constant guess work to avoid hospitalization or DEATH, I think I'll stick to the one without side-effects.

    I also think putting the title of your thread all in caps is extremely arrogant. You seem to be assuming that your post is more important than those by the rest of the forum, and more worthy of drawing attention. If people want to follow your threads or your posts in general, they can easily do that without it becoming a necessity to make your thread titles an eyesore.
     
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  17. Freddd

    Freddd Senior Member

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    Hi Valentijn,

    I an not implying that Rich supports anything. I am saying he provided me information that changed my thinking. Has he not done the same for you and a lot of people here? I would not have reached most of these conclusion without Rich having supplied important pieces of information. You can look at my earliest posts and watch the evolution of my understanding right out in the open. I change my opinions all the time as I learn more. He also did make a post that suggested a change to MeCbl after 3 months of ineffectiveness of HyCbl and later another post that basically said that he now saw no reason not to start with MeCbl of 1mg or under. What he said was no more immobile and unchanging than what I have said. Some of the information I am posting is the same, a lot of it is revised and half of it was unthinkable by me 4 years ago. As I constantly reconceptualize as information is added, it all changes somewhat. Take the ZONES for instance. The first versions were a survey summary based on journal reported research and clarified pragmatically. The second version is based on 10 years more research that has become available and organized by the method of distribution, which is much more exacting, that broad zones based on doses . Now that might not appear to be significant to you. The implications however are potentially far more useful than simple dose related zones. The researchers though only provided the research in the last 10 years to be able to show that. One of the criticisms of MeCbl was that it didn't handle inflammation as well as HyCbl in vitro. Wheatley's new LARGE GORILLA...ADNEOSYLCOBALAMIN paper points out that it is Adenosylcobalamin that handles inflammation" radically" better than HyCbl when it is present in large enough doses. Large enough doses being sufficient to be distributed to all cells needing it at once handling all levels of inflammation and products via diffusion rather than picking off a little piece of inflammation here and there as HyCbl does. She wrote 3 papers on HyCbl and inflammation first. Adenosylcobalamin is where she progressed to as her understanding progressed. That was published months after his death so he can't read it and reconsider his earlier opinions.

    The stylebooks I have, says all caps in titles is fine. They also get into a whole lot of hierarchy of what levels of titltes and such. And I am not a stickler for stylebooks for informal writings or many here would be flunking, me included and maybe especially.

    Arrogance, like beauty, is in the mid of the beholder.

    On the first day of freshman orietation at a noted engineering school the heads of each of several departments gave an introductory hour. One of the things said that sticks in my mind most profoundly is that "Half of everything we teach you here will be proven wrong by the time you retire. Don't get attached to it". The old joke (trueism) also told at that intro lecture is "How fast does physics theory change? One funeral at a time". Thats when that person stops defending his research.

    I spoke with Rich. He is not a systems analyst and doesn't think like one. That is not an insult. He didn't work as one and didn't represent himself as one. I don't know why you take offense at that. He thinks like a biochemical researcher which I don't think like. I do cost/benefit analysis too. So what? As a consultant I worked with a team of people all with different training, skills and ways of thinking and it was productive. If I had found a suitable consulting project I would not have hesitated to invite Rich to join the team precisely because of skills and how he does think (NOT BY WHAT HIS OPINIONS ARE). Agreement of conclusions and opinions isn't necessary. He sent me a bunch of data from the most discussed study he was invloved with. I rearranged the data, reinterpreted the same data, came to different conclusions and sent it back to him along with some of my data showing why I came to different conclusions. We were in dialog on this when I crashed and burned (also invaluable data, which I was eager to share with him) and went away for some months and I came back to hear of his unfortunate death. Something that may not be as readily apparant as our disagreements is that we were agreed an almost the entirely of the things. The differences are that he finds gltathione depletion to be a cuase of FMS/CFS. I step back a level or two and say that glutathione depeltion is a result of the broken methylation (many possible reasons) becasue of genetic folate processing errors or becasue of induced folate processing errors by folic acid instead of L-methylfolate and CyCbe/HyCbl instead of MeCbl/AdoCbl. I also look much harder at neurological damage (personal interest becasue of my own problems) and very much harder at AdoCbl/LCF for mitochondria functioning and the interplay of methylation and ATP. However, on those overlapped areas we agree about 99% about what is going on. That just doesn't get talked about, only the small areas of partial disagreement. I don't know of many people here that don't have both problems to some degree

    It's very helpful to have a knowlegable person with opposing interpretation to discuss things with. If he had survived longer I would be listening to and investigating all the things he would have pointed out. Neither of us is/was a politician. We discuss to lead to better understanding. Despite 3 years of different understanding regarding my personal genetics and B12 and folate responses, he was unwilling or unable to move off of that CblC gentic issue. That seem a possible hypothesis when I started here but he walked me through a much better understanding of folate and upon re-evaluating all the same evidence of how I responded or didn't respond throuhg the decades, AFTER I was able to do comparative tests with methylfolate and review all the old data, it was clear that CbcC affecting polymorphisms were out and folate affecting polymorphisims were in. BE IN GOOD HEALTH (and that isn't even a title.
     
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  18. Freddd

    Freddd Senior Member

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    Hi Vlentijn,

    Are you serious?

    Personally I find hydroxyB12 to be quite effective, and lacking the methlyB12 side-effect of requiring potassium supplementation. If one form works without side-effects, and the other requires constant guess work to avoid hospitalization or DEATH, I think I'll stick to the one without side-effects.

    "Those who don't know history are condemnded to repeat it"

    I had never heard of all this "detox" business until I came over to this board and saw all these people sufferring from "detox" from the SMP. Where I had been posting, NOBODY had detox. Nobody ended up in the ER with low potassium. They didn't believe in it so they didn't ignore it and tolerate it. When they had symptoms relieved by potassium, they took potassium. Because people called these symtpoms "detox" they put up with that for months and years. As many of those "detox" symptoms are identical with symptoms from hypokalemia and are relieved by p[otassium as is hypokalemia, and that hypokalemia is only dnagerous when it is ignored by calling it "detox". I merely identified it for people. The doifference between SMP and active b12 and folate is that with SMP it is a crapshoot if and when "detox" will start up. On the active b12s and folate low potassium occurs quite predictably at the thrird day after the last critical nutrient is started. Hypokalemia is dangerous when ignored because it is called something esle. Would you rather know when you a re likely to have low potassium symptiomsor take your chances for days, months or years.

    I know of no possible way to heal without verious side effects, no matter what assortment of vitamins. It even happens to a few people starting CyCbl, but "rare". Of course HyCbl, 200mcg of l-methylfolate and some amount of Folinic acid start "detox" of one or both varieties, just not quite as predictaby. The side effects are much worde when ignored insteaqd of beinbg prepared and taking care of both forms the days they start. Are you just fear mongering? Check out the history of posts here. See what really happened.
     
  19. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Freddd

    I think what people are objecting to is presenting hypothesis as fact when there has not been independent corroboration.

    We are all different, some do better one type of protocol, and some with another. Some researchers support one hypothesis and some another. Some doctors prefer hydroxocobalamin, some prefer methylcobalamin and some even prefer cyanocobalamin. Everyone does the best they can in light of experience, hypotheses and published literature.

    Thus, I think it is important to present hypothesis as hypothesis--otherwise there could be confusion and it could be taken as established "fact" and followed uncritically--with possible unanticipated detrimental consequences (because it was not understood to be hypothesis, and thus having possible inherent levels of risk).

    In this vein: the terms "induced and/or paradoxical folate deficiency or insufficiency" and "start-up responses" are concepts (as far as I know) from your hypothesis and are not found in published literature (or for that matter, recognized by Rich). So, when writing about them, I think it would be helpful to make clear that they are hypothesis, not established in the medical literature.

    Also, the phenomenon of "detoxification" is widely accepted by researchers and medical practitioners and is often associated with an increase in glutathione. I think very few who worked with the Simplified Methylation Protocol were confused between detox and hypokalemia. Those I know were aware of an increased need for potassium (as was Rich) and acted accordingly with supplementation.

    Sushi
     
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  20. EastWest

    EastWest

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    Today I tried 3 ADB12 sublingually 90 minutes in the morning. After noon, I did 3 again which I chewed enough to crush, then added a drop of DMSO and held the whole thing in my mouth with no swallowing. Occasionally swished it a bit as the saliva built up. I had a very noticeable brightening and sense of the B12 activating with the DMSO, almost no effect with the first sublingual. I held it in my mouth for 20-25 minutes then swallowed.

    I take boron daily as one of the minerals supplements, perhaps that is why I can tell no difference in effect between the two brands. I haven't tried both brands with DMSO yet.

    Thanks for the idea of taking the metafolin a hour before both the B12s.
     

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