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Starting SMP, preferable to just take B12 first?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by sregan, Mar 6, 2013.

  1. sregan

    sregan Senior Member

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    I tried the SMP for about a week and stopped, was having some unpleasant effects (herx?).

    I think I was getting a big energy boost from the B12... Can I just take that without the Folapro and Folinic acid? I think I read somewhere that it was preferable to get your B12 up before starting SMP?

    If that's the case then after I'm comfortable with the benefits of B12 would I start trickling in the Folates?
     
  2. Freddd

    Freddd Senior Member

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    Hi Sregan,

    Almost every time startup to MeCbl is low potassium, and/or low foalte. Sometime it is ATP startup. A real genuine Herx reaction to MeCbl has never been documented. My hypothesis you can prove or disprove for yourself in a few days. Herx and detox as a working hypothesis leads to much tail chaising and little improvement. If it is low potassium and/or low folate you can demonstrate that to yourselves in days. Tricking in the folates causes donut hole folate insufficiency as a little folate starts a lot of healing that can't be maintained without more folate.
     
  3. sregan

    sregan Senior Member

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    Freddd, thank you for responding, as I'm reading the posts here I see the contribution you have made and are making. My sincere thanks for that.

    Herx and detox as a working hypothesis leads to much tail chaising and little improvement.

    Yes definitely, how do you ever know if you are reacting negatively or positively when a negative reaction can be interpreted both ways?

    If it is low potassium and/or low folate you can demonstrate that to yourselves in days.

    I experienced something of a herx on the 4th day of my SMP trial. (1000mcg hcbl, 200mcg MFolate + 200mcg Folicin) felt awful, especially depression wise, and lot of pressure in the pancreas/spleen area. Is there a way to tell if this is potassium or folate deficiency? I'm guessing take some potassium (mg?) and after a time frame if you feel better that was it? If it's is a folate deficiency does one take more folate per B12? What is the rate limiting factor of this reaction or is it all 4 in your Deadlock quartet?
     
  4. Freddd

    Freddd Senior Member

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    Hi Sregan,

    First, read my most recent answer to you on the other thread, and the one next to it, so I wll assume that is read in answering this. At the bottom of this post are the symptoms that point at low potassium and/or l-methylfolate. Symptoms on the respective lists are pretty much exclusive. I did also include overlapping symptoms. Usually a person will have 1-3 or so most rapidly arising symptoms from either or both categories. For potassium a 12-16 oz glass of water with 300-500mg of potassium gluconate (easier on the stomach for this purpose, and in the tablet alread dispersed at about 20% strength compared to straight KCl which can cause chemical burns to the stomach unless highly diluted in food. If this is appearing after several hours taking another l-methylfoalte dose of the same size might work. 200mcg 4x per day is more effective generally than 800 all together. Sometimes, to STOP the mdonut hole insufficiency a 800 or 1600mcg dose needs to be tried to put a definitive stop to it quickly. If one has insuffoicient MeCbl and insufficient Metafolin, then a person can be in the position to switching back and forth between methyltrap folarte insufficiency symptoms and partial methylation block b12 deficiency symptoms. So in methyltrap, a little MeCbl is taken and one comes out of methyltrap with folate deficiency symptoms and suddenly shows b12 deficiency symptoms with then fade back to methylation block sympotms of folate insufficiency and b12 deficiency. it a;l seems very paradoxical which is why it has confused so many people for so long. Only a person working on it from the inside and succeeding is going to figure this out.. That is why ENOUGH of both MeCbl AND Metafolin both needs to be taken to unblock the double whammy of methylation block and methyltrap.




    Symptoms that bear no resemblence at all to any of them need to be considered too but are often either clearer or disappear when the primary responses are managed. What happens if these problems are solved correctly is that the affected symptoms will heal and disappear over a number of months leaving others very obviously untouched ot only partially affected. If a person has 300 symptoms it is terribly hard to tell what is going on. If 3 layers totalling 200 symptoms are cleared up, then the islands of remaining symptoms point the way. Check out the symptoms by nutrients lists I posted on the stages of methylation thread. There are 6 isuch posts in all arranged in categories.


    All of these are flags indicating healing is occurring. Minimizing nervous system response reduces or stops healing, especially of the nervous system. Minimizing ATP response prevents normalization of biochemistry.

    1 - Low potassium, almost everybody when healing starts. – often called “detox”

    2 - Low folate symptoms even with small doses of Metafolin – often called “detox”

    3 - Nervous system activation, everything is perceived as more intense – often called “detox”

    4 – ATP activation, everything is more energetic and intense – often called “detox”


    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.

     
  5. Lotus97

    Lotus97 Senior Member

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    It would be better to take the B12 first, then the folinic acid, and finally the methylfolate (Folapro). Rich actually doesn't say you have to start the supplements one at a time, but if you do decide to do that here's what Rich says about the order
    It is best to start with lower dosages than those suggested above and to work up slowly, to check for tolerance. Some people have found that they are very sensitive to these supplements, and can take only much smaller dosages. Others find that they need somewhat larger dosages than those suggested. For those who wish to start the supplements one at a time, I suggest starting with the Neurological Health Formula first, then adding the lecithin, then the B12, and finally the folates, with FolaPro last.

    This is from the paper on the study conducted by Dr. Neil Nathan and Rich using the SMP protocol. As he says above, some people will need a higher dose, but other might need a lower dose.
    http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf
    • GO SLOWLY. Occasionally, as the methylation cycle blockages are released, toxins are
    released and processed by the body, and this can lead to an exacerbation of symptoms.

    IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full
    dosages. If you have questions, please call our office to discuss them.

    As noted earlier, one patient dropped out of the study at 3 months for a reason not related to
    response to the treatment. The remaining 29 patients completed 6 months of treatment.

    Various patients reported some early exacerbation of symptoms, which in most cases was
    followed by a greater improvement in symptoms. Three of the patients found it necessary to
    decrease their dosage frequency to every second or third day for several days, until they could
    tolerate the full daily dosage schedule.

    Sixteen of 30 patients (53%) reported an initial worsening of symptoms, beginning in most of
    these cases within 3 or 4 days, but in some cases beginning at up to 2 weeks. Most of the
    symptoms were mild, and none of the patients discontinued usage of the supplements during the
    first 3 months. The most common side effects were gastrointestinal (pain, cramps, constipation,
    or diarrhea), reported by 6 out of 30 patients or 20%; increase in pain, reported by 4 out of 30 or
    13%; and increase in fatigue, reported by 3 out of 30 or 10%. Other symptoms, reported by one
    patient each, were a decrease in appetite, poor sleep, weak legs, flu-like symptoms, and an
    increase in anxiety and depression.

    For those who experienced improvement, the time to self-reported improvement on the protocol
    was an average of 5.6 weeks, with a range from immediate improvement (which was rare) to as
    long as 8 weeks before improvement was experienced.
     
    sregan likes this.
  6. Freddd

    Freddd Senior Member

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    So now that you have hopefully looked at those 6 symptoms lists, You see how there are inconnected and most of the symptoms likely respond to more than 1 nutrient. There is often kind of a 4 way round-robin roadblock starting one item at a time. My best idea of how it is best done now, after 10 years of a variety of experiemces of healing everything except the worst of the neurological damage, I would start a combination of AdoCbl and Mecbl as they work synergistically together. I would suggest 200mcg doses of L-methylfolate, 4 per day, becasue of the short halflife. 100mcg combined absorbed AdoCbl/MeCbl plus the l-methyklfoalte will typically unblock partial methylation block and break methyltrap within hours. On the 3rd or 4th day typically a swarm of low potassium symptoms and often donut hole folate insufficiency. Those two things need to be titrated to sufficiency. As you bring the base level up of one the other set of symptoms may become more promenant. Also, with methyltrap, the symptoms flip flop back and forth between b12 deficiency and folate deficiency symptoms in a paradoxical seeming fashion. After these stabilize, often between 1200-3000mg of potassium a day and 800 mcg and 30mg of l-methylfolate, then everything needs to be evaluated. Then the LCG titration begins as the startup subsides from the other items. Constant evaluation to consoder what may be going low is needed. Basically a person should be ready for these things before starting and be taking basic vitamins and minerals. Constant re-evaluation is needed. However, avoid the instant response of thinking in terms where the thinking has been done. Consider the symptoms, not all the intstant fear answers that result in shutting down healing whenever it pokes it's head up. This isn't whack a mole with healing startup being the mole. It's intelligent recognition of what is happening with healing as the goal. This whole healing process is like a maze. Kneejerk answers won't get you through that maze.
     
  7. sregan

    sregan Senior Member

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    Freddd, thank you. I'm going to start again using your recommendation here.

    I've also been reading more of these posts these last few days.

    Saw your latest revised protocol here: http://forums.phoenixrising.me/inde...tocol-with-micro-titration.17818/#post-273588

    Also this post on the stages of Methylation healing here: http://forums.phoenixrising.me/index.php?threads/the-stages-of-methylation-and-healing.21725/page-2

    One thing I was interested was in the half life of the deadlock quartet. You've stated the Methyl Folate is 3 hours, also somewhere that the AdoCbl is 99% gone in 24 hours. I'm cautious about starting again. Today I took just 1/4 of the Jarrow 1mg and 1/4 of the Country life Dibencozide (no folate). I imagine starting methylation like getting a large ship moving. You can't just hit the brakes but need to wait for it to slow on it's own. If symtoms can be resolved with more MethlyFolate and Potassium then great we are not herxing yet... But If a true herx happens I want to know I can hit the brakes. Withdrawing the Folate should do that?

    I was going to ask about EOD (Every other day) or ETD (third day) dosing. What Lotus just posted above from Rich indicates that some of their subjects did just that: "Three of the patients found it necessary to
    decrease their dosage frequency to every second or third day for several days, until they couldtolerate the full daily dosage schedule."

    Regading that you mention this: "Taking l-methylfolate in small dose once a day may turn methylation block off and on again ecah day which will tend to make the folate insufficiency symptoms ("detox') get wporse and worse. These are rthe oscilations of symptoms that gets worse and worse, the longer it is pumped, like a kids swing being pumped higher and higher by the same leg movements.. "

    So I'm guessing that's not the way to go. Better to keep on steady with lower dosages then start and stop...
     
  8. Freddd

    Freddd Senior Member

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    Hi Sregan,

    I imagine starting methylation like getting a large ship moving. You can't just hit the brakes but need to wait for it to slow on it's own.

    I don't find that to be the way it works. Partial methylation block turnes on and off in layers by observation. However, methyltrap is a binary on/off. If you take just enough MeCbl to break out of methyltrap you will then suddenly have b12 deficiency symptoms instead of extereme folate deficiency symptoms. If you take enough MeCbl to break out of methyltrap and enough to prevent the b12 defiency symptoms, then it will go into folate deficiency symptoms. You can imagine anything you want. I wouldn't bet on it though. Medthylation starts. You can either chose to start it and KNOW you are starting it and be prepared for low potassium or you can play methylation roulette and have it possibly start any old time catching uypi unprepared and misinterpreting it.


    If symtoms can be resolved with more MethlyFolate and Potassium then great we are not herxing yet... But If a true herx happens I want to know I can hit the brakes. Withdrawing the Folate should do that?
    So what kind of rigors, extreme chills and fevers have you gotten from the herx reactions in the past? Those are the hallmark symptoms as the bacterial toxic material is extremely pyrogenic; As far as betting on what is happening I would put my money on Low potassium and/ot low folate 95 time out of 100. Then we come to low l-carnitine, Low D, magnesium, SAM-e, D-ribose, biotin and perhaps half a dozen more. Based on my experience I have NEVER seen an actual herx reation form MeCbl, AdoCbl and l-methylfoalte. The odds for genuine herx appear to be less than 1 in 10,000. With most examples of herx the person is over it before anything they can do about it. A herx reaction indicates what HAS happened, massive amounts of bacteria dying all at once releasing the toxins out of their cells into the blood all at once. I I have actually experienced it, from antibiotics as is usual, after 4 months of antibiotic resistant illeness leading up to pneumonia. I have heard a lot of frightening stories that had that word in it but have never seen an actual example from anything other than drugs that kill a lot of bacteria in hours. MeCbl etc doesn't do that. It takes the immune system some months, by experiience and observation, to build up to working properly. There is absolutely nothing about the vitamins that kills bacteria in hours releasing their toxins. That is perhaps some kind of wishful thinking in a way. I would like to be able to claim that kind of immune power to these but there are is a lot of healing that has to happen. I have followed the course of healing closely in hundreds of people.

    Let's look at the half lifes then. While 99% of the B12s are out of the body in a day, it takes about 3 days for b12 deficiency symptoms to start getting worse after a number of doses. The AdoCbl has a 99% loss from the bloodstram in 24 hours BUT once it is in the mitochondria it appears closer to 71 day tissue halflife. The l-methylfolate has about 3 hours halflife. I go into folate insufficiency simply by missing a single dose or having it blocked by potassium.

    So let's examine turning off methylation fast and hard. That happens going into methyltrap. After a single dose of MeCbl that might take a week to go back into methyltrap. That turns off healing. So when methylation block for any reason hits hard the order is like this by my observations. When it happens by itself the person typically wakes up terribly sick thinking they have some horrid virus or something. The fatigue hits like a ton of bricks. Coming OUT of methyltrap can be intense too. First the epithelial cells stop reproducing and things like canker sores, angular cheilitis, IBS, ulcerations in the mouth, throat, stomach and intestines, skin problems. Then emotional and personality changes occur. About a week in body wide inflammation and pain start spreading, joints become increasingly inflamed and painful. The MCS, allergies and asthma come on pretty strong and then immune funtions start going hyper sensitive and hyper reactive, and possibly start doing autoimmine things. Of course if they have never recovered from these things then there is no real change. The thing is, the immune syytems sits on top of the funtionality of both methylationan and ATP. It takes cell reproduction and things like that to ramp up the immune system.

    If you get a real genuine herx reaction and you are still alive (death is rare) 24 hours later you may be blessed. You will have mostly gotten rid of the resitant/hidden bacteria that has made your life misery. When I had a herx reaction with my resistant pneumonia, I was getting sicker and sicker. Nothing worked. The doc ordered in some kind of antibiotics, we were trying 3 a day (backwoods Maine). I was going to end up in the hosipital and possibly dead if it didn't work. If nothing works resistant pnemonia is quite deadly. The herx started about an hour after the injection of antibiotics. I called the doc and he said, if we don't continue the antibiotic it could become resistant to the only thing able to kill it right now and it will kill you. Go outside and keep your fever below 104. (It was 40 below in January and I was sitting in my PJs on the front porch waving at all the bundled up skiers. I probably could have dried 30 sheets that day (Tummo, how many wet sheets can the monk dry on a freezing day with their body heat?).
     
  9. Freddd

    Freddd Senior Member

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    Hi Sregan,


    I was going to ask about EOD (Every other day) or ETD (third day) dosing. What Lotus just posted above from Rich indicates that some of their subjects did just that: "Three of the patients found it necessary to
    decrease their dosage frequency to every second or third day for several days, until they couldtolerate the full daily dosage schedule."

    My opinion is that wouyld be a very unwise thing to do. It is based on incorrect ideas about these things. It's like getting sex advice from a lifelong celbate. I have lived through this. I have succeeded 100% with no equivication of completely curing myself of FMS/CFS/ME. The first pulse of healing is the strongest in my experience. Each tome you turn it off it happens less well and one dosen't heal as much or completley. Nobody else here giving any suggestions here has actually succeeded. Every third day turns methylation on and off over and over and makes oscillations worse. Nobody doing that has gotten well, and I do mean CURED, as in absence of FMS/CFS symptoms. Any of you other cured people out there want to join me on a 10 mile hike?

    You are free to take suggestions from whoever you want to. None of us are doctors. Of course I know of no doctors who will tell you this so there it is. If I am correct you could be 75% recovered in a year if you don't let fear and all the rest stop you. If you do things like every third day, or whatever, you will possibly be having worse effects than ever and we will be having the same conversation a year from now. And then your body might not be as enthusistic about healing. That "impulse towards healing", I don't know what else to call it, wears out after a bunch of false starts. I've seen that too. The best CNS healing I ever had was the first big surge. After that it has been nickles and dimes.
     
  10. sregan

    sregan Senior Member

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    This, and I read this from you somewhere else, sounds like my onset for CFS both times I've had it. It's an unfamiliar ill feeling that makes you think you got something life threatening. The stress then makes things worse and from there an downward spiral. For me it came in waves of getting worse from the initial onset. This year will be 10 years for me with the 2nd onset. I have stayed fairly active and was in the gym 3 times last week (anerobic type workout). I'm probably in better shape physically than most with CFS. I'm hoping that will give me some help in coming out of this.


    Wow, for the first time in years I have had sores in my mouth. I had what looked like a blood blister on the side of my cheek. I assumed (even vaguely remembered) biting myself while eating. Not sure now. And right now have some type of blister in the inside of my lower lip. My GI symptoms have actually lessened somewhat and have more energy in the gym on the days that I tried the HCbl + MFol. Prostate also is more relaxed, not to mention depression has lessened and am actually having optimistic periods where I feel happy (on CBL-MFol days).
     
  11. sregan

    sregan Senior Member

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    The last 2 days I've started with 1/4 jarrow mCbl and 1/4 dibencozide. The 2nd day I added the 1/4 MFolate. Both nights I didn't sleep that well. REM was fairly light and easy to wake from.

    I'm going to try 1/8 of the three today and hope that solves the sleep issue.

    I did take 1/4 MFolate 4 times throughout the day and don't remember an energy drop like I've had on previous attempts with HCbl and only 1/4 MFolate once in the AM. I'm going to try to keep this balanced and work through it by changing the titration on the component supps.

    I've got potassium chelate (99mg per) (http://www.iherb.com/Nature-s-Way-Potassium-Chelate-99-mg-100-Capsules/2000). I've seen reference to Potassium Gluconate here and wonder if that is a better choice?

    I forgot to mention in my last post that my brain fog is way better also.
     
  12. Lotus97

    Lotus97 Senior Member

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    Now Foods sells potassium chloride and potassium gluconate in powder form. Those would be the most cost effective way to supplement with potassium. Potassium chloride is harsher on the GI tract than gluconate. Make sure you don't take your potassium supplements, vitamin C, or iron at the same time as the methylfolate or that will block the absorption of methylfolate.
     
  13. sregan

    sregan Senior Member

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    Thank you Lotus. I've got some Potassium Chloride but will not take that anymore due to stomach concerns. I was wanting to know if the Potassium Chelate I have was safe and/or being used by the SMP folks or if the gluconate was safer and I should get some of that.
     
  14. Lotus97

    Lotus97 Senior Member

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    I don't know the difference between the potassium chelate and potassium chloride other than cost (at least in powder form). There was a customer review for potassium gluconate who said potassium chloride caused them problems with stomach irritation, but potassium gluconate did not cause them any problems although one person did say potassium gluconate caused gastritis and another said it had a laxative effect.
    I can't say for sure what's going on in your case specifically, but if potassium doesn't alleviate all your symptoms you might want to consider other possible causes. It's still a good idea to supplement with potassium as a precaution even if you are following Rich's Simplified Methylation protocol where the need for potassium is much less than if you were following Freddd's protocol. Since you mentioned you were considering switching from hydroxocobalamin to methylcobalamin and adenosylcobalamin that would make your need for potassium greater (although how much would vary greatly based on dosage of B12, methylfolate, and how many other methyl donors you're taking). It would also be good to make sure you're getting enough magnesium since lack of magnesium can make it more difficult to raise potassium levels. Taurine also can help with electrolyte balance although some people have difficulties with sulphur. Magnesium and taurine can also help with the excitotoxicity that often occurs during methylation.

    As for other causes of herx/detox symptoms, Rich has posted about this in various threads. This quote from Rich might be useful in understand what could possibly be going on with you:
    One physician I know gives all his patients the methylation treatment, and then watches the response. If they experience some symptoms that appear to be caused by detox, but they are able to tolerate them, he continues with this treatment. If they have intolerable symptoms that appear to be related to mobilization of toxins, then he stops the methylation treatment and works on improving the status of the gut. When that is working better, he moves on to supporting the liver. His thinking is that the toxins that were being mobilized were being reabsorbed by the gut and sent back to the liver. In order to properly process and excrete the toxins, the gut and liver must both be functioning well enough to handle them.

    My guess is that when there is an inflammation response to methylation cycle treatment, there is an infection. If the inflammation continues without resolution, then my guess is that the immune system has been reactivated, but is not capable of defeating an existing infection. In such cases, I think that treating to support the immune system would be one approach. Another would be to test to determine what pathogen is causing the infection, and then treating it with an antibiotic, antiviral or antifungal, depending on the pathogen.

    I think it's important to note that a healthy person would not have any reaction to the supplements used in the methylation protocols, because their methylation cycle, detox system and immune system would already be functioning normally. So the fact that there is a response, even though it may seem to be deleterious, means that the methylation cycle was partially blocked and that these supplements were needed. However, the way one should proceed from that point on probably depends on the type of response that the individual person has.

    So far, I'm pretty sure that if the following are present, they will need specific treatment, in addition to treating the methylation cycle partial block: biotoxin (including mold) illness, Lyme disease and its coinfections, well-entrenched viral infections, and high body burdens of toxic heavy metals, such as mercury. There may be others of which I'm not aware, but there is some experience with these, at least, which people have reported

    I believe that the partial methylation cycle block is the pivotal abnormality in the pathogenesis and pathophysiology. With respect to the root cause or causes (etiology) of ME/CFS, I have suggested that this disorder arises from a combination of a genetic predisposition and some combination of a variety of stressors, which can be physical. chemical, biological, or psychological/emotional. I've suggested that this combination leads to glutathione depletion, which leaves B12 unprotected, which causes a decreased production of methylacobalamin, which inhibits methionine synthase, which forms a vicious circle with glutathione depletion, making ME/CFS a chronic condition. The retroviruses would fit within the biological stressors in my hypothesis, and certainly could be a root cause. If effective treatment of the retroviruses ends up bringing about recovery from ME/CFS, that will be very convincing as to its role as an etiologic agent. I hope that turns out to be the case for at least some of the PWMEs/PWCs. It may not be true for all of them, though, because this population seems to be very heterogeneous.

    The reason I have included the variety of stressors as etiologic agents is that I have studied the published "risk factor" studies, and have also queried quite a few PWMEs/PWCs as to the events that preceded their onset, and I've found a variety of precursors. The common factor seems to be that they are all things that would be dealt with by the body's nonspecific stress response systems, and these in turn are known to place demands on glutathione.

    In addition to this, there are now many PWMEs/PWCs who have taken the Health Diagnostics methylation pathways panel, and nearly all of them show evidence of a partial methylation cycle block or glutathione depletion, and usually both.

    And when treatment was given in our clinical study that is directed toward lifting the partial methylation cycle block, we observed by testing that this does in fact occur, and that glutathione also comes up automatically. This was accompanied by improvement in symptoms in at least two-thirds of those who were treated.

    Putting all of this together, I think the GD-MCB hypothesis is consistent with the observations and with known biochemistry and physiology. That doesn't mean that I believe that it is scientifically proven, which is a very high standard to meet, and requires considerable investment in time, money and effort, but that it is a valid working hypothesis. I'm hoping to interest researchers and fundors in this model so that it can be more thoroughly tested.

    The methylation cycle is at the beginning of the sulfur metabolism. It is fed by methionine, which comes in as part of protein in the diet. Homocysteine is produced from methionine (via SAMe and SAH) in the methylation cycle, and then methionine synthase "decides" how much should be converted back to methionine, to stay in the methylation cycle. In the liver and kidneys, the BHMT reaction also converts some homocysteine back to methionine. The rest of the homocysteine enters the transsulfuration pathway, which is downstream.

    The way that methionine synthase does its "deciding" is that the cobalt ion in the cobalamin that is its cofactor gets oxidized at a rate that depends on the state of oxidative stress in the cells. The more oxidizing this state is, the more often the cobalt ion gets oxidized, and that temporarily shuts down the methionine synthase reaction and diverts the homocysteine flow into the transsulfuration pathway, which helps to make more glutathione, which counters the oxidative stress. Unfortunately, in ME/CFS this delicate mechanism gets overwhelmed, and the oxidative stress becomes more severe, so that glutathione doesn't recover and get control of it. The result is that methionine synthase becomes partially blocked, and the sulfur metabolites drain down the transsulfuration pathway, into sulfoxidation, and get excreted too much as taurine and sulfate, which depletes methionine. The whole sulfur metabolism becomes dysfunctional, and that takes down the cell-mediated immune response as well as the detoxication system. As well, everything that depends on methylation reactions is affected, including gene expression, synthesis of several needed substances, and the neurotransmitter metabolism. Also, this drains the folates from the cells via the methyl trap mechanism, and that affects things that depend on folate, such as synthesis of new RNA and DNA. The latter is what cause the red blood cells to be too big and too few in number.

    The methylation cycle is so fundamental to so many parts of the body's biochemistry that when it becomes dysfunctional, it causes a host of problems, and this is why people experience so many symptoms, involving so many body systems and organs, in this disorder.
     
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  15. Freddd

    Freddd Senior Member

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    Hi Sregan,

    Just want to say that Jarrow MeCbl went bad a year ago. Enzymatic Therepy is the only brand I can count on for neurological healing at this point. I crashed on the Jarrow and had a reassurgance of Subacute Combined Degneration, which is from actual damage which does not heal as well as the FMS and CFS.
     
  16. sregan

    sregan Senior Member

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    Fredd, is there something wrong with the Jarrow or just not as potent as the Enzymatic? I've got some Enzymatic on order, should be here today or tomorrow.
     
  17. Freddd

    Freddd Senior Member

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    Hi Sregan,

    Yes. I would surmize that they bought a new batch of MeCbl crystal and it did not have the same qualities the previous batch(s) had. This is an unmarked problem. Bought randomly about 5% of MeCbl has excellent neurological and other healing effects by my own tests. I hope it's that high a percentage. This was the very first barrier to healing I found 10 years ago. I wondered why only about 5% of p[eople were having success with MeCbl. I found it varied from near 100% with two brands at the time to zero effectiveness with some brands and no other brands able to maintain the healing for the top brand(s).

    It's not a question of potentcy as far as dose goes. More does not make up the difference. It is a qualitative difference in suspevted to be different variations on the molecule by different bacteria. I have frozen samples of pure crystal of a 5 star and a 3 star MeCbl for anybody with an NMR and mass spec who wants to check out that hypothesis.
     
  18. sregan

    sregan Senior Member

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    Thank you for the explanation... but how do you know now that Jarrow is no good? Is this just based on your (and others perhaps) subjective experience or is there some type of test data?
     
  19. Freddd

    Freddd Senior Member

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    Sregan,

    is there some type of test data?

    I wish. We don't even know what kind of data that would be. I hypothesize that and NMR and mass spec would determine if the molecular mass is different, or a mix of types and NMR could show us if they are different bond angles but the same mass. There is no base line data, no signature of 5 star MeCbl vs 3 star MeCbl.

    While getting clobbered with a hit me in the face SACD attack with a slow intensification of 30 or so symptoms that had me thinking that when I got back from my trip would have to re-compare the MeCbl, the sudden collapse put it hard in my face. When something that worked excellently for 9 years suddenly doesn't , and it is in the most subtle place, the CNS, and suddenly hard CNS symptoms of a certain type hit hard, it isn't subjective is the sense of wondering if anything is even happening. That was clear. It was also clear what had happened. A bunch of people had already been asking about the change before I got clobbered. Then when all of us recovered that I know of by a change of brands, it's pretty well confirmed. So if you are asking what the confidence level is, it's 100% that something in the Jarrow MeCbl changed such that it was no longer CNS neurologically effective. And I did have startup all over again.

    It is unknown what percentage of people's responses are the same, but the entire historical record of 10 years and before does indicate that brand of MeCbl is a determinant of effectiveness, with zero doubt.

    Now that zero doubt only belongs to people who interpret the startup of MeCbl as healing startup and adjust to the startup responses based on that theory. Then when healing has been going solidly for a month or five, when it suddenly turns off, it is very obvious. It makes it so each person can tell what works for them often within hours. One tries a different brand of MeCbl and healing stops and symptoms start coming back in 3 days or whatever. Same with various type of folate. If folic acid or folinic acid doesn't work for a person, whether alone or in combination, it becomes very obvious. One a person succeeds in turning healing on, they can stop guessing and hoping and believing. and floundering around. They can do a comparison, A-B, and know very quickly. I knew in less than an hour that the ENZY was massively superior to the Jarrow when I was in a position to try. When one has compared 20 or more brands it gets very easy. Normally I don't let myself get so debilitated all at once. When one is loosing neurological sensitivity all sorts of things fail to be noticed because of that very lack.

    I backtracked and added in each "most effective" brand and synergistically, something greater than the sum of the parts happened, CNS healing turned on.
     
  20. Freddd

    Freddd Senior Member

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    Hi Sregan,

    Exercise is critical in this recovery. So many have exercise intolerance. I did. For me, the exercise intolerance ended with the AdoCbl. Then exercise ability increased vastly when the LCF was added and I was able to grow muscle again.

    There are about 4 or 5 aspects of sleep disorders that appear with the various deficiencies. A common one is sleep paralysis which basically a part of the brain not falling asleep as quickly or maybe waking up more quickly than the freeze on the body muscles that keeps one from acting out all dreams. This can result in a prolonged period of entry or exit from sleep and some people are disturbed by it. Sleep will change a lot in the first few months as the neurology itself changes. Don't worry about it. The studies on MeCbl and sleep indicate that while people end up sleeping shorter times they get restorative and restful sleep. If one is all anxious about the changes in sleep it becomes self defeating. Other experiences of my own and those of other people indicate that AdoCbl, LCF and l-methylfolate are all important in different ways.

    I've tried potassium chloride partly as a salt substitute, but it really doesn't satisfy me there too well. And as a capsule taken with food. I can manage 500mg capsules of granules with food so it can disperse but I find that potassium gluconate is really the most kind to my stomach. I would imagine the chelate to be gentler than the KCl on the stomach.

    Let's talk about aiming points. Reduced or removed depression is an important aiming point. Quality of sleep doesn't appear to be an effective aiming point. It alters slowly over 1 year or so indicating to me that there is some actually healing that has to occur. Things that change in days or immediate functional items. However, there is a whole chain of functional things that awaits some prior healing. Rapid epithelial healing is a good aiming point. Both lowering depression and increasing healing go together. Increase sensation in nerves, tingling, pain and all that usually indicates healing can be occurring. Some areas of numbness may increase before decreasing as the nerves start changing around. The FMS muscle pains are good aiming points. A decrease of burning pain can occur near 100% in 10 days. The "18" muscle points took about 2 years to fade after MeCbl, but only 9 months and 3 months respectively after AdoCbl and LCF.

    So the epithelial sores are good aiming points for l-methylfolate. In the presence of sufficient b12 their healing is almost entirely driven by l-methylfolate if all other needed cofactors (you know, A, D, C, zinc etc) are present. In each group of symptoms, by those pages of symptoms and nutrients I put up, a person can find their most active "aiming point" symptoms that signal nutritional effectiveness or not for that group. When healing is turned on differences are noticeable daily at first, then each few days and then a week or two, then barely perceptible over a month and then it's gone. In a month it can settle down from hundreds of things happening in a day to a few noticeable changes daily.
     

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