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Simplified Methylation Protocol Revised as of Today

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Mar 30, 2011.

  1. harrycat

    harrycat

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    Rich - can you advise which tests you recommend for people in the uk? I'm assuming the USA labs are not going to work. I have ordered the methylation panel from the Netherlands but stuck at the moment in finding a lab to centrifuge my samples!
     
  2. SaraM

    SaraM Senior Member

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    There was a long post by Rich about all the tests which should be done for a CFS patient. I can't find it here any more. Can anyone tell me where it is?
     
  3. madietodd

    madietodd Senior Member

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    Look at posts #300 and 307 in this thread.
     
  4. madietodd

    madietodd Senior Member

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    Rich -

    I've been on your protocol for 3+ months, have been sick with a head/chest cold for 2 weeks (partly detox?), and have decided to stay on your protocol while I wait for the results of all of the tests you recommended. [Meaning, not trying Freddd's at this time.]

    Meanwhile, I told you about a month ago that except for psoriasis (improved) all of my skin rashes have disappeared. And that my oldest daughter had decided to try the protocol for her skin. She's been detoxing like crazy - lungs and sinus - and she says her skin is clearing up.

    This leads me to a few questions.

    1. Is there one best test to have my children take, to see who has this deficiency? Or could I just test them by putting them on the protocol for a month (to see if they detox at all)?
    2. Does this protocol fix the problem, or just give us the missing pieces? Meaning, is this now a lifelong committment?

    Thanks for your help!

    Madie

    ps - an unrelated question. The holistic health multi has a small amount of folic acid in it. I believe you chose it because it's an easily available multi with much less folic acid than all the others (correct me if I'm wrong!). I thought I was going onto Freddd's protocol, so I bought all of the individual vitamins/minerals, and I have started taking those. The question is: Is this actually a better choice? Or is the amount of folic acid in 2 HH multis too small to make a difference?
     
  5. mellster

    mellster Marco

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    This might have been asked before, but is there a good differentiation between good detox and bad symptoms while on the protocol? What would be typical detox symptoms? Thanks
     
  6. richvank

    richvank Senior Member

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    Hi, Madie.

    I'm glad to hear that the treatment seems to be doing something good for you and your oldest daughter.

    I think the best test panel is the Methylation Pathways Panel from Health Diagnostics and Research Institute in New Jersey. This panel gives direct information about the methylation cycle, the folate metabolism and glutathione. These are all involved in the vicious circle mechanism that gives rise to the other features of ME/CFS and makes it chronic, in my opinion.

    Yes, one can just try the protocol and see if there are results. A month might be a little short, but perhaps younger people would respond faster than older people.

    We don't have a lot of data yet about the longer term. Based on my hypothesis and available research data, it appears that there is a genomic component to ME/CFS that makes a person susceptible to developing it if they are subjected to a high enough and long enough level of some combination of physical, chemical, biological and/or emotional/psychological stressors. If this is true, a genomically susceptible person will always be genomically susceptible, and if they come under a similar load of stress again, they could develop a new case of ME/CFS, though they had achieved recovery from the first one. If we have the mechanism figured out, and I think we do, then it would seem that the odds of avoiding a relapse could be improved my making sure certain nutrients, such as B12, folate and antioxidants, are maintained at good levels. That may mean that it will be desirable to take lower, maintenance dosages of corresponding supplements, or maintain a diet that is rich in these nutrients. But as I say, we don't have a lot of data yet, and I'm largely projecting from biochemical theory.

    I don't think the amount of folic acid in 2 HH multis is enough to make a difference, at least for most people, considering the higher dosages of the chemically reduced (active) folates in the protocol. Freddd (and apparently some others) are particularly sensitive to folic acid. I'm not sure why, but I've suggested that it might be a result of being very low in NADPH, which is made from niacin (B3) by the pentose phosphate shunt on the glycolysis pathway for metabolizing carbohydrates.

    The HH multi has some ingredients that were specifically chosen by Dr. Amy Yasko to support the methylation cycle and related biochemical pathways, so for people who can tolerate it (i.e. who don't have a sensitivity to any of the ingredients) I think it is beneficial to take it. The dosage is pretty low, because higher dosages at first tend to throw some people for a loop at first. Over time the dosage can often be increased to give more of the vitamins and essential minerals.

    Best regards,

    Rich
     
  7. richvank

    richvank Senior Member

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    Hi, mellster.

    Here are symptoms that were reported by various people during the first 6 months that the protocol was being used that I think are due to detox of toxins or die-off of pathogens:

    1. Headaches, heavy head, heavy-feeling headaches
    2. Alternated periods of mental fuzziness and greater mental clarity
    3. Feeling muggy-headed or blah or sick in the morning
    4. Transient malaise, flu-like symptoms
    5. Transiently increased fatigue, waxing and waning fatigue, feeling more tired and sluggish, weakness
    6. Dizziness
    7. Irritability
    8. Sensation of brain firing: bing, bong, bing, bong, brain moving very fast
    9. Depression, feeling overwhelmed, strong emotions
    10. Greater need for healing naps.
    11. Swollen or painful lymph nodes
    12. Mild fevers
    13. Runny nose, low grade sniffles, sneezing, coughing
    14. Sore throat
    15. Rashes
    16. Itching
    17. Increased perspiration, unusual smelling perspiration
    18. Metallic taste in mouth
    19. Transient nausea, sick to stomach
    20. Abdominal cramping/pain
    21. Increased bowel movements
    22. Diarrhea, loose stools, urgency
    23. Unusual color of stools, e.g. green
    24. Temporarily increased urination
    25. Transiently increased thirst
    26. Clear urine
    27. Unusual smelling urine
    28. Transient increased muscle pain

    Here are descriptions of the ones I would consider to be serious adverse effects, also during the first six months, which I wrote at the time (July 18, 2007):

    1. One person had had a history of severe pesticide exposure and also autonomous multi-nodular goiter, which she described as follows: Gradually the right lobe grew to over 4 cm x 4cm, and had to have right lobe out. . . This same surgeon made the decision to leave the left lobe in, as I had always had trouble with thyroid med back then too. So, they restarted my Synthroid and I stayed on that for [a] few more years. I ALWAYS had shortness of breath and became VERY tachycardic upon ANY activity. . . This person started the simplified treatment approach on March 21, 2007 (actually using higher dosages than suggested for FolaPro and Intrinsi/B12/folate). On May 19, she went to an emergency room with tachycardia, chest pain, trouble breathing, trouble sleeping, elevated blood pressure and fever of 100.7 F. She was admitted to the hospital and released the next day. No evidence was found for heart attack. This person later reported the following: I followed up with my PCP and had CT scan of neck and chest and my goiter is causing tracheal compression, again, and breathing is VERY hard. . . My area hospitals can't do this surgery because my goiter grows substernal, deep in my chest. This person has expressed a desire to continue the simplified treatment approach, but is currently exploring the possibility of first having additional surgery on the multinodular goiter.

    2. A second person had a history of lung problems due to both carbon monoxide exposure and exposure to molds, as well as heart-related symptoms. She started part of the simplified treatment approach on May 27, 2007. After having been nearly homebound for ten years, she was able to begin riding a bicycle. However, in early July, 2007, she went to an emergency room twice with severe breathing problems (shortness of breath), a fever of 99.8 to 100.1 F. that eventually lasted for sixteen days, and severe chest and left arm pain. No evidence was found for heart attack. She was diagnosed with an enlarged left atrium and diastolic dysfunction. She has currently discontinued the simplified treatment approach and is under the care of cardiologists.

    3. A third person had a history of autoimmune disease, including Sjogrens syndrome. After her fourth dosage of combined FolaPro and Intrinsi/B12/folate, she experienced a moderately severe autoimmune flare, with numerous joint and soft tissue issues, fatigue, pain, etc. She also experienced a severe flare of Sjogrens syndrome, with very dry mouth, dry eyes, and severe eye pain. Six days after discontinuing the supplements, she had a thorough ophthalmology workup and was diagnosed with autoimmune scleritis. She has been given topical steroids and has reported that her eyes are greatly improved.

    4. At least two persons experienced a temporary termination of peristalsis of the gut and consequent constipation after beginning the simplified treatment approach. In these two cases, induction of diarrhea cleared material from the gut, but did not restore the peristalsis. In both cases, peristalsis restarted twelve days after terminating the folate-containing supplements. One of these persons had a history of treatment with psychotropic drugs, including Klonopin. About 18 hours after starting to get relief from the constipation, she became very sick, with vomiting, vise-like headache, and shaking. She had many bowel movements over a ten-hour period, and then began to feel better. The other had a history of autoimmune diseases, including Sjogrens syndrome and Autoimmune Ovaritis, as well as diastolic dysfunction.

    Best regards,

    Rich
     
  8. madietodd

    madietodd Senior Member

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    Mellster -

    What I got is sudden blinding headache (2x) or milder all-day ache, mild nausea lasting all day, or sudden drenching sweat (3x). I got mild vertigo a few times too. These are all unusual for me. I found that drinking juiced green vegetables stops the symptoms almost immediately; some people also recommend lemon juice. There was a little discussion, not resolved, that maybe I was stopping the detox and not just ameliorating the symptoms. It didn't feel that way to me. Symptoms would also clear up immediately after a bm.
     
  9. mellster

    mellster Marco

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    Thanks for all your replies - I do get the intermediate tiredness/need to nap and the heavy head/headache and some pain/mild nausea, but not too extreme. Just started taking the exact couple of things mentioned and it seems like it started reducing the muscle twitch a little bit, but the jury is still out. I think this will be a good measure as I suppose neurological healing should calm down twitching. I was also asking since I am working so that I can limit higher doses to days where I am at home where it is easier to take care of any detox effects ;)
     
  10. Freddd

    Freddd Senior Member

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    Hi Rich,

    Don't you love non-specific symptoms. I find that almost every time somebody wants to call these symptoms "DETOX" that they are either induced potassium deficiency, induced folate deficiency caused by either paradoxical folate deficiency (folic acid, folinic acid, vegetable food source folate) and/or glutathione, glutathione precursors, NAC, and/or whey. A few are common startup responses of unknown causes.

    Color Code -
    • POTASSIUM DEFICIENCY
    • FOLATE DEFICIENCY
    • BOTH
    • TYPICAL STARTUP RESPONSE FOR UNKNOWN REASONS
    • NEUROLOGICAL STARTUP RESPONSE
    • COMING OUT OF FOLATE DEFICIENCY
    • UNKNOWN
    • FREQUENT LONG TERM MB12 DEFICIENCY SYMPTOMS

    1. Headaches, heavy head, heavy-feeling headaches
    2. Alternated periods of mental fuzziness and greater mental clarity
    3. Feeling muggy-headed or blah or sick in the morning
    4. Transient malaise, flu-like symptoms
    5. Transiently increased fatigue, waxing and waning fatigue, feeling more tired and sluggish, weakness
    6. Dizziness
    7. Irritability
    8. Sensation of brain firing: bing, bong, bing, bong, brain moving very fast
    9. Depression, feeling overwhelmed, strong emotions
    10. Greater need for healing naps.
    11. Swollen or painful lymph nodes
    12. Mild fevers
    13. Runny nose, low grade sniffles, sneezing, coughing
    14. Sore throat
    15. Rashes
    16. Itching
    17. Increased perspiration, unusual smelling perspiration
    18. Metallic taste in mouth
    19. Transient nausea, sick to stomach
    20. Abdominal cramping/pain
    21. Increased bowel movements
    22. Diarrhea, loose stools, urgency
    23. Unusual color of stools, e.g. green
    24. Temporarily increased urination
    25. Transiently increased thirst
    26. Clear urine
    27. Unusual smelling urine
    28. Transient increased muscle pain


    This is a well known potassium deficiency symptom pattern that may start as high as 4.2-4.3.
    At least two persons experienced a temporary termination of peristalsis of the gut and consequent constipation after beginning the simplified treatment approach. In these two cases, induction of diarrhea cleared material from the gut, but did not restore the peristalsis. In both cases, peristalsis restarted twelve days after terminating the folate-containing supplements

    Again here we have possible paradoxical folate deficiency.
    After her fourth dosage of combined FolaPro and Intrinsi/B12/folate, she experienced a moderately severe autoimmune flare, with numerous joint and soft tissue issues, fatigue, pain, etc.
     
  11. richvank

    richvank Senior Member

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    Hi, Freddd.

    Thanks for sharing your insights about the symptoms people have reported on the simplified treatment approach. (I especially like all the colors!)
    You have clearly been a very keen observer of your own experience, and I take your word on it that what you are reporting also represents the experiences of some others.

    As I've also written before, I think we do have to acknowledge that people are unique to some degree, inheriting different sets of genomic polymorphisms, which impact how they respond to treatments. And we also have to deal with the issue of having a fairly heterogeneous population in terms of the disorders that they actually have. I think that the new international criteria for M.E. that have recently been published are a step in the right direction toward tightening the specifications on the diagnosis of M.E., so that we can know that we are dealing with a more homogeneous group when we try to apply the results of a study group to others who have M.E.

    In view of this heterogeneity, I remain cautious in applying the results I see, as well as those you report, to everyone who has M.E. I think the data you present are interesting, but I have to apply a critical eye to it, just as I do to data that I or anyone else generate.

    I know that you have taken a dim view of the possibility that mobilization of stored toxins can account for some of the symptoms reported. I would like to suggest the possibility that indeed, some of the symptoms can be attributed to the deficiencies you have suggested, but that others may be due to mobilization of toxins, and perhaps some can be caused by either, since they are not all very well defined, as you noted.

    I think this is suggested both by observations and by what we know of biochemistry and physiology. I take your word, for example, on the symptoms you have been able to correct by adding potassium, and I think this lines up well with the biochemistry and physiology and what we think is going on during the methylation-type treatments.

    In particular, it is known that folate is needed to produce purines and thymidine, which in turn are needed to make RNA and DNA, and that these in turn are needed to make new cells. If a person is depleted in intracellular folate, it should be expected that their bodies have not been able to produce new cells as rapidly as is needed. One piece of evidence for this is the elevated value of mean corpuscular volume (MCV) that many have on the complete blood count (CBC). When the erythropoietic cells in the bone marrow do not have enough folate, they are not able to make new cells fast enough, and in the case of the red blood cells, they stuff more hemoglobin into the ones they are able to make, causing them to be larger. We should expect that the same problem must exist for other cell types that are rapidly turned over, such as those lining the intestine. I think it is probable that part of the cause of the "leaky gut" experienced by so many as multiple food sensitivities can be traced back to the inability to make new cells to line the gut rapidly enough.

    Given this situation, we should expect that when the intracellular folate levels are raised by treatment that includes both folates and vitamin B12 (the latter being necessary to promote the methionine synthase reaction to use methylfolate and convert it tetrahydrofolate, thus preventing draining of methylfolate from the cells via the "methyl trap" mechanism), the body will now be able to start making new cells at a faster rate to make up for the deficiency of new cells that has existed during the illness.

    As you know, new cells require more than RNA and DNA alone. They need ionic species, amino acids, and fatty acids in particular. The main ionic species they need is potassium ions. There are reservoirs elsewhere in the body for most of the species needed to make new cells. For examples, the muscles are a reservoir for amino acids in the form of protein, and the bones store a great deal of phosphate. But potassium is found mainly inside cells (98%), which are likely in short supply in this illness because of the longstanding intracellular folate deficiency, so this potassium would likely not be very available for making new cells.

    It is therefore to be expected that a potassium deficiency would appear if the rate of production of new cells were suddenly increased, as from a protocol including both high-dose B12 and folate. The known symptoms of potassium deficiency, which shows up as low levels of potassium in the blood (hypokalemia) depend on the individual and the severity of the potassium deficiency. These symptoms involve the heart, the skeletal muscles, the smooth muscles, and kidney function.

    The heart exhibits arrhythmias, and in severe potassium deficiency develops ventricular tachycardia which can lead to death. The skeletal muscles exhibit weakness, fatigue, cramps, fasciculations and rhabdomyolysis (breakdown of muscle tissue). Breathing can become difficult because of effects on the muscles involved in breathing. Smooth muscle problems include constipation and ileus (a paralytic blockage of intestinal transport). Severe potassium deficiency affects the nervous system, causing flaccid paralysis, hyporeflexia, and tetany. Kidney-related symptoms are excessive urination and thirst.

    You have suggested that the two cases of constipation (or perhaps ileus) that were reported on the simplified treatment approach may have been due to temporary potassium deficiency. I think you may be correct about this. I note that additional fatigue as well as weakness was also reported on this treatment, and perhaps they were also due at least in part to temporary potassium deficiency. The transient increased muscle pain that was reported may also have been due to temporarily low potassium. There were two cases of difficulty breathing. One was apparently due to swelling of an existing goiter, but the other may have been at least partly due to temporary potassium deficiency. Perhaps the temporarily increased urination, transiently increased thirst and clear urine that were reported can also be attributed to low potassium. I think it is notable that arrhythmia was not reported. As I have posted in the past, I think that problems with potassium deficiency are likely to be less severe if lower dosages of B12 and the folates are used, as in the simplified treatment approach, so that the body is able to respond more gradually, and potassium intake from food is more likely to be able to keep up with the demand. Nevertheless, there do seem to be some symptoms that can be attributed to potassium deficiency even with a "low and slow" methylation treatment.

    What about the evidence that mobilization of toxins may be responsible for some symptoms on this type of treatment? From the biochemical point of view, it is known that the body's detoxication system relies to a large extent on sulfur-containing substances, including glutathione, cysteine, taurine, and sulfate. We know that the methylation cycle lies at the beginning of the body's sulfur metabolism and that it normally exercises control over the sulfur metabolism. We also know that in M.E. there is a partial block in the methylation cycle and that the sulfur metabolism is dysregulated. In particular, glutathione is depleted in most cases, and often the levels of cysteine and/or sulfate are low. Under these circumstances, we should expect that the detox system will not be operating properly, and toxins will therefore build up in the body. Indeed, many people with M.E. have taken a detoxication profile panel and have typically found low Phase II glutathionation, and sometimes low sulfation as well. Lab measurements in many cases have found elevated levels of toxic heavy metals, in particular, and analysis of the mitochondria have shown elevated levels of both toxic metals and organic toxins in cases of M.E.

    We should also expect that when the operation of the methylation cycle is restored and glutathione is brought up to normal, that the detoxication system would begin to operate more normally, and would start to work down the backlog of stored toxins. The action of the detox system in various cells, tissues and organs is known to first move toxins into the bloodstream. There is a time lag before these toxins are removed from the blood by the kidneys, liver and sweat glands,and are excreted. If the digestive system is not functioning well, more of the toxins excreted into the gut in the bile from the liver will be reabsorbed and can stay in the blood longer. It can be expected that the higher levels of toxins temporarily in the blood will affect the cells of the body in general, and that this might lead to a variety of temporary symptoms.

    There is evidence that toxins are mobilized and excreted when methylation treatment is given. In autism. which shares the partial methylation cycle block with M.E., Dr. Amy Yasko has compiled large amounts of data showing increased excretion of heavy metals during this type of treatment. Some who have M.E. have also observed this in urine toxic metals testing. Repeat mitochondrial analysis in some has shown clearance of toxins formerly found in the mitochondria after being on methylation treatment for a few months.

    Reports of the benefit for ameliorating symptoms of adding substances known to bind toxins in the gut, such as activated charcoal, or substances known to promote increased excretion of certain toxins (weak acid type) by the kidneys, such as lemon juice, are further evidence that toxins are being mobilized during methylation-type treatment.

    Considering symptoms that would be likely to result from increased mobilization and excretion of toxins, it seems that the most direct connection could be made with those that involve the main known routes of excretion of toxins, i.e. the urine, stools and perspiration. Transient changes in the amounts, smell, or appearance of these substances would be very suspect of being caused by excretion of toxins, in my opinion. The metallic taste in the mouth would also be suspected of being due to mobilization of toxins, in my opinion. I think that skin-related issues such as temporary rashes and itching could be caused by mobilized toxins as well.

    I realize that you have attributed several of the reported symptoms to folate deficiency, based on your experience, and I have no reason to doubt your interpretations in your own case.
    However, as I've noted before, I am not sure how widespread this "paradoxical folate deficiency" that you've reported to be caused by taking folic or folinic acid or glutathione-related substances actually is in the M.E. population. It does appear, though, that there are some others who do share your experience. I think it's also possible that some symptoms that are not very specifically defined could be produced by more than one cause in different people.

    So in conclusion, you have convinced me of the importance of potassium deficiency in producing symptoms during methylation-type treatment, even treatment that is more "low and slow" than the protocol you advocate. I am also willing to believe that in your case, and in some others, some symptoms may be caused by induced folate deficiency caused by some substances in some of the methylation protocols. As I've noted in the past, I agree with you that the folic acid form of folate is best minimized. However, I continue to believe, based on the evidence I've cited, that mobilization of toxins is likely to account for some of the reported symptoms as well. So that's where it currently stands as far as I'm concerned, but I am continuing to keep an open mind for more evidence one way or the other, and I very much appreciate your sharing your experience and insights.

    Best regards,

    Rich
     
  12. mellster

    mellster Marco

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    Fredd - how much pure potassium should one take? - most come in bound form, e.g. as potassium gluconate, so it would be good to know how much of those or how much total pure potassium we should shoot for. Thanks!
     
  13. Freddd

    Freddd Senior Member

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    Hi Rich,

    I don't dismiss the possibility of a wide variety of possible causes including actual detox induced symptoms. The problem is in the identification of such. I would very much like to be able to extract-develop the pattern of the actual detox symptoms and what they mean. That is made very difficult when the word "detox" is applied to folate deficiency from just plain not having enough, from paradoxical folate deficiency and from methyl-trap, from low potassium, from B-complex once a day instead of twice a day (not known which short serum halflife factors are causing problem but some do and no doubt some other induced deficiencies and some perceptual changes caused by an awakening neurology and methylation.

    Some of the real detox symptoms may be made much worse by methylfolate and methylb12 deficiencies causing a hyper reactivity to the toxins. Methylb12 is a general detoxifying agent, especially within the CNS, that is destroyed or inactivated in the act of detoxing a wide variety of toxins both chemical and biological. The lack of either or both in sufficient amounts can cause an hyper-reactive response with Multiple Chemical Sensitivity, hyper-reactive nerves, inflammation of all sorts of tissues, augmented allergy responses, augmented asthma responses, increased pain, nausea, IBS, increased edema and so on.

    you have convinced me of the importance of potassium deficiency in producing symptoms during methylation-type treatment, even treatment that is more "low and slow" than the protocol you advocate

    It appears that some responses to b12 and folate are binary; either impaired or not impaired. 10mcg of mb12 is enough to produce normal blood cells if it was caused by b12 lack. In the literature the utilization of small amounts of mb12 is said to be subject to an internal triage system that is not understood. Some things will get enough b12 for a while to correct while other things continue to be starved and malfunctioning. This is probably part of the active delivery system. Some things just will not heal at all until everything the body considers more important are supplied. It isn't supplied round robin. The blood corrections alone are enough to cause a low enough potassium to cause problems even if not below 3.5. The muscles starting to rebuild alone are enough to trigger low potassium. The epithelial tissues healing alone are again, sufficient to cause low potassium. In this test dependent treatment pattern that has developed, if the potassium isn't down to below 3.5 there "is no problem" which is pure bunkum. So low enough potassium to cause problems will often not be recognized because it is merely "functionally" low, not officially low. Each time a folate deficiency develops, the cell formation stops or malfunctions and lesions in the epithelial tissues at least can develop in 24 hours or less. Each time it starts up again and continues for a few days potassium can drop. If the perrson developes edema during low folate then as soon as the water is moved out rapidly (some pounds per day) potassium can drop the very first day. Whether this happens in 10% or 90% of people, and there are so many possible casues when you consider both methyl-trap and paradoxical folate deficiency as well as just plain not enough folate for the demand, it is dangerous to call it "detox".



    In the CFS/FMS cohort it is useful to peel the layers off by going after the most probable first. And all of these things can come and go rapidly. The on and off pattern is very prevelant with the folate deficiencies followed by potassium deficiency. The potassium is very touchy since there may be no symptoms at 4.3 and a couple at 4.2 and even more at 4.0. However, which ones appear first appear quite variable amongst people. For me it is abnormal spasms. Mood, personality and fatigue changes come later. People can change that with a single meal or supplement for a few hours and go into and out of it several times per day. The order with estimates of frequency and totals in excess of 100% because many persons have more than 1, appears to be:
    1. Low Potassium (90%?)
    2. Induced folate deficiency any cause (60%?)
    3. Other possibly induced deficiencies (any of a dozen or so) (30%?)
    4. Actual Detox not hyper sensitized by low mb12/methylfolate (appears to be under 10-20%?)
    We should expect that the same problem must exist for other cell types that are rapidly turned over, such as those lining the intestine. I think it is probable that part of the cause of the "leaky gut" experienced by so many as multiple food sensitivities can be traced back to the inability to make new cells to line the gut rapidly enough.

    In me, IBS and other such symptoms develop in 4-5 days of folate deficiency and takes about 5-10 days to diminish after ending the deficiency. The intestinal epithelium is very sensitive to a lack of methylfolate. For me, the order of onset is angular chelitis in 24 hours, bumps under skin of scalp in 24-48 hours, open acne type lesions on scalp in 48-72 hours, similar facial lesions in 72-96 hours, IBS in 96-120 hours, rest of body epidermis in 5-8 days. I've been through hundreds of such cycles, all my life. However, until recently I have never in my life maintained sufficient methylfolate for the cheilitis to heal fully. I have scars upon scars upon scars around the corners of my mouth from a lifetime of this stuff. As open sores they get infected easily too.


    The heart exhibits arrhythmias, and in severe potassium deficiency develops ventricular tachycardia which can lead to death. The skeletal muscles exhibit weakness, fatigue, cramps, fasciculations and rhabdomyolysis (breakdown of muscle tissue

    Another confounding issue with this entire set of symptoms is that they are also caused by mb12 and/or adb12 deficiencies by both direct mitochondrial failure and neurological malfunctions among many other things. The rhabdomyolysis is a cause of release of "stored" b12 into serum. It's a hard way to maintain serum b12. Timing of symtoms and variability of symptoms can be as much of a tipoff as the symptoms themselves.

    However, I continue to believe, based on the evidence I've cited, that mobilization of toxins is likely to account for some of the reported symptoms as well.

    Probably. However it is impossible to tell what they are without eliminating all the other stuff first.

    Smooth muscle problems include constipation and ileus (a paralytic blockage of intestinal transport). Severe potassium deficiency affects the nervous system, causing flaccid paralysis, hyporeflexia, and tetany. Kidney-related symptoms are excessive urination and thirst.

    Tetany can also be caused by too much calcium in relation to other minerals. Yet again a confounding factor.

    Kidney-related symptoms are excessive urination and thirst.

    I didn't know that. Thankyou.

    However, as I've noted before, I am not sure how widespread this "paradoxical folate deficiency" that you've reported to be caused by taking folic or folinic acid or glutathione-related substances actually is in the M.E. population

    In coming into this forum fresh, these folate deficiency symptoms of whatever cause were very outstandingly obvious as extremely frequent compared to the wd forum. It was clearly an artifact of treatment as the people on the active b12s with metafolin who didn't take glutathione (precursors) just plain didn't experience it with any frequency though a few did. I'd literally never seen such a concentration of people suffering so severely from this. It has taken me several years and the personal experience from multiple causes to see it and understand it. There are more people experiencing it than will post about it on the forums but will tell me privately.

    I think it's also possible that some symptoms that are not very specifically defined could be produced by more than one cause in different people.

    I couldn't agree more. So for instance, on the list I have 11 types of muscle pain with various causes described.You have seen the most up to date version of that so yopu are aware of the distinctions being made. You indicated you weren't sure how it could be used. If it is all rolled into one all encompassing fuzzy definition there is no clarity in it. It becomes like "neuropathy" being on the official b12 deficiency lists. That covers so many different things of different causes that it is almost meaningless. Calling low potassium "detox" and low folate from half a dozen causes "detox" only causes confusion and actual danger to the persons because the response is wrong based on an incorrect word beibng applied too widely. A friend of mine named her software company "Fine Distinctions". Without making fine distinctions this whole mess will never be understood.

    In making more distinctions about ME to get a better definition perhaps it will help. However, the wrong distinctions, or at least incorrect understandings and assumptions, can hinder understanding.

    In view of this heterogeneity, I remain cautious in applying the results I see, as well as those you report, to everyone who has M.E. I think the data you present are interesting, but I have to apply a critical eye to it, just as I do to data that I or anyone else generate.

    Over specificity can be as similarly large problem as under specificity. That's what stepwise refinement is about. Without enough specificity root causes can never be found. With over specificity, root deficiency effects and needed cofactors get confused with root causes. I'm working on a "family tree" of all these things. They appear to fall into place rather well. If one takes ME to be the effects of CNS mb12 deficiency primarily modified by the other 3 b12 deficiencies and the folate deficiencies and other cofactors, it appears that way because of the central neurological symptoms and modified by additional things. FMS and CFS appear to have a different balance of the 6 primary deficiencies along with different secondary deficiencies.

    The metallic taste in the mouth would also be suspected of being due to mobilization of toxins, in my opinion.

    Well, let's look at the things that do show up when looked for. Perhaps it is due to mobilization. However, when an abcess opens up and starts draining into the mouth you can get that metallic taste. When there are gum infections you can get that taste. When there is periodontal disease you can get that taste. These are ALL toxins that are draining into the mouth but from correctable causes that have nothing to do with detox. Everybody who doesn't floss every day is at risk. Everybody with impaired immunity from lack of folate/mb12 is at risk of out of control gum infections and if they also don't floss double trouble. Further mb12 deficiency causes multi sensory hallucinations from metallic tastes and other tastes, altered sense of tase, lack of sense of taste, to strange smells, lack of smells, altered smells, and noises that nobody else hears and movement out of the corner of the eye nobody else sees and voices you can't quite make out. Further when non-functioning nerves start coming back all sorts of weird tastes, smells etc can happen even more. If there is a metallic taste after the person has established good oral health and maintains it by brushing and flossing every day and has been checked for absesses by a dentist, and their gums don't bleed when brushed I will be more likely to grant it some credibility. Blood tastes metallic. Then there is the smell test. If a person has bad breath they are going to have "tastes" including espcially metallic if the nerves are working and they haven't totally learned to ignore it. I can smell a person with peridontal disease across the room. I can walk into a confined airspace such as a house and identify peridontal disease even if the person isn't home at the time. In that case it smells something like the stink put into natural gas. When I worked in the field and was in a lot of houses I identified a number of natural gas leaks walking in the door. I worked at supervising more than a dozen insurance companies dental plans for 20 years among other things. This is like they found after all the sickness from Desert Storm. When all these "strange" conditions were given the checkout they should have had from the beginning, more than 90% were diagnosed with known conditions, including valley fever, CFS, FMS etc. Only a few with puzzles remained. How many here are at full maintenance condition in their mouths? 10%? 20%? How many floss every day without ever skipping it? 10%? 20%? Look at all the mouthwash that is sold to mask the stench. That stench has a taste.


    I think that skin-related issues such as temporary rashes and itching could be caused by mobilized toxins as well.

    Mb12 and folate deficiency causes a multitude of these as well as itching with no rash. Again these are among the most common b12 deficiency and folate deficiency problems. When methylation gets going and these get healing the whole layer of badly formed tissue can be pushed to the surface and shed by well formed tisues.


    As I have posted in the past, I think that problems with potassium deficiency are likely to be less severe if lower dosages of B12 and the folates are used, as in the simplified treatment approach, so that the body is able to respond more gradually, and potassium intake from food is more likely to be able to keep up with the demand.

    The BIG problem I have with that is that for those with low CNS levels of cobalamin regardless of serum levels of cobalamin (as found by studies of CSF cobalamin levels of those with CFS and FMS) is that the CNS damage can continue to worsen for years more causing more damage and more permanent damage. Years of delay has cost me dearly and will cost folks here dearly too. It doesn't pay to keep starving your brain and spinal cord, for additional years or decades, of what it needs to heal, if started soon enough. I have had person after person tell me that they had no idea that they had so much neurological damage until their nerves start functioning again and are obviously damaged. Damage disappearing from awareness becasue of lack of neurological funtionuing might allow a person to keep do what they do until it breaks down even further. Avoiding having to take potassium as a supplement seems like a very poor reason to increase damage for years to ones central nervous system.
     
  14. harrycat

    harrycat

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    I have read these posts with interest. Since being on the SMP - about 2 weeks - with some extra c, d, magnesium, potassium and fish oil things are looking up. My neck (which has never improved in almost 20 years) is consistently the best it's ever been. I'm amazed each day I wake up that it's still good and this isn't a flash in the pan. I can't put into words how happy I feel about this one thing - just to have a neck that is looser and moves more freely without as much crunching and cracking is wonderful:)

    My sleep is better too. Initially I had a strange experience of still waking a lot but the night feeling incredibly long - so I felt like I'd had 2 or 3 nights sleep in one go! Strange but there it is. The last 3 nights I have just slept much more solidly than I can ever remember. Again- priceless to me.

    My facial skin is puzzling me. The first 3 days on the SMP my skin was transformed from dry, flaky round my nose and chin, slight cuts at corners if mouth, to smooth and almost perfect. It seemed to be after the hydroxyb12 drops that it improved. For the last week it hasn't been as good and I don't know why. Now it's more flaky again when I wake in the morning especially and the small cuts are slightly visible. Is this suggesting I need more b12? I know rich suggests staying on the SMP as it is for 3 months ... But in my case I wonder if the improvements plus this indication suggest I need a larger dose? The trigger point in my jaw that was improving also now seems to have backtracked (although a 15 year collection of them in my trapezius is softening!!)

    I'm going to get the metabolic profile, amino acid plasma and a GI test ASAP and still waiting for the methylation panel results....
     
  15. lucyhem

    lucyhem

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    Montague, MA
    My experience w supplements is that i generrally respond in seconds, minutes, hours or days if i have a good response. Rarely has my initial response improved over weeks or months. When I tried Deplin a few months ago I had am immediate dramatic response that then waned. I am thinking that three months is a long time to stay with the protocol without tweaking it if things continue as they are now. Rich, I appreciate your care and caution, but I also feel, like Fredd, a sense of urgency about my nervous system which is having many frightening symptoms. I am thinking to go another week and then try another from of B12. I am taking Hydroxy now. Any harm in trying that?
     
  16. richvank

    richvank Senior Member

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    Hi, Lucy.

    I think you should do whatever makes sense to you, given your situation and results so far. There's nothing magic about the three months. I've suggested it because some people take time to respond, and this should be an adequate time to see if the protocol is going to help. If you tend to be a fast responder, then you may be able to tell what's going to happen sooner. So I would say, go for it if it makes sense to you. I'll be interested to see if things improve for you.

    Best regards,

    Rich
     
  17. richvank

    richvank Senior Member

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    Hi, harrycat.

    Quite a few people have reported some positive developments early on, and then have come some that aren't so great. I've interpreted this latter effect as being due to the detoxication system beginning to operate more normally, mobilizing toxins.

    I think you may need to give it some more time to see if things will turn around again, but it is possible that more B12 would help. If you are able to tolerate the symptoms you are experiencing at the current dosage, you might consider increasing it. Different people have differing requirements because of the differing genomic polymorphisms they have inherited, so it isn't possible to state exactly what the dosages should be for everyone.

    Best regards,

    Rich
     
  18. Freddd

    Freddd Senior Member

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    Hi Harrycat,

    Sounds like things are progressing. You NOW have some aiming points. You know what changes you are looking for. The skin changes and the sores at the corners of your moutrh suggest that you need more Methylfolate and/or mb12, probbably "and". Those are usually the key. However, it can also indicate low folate because of an induced folate deficiency for any of the usual reasons including the healing itself depleted it. However, certain secondary basics from vit A to Zinc and even b-complex only once a day, can be involved so start with the most likely and go from there. Since it is renewed every day it's easy to test the hypothesis. Isn't it great to have decent skin again? On your skin you can see the changes in a day or so as you get practiced. Not everybody has such easily seen changes. Some have mood changes just as variable. Good luck. keep it going.

    A common symptom of ME is a neck with painfully tight muscles pulled out of alignment and even pulled into a reverse curvature that is extremely "through the roof with a touch" pain. There were days I literally could not lift my head off the pillow for the pain and had to put on a soft collar to get a little support to get up. This appears to be partly neurological and partly mitochondrial in the mix of symptoms from the analysis I have done.
     
  19. Freddd

    Freddd Senior Member

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    Hi Lucyhem,

    When I tried Deplin a few months ago I had am immediate dramatic response that then waned

    This is a very common response to these things. Usually it appears to be running out of somethiong else. When "A" is the most limiting factor, add "A" makes noticable progress. As soon as it is sufficienct, it's utilization often causes something else to be the most limiting factor. Adding all of the 20 or 30 other items 1 at a time trying each one in turn until it works and then it stops again with something else now the most limiting factor. It can take years to work through 20-30 items 10 times trying to find the magic BB each time. it is possible to have sustained healing. When I was comparaing mb12 brands the "scratch" mb12 supplement was what each other btrand was tested agianst. If there was fallback, the measure of how good it was depended upon how rapidly and severely there was reversal. Within 7 days the zero star brand had all 5 testers refuse to continue because the fallback was so fast, hard and complete. With the Jarrow and Enzymatic Therapy there was continued progress and no fallback. Instead additional things upped the completeness and speed of healing if they had become the most limiting factors at there present level. So 50mg more zinc made a huge difference, 5000IU up from 2000iu of D made a small difference, SAM-e made a moderate amount of difference. L-carnitine fumarate made a HUGE difference. Which things or combinations of things is individual. For people who only take a little C, that can make a big difference.

    The whole method I use is to be able to feel the changes rapidly and then tune for them trecognizing that healing doesn't always feel good. Some tissues itch like hell when they are healing, at least they did for me. Nerves can cause intense and terrible pain while healing, but usually for a short time, in pulses for the worst. There is a progression from jolts of pain to intense tingling to heat to hyper sensitive to more normal feeling and this can vary. "BAD" changes are feeling the neuropathies progressing up the arms and legs, feeling of feet and legs towards numbness and lack of awareness. Sometimes one simply feels "change" and can't tell the direction for a while.

    Starting in a couple of days I'm going to be traveling, camping and visiting friends and cousins I haven't seen in a year or more and in one case, 50 years. It turns out all my Eastern cousins I haven't seen or hear from in decades moved west. I will sign in and try to at least read things and offer probably brief comments but I won't always have much access.
     
  20. lucyhem

    lucyhem

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    Montague, MA
    I have read these posts with interest. Since being on the SMP - about 2 weeks - with some extra c, d, magnesium, potassium and fish oil things are looking up. My neck (which has never improved in almost 20 years) is consistently the best it's ever been. I'm amazed each day I wake up that it's still good and this isn't a flash in the pan. I can't put into words how happy I feel about this one thing - just to have a neck that is looser and moves more freely without as much crunching and cracking is wonderful:)

    That is great to hear about your improvements. What was going on w neck? Mine is like a steel girder. I have developed stenosis in my neck from all the tension. I wonder if it is nervous system related. It is unrelenting and painful especially when I wake. Anything like that?
    Wonderful to hear about good sleep.


    My sleep is better too. Initially I had a strange experience of still waking a lot but the night feeling incredibly long - so I felt like I'd had 2 or 3 nights sleep in one go! Strange but there it is. The last 3 nights I have just slept much more solidly than I can ever remember. Again- priceless to me.
     

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