The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Glutathione: How long does initial detox last?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by lizw118, Mar 27, 2012.

  1. lizw118

    lizw118 Senior Member

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    Hi all
    I have been taking glutathione for a couple of weeks now in addition to the methylation supplements. I have noticed that on some days I am in a rotten mood and my skin looks bad. I wonder if this could be a detox reaction. Is that possible? I just started taking ALA and charcoal in hopes that I can move toxins out of my body faster. How long does it take to get built-up toxins out of the system after starting glutathione?
    Thanks
    Liz
     
  2. Lotus97

    Lotus97 Senior Member

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    Hi, Liz. Since this is a relatively old thread I'm wondering if you've figured out what was causing the detox because methylation, ALA (Alpha Lipoic Acid), and Glutathione all can cause detox reactions in some people. I've found that for the people who need to detoxify the most also have the hardest time doing so. It's a true, but unfortunate irony.
     
  3. Lotus97

    Lotus97 Senior Member

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    As for Alpha Lipoic Acid, both Rich and Andy Cutler say that it can mobilize mercury and possibly cause it to be redistributed in the body including in the brain. One of the things I loved most about Rich is that he understood that everyone is different and so he custom-tailored his responses to each person's unique situation rather than a one-size-fits-all answer based only on one's own experience. He explains the possible consequences of taking too large a dose of methylcobalamin and methylfolate. This from Rich:

    "I actually prefer including both folinic acid and 5-MTHF. 5-MTHF is the form needed by methionine synthase, which is the enzyme with the partial block. Many people's cells are able to convert folinic acid to 5-MTHF well, but many others have inherited genetic polymorphisms that slow this conversion down considerably. The polymorphisms in the MTHFR enzyme are a good example, and these are very prevalent in the population.
    Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.

    I prefer hydroxocobalamin for several reasons. One is that it allows the cells to control the amounts of the coenzyme forms of B12 (methylcobalamin and adenosylcobalamin) that they make, so that they can be matched to the need. Taking methylcobalamin in large dosages by injection or sublingually can overdrive the methylation cycle, as evidenced by a major rise in sarcosine, which I've seen in amino acids testing on some people who have been on this treatment for a while. I am not comfortable with overdriving the methylation cycle, both because I think it slows flow down the transsulfuration pathway and thus limits the normalization of the balance of the sulfur metabolism, including cysteine, glutathione, taurine and sulfate, and also because I am concerned about the possibility of overmethylation of DNA, which could have other deleterious effects.

    My other concern is that methylcobalamin is known to be chemically able to methylate inorganic mercury. Many PWCs have significant body burdens of inorganic mercury as a result of having amalgam fillings in their teeth during an extended period while glutathione has been low, so that they have not been able to detox mercury at normal rates. Methylmercury can cross the blood-brain barrier readily. Mercury is a potent neurotoxin if it gets into the brain. This problem has been observed in guinea pigs. I don't have solid evidence for it in humans, but have heard from perhaps three people who may have had this problem, based on what they have reported. So I prefer to be cautious.

    This having been said, some people have had good experience with methylcobalamin. It can be especially helpful if a person has a shortage of methyl groups, though that can also be helped by taking some additional trimethylglycine (some of which is in the multi that is part of the simplified treatment). or some SAMe. It's used a lot subcutaneously by the DAN! doctors in autism treatment, and as you probably know, freddd on this forum advocates its use as well. In his case, because of a mutation in the intracellular B12 processing enzymes, his body is not able to utilized hydroxocobalamin readily. But I believe that this is a rare situation, based on the published literature. freddd does not agree that it is rare, based on his experience.

    Best regards,

    Rich"

    He also explains why some people benefit from Glutathione while others suffer adverse reaction.

    Hi, all.

    The question of whether to supplement glutathione in some way in conjuction with treatment of the partial methylation cycle block in ME/CFS often comes up. There is some recent research that appears to shed some light on this issue, so I would like to
    review the status of at least my understanding of it.

    As I see it currently, there are three groups of people with respect to their response to
    adding glutathione to methylation treatment:

    1.There is a group who benefit from this addition, in terms of their symptomatic response.
    2.There is a group who benefit initially, but as time goes on, it causes their symptoms to worsen.
    3.There is a group who experience immediate worsening of their symptoms.

    I dont know what fraction of the ME/CFS population is in each group.

    I would like to suggest what I think is going on in each of these groups.

    I suggest that the first group have inherited normal genotypes of their intracellular B12 processing enzymes, and they also have normal status of vitamins B2 and B3. In this group, the glutathione can be recycled at a normal rate when it becomes oxidized by reactive oxygen species that are part of the oxidative stress in ME/CFS, by the glutathione reductase reaction, which requires both B2 and B3. Furthermore, glutathione
    is able to play its normal roles with respect to the intracellular processing of vitamin B12.
    In particular, the Cblc enzyme (also known as MMACHC) uses glutathione to remove the upper ligand from incoming forms of B12 (cyano-, methyl- or adenosyl-) by the formation of glutathione conjugates of these ligands (PMID: 19801555).
    In addition, it appears that glutathione also reacts with the resulting aquocobalamin to form glutathionylcobalamin. Glutathionylcobalamin is chemically more stable than the other forms of B12, but Cbcl is normally able to retrieve cobalamin from glutathionylcobalamin so that the cobalamin can be used to form methylcobalamin and adenosylcobalamin in the amounts needed by the cell (PMID: 21429294).
    Thus, glutathione appears to serve not only as a reactant in the metabolism of B12, but also as a protector of B12 from reactions with toxins, and a buffer to store B12 until it is needed by the cell.

    I suggest that the second group have inherited normal genotypes of their intracellular B12 processing enzymes, but they have a deficiency in B2 or B3 or both, so that the rate of the
    glutathione reductase reaction is too slow to keep up with the oxidation of the glutathione. As a result, though the supplemented glutathione is initially beneficial to them, over time it becomes a detriment, because the ratio of reduced to oxidized glutathione drops too low, and this worsens the oxidative stress of the cells.

    I suggest that the third group has inherited an inborn error of metabolism involving the Cblc enzyme. As a result of this, when glutathione reacts with B12 to form glutathionylcobalamin, their genotype of the Cblc enzyme is unable to retrieve the cobalamin from the glutathione to use it to form methylcobalamin and adenosylcobalamin. If glutathione is supplemented, this situation is made worse for this group. In addition, this group is unable to make use of hydroxocobalamin as their B12 supplement
    (PMID: 21497120), because it is converted to glutathionylcobalamin in their cells (even without supplementing glutathione) and is therefore made inaccessible. I suggest that Freddd is in this group, and this explains why he cannot tolerate supplementing glutathione, why he cannot make use of cyanocobalamin or hydroxocobalamin, and why he must use high dosages of methylcobalamin and adenosylcobalamin, applied either sublingually or by injection. This raises the concentration of these species in the blood stream, and enough of them is able to diffuse into the cells through their plasma membranes to be used directly without intracellular processing, thus supplying the need of his cells for methylcobalamin and adenosylcobalamin.

    Best regards,

    Rich
     
  4. Freddd

    Freddd Senior Member

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    Hi Liz,

    When I tried glutathione precursors including NAC, I had terrible "detox". I was doing this with 10 other people in a trial, all of them successful with the AdoCbl, MeCbl and l-methylfolate. They all got clobberred with "detox". We stopped the trial after 6 weeks and we were all quite ill again, a terrible setback and return of all the old symptoms. These lasted 6 months beyond the end of our trial until we all took larger than usual doses of AdoCbl, MeCbl and L-methylfoalte. We found that taking the L-methylfolate first was important as it appeared to allow a lot more retention of the larger than usual doses of AdoCbl and MeCbl we all took to reverse the "detox' symptoms". We all sucessfully reversed the symptoms over a couple of weeks. My additional neurological damage has never quite gotten back to where it was before the glutahtione trial. From a personal point of view it was a disaster for me. From an informational viewpoint it demonstrated that the symptoms line right up with the methyl trap version of paradoxical folatge deficiency. Good luck. I hope you find what helps. BE IN GOOD HEALTH.
     
  5. Adster

    Adster Senior Member

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    The other possibility for a "detox" reaction to glutathione and precursors such as NAC could be a die off or herxheimer reaction from a Chlamydia infection being killed. My understanding is that it has been shown that these agents, disulphide bond reducers, are effective at killing the elementary body stage of these infections.
     
  6. alex3619

    alex3619 Senior Member

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    I want to point out that glutathione drives the desaturase enzymes (their activity it associated with glutathione status) which means you can make more arachidonic acid. This is probably over-utilized in us. leading to more pro-inflammatory eicosanoids. This is a flu-like feeling with headaches in its full manifestation.

    Until the anti-inflammatory and other processes that correct excessive arachidonic acid metabolism are in place such symptoms may continue. I am not entirely sure how to quell this reaction - omega-3 fats are traditional, someone here take quercetin for that response, I take resveratrol. Its possble that normalization of body chemistry can correct this over time. Its also possible that this is only one of several mechanisms in play.

    I do note that on resveratrol the "low potassium" symptoms I used to get disappear. I don't think most of us are potassium deficient on methylation protocols. I think the extra potassium is acting like a drug, not to fix a deficiency. I could be wrong of course: we are all guessing.
     
  7. Freddd

    Freddd Senior Member

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    Hi Adster,



    You know, I've actually had a herxheimer reaction when a drug resistant pneumonia was killed of by a combination of really nasty anitbiotics. The first 6 antibiotics, in sets of 3, tried had falied to touch it at all. It was really really nasty for a day or so, herxheimer reactions are fortunatly self limiting. You get a big kill off of bacteria and the toxins are released. This happens with the fast killoff from antibiotics. I find exactly reference one in Google scholar in one of Rich's papers, an early version before methylation theory.



    http://www.aliveandwellsf.org/articles/NEW%20ARTICLES/GSH_chronic_fatigue.pdf from a conference presentation in Wisconson in 2004. He suggests that it could cause so much immune response, as a startup response to glutathione.



    There are also some cautions that should be exercised. When repletion is begun in patients who have been GSH-depleted forextended periods of time, their immune and detoxication systems can begin to function at higherlevels of performance. If their bodies have accumulated elevated levels of toxins (especially mercury) and infections, glutathione repletion can cause significant Herxheimer-type reactions as pathogens are killed and toxins are mobilized. Careshould be taken to proceed slowly and cautiously in such cases in order to avoid moving toxins into the central nervous system or exacerbating symptoms to a level that is intolerable to the patient

    .

    There are a multitude of references of Herxheimer reaction to Chlamidia, with antibiotics and combination antibiotics in peer reviewed articles, including Herxheimer himself. However, I can not find a single article, and none are referenced in the paper that include Herxheimer reactions, at least in the titles. In searching Google Scholar there are no such crossover references of glutathione CAUSING Herxheimer reactions. There are lots of papers discussing glutathione in terms of the paper in which Herxheimer is also mentioned. However, there are no papers discussing Chlamidia in terms of glutathione causing herxheimer reactions.



    One patient case history.



    Six hours later the patient developed severe fever, chills, rigors, headache, severe myalgia and photophobia and was prostrate in bed overnight. Self-administered paracetamol did not relieve the symptoms, which largely subsided spontaneously after 8 hours.



    http://roczes.ovh.org/borelioza/Suggested_Therapy_Of_Chronic_Systemic_Chlamydial_And_Chlamydial-Mycoplasmal_Co-Infections -20Prof. Garth L. Nicolson.pdf



    Herxheimer reactions (or ‘die-off’ reactions involving chills, fever, night sweats, muscle aches, joint pain, short term memory loss and fatigue or a general worsening of symptoms) usually occur for days to weeks due to release of bacterial cell wall degradation products and stimulation of interleukins or chemical messingers that cause worsening of some signs and symptoms





    https://chronicillnessrecovery.org/index.php?option=com_content&view=article&id=161

    increased fatigue, joint or muscle pain, skin rashes, photosensitivity, irritability, paresthesia, dizziness, sleep disturbances, asthenia, muscle cramps, night sweats, hypertension, hypotension, headaches (especially migraines) and swollen glands. Also reported are heavy perspiration, metallic taste in mouth, chills, nausea, bloating, constipation or diarrhea, low grade fever, heart palpitations, tachycardia, facial palsy, tinnitus, mental confusion, uncoordinated movement, pruritus, bone pain, flu-like syndrome, conjunctivitis and throat swelling.



    These symptoms are a consolidation of folate deficiency symptoms from multiple sources crossed with symptoms relieved by L-methylfolate. The side effects of Cerefolin with NAC are 100% part of the list. The consolidation of websites talking about NAC and glutathione detox yielded lists of symptoms and the many symptoms onset over months in the N=10 glutathione trial I did years ago responding to L-methylfolate, all of which are part of the below and contributions from people here at this board after their methyltrap or paradoxical folate deficiency sets of symptoms relieved by l-methylfolate.



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

    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Normal alternating with constipation, Headache, Increased malaise, Fatigue, 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.



    While many of the symptoms on the lists overlap, there actually is no way one could be confused from another. First, “Detox” or folate deficiency by whatever cause have symptoms that start small. Most of the more serious symptoms occur weeks to months after a Herxheimer reaction is long over. A Herxheimer reaction doesn’t start with itching under the scalp erupting into acne accompanied by angular cheilitis and depression. The severe symptoms, like confusion, loss of reflexes and the like happen after months to years as Subacute combined degeneration develop.



    I’ve had a Herxheimer reaction. It comes on like gangbusters and fades relatively quickly depending upon the body’s ability to detoxify the bacteria products except for some very persistent bacteria that is killed in several batches, according to the research. In my case I was 21 years old and not debilitated. I was back out skiing on the professional ski patrol one week after the antibiotic worked. I had one day that was totally from hell. I called the doctor as it started and he explained what was happening and said I should be glad as tomorrow I had to go to the hospital if these didn’t work. I was holding at just below 104 degrees. He said go sit outside until my temperature was under control. It got up to 20-30 below zero F during the day at that time. We were in the back woods of Maine. There wasn’t much choice. After some days muscle pain builds up of several types of muscle pains.



    “Rigors”, chills, photosensitivity, severe fever, swollen glands, migraines, heavy perspiration, muscle cramps (Hypokalemia), uncoordinated movement, pruritus (that one you find on the Hypokalemia list), bone pain, conjunctivitis and throat swelling are not in any way to folate deficiency or the typical NAC or glutathione “detox” reaction. It typically takes weeks to months for these methyltrap folate deficiency symptoms to equal the intensity that Herxheimer reaction hits in hours and to advance to the really serious ones that hit rapidly in Herxheimer reaction.



    If a person looks at the symptoms and the circumstances of sudden onset, and then check symptoms in reference works, formal and informal, anywhere I could find, except in sites that don’t “believe” in Herxheimer reactions, the difference is very clear. Those sites lump Herxheimer reaction under “detox”. However, they still have the symptoms the same.



    From what I have seen almost all the people that had the “detox” response to glutathione and/or NAC and chased it down determined it to an induced folate deficiency and when continued long enough also had startup responses to MeCbl and AdoCbl all over again after developing applicable symptoms over the several months following the 6 week glutathione trial. The symptoms showed no signs of relieving for 6 months until substantially larger and more frequent doses of L-methylfolate , AdoCbl and MeCbl temporarily, largely reversed most of the symptoms except the additional neurological damage.



    So I can see a very high risk of mistaking one thing for another. I have seen startup effects, Paradoxical folate deficiency AND Hypokalemia, mistaken called Herxheimer reaction dozens of times, and always be these two startup induced deficiencies. While perhaps there could be a Herxheimer reaction from Chlamydia with antibiotics, the likelihood from glutathione appears minute while the likelihood of mistaking the symptoms of folate deficiency is very easy. However, as there are always the 5% mystery cases still not clear, I should add these to the decision tree so it can be seen if it comes up as that could be critical for somebody’s life.



    You bet your life is a dangerous game and a person needs every advantage they can find.
     
  8. Freddd

    Freddd Senior Member

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    Hi Alex,

    Very interesting. That might tie in to Carmen Wheatley's paper Large Gorilla.... Adenosylcobalamin which points out the radical effectiveness of AdoCbl for inflammation. When I started MeCbl on top of only all my standard things most of the inflammation was strongly diminsihed in 10 days and gone in a month. It would appear that I have and average MeCbl to AdoCbl ability becasue it went about half way for turning my nitochondria back on compard to the total effects of MeCbl and AdoCbl in that department. After everything beinb inflammed for decades I no longer have such and my CRP is below 1.0.

    Interesting on the resveratrol though I can't say that I notice any effect from it at all though I do take because it looks "likely" to be of benefit even if I can't pin it down.

    I have potassium tests that show I have a very difficult time keeping my serum potassium above 3.8. However I do take a a diuretic that is not potassium sparing. It never casued me trouble until the induced folate problems.
     
    alex3619 likes this.
  9. grapes

    grapes Senior Member

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    I have done a Meyer's Cocktail with glutathione and also on a glutathione cream...and my detox was obvious and not fun, but at least I know it's a good thing.
     
  10. Freddd

    Freddd Senior Member

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    Hi Grapes,

    I'm sorry to tell you that glutathione "detox" is no such thing, that is a dangerous myth. It is actually acute MeCbl deficiency which causes methyltrap causing acute methylfolate deficiencies. It took 2 weeks of glutathione to start causing demyelination of nerves. For me at l;east 10mg of MeCbl injected 3 times a day and 15-30mg of l-methylfolate in divided doses a day started correcting those "detox" symptoms and except for the nerve damage was corrected in 3 days. From there I went into copper and boron deficiency, a pretty typical progression into trace minerals while undergoing refeeding syndrome.

    Here are how my symptoms map to nutrients. If your symptoms match up with the symptoms on this list, especially group 2a, 2b and group 3 of symptoms.

    Version 2.21 12/06/2016 A work in process, incomplete, limited testing, people come in many variations, use at your own risk.
    INDUCED DEFICIENCY SYMPTOMS FROM REFEEDING SYNDROME. This can follow 5 days of food deprivation, anorexia, or sort of a pinpoint starvation via vitamin or mineral or amino acid deficiencies. Whatever the “most needed” item is will often cause a strong response. The first usual notable symptoms occur on typically the third day of starting a previously insufficient nutrient. For instance it was noted in the 50s with injections of B12 with potassium deficiency (hypokalemia) as a side effect. It is dangerous and can be unpredictably fatal if not corrected and the cause is continued. When they say people are dying in Syria after they have been starved and given food, they are often sufferring REFEEDING SYNDROME. When previous symptoms return

    Group 1 – Hypokalemia onset. Often called “detox”. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with CyCbl (Cyanocobalamin) it is very common with MeCbl (methylcobalamin) and AdoCbl (adenosylcobalamin) and less so with HyCbl (Hydroxycobalamin).

    There does not appear to be a clear order of onset. The order of onset varies widely from person to person but many appear consistent for each episode for any given person. There tend to be more and more intense symptoms as it gets worse. Some people have ended up in the ER because of not recognizing the symptoms.

    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 hypokalemia and l-methylfolate deficiency
    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation

    Group 2b – Either or both hypokalemia and l-methylfolate deficiency
    Headache, Increased malaise, Fatigue

    Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency, partial methylation block to methyltrap on 1 or more internal triage levels. Frequently called “NAC DETOX” or “GLUTATHIONE DETOX”. Can be caused by folic acid, folinic acid and for some people, like me and quite a few others, excess vegetable folates. Further excess B1, B2, B3 and/or inositol can increase methylfolate deficiency symptoms.

    These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

    Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.
    Old symptoms returning in a general sense, a person may have had onset of these hundreds of time if they are on the borderline
    Edema
    Angular Cheilitis, Canker sores,
    Skin rashes, increased acne, Increased itchy acne on scalp and face, Skin peeling around fingernails, Skin cracking and peeling at fingertips, painful cracks in the skin at the corner of fingernails at approximate right angles to nails, can take months to occur and it may be only non mood or neurological symptoms.
    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation
    Headache, Increased malaise, Fatigue
    Increased hypersensitive responses, 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
    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract,
    Coated tongue, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,
    Longer term, very serious:
    Loss of reflexes, Fevers, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, bleeding easily.

    Group 4 - HyCbl onset, degraded MeCbl onset, MeCbl after photolytic breakdown onset.
    Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.

    Group 5 – Copper deficiency after methylation startup has been achieved which often starts refeeding syndrome. 50mg or more of zinc has been indicated as a possible cause. 200-400 mg of zinc has been linked to copper deficiency. Excess supplemental or environmental manganese is linked to copper deficiency. Any or all symptoms can occur at “low normal range” copper tests.

    Demyelination of nerves similar to Sub Acute Combined Degeneration except that methylation and ATP startup has occurred, and copper deficiency favors damage to the upper motor neurons with perceived muscle weakness. Brittle nails. Sleep disorders. Mood (especially depression perhaps) and personality changes. Connective tissue breakdown. Spider veins. Varicose veins. Shrinking gums. Gum disease not responsive to usual measures. Unstoppable tooth decay on exposed areas without enamel. Low testosterone

    Group 6 – Excess P-5-P, an active form of B6 that appears to drive hematocrit.
    High hematocrit. The blood thickens and doesn’t pump as easily. Deep vein thrombosis can result. Other suspected circulatory hazards. Sometimes linked to high testosterone when lowering P-5-P might reduce it.

    Group 7 – Excess B-vitamins affecting methylation
    When taking the active B12/folate deadlock quartet (AdoCbl, MeCbl, Metafolin, L-methylfolate) Excess B1 - Thiamin, Excess B2 – Riboflavin, Excess B3 – Niacin and/or Excess Inositol can all produce an excess need for potassium to deal with Groups 1, 2a and 2b symptoms and/or produce an excess need for l-methylfolate to reduce groups 2a, 2b and 3 symptoms. A person might not be able to correct by taking potassium or folate and may need to reduce B1 <= 15mg/day, B2<= 10.2mg/day, B3 <=50mg, and inositol below an unknown quantity.

    Group 8 – Boron insufficiency.
    Arthritis swelling and pain, can be reduced by Boron
    Contribution to fatigue, neurological effects.
    Runaway tooth decay
    Loss of calcium in bones and teeth

    https://www.organicfacts.net/health-benefits/minerals/boron.html

    Although all of the deficiency symptoms of boron are not fully understood, it is known that boron deficiency might result in the abnormal metabolism of calcium and magnesium. Some of the other symptoms include hyperthyroidism, sex hormone imbalance, osteoporosis, arthritis and neural malfunction.
     
  11. grapes

    grapes Senior Member

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    Thanks Freddd for your brilliant thoughts on this! As far as a MeCbl deficiency, I suddenly became unable to be on MeCbl when I caught that it was soaring my serum B12 to over 2000. Same with Adenosyl. So I switched to HyCbl (Hydroxycobalamin) about 3 months now, which got rid of the "low B12" symptoms from my methyl issues.

    I've also been on folate for a good 9 months--400 mg, though I ran out about two weeks ago and only restarted about three days ago.

    All I know is that since I got glutathione in those two Meyer's Cocktails, I started getting a daily constant headache on top of my typical detox fatigue...so now you make me wonder if those corresponding two weeks off of folate did this.... I don't have a copper deficiency--in fact, my copper has been far too high for two years, then finally got it down just this year. Boron....I need to test.

    Group 1 – Hypokalemia: I always have higher in the range potassium, but it won't hurt for me to test this week.

    Group 2a - Both hypokalemia and l-methylfolate deficiency The diarrhea alternating with constipation does not fit, but I do have a borderline folate deficiency according to Spectracell as of a month ago. And I HAVE noticed constipation in the evenings the last several days....thought that might be due to finally lowering my high iron....

    Group 2b – Either or both hypokalemia and l-methylfolate deficiency Since it lists a headache with fatigue....that makes me wonder since I've had a constant one for 1 1/2 weeks now...and again, Spectracell shows I have a "borderline" folate deficiency...i.e. I was 37 and reference range is >32.

    Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency, partial methylation block to methyltrap on 1 or more internal triage levels. Frequently called “NAC DETOX” or “GLUTATHIONE DETOX”. I'm not on folic or folinic--in fact, can't be on folinic. But I have been taking inositol the last few weeks with Berberine to help lower high testosterone...on top of taking 1/2 tsp phosphotidylcholine daily. This gives me a big hmmmmmmmm

    Groups 4 - 8 symptoms or situations don't seem to fit me.

    So your brilliant reply to me makes me wonder if this is all about my borderline folate deficiency...i.e. my constant headache especially, or the inositol I've been on.

    Let me state that I outright started detoxing copper a month ago. It's the third time I've detoxed in two years and am keenly aware of when I start detoxing. i.e. I get copper color stools and excess fatigue. It seems to have been started by me upping my lithium to 10 mg for a week (from 5 mg) after reading that it helps B12 get to the cells better. The copper detox ended a week ago, but my detox fatigue did not, which is not normal for me....and neither did the headaches stop, which have occurred for two weeks...in CONJUNCTION with taking inositol.....hmmmmm
     
  12. Freddd

    Freddd Senior Member

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    Hydroxycobalamin is perhaps as much as 1% as effective MeCbl and AdoCbl. Of course, they raise the cobalamin level more. They are the Human active and effective kinds, the AdoCbl sits in the mitochondria and the MeCbl circulates until used or excreted. Methylfolate increases the serum halflife of MeCbl. Last time my Cbl was tested it was > 220,000pg/ml. I Inject 10,mg 3 times a day to maintain my nervous system along with 30mg of methylfolate.

    The folate deficiency symptoms with methyltrap is caused by MeCbl NOT being in the cell when it is needed for cell division, then the methylfolate is dumped out of the cell and the "fail" symptoms are folate. HyCbl can cause methyltrap too becasue it is NOT MeCbl in the cell when needed depending upon all sorts of things. All the symptoms on the list below respond to MeCbl/AdoCbl. Some of them may respond with HyCbl for some people. The Cbl numbers are worse than useless except for telling you the house is already burned down. The folate deficiency symptom free range is likely between 7.5mg and 30mg with MeCbl/AdoCbl. HyCbl likely won't do that.

    My problems with potassium start at about 4.3 and below. I can't move it out of tissue into serum fast enough to meet need. It appears pretty common. It also is the number one most common potentially fatal side effect of healing.You can't possible respond fast enough to save your life going by numbers. Go by symptoms and have the potassium at hand. I know people who ended up in the ER



    SYMPTOMS LIST 01/03/2014 V 1.0
    In this post this is a list of symptoms that are mine, and others experience of these nutritional items in relieving their symptoms, and in a very few instances reflect research and successful practice, such as p5p for Hcy and Liver extract studies of several disorders in old journals. In some instances the same symptoms might have different combinations of nutrients.

    These symptoms responded almost entirely or entirely with basics 5 star MeCbl – methylcobalamin – Methylb12 - Mb12 - Mecobl . Many started improving in hours. Others took 9 months to correct.

    morning joint stiffness and pain
    paleness
    acid reflux
    nausea
    daily vomiting
    standing with eyes closed, lose balance
    hands feel gloved with loss of sensitivity - glove anesthesia
    feet feel socked by loss of sensitivity - stocking anesthesia
    glove and stocking anesthesia
    neuropathic bladder
    unable to release bladder, mild to severe
    unable to fully empty the bladder
    fecal incontinence - occasionally to frequently
    diminished hearing - gradual onset or present for life, sudden return possible
    tinnitus - ringing in ears
    always feeling cold
    intolerance to loud sounds
    intolerance to multiple sounds
    sleep disorders
    non restorative sleep
    Night terrors
    Prolonged hypnagogic or hypnopompic states transitioning to/from sleep
    Sleep paralysis
    alteration of touch all over body, normal touch can be unpleasant and painful
    alterations and loss of taste
    taste hallucinations
    smell hallucinations
    sound hallucinations
    visual hallucinations
    alterations and loss of smell
    loss of smell and taste of strawberries specifically
    loss or alteration of smell and taste of potato chips specifically
    roughening and increased raspiness of voice, mb12 can smooth it in mid word
    blurring of vision - can be sudden onset and sudden return
    Visual impairment can be seen; ophthalmological exam may show bilateral visual loss
    optic atrophy
    centrocecal scotomata
    hypersensitivity/intolerance to bright light
    intolerance to loud sounds
    intolerance to multiple sounds
    burning muscle pain
    diminished hearing - gradual onset or present for life, sudden return possible
    tinnitus - ringing in ears
    sore burning tongue

    This is a list of symptoms that are mine, and others experience of these nutritional items in relieving their symptoms, and in a very few instances reflect research and successful practice, such as p5p for Hcy and Liver extract studies of several disorders in old journals. In some instances the same symptoms might have different combinations of nutrients.

    These symptoms responded strongly first to 5 star MeCbl and then Metafolin with basics. Many started improving in hours. Some took 7 years to correct.

    Bursitis
    stomach not emptying
    frequent vomiting
    acid regurgitation
    dyspepsia
    flatulence
    altered bowel habits
    abdominal pain
    loss of appetite for meat, fish, eggs, dairy, the only b12 containing foods
    nutrient specific anorexia
    intermittent constipation
    intermittent diarrhea
    irritable bowel syndrome
    sores, ulcers and lesions along entire GI tract or any part
    anorexia
    Bulimia
    Hypersensitivity to touch
    Hypersensitivity to odors
    Hypersensitivity to tastes
    Hypersensitivity to clothing texture
    Hypersensitivity to body malfunctions, symptoms
    Hypersensitivity to sounds and noises
    Hypersensitivity to light and visual stimuli
    Hypersensitivity to blood sugar changes
    Hypersensitivity to internal metabolic changes
    Hypersensitivity to temperature changes
    burning bladder (no UTI)
    painful urgency (no UTI)
    burning urethra (no UTI)
    Low blood serum level - below 550pg/ml, Japanese Standard
    elevated MCH (Mean Corpuscular Hemoglobin)
    elevated LDH
    big fat red cells (when said this way usually with happy or healthy modifying it completely misinterpreting results of MCV
    platelet dysfunction, low count
    white cell changes, low count
    hyper segmented neutrophils
    headaches
    inflamed epithelial tissues - mucous membranes, skin, GI, vaginal, lungs
    inflamed endothelial tissues - lining of veins and arteries
    mucous becomes thick, jellied and sticky
    asthma
    chronic cough that mimics asthma but isn't
    chronic sinus congestion
    dermatitis herpetiformis, chronic intensely burning itching rash
    frequent infected follicles or acne type lesions all over body
    chronic infections, many varieties possible
    Seborrhic dermatitis
    dandruff
    eczema
    dermatitis
    skin on face, hands, feet, turns brown or yellow if anemia occurs
    poor hair condition
    thin nails
    transverse ridges on nails, can happen as healing starts
    mouth sensitive to hot and cold
    sore burning tongue
    beef-red tongue, possibly smoother than normal
    sore mouth, no infection or apparant reason
    teeth sensitive to hot and cold
    canker sores


    with p5p added

    Elevated blood serum Hcy, borderline or higher


    These symptoms responded relatively partially first to 5 star MeCbl and then very strongly to Metafolin with basics. Many started improving in hours. Some took 7 years to correct.




    splits/sores at corners of mouth -angular cheilitis
    impaired white blood cell response
    poor resistance to infections
    easy bruising
    pronounced anemia
    macrocytic anemia
    megablastic anemia
    pernicious anemia
    decreased blood clotting
    MCV > 93 first warning,
    MCV > 97 alert
    MCV > 100 outright macrocytosis
    MCV > 105 urgently needs treatment, severe problem

    Plus Vitamin E
    Child with neural tube defects

    mother of child with neural tube defect

    These symptoms responded not at all first to 5 star and then very strongly to Metafolin with basics. Many started improving in hours. Some took 7 years to correct.


    lack of dreaming
    MCV > 100 outright macrocytosis
    macrocytic anemia
    metallic taste in mouth
    Widespread body & muscle pain responding to NSAID
    Joint pain responding to NSAIDS
    splits/sores at corners of mouth -angular cheilitis


    Sexual related symptoms, both men and women – These responded with the most response to lesser responses in order to MeCbl, Metafolin (l-methylfolate), AdoCbl, L-carnitine fumarate

    reduced libido - loss of sexual desire
    loss of orgasmic intensity
    unsatisfying orgasms
    inability to orgasm
    loss and/or change of genital sensations
    burning genital skin sensation
    unable to feel aroused
    numb genital skin
    low sex hormones

    MEN

    In order of response – MeCbl, AdoCbl
    low testosterone men

    In order of response – MeCbl, Metafolin, AdoCbl, L-carnitine fumarate
    erectile disfunction men

    In order of response – MeCbl, Metafolin, AdoCbl
    low sperm count
    poor sperm motility
    Poor sperm quality
    no sperm


    WOMEN

    In order of response – MeCbl, AdoCbl
    low testosterone
    low estrogen

    In order of response – MeCbl, Metafolin, AdoCbl, L-carnitine fumarate
    post partum depression
    post partum psychosis

    In order of response – MeCbl, Metafolin, AdoCbl
    Frequent miscarriage

    In order of response – MeCbl, Metafolin
    False positive pap smears, defective cells
    menstrual symptoms
    amenorrhea


    Approximate timing of my startup of individual items that being considered here, this gives a quite distinctive pattern for each nutrient or set of nutrients: 03/04/13, Version 1.1

    Others mentioned similar patterns and variations.

    1. Initially – Mecbl

    2. +5 months 400mcg SAM-E

    3. + 4 months AdoCbl

    4. + 3 months titrate +50mg zinc

    5. +4 years 400mcg Metafolin

    6. +1 year LCF

    7. + 1 month TMG 1000mg/day

    8. 30mg MeCbl injections (3 or 4) daily,

    9. +0 Reduce SAM-e to 200mcg

    10. + 4 years remove TMG

    11. +6 months increase SAM-E to 800mcg

    12. Next 1 year titrating Metafolin and finding all the reasons I get folate insufficiency, early partial methylation block by effect.



    These symptoms are what responded very well to CNS penetrating doses of MeCbl either as 50mg sublingual single 4-5 hour dose or 4 x 7.5mg or 3 x 10mg or for some 2 x 15mg subcutaneous MeCbl injections. Metafolin in some way enhances retention of AdoCbl and MeCbl with excretion visibly decreased. A sublingual dose of 1-2 tablets each hour added for 12 hours appears to generate substantial CNS penetration as well.



    CNS penetrating dose MeCbl – AdoCbl – Metafolin – Omega-3 oils


    Elevated CSF Hcy
    Low CSF cobalamin
    limbs feel stiff
    Drowsy


    CNS penetrating dose MeCbl – AdoCbl
    dimmed vision - usually not noticed going into it because change can be very slow or present for life
    Clumsiness


    CNS penetrating dose MeCbl – AdoCbl - Metafolin


    Slow to adapt to night vision


    CNS penetrating dose MeCbl – AdoCbl – Metafolin – LCF


    Difficulty in word finding



    CNS penetrating dose MeCbl – AdoCbl – Metafolin – Omega-3 oils


    Brainstem or cerebellar signs or even reversible (with mb12) coma may occur
    demyelinated areas on nerves
    subacute combined degeneration
    axonal degeneration of spinal cord
    unsteadiness of gait
    ataxic gait, particularly in dark
    positive Romberg
    positive Lhermittes
    Loss of motor control over some or all of toes
    Loss of motor control over part or all of feet
    Loss of sense of joint position
    sudden electric like shocks/pains shooting down arms, body, legs shooting down from neck movement
    sudden "ice pick" pain
    decreased reflexes
    brisk reflexes
    Foot Drop
    tripping over toes
    injuring toes catching top of toes on floor
    general feeling of weakness


    Approximate timing of my startup of individual items that being considered here, this gives a quite distinctive pattern for each nutrient or set of nutrients: 03/04/13 Version 1.1

    Others mentioned similar patterns and variations.

    1. Initially – Mecbl

    2. +5 months 400mcg SAM-E

    3. + 4 months AdoCbl

    4. + 3 months titrate +50mg zinc

    5. +4 years 400mcg Metafolin

    6. +1 year LCF

    7. + 1 month TMG 1000mg/day

    8. 30mg MeCbl injections (3 or 4) daily,

    9. +0 Reduce SAM-e to 200mcg

    10. + 4 years remove TMG

    11. +6 months increase SAM-E to 800mcg

    12. Next 1 year titrating Metafolin and finding all the reasons I get folate insufficiency, early partial methylation block by effect.


    These symptoms are what responded very well to L-carnitine fumarate AND AdoCbl for the first two items


    L-carnitine fumarate – AdoCbl – Metafolin - MeCbl


    weight loss involuntary
    muscular atrophy
    exercise does not build muscle



    L-carnitine fumarate – Metafolin – AdoCbl - MeCbl

    weight gain, watery fat
    edema


    L-carnitine fumarate – AdoCbl – MeCbl – Metafolin


    mild to extremely severe fatigue
    continuous extremely severe fatigue
    easy fatigability
    severe abnormal muscle fatigue up to and including apparent paralysis leading to death
    weakness
    muscle pain especially around attachment points to bones
    Eighteen severely tender muscle spots of FMS



    AdoCbl – L-carnitine fumarate


    exercise debilitates for up to a week, making things much worse
    accumulating muscle pains following exertion
    sore muscles throughout body
    lack of muscle recovery after exercise
    High urinary MMA



    AdoCbl – L-carnitine fumarate – Metafolin

    congestive heart failure
    Elevated CSF MMA
    Elevated uMMA


    Approximate timing of my startup of individual items that being considered here, this gives a quite distinctive pattern for each nutrient or set of nutrients: 03/05/13, Version 1.1

    Others mentioned similar patterns and variations.

    1. Initially – Mecbl

    2. +5 months 400mcg SAM-E

    3. + 4 months AdoCbl

    4. + 3 months titrate +50mg zinc

    5. +4 years 400mcg Metafolin

    6. +1 year LCF

    7. + 1 month TMG 1000mg/day

    8. 30mg MeCbl injections (3 or 4) daily,

    9. +0 Reduce SAM-e to 200mcg

    10. + 4 years remove TMG

    11. +6 months increase SAM-E to 800mcg

    12. Next 1 year titrating Metafolin and finding all the reasons I get folate insufficiency, early partial methylation block by effect.





    MeCbl - AdoCbl – L-carnitine fumarate – Metafolin

    shortness of breath, oxygen hunger
    heart palpitations


    MeCbl - AdoCbl – L-carnitine fumarate

    extremely sore neck muscles reversing normal curvature of neck
    painfully tight, stiff muscles, especially legs and arms
    frequent muscle spasms anywhere in body
    weak pulse



    MeCbl - AdoCbl

    Confusion
    Disorientation
    Difficulty in word finding


    MeCbl - AdoCbl - Metafolin

    irritable
    depression
    SAD - Seasonal Affective Disorder
    mental slowing
    personality changes
    chronic malaise
    poor concentration
    moodiness
    tiredness
    mood swings
    memory loss
    listlessness
    impaired connection to others
    mentally fuzzy, foggy, brainfog
    dizziness - even unable to walk
    Vertigo


    MeCbl – Metafolin – AdoCbl – L-carnitine fumarate

    psychosis, including many of the most florid psychoses seen in literature, megaloblastic madness
    Alzheimer's
    delirium
    dementia
    paranoia
    delusions
    hallucinations - multisensory
    anxiety or tension
    nervousness
    mania
    Widespread pain throughout body



    A caution, those with anxiety and panic symptoms may respond with extreme moods of increased fear, anxiety, panic, anger rage, homicidal rage and profound depression, usually in repeatable sequences following LCF or ALCAR even at levels of 1mg oral. A micro titration of carnitine would be cautious. While most find the moods intolerable, certain persons have been able to tolerate these (both past) and current, to find they can fade after some months of consumption. A few people may find similar, maybe somewhat lesser, response to MeCbl or more likely AdoCbl. As these are less controllable than LCF which can be micro dosed, they should be considered first.
     
  13. grapes

    grapes Senior Member

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    If I'm translating correctly the unstated implication of what you posted, it appears I need to still add in "some" MeCbl with my HyCbl...the latter I currently need to treat low B12 symptoms with high serum B12...and the high serum B12 from having been on MeCbl before with methylation issues which kicked in. Yet, what good will adding in some MeCbl if it's not getting to my cells??

    By the way, after "getting it" that my symptoms may be due to folate deficiency, I took an additional 200 mcg of my l-folate last night (I take 400 mcg every morning). And voila, I woke up with no headache this morning. We'll see if that continues with extra l-folate taken before bedtime....
     
  14. Freddd

    Freddd Senior Member

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    Salt Lake City
    Hi Grapes,

    I have done a lot of trials. I have found that ANY other cobalamin taken at the same time (and is as much as 25% or more of the dose of other cobalamin (AdoCbl, HyCbl, CyCbl) can compete for being taken into a cell for use, and if it isn't MeCbl there can be methyl trap, in which when the MeCbl is needed and something else is there instead, there is a cell failure that produces acne type ;lesions or other epithelial problems at least (which can be seen). No matter what the size of the HyCbl about 10 mcg a day get converted IF EVERYTHING WORKS RIGHT, TO mEcBL AND THEN AdoCbl, each conversion needing an enzyme and ATP to convert and which factors require MeCbl, AdoCbl, L-methylfolate and the right carnitine for your body. HyCbl consumes both MeCbl & L-methylfolate products and ATP in converting the HyCbl to MeCbl. Healing with MeCbl does best with over 100mcg absorbed MeCbl into the serum which a 1000mcg tablet will likely do. HyCbl is worse than useless. After you get healing gopng well and get rid of the symptoms, then try the HyCbl if you want to and see if the healing reverses and the symptoms come back.

    The serum half life of cobalamins in the serum not wrapped up in TC2 is such that 98 to 99% are excreted by the kidney within 24 hours, 99% plus at 2 days. A serum level of 2000pg/ml means that your 5 liters of blood have 10mcg total in circulation. That is what is left after all the excretion typically. Right after taking it or even while absorbing it the serum half life is 20-50 minutes. At 12 hours in the serum half life is 4-5 hours. For the next 48 hours the serum half life averages 12+ hours. When you absorb 100 mcg from a sublingual MeCbl it is at about 20,000pg/ml for less than an hour. During that time it diffuses into most all the cells that need it. Having the high serum level for a little while aids penetration of the cells in all the body's tissues.

    As long as you continue the HyCbl it makes the methylfolate less useful. When my MeCbl has been broken down by light to some fraction of HyCbl I get acne type lesions and sores at the corner of my mouth in a day. Generally MeCbl heals better all by itself becasue it is the active form that is absorbed and doesn't require the same set of deadlock nutrients to convert HyCbl and folic acid to the active forms.

    Good that your headache is letting up. You have an active indicator possibly. I would expect a handful of additional symptoms to improve over a week or so without HyCbl and with more methylfolate. More methylfolate doesn't overcome HyCbl, different cause same symptoms. Makes it confusing. It is possible to have both kinds of problem at the same time while other compartments of tissue are healing making it even more confusing. My partner decided to try 15,000mcg (15mg) methylfolate instead of 4,000mcg a day. Her cracked skin on her finger tips and at the corners of nails that have been there for years are gone. She was quite surprised as she only had a few symptoms, and another that healed was some kind of gastric inflammation. .Good luck.
     
  15. grapes

    grapes Senior Member

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    OK, let me make sure I'm understanding....you are proposing stop the hydroxyB12 and increase the L-folate and for a week, right?? Since I've been on 400 mcg l-folate, and last night added 200 mcg and had no headache today....I'm thinking doing the same for a few days, then perhaps 400 mcg and 400 mcg.

    And I think you are proposing this because hydroxyB12 consumes both methylB12 and folate, plus ATP, in the process of converting the hydroxy to methyl in the body. Then you are proposing to get back on hydroxy B12 and see what happens, right?

    (By the way, I looked at my notes and have only been on hydroxyB12 for about 5 weeks with definite removal of B12 deficiency symptoms)

    Here are things I am also trying to analyze:

    1) Ben Lynch states that MethylB12 needs to be carried by transcobalamine, and glutathione is needed for that binding. My glutathione was quite low when I tested it a month ago--probably due to two years of high copper with two detox sessions. Today I had my third and last Meyer's Cocktail with glutathione...and it makes me wonder if I'd now absorb methylB12 better---my B12 was "over 2000" just over a month ago with clear symptoms of deficiency when I had been on a combo of methyl and adenosyl.

    2) Rush states many people with CFS appear to have elevated levels of B12 in their blood, while their bodies are not able to use it properly---definitely me. But he then says the Methylmalonic Acid test will be HIGH if B12 is being sidetracked, but my MMA was NOT high five weeks ago when my B12 was "over 2000" with symptoms of low B12 i.e. .11 (.40). He then stated that if you’re low on adenosylcobalamin, the patients’ methylmonic acid levels will be high or pushing high. Again, mine wasn't high. I'm unclear what all that means for me....

    3) You have stated that Hydroxycobalamin is perhaps as much as 1% as effective MeCbl and AdoCbl. Yet hydroxy has done a great job removing my low B12 symptoms, while Methyl sent my B12 up to 1500 late last year, then over 2000 by late Feb. 2017 with a combination of methyl and adenosyl...and worsening B12 deficiency symptoms. I'm just not experiencing that hydroxy is so much less effective for me right now. Also, I have two homozygous COMT mutations and one heterozygous COMT, and Nutrahacker with all three recommends Hydroxy B12!

    4) Rich stated he prefers hydroxocobalamin because it "allows the cells to control the amounts of the coenzyme forms of B12 (methylcobalamin and adenosylcobalamin) that they make, so that they can be matched to the need." I like that, and it fits how I am feeling better on it. I also see he stated that you aren't able to utilize hydroxy well because of a mutation. But heck, I'm doing well on it!

    5) Help me understand this: "HyCbl consumes both MeCbl & L-methylfolate products and ATP in converting the HyCbl to MeCbl." How can hydroxy consume methyl when it's converting to methyl? Are saying that because it's a methylation process, it's using folate to break it down to more methylB12? That's kinda funny, if so.
     
    Last edited: Apr 3, 2017
  16. Freddd

    Freddd Senior Member

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    Salt Lake City
    Hi Grapes,

    I'm sorry. I don't think I can explain it in a way you seem likely to understand based on all of your hypothesis and so on pulling you in a direction the opposite of what this protocol would. I went to over 100 doctors before figuring it out. 100% of them were wrong. I cured myself of CFS, FMS, MCS, IBS, about half of my neuropathies, asthma, food sensitivities, congestive heart failure and holding my own on other things. I lost 85 pounds of water, 40+ pounds of fat and rebuilt 50 pounds of atrophied muscle, over 5 years. You have all the clues I can give you. Being able to beat this illness is difficult. It takes constant decisions of what needs to be corrected and how as the symptoms change constantly the first year or so and then slower as most of the symptoms are gone.


    "Help me understand this: "HyCbl consumes both MeCbl & L-methylfolate products and ATP in converting the HyCbl to MeCbl." How can hydroxy consume methyl when it's converting to methyl? Are saying that because it's a methylation process, it's using folate to break it down to more methylB12? That's kinda funny, if so."


    "Are saying that because it's a methylation process, it's using folate to break it down to more methylB12? That's kinda funny, if so.""
    To convert HyCbl to MeCbl, you already need MeCbl that is involved in over 600 chemical reactions including including the making of enzymes and the making of ATP.

    In other words to convert HyCbl to MeCbl (the body has some ability to reclaim broken down MeCbl (HyCbl) and requires that the products produced by AdoCbl, MeCbl, L-methylfolate and l-carnitine of the suitable variety for your body. all must be present for the reclaiming of HyCbl Light breaks down MeCbl to HyCbl. In studies by the way HyClb only works on about 2/3s of the symptoms being studies. It doesn't work for the other third of people. That has been speculated to be for all sorts of reasons.

    In converting HyCbl to MeCbl first the methylfolate or MeCbl donate a methyl group or is routed via SAM-e but still originates or is handed on by MeCbl/methylfolate. It takes the methyl group from one MeCbl to convert HyCbl, plus ATP plus enzyme to push the uphill energy reaction to MeCbl. It costs more than one MeCbl to convert each HyCbl. It sort of eats it. So it is really quite funny in a very sad way. HyCbl is another competitor for that methyl group that makes the MeCbl so special and is needed to convert HyCbl to MeCbl and then to AdoCbl which makes that very expensive, a second round of enzyme and ATP to convert the MeCbl to AdoCbl. And a lot of people do that poorly.

    In my experience almost everybody who reacts to MeCbl also reacts similarly to AdoCbl indicating that converting leaves a lot of hole for many people and that means poorly working mitochondria.. So if a person doesn't have what it takes to convert the HyCbl it can't work and causes faulty cellular reproduction and/or faulty cell growth. My muscles were the last things that grew/recovered after everything else was fixed. I really wish Rich hadn't died when he did. On one of his replies he did say that it is quite possible the AdoCbl and MeCbl work better than HyCbl. He also said near the end that if the simplified methylation method doesn't work significantly in 3 months that switching to the active might help. The problem is that it is far more complicated. I've never been able to come up with a simple version. We were in the middle of some discussions and comparison and reanalysed the study data (the one he worked with). I have to say that sometimes there is nothing like experience to know how something works, or in about 99% of nutritional situations with B12/folate doesn't work.

    The worsening symptoms you speak of are the ones caused by refeeding syndrome, induced deficiencies of the body trying to heal and not have the exact item needed. B12 and folate works in the body in such a way that some "compartments" are healing at the same time as other compartments are in deficiency with worsening symptoms. That is a flag of healing saying "Give me more of the right nutrients. That's what groups 1-8 are about. That is a roadmap to induced deficiencies, what you get when you take active B12s and active folate. Low potassium can be fatal. Healing can be dangerous. If you don't understand the correction of induced deficiencies instead of theories that don't take that into account, it is potentially dangerous to do.
     
    Last edited: Apr 4, 2017
  17. grapes

    grapes Senior Member

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    No, I'm listening. I just have to throw out my own thoughts in my "process" of figuring this out and re-wiring my thoughts. You are clearly far ahead of me in all this...and I'm willing...

    You hit me square in the face when you said this: In my experience almost everybody who reacts to MeCbl also reacts similarly to AdoCbl indicating that converting leaves a lot of hole for many people and that means poorly working mitochondria... Because yes, both MeCbl and AdoCbl sent my B12 sky high and yes, I do have a mito issue, which I think happened due to massive mold exposure a few years ago, and which never fully got out of me. I require a very high amount of ubiquinol to function, and am also on PQQ, Shilajit Extract, l-carnitine, arginine, lithium 5 mg and other recommended supps from the results of my OAT testing. My supplements are massive. If I lower my ubiquinol to 500 mg, I become breathless. So back up I'm forced to go.

    I am also on Welchol to get the final bit of mold out of me.

    Look, I will definitely go your suggested route---staying off hydroxy starting today, and being on higher amounts of l-folate. Just the fact that Spectracell showed I'm borderline with folate is telling, just as my headache went totally away for two days now...from taking an additional 200 mcg of folate at bedtime two nights in a row. I'm picturing doing the 600 mcg total of l-folate for two days, and moving up to 800 mcg total, half in the morning, half at bedtime. But that is where I'm not sure what to do next... I'm assuming that since just adding 200 mcg of folate at bedtime took my headache away, I react well to folate and 800 mcg or even 1000 mcg might be a great amount for me, but don't know for sure yet.....

    Would I start back on MethylB12 in a week...in a few weeks?? I need to figure that out, plus starting amounts of methyB12...

    By the way, Spectracell showed I'm borderline not only for folate, but b6, pantothenate and biotin, plus manganese, Chromium and Imunidex. I've been on one cap of Seeking Health's B-Minus for many months--four of the six B contents are what I'm borderline in...so my plan is to take 1 1/2 caps a day for awhile and perhaps move up to 2---I'm hesitant to move straight to 2 as the B6 made me feel AWFUL in higher amounts over a year ago. I'll also up the folate.

    If I'm missing something in my plan, please let me know....
     
  18. grapes

    grapes Senior Member

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    Oh and adding to what I wrote above....Spectracell showed that the only "functional deficiency" I have is CoQ10. I was bowled over, as I take 1000 mg of liquid ubiquinol daily (if I go lower, I suffer...if I use caps, I suffer), plus 300-500 mg of ubiquinol caps anyway in addition to the liquid. So I decided to add in ubiquinone at 600 mg, which I've done a week...so we'll see. They recommended 100 mg of ubiquinone, which made me laugh in derision considering how much ubiquinol I need to function....
     
  19. Freddd

    Freddd Senior Member

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    Salt Lake City
    @grapes
    .I would start the MeCbl immediately. If you have a brand that makes noticeable differences before it is even done absorbing that would be a good starting place. 1mg, 1000mcg with a real noticeable effect is good. On the days you take AdoCbl, once or twice a week is usually good, take it about 6 hours after the MeCbl. That avoids most interference between them and will allow for the best takeup. I had copper and boron deficiencies by recognition of healing of symptoms. They cost me my upper teeth before we figured out what was doing it.. I started just in time to save my lower teeth. So get the MeCbl working. I found better results at a given daily dose with l-methylfolate with taking it 3 to 4 times a day becasue of short serum half life. Many people have a dramatic difference based on type of l-carnitine. My experience is that about 90% of people do well with the L-carnitine fumarate , the actual kind of carnitine that transports the fats to the mitochondria. SOme have no effect from LCF. About 10% have great results with ALCAR. It's one or the other. There is another form that might work well. Jarrow has a liquid freebase carnitine in a bottle, great if you have to titrate, or capsules. That often works for both groups of people. I needed 2 doses a day of the freebase carnitine instead of one dose for LCF, again something to do with serum half life.

    A caution, some people, when they get the all these nutrients working well, have their blood pressure shoot up with CoQ10. I take it now and can't feel a thing from it. When I first started MeCbl and took CoQ10 my BP went up to 190/90 from about 135/70, in 2 hours. So be careful. I had rapid improvement each time I increased methylfolate.but also my potassium need went up (healing flag, cell making). Correct the potassium and know it is indicating healing. Low potassium makes one feel miserable with the symptom on the lists. I have had to take between 1200 mg to 3000 mg of potassium for the past 14 years. I see nothing wrong with increasing the folate 50 to 100% in a day and then maintaining it as you see what symptoms improve. On lower doses you might not see much improvement compared to how many more deficiency symptoms you get. That is a flag as well, healing needs more folate than you are taking.

    Another thing to try is an active form of B6, P5P. Also pantethine is an active form of pantothenate. It might be more effective, less conversions. But before trying to different forms, you need to get the basic 4 going, the MeCbl, AdoCbl, methylfolate and carnitine..

    I increased manganese, boron, selenium and molybdenum when I was still having trace mineral problems and I got a decrease of symptoms and increase in healing flagged by potassium, 300mg a day increase but don't know which. They often come together becasue of depleted soils don't have it for the growing foods.

    This is complicated but just plugging along adding one thing at a time. It is combinations, when people have this refeeding syndrome a characteristic is they have a whole lot of induced deficiencies, and over time all the trace minerals usually show up more slowly than the methylation/ATP influencing nutrients. Once you get going on these things and symptoms are changing it works well to look at the induced symptoms. SOme b-complex components can drive the need for folate and potassium too high. That is detailed in the refeeding list. Again, that is a later thing after you have all these things working and stable. Then it becomes fine tuning. Some symptoms changing are the effects of them healing. Some are induced by healing and causing deficiencies. It's important to recognize which is which. I hope this helps to explain. the things. One thing to remember, some things have a genuine maximum and others are only a statistical statement like B12.

    And an important distinction. The symptoms that change the same day or next are usually healing symptoms. Suddenly worsening or appearing symptoms on the third day or so after a change are refeeding syndrome symptoms and need to be corrected and will respond starting in hours to enough of the right nutrient.. Heal well.
     
  20. grapes

    grapes Senior Member

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    OK, here's the plan:

    1) Get on 1mg, 1000mcg methyl B12...and Adeno B12 only once or twice a week, six hours after the Methyl. Am I assuming correctly that because I have upped my folate to 800 mcg then 1000 mcg, the methyl B12 will get to my cells (unlike when B12 was over 2000 with deficiency symptoms)??

    2) Take l-methylfolate 3-4 times a day due to short half life...

    3) I've been on l-carnitine for over a year. Was on 1500 fumerate, but now on 500 taurate, sadly, which was a mistake to buy. I do have a bottle of ALA 600 mg with ALCAR..but am concerned about taking ALA.... I need to buy it without ALA or get fumerate....

    4) I am already on P5P--it's in the B-Minus by Seeking Health at 20 mg. But since Spectracell says I'm borderline with B6, I started taking 1 1/2 caps today to equal 30 mg to see how I do. If I'm fine, I'll move to 2 caps to equal 40 mg.

    5) I'm also already on minerals....Trace Minerals Complex II by Seeking Health. The only borderline's according to Spectracell are chromium and Manganese, so adding more of those.
     

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