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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

    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?
  2. Lotus97

    Lotus97 Senior Member

    United States
    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

    United States
    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,


    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,

  4. Freddd

    Freddd Senior Member

    Salt Lake City
    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

    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

    Logan, Queensland, Australia
    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

    Salt Lake City

    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. 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. -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

    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

    Salt Lake City
    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.

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