Almost everywhere I turn in the treatment of CFS and FMS I see references to glutathione or glutathione producing precursors. There are a variety of theories leading to this idea. Like many I have been looking for ideas for years. I am essentially healed of FMS and CFS. I don't have enough symptoms left to qualify as a diagnosis, and of those remaining they lack the severity and punch they once had. I am for all intents and purposes healed. I still have some damage from years of b12 deficiencies. I still have some symptoms, of aging perhaps, as I'm 61 now, much older than when I started this journey. As I have followed a road of incremental improvment, I continue to look for that last cofactor that sets the residue of symptoms right. I had great hopes for the glutathione precursors. Instead of major improvment I had a major setback. Symptoms came thundering back in days that had been gone for more than 5 years. The trial lasted for 6 weeks until I called it quits when the direction of neurological change was clearly towards rapidly increasing neurological deterioration with increasingly numb feet, increased paresthesias, increasing irritability, decreased energy, brainfog, depression, angular cheilitis, headaches, memory impairment, sore muscles, sore joints, uncontrollable spasms in my legs and sides, nausea, loss of appetite, frequent indigestion, bloodspot itchy eyes, stuffy nose, hayfever. These symptoms had all been gone or mostly gone for 5 or more years since a year after starting methylb12. Every one of these were former symptoms of mine relieved by methylb12 and/or methylfolate. According to one website, http://www.beccashealthtips.com/symptoms.html symptoms for glutathione caused detox reactions are low energy, achy muscles, light headedness, headaches, flu like symptoms, coated tongue, runny nose or allergy symptoms, stomach aches, uneasy digestive tract, fevers, feeling like throwing up, and sometimes old symptoms that have been suppressed. The symptoms listed for folate deficiency on other web sites are irritability, depression, sluggishness, forgetfulness, diarrhea, loss of appetite, gastrointestinal complaints, fatigue, macrocytic anemia, paleness, red sore tongue, reduced sense of taste, weight loss, confusion, difficulty walking, loss of reflexes, dementia, muscle weakness, bleeding easily, heart palpitations, behavoral disorders and angular cheilitis. All of the symptoms not relieved by increased methylb12, increased potassium and increased calcium, those which lasted for 6 months past the end of the glutathione precursor trial were relieved within 3 days by increasing methylfolate from 800 mcg/day to 4800mcg/day. I did not immediately recognize all the symptoms as a hard folate deficiency since I had never had that before. I attributed them all to the methylb12 deficiency with which I was far more familiar. The cheilitis had always been unaffected by methylb12 and was this time. I hardly had noticed it at the time with all the other far more unpleasant and stronger symptoms. I find it normal that methylfolate immediately relieves methylfolate deficiency symptoms. Thats the way it happened last time but I had far few of them. I find it unusual that methylb12 and methylfolate immediately relieved all of the "detox" symptoms unless the root of the detox effect was to induce major methyb12 and methylfolate deficiencies with potassium and calcium balance upset too. When I first started methylfolate I noticed that it decreased the amount of b12 visible in my urine significantly. Within hours of taking glutathione precursors I started lossing a very nloticable amount of b12 in my urine. I diod not at the time attribute it to the decrease of folate in my system. This less continued tghe entire 6 week trial and decreased afterwards but never returned to the pre trial level. Within hours of when I took the increased level of methylfolate, b12 disappeared from my urine. Now 5 days later my urine is still clear most all day of visible b12 depsite injecting 30mg/day of methylb12. So whether or not glutathione does anything directly to methylb12 it appears to do something immediately to methylfolate in the body causing largescale excretion of b12 from the body. As a result both methylb12 and methylfolate are depleted within the body causing immediate deficiencies as demosstrated by immediate onset of certain funtional methylfolate deficiency symptoms. These items can't be restored and deficiency symptoms reversed as long as glutathione precursors continue to be taken. However, after cessation of glutathione precursors, within days methylb12 and presumably methylfolate can be restored but only by large increases of doses. I do not know what casues the lingering effects glutathione precursors on these subtances preventing 800 mcg of methylfolate daily from restoring normal folate funtioning over a 6 month period. I doubled the methylb12 within days of cessation as 15mg/day wasn't stopping progression of the deficiency symptoms. 30mg/day of methylb12 injection SC did stop them and started reversing them within a day several days after cessation. So, calling them "detox" symptoms lead to no useful treatment except to discontinue the glutathione precursors which did not in any way alter the symptoms. They continued on unchanged. However, to consider them methylb12 and methylfolate deficiencies along with an upset mineral balance and treating them for that resulted in their near immediate cessation. Let’s consider "point of view". How we think and talk about things is definitely influenced by point of view and the theoretical basis on which we base our thinking. This applies to everybody. So Person X has a point of view on one basis and person Y on a different basis. Persons X and Y see a set of symptoms following a sequence of supplements. They both see the same things. Have you read the Sufi story of the 4 blind men and the elephant" or "The Dermis Probe" in a more modern version? The 4 blind men are all describing different small pieces of the elephant and yet their descriptions appear entirely at odds when one doesn't know that each one is describing only the leg, trunk, side or tail. So Person X sees a sequence and results and calls it "Detox reaction" and Person "Y" calls it "Intensified deficiency symptoms". These sound contradictory and yet are not necessarily mutually exclusive. They may just be a way of describing something based on a different aspect of it or a different understanding based on different theoretical basis. So calling it a "detox reaction expressed as intensification of symptoms normally associated with xyz deficiency" makes the combination. A “detox reaction” describes a process. “Intensified deficiency symptoms” describe a type of effect. So in a “detox reaction” a variety of things may happen. The reaction may deplete for some reason various nutrients or change a balance. Many of these items we are taking about are actively involved in detoxifying various types of toxins. In some of these events the active substance is destroyed as it detoxifies the item. In some cases the vitamin itself may be directly destroyed or excreted as part of the detoxification effect. A detoxification reaction by it’s very nature is limited and is over shortly after the toxin(s) is depleted. So in the case of cyanide, mb12 depletes the cyanide within days when massive amounts of b12 are used and it is over before the person dies of cyanide poisoning. The same thing happens with nitrous oxide. It destroys mb12 and is cleaned out of the system by doing so. With mercury, as the previously posted model shows, which is approximate as there are many things we don’t know about it, when it is methylated by mb12 then it is subject to excretion in the bile at about 1% per day, in excess of 97% a year. After a while, a couple of years more or less depending upon assumptions, there is no significant amount of mercury left. Botulism toxin requires days to months to neutralize fully. A die off of bacteria can release a sudden pulse of toxins from the bacteria. Again, the toxins are gone quickly and the body heals. Some toxins are difficult to get rid of and can have toxic effects for years. These are toxic effects, not the results of getting rid of the toxin. Vitamin deficiency symptoms can go on indefinitely and get progressively worse until something is done to reverse them. Only the vitamin in question will help. No substitutes work. In the case of glutathione and it's precursors, for whatever reasons, it appears to induce deficiencies of at least methylb12 and methylfolate, though which is impacted worse I can't say. It also appears to deplete or upset the mineral balance of potassium and calcium. Working from the point of view of vitamin deficiencies induced by glutathione or glutathione precursors for unknown reasons and treated as such allows prompt reversal of the symptoms. So the viewpoint that the symptoms are intensification of methylb12 and methylfolate deficiency symptoms allows the pragmatic result of immediate effecive corrective treament. Many severe methylb12 deficiencies provoke very strong immediate reactions from methylb12. Severe methylfolate deficiency provokes stonger immediate reactions than mild deficiency.