Hi Vegas, I haven't appreciated a noticeable difference between different ratios of methyl/adenosyl. This tends to be a rather subtle thing. It mostly can't be appreciated until a person has reached an appreciable level of equilibrium and startup responses have all faded, perhaps 9-12 months in after a person has reached a point where further increases in mb12 make no noticeable difference. I am in position to recognize it more clearly because of the relatively limited interchange I have amongst types of cobalamin. Based on history I have some interchange but probably not as much as you. I was 9 months in on mb12 and I had enough interchange that my mitochondria were working pretty well by that time but not as well as after the adb12 and l-carnitine fumarate where there is enough for CNS/CSF penetration. Mood and personality changes are the most affected by the ratio. And some people have found that too much adb12 compared to mb12 induces changes similar to an actual deficiency of mb12 in mood and personality. What the exact ratio is however, varies considerably from person to person and comes into play during the fine tuning portion of things. One possibility relates to the fact that Methylmalonyl Coenzyme A mutase uses adenosyl as a cofactor. In this regard some benefits could be ascribed to the relative abundance of adenosyl to facillitate this reaction. Methylmalonyl Coenzyme A mutase is involved in the catalyst of Methylmalonyl-CoA to Succinyl-Coenzyme A, which is comprised of succinic acid and Co-Enzyme A. As I suspect you know this enzyme is critically involved in fatty acid synthesis and the Kreb's Cycle...core problems in CFS. Yes, that is is the purpose of adb12 in the mitochindria. It is aided by the transport of fats into the cell by l-carnitine fumarate and that is increased about 50% according to research by Alpha Lipoic acid. Sufficiency allows energy generation in muscles and neurons. This invloves that whole area of exercise intolerance, muscle atrophy, mood and personality changes. It is critically important, but is still just one function. I was able to convert enough to allow some of this to occur but not for new muscles tissue to form or for mitochondria to increase in existing muscle. That changed in literally one day when I actually tried adb12. When I added the L-carnitine fumarate and the alpha lipoic acid my aerobic exercise period changed overnight from 17 minutes, which was a struggle to reach, to 34 minutes easily. Do you have a replacement brand of adenosyl you could recommend--one without folic acid? Very unfortunately no. However, I think taking it in a method that limits the hours of folic acid in the serum is important to being able to tolerate it. So it appears that a single larger dose that achieves a deeper tissue penetration each few days or week would minimize folic acid exposure and still maintain adb12 equilibrium. If adenosyl can repeatedly, by itself, produce reactions, that are suspended when it is discontinued, I think there is a good chance its use has a causative role. I think that is only happening because you are not at an mb12 equilibrium such as produced by 20mg or so sublingual daily. Are you suggesting that what I perceive as "detox" symptoms are purely correlated to a vitamin deficiency and are not side effects of increased detoxification and immune response? This is more complicated. Let's start with "perceive". I started out at the MGH neurology forum. Everybody there had neurological problems that were perceived as their primary problem, some quite advanced and in wheel chairs. After that board was taken over by trolls I went elsewhere, wrongdiagnosis forums. I joined an ongoing b12 deficiency forum that was already in progress. At that forum/thread, which is near 3000 views a day now, lots and lots of people come by. They perceive their main problems as mysterious or b12 deficiency or neurological or a wide variety of things. For the most part they have done little reading on "detox" ideas. It has a bunch of vegetarians and people in a wide variety of stages of the problems including a substantial portion who clearly have FMS/CFS but have docs reluctant to diagnose them with anything. There is a lot of that universal diagnosis of "Its All In Your Head" (IAIYH) which we see around here too. Then there is this board. I've been kicked off a few others by saying things the management didn't like, such as vitamins that are not the house brand or saying there is a cure for a lot of folks who have made their identity as FMS/CFS victims and want to be supported in that. Petty tyrant types don't like me. However, despite the wide difference in diagnoses and perceptions, the symptoms at all three of the main boards I have posted at are virtually identical. They all draw from the same universe of symptoms as are in the list I have posted here and there, and while there is some variability in which ones each person has, they all have lots of them from most every category. Looking at the symptoms you could not tell the populations of the boards apart or who was likely to be at which board. As the list includes discreet and overlapping of symptoms of body-adb12, body-mb12, CNS/CSF-adb12, CNS/CSF-mb12 and methylfolate what is seen is clusters of which deficiency sets the people have. But again, that is an individual distinction that is not readily apparent when looking at the populations. The biggest single difference is that many people at this board have already tried a hydroxycbl plus folinic acid based protocol whereas at the other boards they have generally used cyanocbl and/or hydroxycbl but NOT folinic acid. What was apparent from day one is that those taking the hycbl plus folinic acid had far more, far worse and far longer intensification of a symptoms set they called "detox" reactions. Those symptoms are for the most part on the list and are usually a combination of severe folate deficiency symptoms and a worsening of part of the b12 deficiency symptoms. These are different from the "startup response" symptoms which tend to end within a few months as the cause of the symptoms heals whereas here I have met many who have had "detox" without end, sometimes for years. When they confuse the "startup" response symptoms with the "detox" symptoms they often go off the items that cause the startup symptoms, which go away in a couple of days usually without the mb12 whereas the "detox" often go on and on without letup after they stop the things that caused it. As the "startup" response symptoms are the same in all the forum populations regardless of the perceived primary complaint and/or diagnoses but are similar based on symptoms, there is nothing to distinguish the populations except what they call that intial response to mb12/methylfolate. If they call it "startup response" and consider them to be signposts to healing, they heal. If they call them detox and stop the active protocol because of them, they don't heal. If they are taking folinic acid and hycbl the "detox" continues indefinitely in many cases. In the cases of "glutathione detox reaction" or "NAC detox reaction" they are 100% methylfolate, mb12 and adb12 deficiency symptoms and are quickly reversible with adequate repeated doses of the those. So, while those are clearly sloppy language usages, the misperception of those as "detox" makes them untreatable instead of readily and quickly reversible though if they are allowed to go on long enough for damage the damage takes awhile to heal, or not, depending upon severity. Is it your view that taking methyl/adenosyl/methylfolate does not have the capacity to increase glutathione and improve the functioning of the immune system? Do you think that these changes would take place without any symptomatic response? Again, some of this at least is perceptual. I've had people tell me that their response to and absorbed dose of 100-200 mcg of mb12 starting less than an hour after starting the sublingual is detox. Whatever effect that mb12 has on the immune system, and it does have an effect, takes place starting in days, not minutes and hours. And consider that 200mcg of absorbed mb12 has the methyl group donor capacity of 0.1mg or so of SAM-e which is really very little and would not produce a perceivable effect in anybody. So whatever mb12 is doing at that quantity isn't high powered methylation. Experience indicates that it takes some weeks typically and runs to months for the immune system to get working a lot better. And according to Rich, and I have no reason to doubt what he says on this, the mb12 and cofactors do indeed increase glutathione. I have had another researcher tell me in a phone conversation that "there is no safe way to take glutathione". Only about half of what mb12 does in the body is readily perceivable. Much of it happens below the level of perception. Experienced a herxheimer reaction from antibiotics or antifungals Yes, from antibiotics with some unidentified resistant pneumonia that responded to the 3rd combination of 3 antibiotics tried. That can happen starting in hours as the antibiotics kills the bacteria outright and spills their toxins into the blood. A herxheimer reaction can be very serious but is mercifully short. and goes on for some hours in most cases. It doesn't go on for weeks or months. http://en.wikipedia.org/wiki/Herxheimer_reaction The Herxheimer reaction (also known as Jarisch-Herxheimer or Herx) occurs when large quantities of toxins are released into the body as bacteria (typically spirochetes) die during antibiotic treatment. It is classically associated with syphilis. Typically the death of these bacteria and the associated release of endotoxins occurs faster than the body can remove the toxins. It is manifested by fever, chills, headache, myalgia (muscle pain), and exacerbation of skin lesions. Duration in syphilis is normally only a few hours. The intensity of the reaction reflects the intensity of inflammation present. The reaction is also seen in other diseases caused by spirochetes, such as borreliosis (Lyme disease and tick-borne relapsing fever) and leptospirosis, and in Q fever. Similar reactions have also been reported to occur in bartonellosis (including cat scratch disease), brucellosis, typhoid fever, and trichinosis. However, mb12 doesn't kill bacteria outright and quickly. Instead it repairs the immune system a little at a time until antibodies and white blood cells and such are being normally produced and that takes a while and comes up slowly. And again, in the case of metals, a quarter of a mg of mb12 can affect very little metal, if at all, dealing in mcg quanties, very slowly if at all. However, a quater mg of mb12 can trun the volume of the nervous system form barely functioning to high in 60 minutes. A quarter mg of adb12 can kick start 10% of the mitochondria in the body in a few hours. These are very noticeable and necessary and perceived very potent reactions which are often misinterpreted. So if you were to describe in specific detail what reactions occurred from mb12 and how quickly it might be possible to identify some as "detox" response. However, it wouldn't be the reactions everybody has regardless of cause of deficiency most likely. It wouldn't likely be the things that happen immediately. And it definitely isn't the things identified as glutathione detox reaction or NAC detox reactions as those are demonstrably outright deficiency symptoms or the intensified deficiency symptoms from folic or folinic acid which are quickly reversable with Metafolin, mb12 and adb12. So far everything I have seen attributed to near instantaneous mercury detox from a fraction of a mg of mb12 for instance has nothing to do with mercury except the idea. And other "detox" reactions would not be the same startup responses everybody else has. I would be interested in seeing identifying what things might actually be real honest to goodness "detox" since most claimed "detox" from mb12. If the word "detox" were not so overused to describe worsened deficiency symptoms or induced deficiency symptoms or the usual startup responses I wouldn't be so skeptical. I've spent a long time at data analysis. In the mb12/adb12/methylfolate world where most deficiency symptoms are attributed to many other things and misdiagnosis is the norm and so few actually experience healing, a multitude of inaccurate diagnoses are the norm and docs have no idea what the path of healing looks like because they have never seen it even once, all sorts of ideas and theories are floated. When hydroxycbl and cyanocbl leave 2/3 of active b12 deficiency symptoms untouched all sorts of wrong theories dominate. I am interested is seeing what real genuine mb12/adb12 induced detox actually looks like. I have never seen a convincing description and I've listened to a lot of people describe startup and healing and the things they run into. And if you want to attribute the many things of a usual startup response to detox, then show me why everybody doing it has all these toxins in their body at such high levels. maybe that is normal. Then I went through it too. I went through a very intense multi month set of startup responses. In the first ten days my burning bladder, burning beef-red tongue, burning muscles all stopped burning and stqarted returning to normal. My energy increased tremendously, I could focus my eyes again and so on. I'll try to locate the writeup I did for my docs at the time of the first 3 weeks. All the pains came across in high definition. My symptoms went wild and by the end of 10 days it was clear that I was healing one thing after another. But it took 4 months to settle down. At 9 months I was able to start reducing most of my meds and reduced my pharmacy bill from $1500/month to under $100/month over the next few months. Then it took years of rehabilitation to build up muscles and capacity again. Each time things slowed down I looked for what would intensify (not worsen) the symptoms again and continue healing them. It worked. Believing strongly that it is "detox" doesn't make it so.