To freddd re: Active cobalamin treatment
Thank you for the comprehensive reply. You've given me a lot to consider, and I'm going to have to do some studying and thinking before I will be able to put together a decent response to all the various issues you touched upon. I just want you to know that I did receive your message. Reading it was something like the proverbial "trying to drink from a fire hose," but I plan to read it again in small pieces!
I appreciate interacting with you about this, because it forces me to take a closer look at the biochemical issues involved with B12 and folate. You've correctly noted that the recovery of people on the protocol I have suggested is slow, and that is something I would like to see improved, if it can be done without causing other intolerable problems for them. There's no question in my mind that glutathione depletion and a partial block in the methylation cycle are core biochemical issues in most cases of CFS, and folate and B12 are key to fixing these problems. How best to go about it is what I want to understand better, and I think that interacting with you is going to help me in that pursuit. (I'm not "wedded" to the current Simplified Treatment Approach." I suggested it partly as a way to test the GD-MCB hypothesis for CFS, and partly to help people with CFS now, even though we don't yet understand all the details.) And along the way, maybe I will be able to help you to find answers to some of your questions, too.
I would like to bounce a couple of hypotheses off you even though though they are still half-baked. Let's assume for the moment that you are right in claiming that the high dosages of methyl B12 that you advocate do not end up causing mercury neurotoxicity problems in the brain. (Note that I'm not totally on board with you on this, but let's make that assumption for purposes of this discussion.) If methyl B12 has the ability to methylate mercury (which it does), and methylmercury can readily cross the blood-brain barrier (which it can) how could this be explained?
My understanding of the biochemistry of mercury in the brain is that it is transported in as organic mercury, such as ethylmercury in the case of the kids who received the vaccines with thimerosol preservative in them, or methylmercury in the case of the people eating a lot of fish, because the organic forms are able to cross the blood-brain barrier readily. Once inside the brain, my understanding is that the organic forms revert to inorganic mercuric mercury, which binds primarily to sulfur atoms in enzymes and other proteins, and that this is the form that actually causes the neurotoxicity.
Some years ago I suggested that perhaps a way to get the mercury back out of the brain might be to use high dosages of methyl B12 to methylate the mercury, so that it would be able to pass back across the blood-brain barrier and be removed from the brain. I didn't encourage people to try that, though, because I was concerned that if there was inorganic mercury elsewhere in the body, these high dosages of methylmercury might move it into the brain, and I couldn't be sure that the mechanism I suggested for removing mercury from the brain would really work.
I'd like to suggest that perhaps you have unwittingly (sorry about that word
)already performed that experiment. Perhaps if one uses enough methyl B12 for a long enough time, one can achieve a net effect of moving mercury out of the brain, even though perhaps some mercury would be moved in initially.
I don't know if this is true. I'm just throwing it out there. I think it could explain why you don't see a problem with mercury neurotoxicity when you use these high dosages for extended times. If this does in fact work this way, it would be a very important development, because we have not had a way to remove mercury from the brain, and the usual residence times of mercury in the brain have been estimated to be measured in years.
One other thing, as long as I'm bending over backward
, let's also suppose that you are right in claiming that your high-dosage active B12 treatment does not produce extended detox symptoms. (Again, I'm not totally agreeing with you on this, but let's make that assumption.) Given that people who have had a dysfunctional sulfur metabolism, and hence a dysfunctional detox system for many years can be expected to have accumulated large body burdens of toxins, why wouldn't these cause problems on your treatment?
It is known that B12 is one of the most chemically reactive substances in the body when its cobalt ion is in the +1 oxidation state, which it is at a certain stage of its cycle in methionine synthase. It has been called a "supernucleophile," which means that it is very reactive with substances that would tend to remove electrons from it, i.e., to oxidize it. Many toxins are electrophiles, which fill the bill. Perhaps by using such high dosages of methyl B12, you are using a lot of the excess B12 as a toxin binder, and in that way are removing toxins via the kidneys, into the urine, thus clearing them out rapidly and avoiding a drawn-out detox reaction. Again, I don't know if this is true. I'm just throwing it out as a possible hypothesis. I think this would explain things, including the fact that Amy Yasko has found that some patients need fairly large dosages of B12 to experience improvement, and I think your dosages are higher than hers are.
I'll get back to you again after I've had a chance to do some homework on the other issues. These two are the ones that I think are most crucial in trying to mesh what you have reported doing and finding to what seems to make sense to me in terms of known biochemistry. I of course haven't seen the detailed observational data to back up the claims you have made, but I'm willing to entertain the possibility that you have such data, and that you have correctly interpreted what you have seen. If so, all of this has to fit together somehow, since the truth is the truth. As you can see, I'm a hardheaded scientist, not a postmodernist.
Best regards and thanks again,