***Hi, Stressman.
***My responses are at the asterisks below:
I started this thread on a note of surprise at discovering that IBS sufferers have very similar pathologies to PWC’s, and wondering why the condition precipitated to CFS in some but not in the case of PWIBS’s. It seemed to have something to do with toxic load, perhaps less in the PWIBS group than in PWC’s. Maybe.
***Maybe so. I think that genetics could also be a factor, as well as the particular species of bacteria involved. In CFS, it is not clear to me whether the problems in the gut cause glutathione depletion and the ensuing partial methylation cycle block, or whether the cause and effect is the opposite of this. Dr. de Meirleir believes that the former is true. I can envision mechanisms in which the latter might be the case. Namely, low glutathione should lower stomach acid production, and methylation deficit should lower pancreatic enzyme secretion, both of which should lead to problems in the digestive system. Perhaps the cause and effect can go either way, depending on the particular case.
So let’s go back to before the middle P, precipitation. The familiar stuff, stress, lowered glutathione, reduced resistance to toxicity especially heavy metals, mercury etc., and viral reactivation (severe EBV in Curly’s case). So where did all the selenium (Se) go (I’ll expand on this later)? The answer is 1/ gobbled up by the free mercury (Hg) and 2/ gobbled up by the reactivated viruses, which feed on Se. To the extent that, if they are starved of the Se, they mutate and start to get really rowdy. So, a body with little or no Se, hence little or no chance of making any more glutathione.
***I'm with you on Hg binding Se, but I hadn't heard that EBV lowers Se. Here is the abstract of a paper by Edwards et al. that lists some viruses that do code for a selenium containing enzyme. Later they added hepatitis C to this list:
Biol Trace Elem Res. 1997 Jan;56(1):63-91.
Genomic structures of viral agents in relation to the biosynthesis of selenoproteins.
Taylor EW, Nadimpalli RG, Ramanathan CS.
Computational Center for Molecular Structure and Design, University of Georgia, Athens 30601-2352, USA.
wtaylor@rx.uga.edu
Abstract
The genomes of both bacteria and eukaryotic organisms are known to encode selenoproteins, using the UGA codon for seleno-cysteine (SeC), and a complex cotranslational mechanism for SeC incorporation into polypeptide chains, involving RNA stem-loop structures. These common features and similar codon usage strongly suggest that this is an ancient evolutionary development. However, the possibility that some viruses might also encode selenoproteins remained unexplored until recently. Based on an analysis of the genomic structure of the human immunodeficiency virus HIV-1, we demonstrated that several regions overlapping known HIV genes have the potential to encode selenoproteins (Taylor et al. [31], J. Med. Chem. 37, 2637-2654 [1994]). This is provocative in the light of overwhelming evidence of a role for oxidative stress in AIDS pathogenesis, and the fact that a number of viral diseases have been linked to selenium (Se) deficiency, either in humans or by in vitro and animal studies. These include HIV-AIDS, hepatitis B linked to liver disease and cancer, Coxsackie virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which Se is a potent chemoprotective agent. There are also established biochemical mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic effect, suggesting that hemorrhagic fever viruses should also be examined for potential virally encoded selenoproteins. In addition to the RNA stem-loop structures required for SeC insertion at UGA codons, genomic structural features that may be required for selenoprotein synthesis can also include ribosomal frameshift sites and RNA pseudoknots if the potential selenoprotein module overlaps with another gene, which may prove to be the rule rather than the exception in viruses. One such pseudoknot that we predicted in HIV-1 has now been verified experimentally; a similar structure can be demonstrated in precisely the same location in the reverse transcriptase coding region of hepatitis B virus. Significant new findings reported here include the existence of highly distinctive glutathione peroxidase (GSH-Px)-related sequences in Coxsackie B viruses, new theoretical data related to a previously proposed potential selenoprotein gene overlapping the HIV protease coding region, and further evidence in support of a novel frameshift site in the HIV nef gene associated with a well-conserved UGA codon in the 1-reading frame.
PMID: 9152512 [PubMed - indexed for MEDLINE]
And so to Se. Here was my second surprise. CFS literature is heavily interwoven with various detox procedures, mainly for Hg because it’s about the worst there is, but also for all the rest. Why, when all a person needs to do is to pop some Se? Se and Hg form a bond (mercuric selenide, HgSe) as strong as two bulldogs with jaws locked together. Much stronger than any sulphur bond. I wouldn’t dream of pumping my precious offspring full of DMSA/DMPS anyway. Ugh!
***It's true that Se and Hg form a very strong bond, which takes both out of bioavailability. It's also true that Hg binds much more strongly to Se than to the sulfur in sulfhydryl form.
With regard to DMSA and DMPS, I know physicians who use them, and who report good results with them, but I've also heard from people who have had bad responses to them. People who do not tolerate sulfur-containing foods or supplements don't do well with them.
In a large number of studies of sea birds, fish and even one on human cadavers, Hg and Se was found in approximately 1:1 molar ratio in the form of bound HgSe. This is almost completely non-toxic, to the extent that the body doesn’t even try to get rid of it. It accumulates in various parts of the body, including the brain (note!), and seems to stay more or less for life without toxic liability. So our famous poisonous fish, oozing Hg from the gills seems to be a folk myth in most cases. Swordfish, for example, are high in Hg. True. But they are higher in Se than Hg which means that all the Hg is bound, leaving an excess of Se. Which is very good for you, of course. The bound Hg does absolutely nothing. Wow. Wow… Steer clear of Pilot Whales and some fresh water fish though. They have more Hg than Se, so there is some free Hg to do its dirty work.
***I've read these papers, too. I just haven't had the courage to recommend use of high-dose selenium to bind mercury. I asked Dr. David Quig of Doctor's Data Lab what he thought about this at an autism conference a few years ago. He has specialized in heavy metals toxicity. He wasn't ready to recommend it for young children with autism, because he didn't know what the long term effects might be, but he said that if an old man (like me!) had Hg toxicity, he might consider it! As you noted, the animals seem to do O.K. with this Hg-Se complex,though. Se does have toxicity, so avoiding too high a level of "free" Se in the body would be important with this treatment. As far as I know, the toxic effects of Se are reversible if it is discontinued, though. The first symptoms of Se toxicity involve the nails and hair, I believe. I guess no one has had the courage (or has been able to get IRB approval, perhaps) to do this kind of study on humans. Getting funding for it would also be problematic, I think, both because Hg toxicity is sort of a political and legal football, and because there would be no possibility of patenting the treatment, having a monopoly, and deriving a tidy profit from it. From a purely scientific perspective, though, it looks tantalizing as a way to deal with Hg toxicity, and perhaps a way to deal with it in the brain.
***Another approach I have also kicked around on the internet boards, but still don't have the courage to recommend, is the possibility of trying high-dose methyl B12, after having cleared the inorganic mercury out of the rest of the body, beside the brain. Methyl B12 chemically has the ability to methylate mercury, which in theory could enable it to cross the blood-brain barrier and come back out of the brain. B12 in general is very nontoxic, so high doses would probably be O.K. The downside would be that if there was still inorganic mercury in the body, this could be methyated and possibly moved into the brain, which would be the opposite of what one would be trying to achieve. Again, I don't know of data on experience with this approach, particularly in humans, and the issues involved in doing such a study in humans would be essentially the same as with Se, though B12 has lower toxicity.
So that’s why I’ve started Curly on Se. I knew it was good, but I didn’t know it was THAT good when we started. It’s also good for cadmium, arsenic, lead, platinum and it even has a little go at aluminium (aluminum across the pond).
***I hope it pays off for her, and I'm glad that you are using a pretty reasonable dosage. I'll be very interested in how it goes for her.
Given enough Se then, there would appear to be no liability to adding molybdenum, MSM and ALA at suitable later dates, as a general spring clean.
Words of wisdom welcome please!
***I'm not sure my words contain all that much wisdom. I do appreciate being able to kick these things around with you, though.
***Best regards,
***Rich