Lonestar Health

Right after we formed the company Dr Bounous and I traveled to Harvard University for a conference We met Dr Paul Cheney - one of the co discoverers of Chroni...c Fatigue Syndrome It just so happened that Dr Cheney was very interested in addressing a glutathione deficiency he was seeing in this population I offered Immunocal - unfortunately this study was never published but Dr Cheney spoke to various audiences about his findings Below is a transcript of one discussion Sorry for the length - but I am sure you will be fascinated as I was Paul Cheney, M.D. February 5-7, 1999. Afternoon workshop using case studies and slides. "This session is on the clinical management of Chronic Fatigue Syndrome. And I'll go through a series of slides that I think outline a number of key issues and their management, and then go through a treatment paradigm [pyramid actually, I think] that I developed over many years to treat these patients. Then maybe we'll open up to questions. One of the things that I think is important to know about these people is that they're complicated in the beginning, but I think they become ever more complicated at time goes on. I'm constantly amazed at how complicated the disease is, especially as the years roll by. We'll discuss some of the reasons why. I think they are, interestingly, most approachable from a therapeutic standpoint in the early stages of the illness. But as things go along, they can be more and more difficult. I think there's an end stage to this disease that may not be well treated no matter what you do, and we'll talk a little about what makes those people so treatment resistant. I'm going to begin by sort of coupling to the talk this morning about this glutathione defect. I believe this glutathione deficiency is the key problem particularly over time, and makes the patients very difficult to manage from a detoxification standpoint. Because every time you try to intervene and detoxify when they have this underlying defect, you actually make them quite ill. You can actually put them in the hospital attempting what appears to be a good detox program that works in a lot of people, but will not work in this subset of very sick and treatment-resistant people, which is mostly what I see. Another little caveat to note is that I don't know if what I'm going to be saying will generalize to all chronic fatigue syndrome. It seems like I have a larger collection of sicker, more treatment-resistant patients. That's kind of what I see. So when people say, "Well I did this-and-so and that-and-so and it worked on everybody and they were well," I never see that. Maybe we're not looking at the same group of people. I think there are milder forms of this disease that may very well respond to all kinds of treatment forms. The glutathione resistance or glutathione deficiency was first noted when we began measuring whole blood glutathione levels and began to see these low to low normal glutathione levels. We were also looking at functional markers of glutathione, such as lipid peroxides. Both blood lipid peroxides and urinary lipid peroxides, which is an endpoint functional indicator of glutathione functionality. We're also seeing other functional indicators of glutathione problems such as citrate elevation and alpha ketogluterate (sp?) depression on organic acid analysis. What was curious to me was that in many ways we were able to make progress on just about everything that we cared to clinically measure as we applied our therapeutic regimes--we saw a lot of people getting better--we saw a lot of things getting better, except this glutathione. It seemed to be extremely resistant to therapy. It was as if something was hanging on and preventing our ability to change this system. I don't know, and I still don't know to this day, why that is. But whatever is doing this, is a key to this illness, I think. This is just a slide of the degree and the reality of this glutathione defect. Seen in red on the left, relative to control groups in blue, they sit right at the margins of normal (although you see some that are extremely low). They sit right at the bottom edge of normality. In addition to this, to indicate that yes this is not only a low glutathione functionally important, is the evidence of urinary lipid peroxides, shown on the right, their urinary lipid peroxides are high, almost double that of the normal population. In addition to this, we saw extremely low serum Vitamin E levels. If you had a glutathione defect, you might expect to see defects in holding vitamin E in its reduced state as it's typically cycled with glutathione between its reduced and oxidized states. And, indeed, vitamin E is very low and it's very treatment-resistant. You can get lots of vitamin E and not have much of an impact which I think again is an aspect of this glutathione deficiency. If you can't recycle vitamin E, whatever you're getting, just gets oxidized. You may also have problems with oxidizing vitamin E in the GI tract. We also noted some generally low red cell selenium values. But they're even lower in white cells, specifically lymphocytes, which I think is interesting in itself. The point being that this selenium defect may actually be compartmentalized. That is, in some areas of the body the selenium level might be OK, but it other areas of the body it might be specifically depleted. I think it's extremely depleted in the white cell. Of course, if you deplete selenium you're going to cream the glutathione functional system. We also got interested in this low selenium from the standpoint of the emergence in HIV disease or the discovery of a gene. It's a glutathione-peroxidase encoding gene present in HIV which upon rapid cycling consumes large amounts of selenium within the cell where HIV resides. This selenium consumption effect can essentially wipe out glutathione synthesis and then produce apoptotic cell death. So the hypothesis is that perhaps the mechanism of CD4 depletion in HIV infection may be involved in this selective selenium depletion of cells in which HIV sits, and knocking out glutathione is producing apoptotic cell death. So the fact that we were seeing selenium depletion in lymphocytes which exceeded the selenium depletion in red cells and by other measures suggested there might be some compartmentalized issue involving this glutathione defect which is going to be even more problematic from a treatment standpoint. Because what if the glutathione levels or the selenium levels are OK in some parts of the body and then really depleted in other parts of the body? That makes it very difficult to treat because if you treat for the selenium defect, you might over-treat in one part of the body just to restore another part. And it doesn't even get at the dynamic issues involved. So we thought we were getting closer to the problem or at least why the problem was so treatment-resistant. To me, this is a most extraordinary paper, published by Anthony Falci, an expert and head of NIAID and our leader in the HIV world at NIH. But he's also a glutathione expert. And he showed in this paper, published in PNS in 1991, that glutathione is an impressive anti-viral weapon. Under cell conditions designed to produce log order growth in HIV, simply by raising glutathione levels to 15 millisomething (word?), you can wipe out that exponential growth, which is the white line, down to the yellow line, which is the flat line. You can flat-line HIV growth simply by raising glutathione in-vitro in the cell culture. Now 15 millisomething (word?) is only three times physiologic. If you raise the physiologic doses, which is 5 millisomething word?), you get an intermediate line--a suppression of HIV, but not a wipeout. By the way, this also applies to other cytokine-induced augmention of HIV in cell cultures, such as TNF alpha and IL-6 when injected into cell cultures also augment HIV growth, not as well as somethingesters (?) do, but quite nicely. Again 15 ml (?) glutathione wipes out the cytokine effect. These two issues I thought were very important to me because it meant that chemicals or toxins such as fourbellesters (sp?) can induce endogenous micro-organism replication rate, especially in the presence of glutathione deficiency. And immune-activation states can also induce the activation of endogenous microbes in the presence of glutathione deficiency. And that might explain why in this, quote, immune-activation state that we call Chronic Fatigue Syndrome you see a lot of endogenous viral activation such as EBV, CMV, HHV6, mycoplasma incognitus, chlamydia pneumonia, candida, and on and on and on. You see the activation of this microbial ecology, and why is this happening? It could be that it happens because cytokines in excess stimulate these organisms, especially in the presence of glutathione deficiency. The converse is true, however. In the presence of good glutathione levels, it's very difficult for that to happen. This is a diagram of what might be going on in the initial stages of this disease, Chronic Fatigue Syndrome. Namely, some virus gets into that person, or activates, which has one of these glutathione-peroxidase encoding genes, producing rapid cycling production of seleno-proteins [selenium-bound proteins]. Those seleno-proteins don't do much functionally, but they consume vast quantities of selenium, anywhere from two to 16 selenium atoms per seleno protein. Upon selenium depletion, you wipe out glutathione synthesis and functionality, resulting in rapid viral replication, redox (?) shift causing energy drops and detoxification failure at the cell level. If glutathione deficiency drops low enough and redox shift rises high enough, this cell simply dies, an apoptotic death. [Inaudible question.] I don't know. I don't know what the factors are that govern this. It's just an important idea. If this is going on, you might expect to see specific compartmentalized selenium deficiency in the cells in which viruses like this sit. Now the cells that propose to cause chronic fatigue syndrome, typically sit in the lymphocyte fraction, such as EBV, HHV6 and so forth, and they would be expected to produce a greater effect of selenium depletion in the white cells than other places. Conclusions from all of this are: Glutathione has potent anti-viral properties--if you raise the glutathione level you can stop the replication of most any, at least, intracellular pathogen. chronic fatigue syndrome patients are glutathione deficient. Glutathione deficiency itself has a potent pro-viral effect. That is, not only does (high?) glutathione levels tend to act as an anti-viral, but glutathione deficiency produces a pro-viral effect. It can actually augment viral replication. Augment it from the case of toxins, toxins could augment viral replication and also cytokines themselves. So immune-activation states would itself augment these things. A seleno protein encoding gene would provide a significant survival advantage to any microbial pathogen. What a great gene to have if you're a virus. Because if you have this gene, you can't be killed. And some of the most vicious viruses on the planet--the hemorrhagic fever virus, such as ebola--ebola has this gene in spades. HIV has this gene in spades. Hepatitis B and C have this gene. Other viruses are expected to have it. HHV6, strain A, is thought to have it because it's a lytic virus. The most interesting possibility is that this gene can be passed around from virus to virus, especially by retroviruses. Retroviruses have the unique capacity to insert pieces of themselves into the DNA of both human host genomes and also into viral genomes. So HIV could actually be spawning new and more virulent virions simply by stashing a gene like this in the next piece of DNA it sees in which it co-habitates. And that's interesting because HIV, HHV6 and mycoplasma incognitus all co-habitate and co-infect exactly the same lymphocyte cell linings. Therefore, the opportunity for transmission or sharing of this gene exists. The reason I mention all of this to begin with is because I'm trying to set the stage for how important it is to address this glutathione defect. It could be THE major issue in this illness. Maybe not so much in the beginning, but over time become the major issue. Because we're dealing with a sub-group of people who have cellular detox failure and all that that causes. Because if you have cell detox failure, you become a canary to your environment. You are vulnerable to the lowest common denominator of the toxin that you happen be be exposed to, or have. If you have mercury in your mouth, you become mercury toxic when you get this glutathione defect. Because a major defense, perhaps the major defense, against mercury toxicity is in fact glutathione. If you have a toxic GI tract--and everyone in this room has a toxic GI tract--portal circulations are intrinsically toxic, they always have been and they always will be. If you get a glutathione defect, then you become vulnerable to your own cell toxicity, specifically the portal circulation. Of course we can modulate that toxcicity by giving you a bad gut ecology, wiping out your good flora, populate you with some bad flora and make things even worse. But even under the best circumstances, this glutathione defect would make it very difficult to achieve health simply by addressing only gut ecology. Because even normal gut ecology is too toxic when you have this problem. The point is that the glutathione defect is a central issue in any detoxification program. You can't be looking at sources and addressing those when you have detox failure. That's why a lot of CFIDS patients don't do well under a lot of detoxification programs. What we got interested in... we found out that when you give oral reduced glutathione, it helps a little bit in some people, especially these pressure toxic headaches they get. But when you keep raising the dose, it actually gets sick again, and was never a very impressive response. When we tried NAC [N-Acetylcysteine], we saw some evidence of toxcicity. In the use of NAC--I'm concerned about high-dose NAC in this disease. I think it may be toxic. We tried other methods to affect glutathione. Nothing seemed to be working. Then we got wind of this product [called Immunocal]... it's basically undenatured whey protein, lightly denatured to preserve the peptide action of this milk protein. It's concentrated to about 90 percent protein and it's very, very lightly denatured. In fact, the more lightly they denature it, the better the action appears to be. And the more they denature it, the less active it appears to be. In fact, if you denature it completely, down to its constituent amino acids, it really doesn't work well at all. People who normally have milk protein allergy seem to tolerate this, by and large. Not 100 percent, but by and large. This is the data from a six month study. There were eight people entered into the study, seven of them completed the study. We got data on seven of them. One dropped out at three months for a reason involved with the design of the study. The first three months of the study we treated with two packets a day, and then the second three months, half were randomized to two packets a day and half were randomized to one packet a day. We wanted to see if you could tell a difference clinically or by other means between one packet a day versus two packets a day. We did this because there was some indication that the more you treat with this, the higher the dose, the better the effect. This is urinary lipid peroxides combining both the two packs a day for six months, followed by the two packs a day for three months and one pack a day for three months. You can see there's a nice steady drop through six month in urine lipid peroxides, which is an endpoint functional marker of glutathione. When you segment out the two packs a day for six months group, they have a much nicer drop. When you look at the group that goes from two packs a day to one pack a day, you can see this nice dip where they started going back up (in their urine lipid peroxides). Suggesting that one pack a day doesn't work very well. By the way, you can extend this--there are people, I've discovered since the study was done, that do really well on three packs a day and not very well at all on two. So clearly there is a dose response issue. Two packs a day would probably be my recommended starting dose, but I wouldn't hesitate to go up if if seemed like it wasn't working. (Explains guy who dropped out of study.) The red line stops because this is a guy who dropped out of study after three months because he had gotten tremendous results from two packs a day. He was randomized to one pack a day and he refused to do it, so he withdrew from study. He said, "I've got something that helps me. Goodbye." There are 10 grams in a pack. [Someone asks him what his source is.] I'll talk with you later. This is a generic talk. I don't sell anything... I don't mean to sell anything. [But we all know that Dr. Cheney was talking about Immunocal, don't we?] This is whole blood glutathione. This is interesting. When we looked at whole blood glutathione, there was almost no change. There was a little drop at month two, it was almost like the system got engaged. Glutathione that wasn't being used was suddenly being used and the glutathione stores actually dipped at the second month, and then they started to come up. You can capture that at month three. And at month six it started to come up. But overall not much change in the actual whole blood glutathione. Suggesting to me that it isn't whole blood glutathione status that this is affecting. It's affecting the whole glutathione system. So what you're not seeing here... it's like you're looking at a whole sink filled with glutathione and you're not seeing the dynamism, the utilization of glutathione. As evidenced by dropping of the urine lipid peroxides. Or yet, there's some other aspects of this product I don't understand. But you can see that this group had borderline glutathione levels. I have a feeling according to other reports that if they had severely depleted [whole blood] glutathione levels, then you see rising glutathione levels, if they're severely depleted. But in these marginal cases, we just didn't see much. [Question: What about 5 or 10 packets a day?] I'll get to that... it is an interesting idea. This is the exciting stuff. We wanted to see not only if this product improved glutathione functionality, which it did, but we also wanted to see if it knocked out micro-organisms, like the PNS article said it would. So we measured for IgM (visa?) the inverse dilutions of IgM for chlamydia pneumoniae. Chlamydia pneumoniae is an intracellular pathogen. It's a common cause of hospital-acquired pneumonia. It ubiquitously infects the population, but seems to activate under certain conditions. And if it activates, some of the clinical conditions of this organism are chronic sinusitis, pharyngitis, and laryngitis. But it also gets into the central nervous system. In a study published by a neurologist out of Vanderbilt showed tha chlyamdia pneumoniae may be a very important pathogen in multiple sclerosis. Indeed, data they shared with me recently (and this is coming to publication soon) showed that 80 percent of the cerebral spinal fluid of MS patients is actively infected with this organism. Versus 15 percent of other neurological diseases that are not MS. In a journal-published article on neurology, aggressive treatment for chlyamdia pneumoniae rapidly reversed an acute exacerbation of multiple sclerosis. So we measured IgM levels for this pathogen at Vanderbilt. Most laboratory measurements of this organism are not very good, so this is a research grade assessment, and probably may not generalize to the run-of-the-mill types of tests that you might get in your local labs. But IgM elevations of 1 to 1600 (?) dilutions is evident of significant active infection with this organism. Six months later, it just wiped it out. IgM just fell to normal levels. It didn't really matter whether you were taking one pack a day or two packs a day. Just wiped it out. Makes you wonder what this might do for MS. Think about that. We also looked at mycoplasma fermentans and mycoplasma penetrans. Both of these pathogens have been linked to Gulf War Syndrome. They've been linked to chronic fatigue syndrome. Again, they may be a relatively ubiquitous mycoplasma species, intracellular, and can cause a variety of problems when active. Again, by PCR done in Irvine, California. We were able to show that this product also wiped out mycoplasma incognitus and penetrans. By the way, this study was designed to do some microbial testing on everybody, but not everything on everybody. The patients were allowed to pick and choose depending on what we had in their chart before. We weren't able to do everything on everybody because they were paying for this. Then we looked at HHV6. It was a little mixed here. We tested three people By the way, this study was designed to do some microbial testing on everybody, but not everything on everybody. The patients were allowed to pick and choose depending on what we had in their chart before. We weren't able to do everything on everybody because they were paying for this. We did HHV6 rapid culture testing, which is a technique developed by a company in Wisconsin. This particular culture technique uses an intermediate (captures fiberglass?) cell line, so that you are positive only if you are really infected, so it reduces false positives to zero. That is, uner these conditions, all normal people are negative. You have to do that because HHV, both A and B strains, are relatively ubiquitous. Under these conditions, we had two positives and one negative at beginning of study. The person on two packs a day went to zero culture (negative); the person on one pack a day stayed positive. The person that was negative stayed negative. Suggesting that maybe this isn't as good against viruses as it is against bacteria, but at two packs a day it might be good against viruses. Again, the numbers (of participants) are a bit small. But to me, the satisfaction of this is tremendous because I'm always faced in this disease population--well, are they sick from EBV? or are they sick from HHV6? or are they sick from mycoplasma incognitus? or are they sick from c pneumoniae? And the [traditional] treatment for mycoplasma and cpneumoniae is 18 months of triple drug antibiotic therapy. And if we're wrong on this issue, we've wiped out their gut flora and leave them a gut ecology cripple for the rest of their lives. So now what we have is a nice way to address almost any micro-organism that happens to be there. [Using Immunocal.] Just as the PNS article suggested. [Someone asks if there is a protocol to give people with HIV this product.Cheney responds yes.] Finally, how did the people feel? Their glutathione functionality improved, though their glutathione levels were marginally improved, and they had significant wipeout of micro-organisms. How did they feel? Five out of six (seven?) felt significantly better. Three of those five thought this was the best thing they had ever tried. They said it was tremendous. In fact one dropped out of the study because he refused to stay on the protocol at only one pack a day. There were a couple of non-responders. But you'll notice that the two packs a day were the best responders. There is a differential issue still imbedded in this--namely the dose. The dose might need to be upped to see maximum benefit in certain individual cases. They're continuing to do well. I guess I should give you some caveats about what these patients said.There's a woman in Manhattan and she said for the first time since she's had this illness, she had a sense of well-being. As opposed to feeling ill.She felt that was her major benefit. We classified her as a good responder. We had a mother-daughter pair. The daughter had Multiple Chemical Sensitivities--wore a mask everywhere, was wheelchaired around, very sick, bedridden, essentially taken care of by her parents, fed and bathed and dressed. Anyway, she probably had the very best response. Her Multiple Chemical Sensitivities disappeared. And she's now walking around and thinking about going back to school and, at last report, she's doing extremely well. She was probably the sickest. Her mother was not nearly as sick as she was... her mother had a significant improvement in energy and is doing very well too. We had a man who was a businessman in Charlotte. Every time he pushed himself, he crashed. He could do some things, but every time he went past his boundaries, he crashed. He stopped doing this [on Immunocal]. And then we had an attorney in San Francisco who felt a little better energy. Could tell she was on the product, but nothing to write home about. Would classify her as a fair responder. Then we had a couple of non-responders. Interestingly, these two non-responders were NOT the sickest. They were probably the wellest of the seven. I have some serious doubts about their compliance with this. It was very difficult to assess them because they were both working and there were a lot of things going on in their work and it was hard to assess them. Neither of them could tell much difference.

Very interesting.

Proudly presenting https://t.co/I5oSkP1bgN. Check it out and let me know what you think!