Richvank (or anyone) ? re glutathione + postexertional malaise

Discussion in 'Fibromyalgia Main Forum' started by mbofov, Oct 16, 2008.

  1. mbofov

    mbofov Active Member

    Hi Rich - you have repeatedly stressed the link between a block in the methylation cycle, consequent glutathione depletion, and CFIDS. I’ve read your papers and sort of grasped the principles involved, but never understood how glutathione depletion could cause post-exertional malaise (crash, complete energy depletion), which lasts for 2-3 days. I came across an article today which gave me some ideas and I'd appreciate your feedback.

    You may have covered this in one of your posts already, and if so, my apologies. I may be trying to re-invent the wheel here . . . .

    I re-read an article today in which Dr. Cheney talks about CFIDS patients having alkaline venous blood. (

    The article states that “Blood alkalosis inhibits the transport of oxygen to tissues and organs, constricts the blood vessels, and lowers overall circulating blood volume. . . . The purative cause of the alkalosis is the GLUTATHIONE DEFICIENCY [my caps] that is pervasive in CFIDS. Low glutathione causes an elevation in citrate, which in turn lowers a substance (2.3 DPG) that controls the release of oxygen from the hemoglobin. Our blood could be full of oxygen, but without enough of this substance it cannot break free of the hemoglobin and get into the cells. This causes oxygen deprivation in the tissues (hypoxia), which makes the body switch over to anaerobic metabolism, and that produces tissue acidosis, which can be painful.”

    In another article (, Dr. Sarah Myhill says this about CFIDS fatigue: “. . . .the basic pathology in CFS is slow re-cycling of ATP to ADP and back to ATP again. If patients push themselves and make more energy demands, then ADP is converted to AMP which cannot be recycled and it is this which is responsible for the delayed fatigue. This is because it takes the body several days to make fresh ATP from new ingredients. When patients overdo things and "hit a brick wall" this is because they have no ATP or ADP to function at all.”

    This sounds a lot like the post-exertional crashes I and other CFIDS patients experience.

    What I’m wondering is, could blood alkalosis (due to glutathione depletion) and subsequent oxygen deprivation in tissues, be the cause or part of the cause of the problem CFIDS patients have with recyling ATP? In other words, could blood alkalosis be the cause of post-exertional malaise? (in reality, complete energy crashes - I hate the word malaise - it doesn’t begin to describe the feeling of crashing)

    I’d really appreciate your input on this. I know none of this is new information, but I was just putting pieces together in a different way, for me at least. And even if there isn’t a direct correlation between blood alkalosis and problems recycling ATP, the Cheney article does seem to be further validation of the link between glutathione depletion and CFIDS.

    For those interested, the Cheney article talks about using a rebreather machine to increase levels of 2.3 DPG, but later said that breathing exercises would accomplish the same thing, in a safer way. He also recommends undenatured whey to boost glutathione levels. Here are the breathing exercises:

    1) Inhale through your nose for 4 seconds

    2) Hold your breath for 7 seconds

    3) Exhale through tightly pursed lips for 8 seconds, creating "back pressure" (you should be able to hear the air being forced out of your mouth as you do this.)

    Do this 8 times in a total of two and a half minutes. Do this twice a day - a grand total of 5 minutes a day. That's all it takes. (If you feel lightheaded, just do it 6 times or until you begin to feel lightheaded, then build up to 8.) You must be very faithful and consistent for this to work, and it takes weeks for the body to adjust the 2,3 DPG levels. But your oxygen transport will get better and better over time.

    [This Message was Edited on 10/17/2008]
    [This Message was Edited on 10/18/2008]
    [This Message was Edited on 10/20/2008]
  2. mbofov

    mbofov Active Member

    bump bump bump bump
  3. mbofov

    mbofov Active Member

    Thanks so much for your suggestions. I did a little searching and it looks like he responds to posts with "richvank" in it, so I changed mine.

    Also, will do a search for Cheney breathing as well -

  4. Forebearance

    Forebearance Member

    I like your pieces, Mary!

    It sounds like an interesting possibility.

    I wonder how the two processes you found would fit together with Dr. Shoemaker's finding that neurotoxins cause impaired microcirculation. And restrict the amount of blood that can get into tissues.

    It sounds like all three things are leading to similar types of problems.

    In other words, no wonder we're so messed up.

  5. mbofov

    mbofov Active Member

    Shoemaker's findings definitely sound similar - if not enough blood gets into the tissues, there won't be enough oxygen, etc.

    What I really found interesting about the Cheney piece was that the blood could be full of oxygen, and not be able to utilize it. I had read this before but never carefully enough ... I had just thought he was saying something about not enough oxygen in our blood, blah blah. hmmmm.... seems it's important to pay attention to details!


  6. Forebearance

    Forebearance Member

    Yeah, I remember he had a graph about blood oxygen levels in his video lecture of Sept 07 (was that when it was?). Anyway, the video lecture sold by the Dallas-Fort Worth CFIDS support group.

    It showed that the blood coming back from the extremities to the heart/lungs had a lot of oxygen still in it. It should have had a lot less oxygen in it, if the body had been using oxygen normally.
  7. mbofov

    mbofov Active Member

    Thanks, Forebearance. I've never seen any of Cheney's videos, but I would have liked to have seen that. It just seems the problem with oxygen utilization would have to have something to do with post-exertional malaise.

    I wrote my doctor about putting the different "pieces" together (am still waiting to hear back from him), and one of my kids suggested sending it to the original researchers - Cheney and Myhill, (and Rich, which I've done here). So I'll do that - have no idea if they'll respond, but you never know --

  8. richvank

    richvank New Member

    Hi, Mary.

    The talk by Dr. Cheney to which you referred was given 6 years ago. Dr. Cheney's views have changed quite a bit over that time, and I'm not sure that he would still subscribe to what he said then. These days he is talking about oxygen toxicity and a problem in oxygen handling in the cells. I can't speak for him about his current views, because I don't completely understand what he is saying, but I can tell you what I think causes the post-exertional fatigue in CFS.

    As you noted, I subscribe to glutathione depletion in response to a variety of stressors as being the initial step in the pathogenesis of CFS. It becomes chronic when it brings on the methylation cycle block.

    When glutathione is depleted in the mitochondria of the muscle cells, the concentrations of reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) rise, because glutathione is the basis for the antioxidant system.

    The reactive oxygen species inhibit the activity of certain enzymes in the citric acid cycle and the respiratory chain of the mitochondria. This is well established in the literature. This lowers the rate of production of ATP, and causes a rise in ADP.

    If a PWC continues to use her/his muscles in this situation, I suspect that two things happen that can lead to post-exertional fatigue. First, the reactive oxygen species rise to even higher concentrations, and they damage the inner mitochondrial membrane. Dr. Howard at Acumen Lab in the UK has observed damaged inner mito membranes in the neutrophils of PWCs. I expect that this damage takes time to repair. Second, the mechanism that Dr. Myhill described (which she got from Stephen Sinatra's book, and which he got from others) takes place, i.e., the ATP degrades to ADP, AMP, and adenosine and inosine, and these smaller molecules are exported from the cells. Thus, the cell must start over to build up ATP, and it needs ribose to do this. Ribose is synthesized slowly, especially in a cell that needs to use its glucose for energy production by glycolysis, because the mitochondria are dysfunctional. The evidence for this effect is the benefit some PWCs receive from supplementing D-ribose.

    So I think the post-exertional fatigue could be caused by both the damage to the mito membranes, which are slow to be repaired, and by the need to build up the substrates for ATP from scratch, which also takes time.

    When alkaline venous blood is observed, I suspect it is due to lowered production of carbon dioxide by the dysfunctional mitochondria. There are several papers in the literature reporting hypocapnia (low CO2 concentration in exhaled air) in CFS. This is commonly interpreted as being due to hyperventilation, even though ventilation has usually not been measured to see if this is actually true. I think this interpretation is in error, and in fact, the hypocapnia in CFS is due to low production of CO2 by the mitochondria, as a result of the slowing produced by glutathione depletion, as described above.


    [This Message was Edited on 10/22/2008]
  9. mbofov

    mbofov Active Member

    This is an overdue thanks to your reply. I was supposed to get an e-mail that you had responded but never received one, and just saw your answer today.

    I'll have to read it over more carefully, but I really appreciate your taking the time to answer me.

    I'm still doing the methylation protocol off and on, still detoxing. A few days ago I started taking r-lipoic acid, which I read is more effective than alpha lipoic acid. It's supposed to help glutathione recycle. Well, I think it's causing a detox reaction, not severe, but I can feel it. So I guess that's a good thing too. It gets so old, this near-constant detoxing, but hope I am getting near the end.

  10. Elisa

    Elisa Member

    Hi Mary!

    I really like your thread.

    As a former patient of Dr. Cheney, I'll never forget when he said to me - if you can increase glutathione high enough for long enough all CFS patients would get better/recover. It was a shocking statement and at that time all there was was whey protein - to supplement the precursors to glutathione.

    Anyway, I wrote on another thread a while back that I had been intrigued by the patches by LifeWave - they use nanotechnology to stimulate accupuncture points/meridians to increase certain functions of the body. There are 5 patches - one for sleep, one for energy, one for pain, one for glutathione (my point here) and one for carnosine (also one for weight loss). The glutathione patch increases production by 300%.

    So do they work? I can say so far for me a resounding YES (and I don't sell them or anything) for the sleep patch and pain patch. My Dad is using the energy patches and he LOVES them - and he is VERY discriminating. I have the glutathione patches and am going to try them for a few minutes - cause I am a bad detoxer - meaning I really suffer. I have used glutathione cream by a compounding pharmacy and yikes - the sore throat and aching etc just aweful. So I am more than a little apprehensive.

    But if increasing glutathione is key this may be a workable route...

    Dr Cheney said the only other situation he knew of which allowed a person to recover from CFS was a coma - he said some of his patients had been in accidents and were in comas and came out recovered. He believed coma was a deep healing state. So that's a clue for us too.

    Thanks again Mary for sharing your observations - I crash so much and would love to find some preventative tools. So far I have found hot liquids (like large decaf latte no sugar - just decaf and skim milk) seem to help - probably with hypovolemia (low blood volume). It's either low blood volume (and all that goes with it) or low sugar - there something there for me.

    All for now, God Bless,

    [This Message was Edited on 11/16/2008]
  11. mbofov

    mbofov Active Member

    I remember your earlier post about the glutathione, sleep and energy patches. They sounded very interesting and I looked them up after reading your post. They do sound a little strange, but no stranger than some of the things I have tried to get well! But they are a little pricey and I just don't have extra money right now. It's interesting that your dad is getting good results.

    Let us know how you do when you try the glutathione patch.

    Have you tried the methylation protocol at all? I'm still sticking with that too, but it's so slow because I have to keep stopping.

    You might also want to check out r-lipoic acid. I'd taken alpha lipoic acid before with no noticeable effect. Then I read about the r-lipoic acid, supposed to be rather more effective than the alpha kind, and I think it made me detox. It is supposed to increase glutathione levels too.

    It sounds like my crashes are different than yours. When I overdo it, I usually don't know until about 6 hours later, when I start to get achy and very tired, and then the next day total exhaustion has set in, which lasts for a couple of days. It's not a sudden thing like a drop in blood sugar. I think it is more along the lines of what Dr. Myhill talks about, the switch to anaerobic energy prodution and:

    “. . . .the basic pathology in CFS is slow re-cycling of ATP to ADP and back to ATP again. If patients push themselves and make more energy demands, then ADP is converted to AMP which cannot be recycled and it is this which is responsible for the delayed fatigue. This is because it takes the body several days to make fresh ATP from new ingredients. When patients overdo things and "hit a brick wall" this is because they have no ATP or ADP to function at all.”

    Take care --