1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Ergonomics and ME/CFS: Have You Hurt Yourself Without Knowing It?
Having a chronic illness like ME/CFS can make it hard to avoid problems that come from bad ergonomics. Jody Smith has learned some lessons the hard way ...
Discuss the article on the Forums.

Exercise, glutathione and inflammatory response

Discussion in 'General Treatment' started by kaffiend, Nov 9, 2011.

  1. mellster

    mellster Marco

    Messages:
    799
    Likes:
    178
    San Francisco
    I would love to keep this thread alive as I have so many questions regarding exercise. One is my intolerance to jogging/running which I always could only keep up for a limited amount of time and CFS cut that in half (obviously could do hardly any at first for months) after quite some recovery. The thing is that I don't breathe fast or heavily or pant even during/after strenuous exertion, in fact sometimes I think I don't breathe vigorously enough, but rather what happens is that my torso seems to cramp and I get aches and pains fast during the running motions. I am trying to increase my endurance now and the thing is if I don't leave the pavement, i.e. just walk very fast (so that it looks funny), I can do that for quite a while. I don't have EDS or related issues. I was wondering if cytokines can kick in that fast (within 10 minutes) and whether maybe my body interprets this jarring motion as some sort of trauma and refuses to cooperate for a longer time. Of course it could be some obscure heart or lung issue, but I have checked out fine so far and also on the treadmill I do better than on uneven hard pavement outside where the jarring is greater. I think this is basically a variation of the "I can do quick short spurts but not long-term exertion" symptom mentioned above. It is like an instant inflammatory response (which I still prefer over PEM/PENE which seems to be mostly gone now). Any ideas? thx & cheers
    merylg likes this.
  2. Marco

    Marco Old blackguard

    Messages:
    1,279
    Likes:
    959
    Near Cognac, France
    I'd be interested in this thread continuing also.

    I'm adding a few papers on information which I'm sure is already very familiar to you all, but I find I need to constantly remind myself of certain basics.

    The role of glutathione and glutathione agonists in exercise; endurance and oxidative stress is well established. Here's a review :

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129149/


    Rather than the role of glutathione in a normal population/athletes, I'm more interested in the findings in various pathologies that may share common disease pathways with ME/CFS e.g :

    COPD (chronic obstructive pulmonary disease) may not seem very relevant on the face of it but it does now appear to be an inflammatory immune disease (e.g. cigarettes act as an irrritant rather than causing the symptoms directly). NAC was found to reduce oxidative stress and increase exercise endurance by 25% in COPD patients.

    http://docs.google.com/viewer?a=v&q...qdI4zS&sig=AHIEtbRNF5QrCDVEwFLY2Pa0RlILcikHsw

    NAC reduces oxidative stress and neuroinflammation in a rat model of experimental autoimmune encephalomyelitis. This is proposed as an analogue of the disease process in multiple sclerosis. Apart from the obvious 'encephalomyelitis' - its my experience that my exercise intolerance and PEM is a central (possibly brain) issue rather than due to muscle fatigue. Not only can I go from fully mobile and pain free to unable to walk in the space of a few minutes but cognitive effort can also provoke PEM and the inability to walk and physical exertion also exacerbates my cognitive symptoms.

    http://www.jautoimdis.com/content/2/1/4

    Finally, one doctor's views on glutathione and autoimmune disease :

    http://drknews.com/glutathione-recycling-for-autoimmune-disease/
    mellster and merylg like this.
  3. mellster

    mellster Marco

    Messages:
    799
    Likes:
    178
    San Francisco
    Thanks, Marco. I definitely felt exercise improvement when starting NAC 2-3 times per day. I have recently stopped it as I don't want to continue too many supps forever but I may start it again to verify its benefits.
  4. Marco

    Marco Old blackguard

    Messages:
    1,279
    Likes:
    959
    Near Cognac, France
    Worth a try Mellster.

    Did you by any chance read the references Dolphin posted some weeks ago to a series of Italian studies looking at muscle abnormalities in ME/CFS?

    This is a summary/hypothesis paper from 2007. There are later studies from the same team :

    http://cfids-cab.org/cfs-inform/MitochondrialATP/fulle.etal08.pdf

    I meant to follow these up by contacting the researchers to see if I could get the full papers Dolphin posted the abstracts to but got sidetracked by having to prove to the authorities that I'm not 'yanking their chain'.
  5. mellster

    mellster Marco

    Messages:
    799
    Likes:
    178
    San Francisco
    I have glanced over it and would be very interested in a follow-up. This sentence: "A number of investigators have focused on whether CFS is associated with defective oxidative metabolism of the skeletal muscle." rings a bell with me cause this is always how I felt. I feel the inflammatory ache/reaction is in my skeletal muscles, esp. ribcage and activities that are torso-heavy such as kickboxing or jogging almost always triggers more pain the longer I perform them while there is almost always a "background" inflammatory pain present, even during inactivity (although it has lessened thankfully). Also, too much sedentary lifestyle can increase pain and stiffness as well, esp. in the mornings, so it is a delicate balance on how much exercise needs to be done which is a typical issue for FM dominated CFS. Often stretching and yoga is the preferred choice and actually can lessen the pain while more strenuous aerobic, jarring exercise might increase it. However I always loved sports and hope we will find ways to treat us before and after hard sessions as well as with a continuous protocol to eventually find a good balance where we are not overly limited anymore by this bs condition - hopeful at last ;) Thanks for following up on this. cheers
  6. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    747
    Hi, guys.

    You have probably read my posts on glutathione, mitochondria and exercise in ME/CFS before, but I just want to reiterate some things here on this thread, in case there are people reading this who haven't.

    As you probably all know, the muscles are powered by ATP, and the lion's share of the ATP is normally produced by the mitochondria.

    There is considerable evidence for mito dysfunction in ME/CFS, especially the work of Myhill et al. in the UK.

    This mito dysfunction means that the rate of production of ATP is limited, as is the utilization of oxygen and the production of carbon dioxide. These have all been documented by lab testing.

    The use of both carbs and fats for fuel in ME/CFS is limited to lower rates than normal. Amino acids from protein are more readily burned for ATP production in ME/CFS. This accounts for the lower weight gain and higher energy status that most PWMEs experience if they adopt a high-protein diet.

    The initial cause of the mito dysfunction in ME/CFS is a drop in glutathione and a corresponding rise in oxidative stress. This inhibits enzymes in both the Krebs cycle and the electron transfer chain (respiratory chain) in the mitochondrion, and therefore limits the rate of production of ATP. These features have been documented by lab testing.

    As time goes on, additional factors exacerbate the mito dysfunction. These include lack of sufficient creatine, carnitine and coenzyme Q10. These all require methylation for their synthesis, but the methylation cycle becomes partially blocked because of a chain of events involving a functional deficiency of vitamin B12, which is caused by the depletion of glutathione. In addition, toxins and pathogens build up over time because of the dysfunction of the immune system and the detox system that result from the vicious circle involving glutathione depletion and the methylation cycle partial block. Furthermore, the cells become unable to properly regulate their essential minerals levels, because there is insufficient ATP to power the membrane ion pumps. All of these aspects have also been documented by lab testing.

    It's true that many PWMEs experience some benefit by boosting their glutathione levels by various direct means. However, these gains are only temporary. If the boosting is stopped, the benefits disappear. This is supported by the experiences of many PWMEs over several years.

    The way to bring permanent benefits for most PWMEs is to address the partial methylation cycle block with active forms of folate at RDA-level dosages, together with high-dose B12 (hydroxocobalamin, methylcobalamin, and/or adenosylcobalamin, but not cyanocobalamin), taken either sublingually or by injection (some other nutrients will likely be necessary, also, depending on deficiencies). This will correct the partial methylation cycle block and will also cause glutathione to come up automatically and to stay up, in most PWMEs. This has been shown by a clinical study.

    Some exercise is beneficial, as noted by others here. However, overexercising likely damages the mitochondria, due to the elevated oxidative stress. If mitochondria become severely damaged, they are destroyed by autophagy, and new mitochondria are normally produced by fission of existing mitochondria. I am concerned that if too much exercise is undertaken in ME/CFS, over time the damage to the mitochondrial DNA by the oxidative stress may be severe enough that it is no longer possible to replace damaged mitochondria with healthy new mitochondria. I think this can result in a chronic deficit in energy availability for cells, including muscle cells, even after the vicious circle mechanism is corrected.

    So my message is please don't overdo exercise while you have this vicious circle mechanism in play, and please give a methylation-type treatment a try if you have not already done so, because I believe it is the best hope for fixing this problem.

    Best regards,

    Rich
    anne_likes_red likes this.
  7. mellster

    mellster Marco

    Messages:
    799
    Likes:
    178
    San Francisco
    Thanks Rich, this is good advice, esp. for those of use who like to go with the "head through the wall" ;) I have been methylating for quite a while but never had specific lab tests other than monitoring of vitamin and mineral levels done - so maybe it's time for some metabolic pathway or genetic testing, but I hope the Montoya study will do parts of that. One question I have is if the body is running out of energy (ATP, glutathione), why would the respiratory system not pick up and signal that, i.e. increased/faster breathing to get more oxygen into the system and increase energy? This is puzzling to me. Thanks and cheers.
  8. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    747
    Hi, mellster.

    I think the reason for that is that the mitochondria are not demanding more oxygen, because they are unable to use it. They are limited in ME/CFS not by oxygen supply, but by blocks in enzymes that are upstream from where they use the oxygen. In fact, Dr. Cheney finds that if he artificially gives his patients more oxygen using a mask, it is toxic to most of them. I think the reason is that supplying more oxygen than the mitochondria can use will result in production of more superoxide ions: (O2)- . Normally, the oxygen molecule is supposed to receive four electrons and four hydrogen ions to produce two molecules of water: H2O. If there is too much oxygen supplied, some of the oxygen molecules will get only one electron, and that makes superoxide, which is an oxidizing free radical, and that makes the oxidative stress worse in the mitochondria, producing more damage and shutting down the ATP production even more.

    Lab testing can be very helpful for finding out what is going on in a person's sulfur metabolism and energy metabolism, and determining what to do to correct them, if they need it.


    Best regards,

    Rich
    mellster likes this.
  9. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,220
    Likes:
    4,524
    australia (brisbane)
    Has anyone used creatine and found it helpful as it can help improve anaerobic metabolism. Also many people put a few kilos of water weight on in the first few days, i wonder if this could help with POTS/OI symptoms as it could potentially increase blood pressure as well.

    cheers!!!
  10. kaffiend

    kaffiend Senior Member

    Messages:
    166
    Likes:
    122
    California

    These are some great studies; many thanks for posting. I think that glutathione recycling is an interesting aspect as well.

    Rich, I've benefited a lot from methylation cycle supplements (particularly methyl b12; others do nothing for me). I've learned a lot from your posts and really appreciate your efforts. However, I still experience delayed (starting the next day) and persistent (for 48-72 hours) post-exertional symptoms such as increased resting heart rate/palpitations, memory/attention problems, dizziness, generally feeling awful.

    I can't attribute this fully to a methylation cycle defect that needed correcting, although that seems to be part of it. Something else in my case (immune and/or HPA axis dysfunction) is limiting complete recovery. There are a lot of similarities to overtraining syndrome (I've been there) but ME/CFS has something different to it. With overtraining, I've always recovered with a couple of weeks off. Interestingly, when I first became sick in March 2010, I was in Germany working on dissertation research and wasn't exercising at all.

    My current stage of recovery seems to involve pro-inflammatory cytokines that are doing something to disrupt the redox status of immune cells or activity of glutathione reductase.
  11. anne_likes_red

    anne_likes_red Senior Member

    Messages:
    835
    Likes:
    250
    That's a good link Kaffiend. Thanks :)

    Excellent post below thanks Rich - it ties up a few "loose ends" for me. (My head's full of loose ends - I always appreciate a few less!)

    I'd also like to know if anyones found real benefit from taking creatine, how much and how often??

    Thanks,
    Anne.
  12. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,220
    Likes:
    4,524
    australia (brisbane)
    Dosage wise there are 2 strategies, one is just 5-10mg of creatine powder a day, another is a loading phase for 5 days were they use 5 mg 4 times a day for a total of 20mg for 5 days and then switch to maintenance dose of 5-10mg a day. I have used this pre cfs and it helped with exercise and increased strength. But cfs is a different stories i suppose.

    cheers!!!
  13. kaffiend

    kaffiend Senior Member

    Messages:
    166
    Likes:
    122
    California
    Creatine absolutely works as a sports supplement at 5-10g per day. I can't say I've ever noticed benefits for ME/CFS symptoms but years of resistance training may have me at a ceiling already. I've never had any weakness I could attribute to muscle fatigue; it's always been central exhaustion, although I would get unusual muscle cramps from a very low threshold of effort. It would make sense to supplement anaerobic metabolism per results of Chris Snell and the work of the Pacific Fatigue Labs. Extra water intake is good if anyone decides to try it.
  14. anne_likes_red

    anne_likes_red Senior Member

    Messages:
    835
    Likes:
    250
    Thank you for the replies! :) :)
  15. bertiedog

    bertiedog Senior Member

    Messages:
    422
    Likes:
    238
    Hi Rich

    I know that in the past you have talked about how we don't use protein and fats properly in this illness could you explain a little more fully about this please.

    (I have been taking practically all the methylation supplements plus Q10 and Carnitine since 2007 and I sure this is the reason I have not suffered with stuff like brain fog and can feel quite well provided I don't have a throat infection or do too much and ignore pacing).

    Having gone pretty low carb these past 3 weeks because I am finding my blood sugar stays a little too high all day long my initial energy is better but I find that still the energy runs out after 20 minutes walking at a reasonable pace. This has never changed since crashing completely in 2000 despite reducing the carb content of my diet considerably and also raising the protein and fats I eat. I can tell that it is definitely beneficial for me to eat low carb with more fats and protein but one side effect I haven't been able to get over is frequent morning headaches from the drop in blood sugar over night. Its obvious my brain prefers my blood sugar to be around 108 or 6.0 during the day which is a little high and just cannot seem to adjust to the lower levels through the night despite being low carb during the day, it just doesn't bring my bs down enough.

    I do realise that this is probably a side effect of having to take 5mg Prednisolone daily because my adrenals just don't function and also I have to take a range of thyroid meds because of autoimmune thyroid disease. However I had terrible problems with hypoglycemia for many years before going on the steroids so blood sugar issues have been a problem for me for years. Actually I think it could have been caused by my eating a high carb diet for all my life which would have been 50 years until I started reading about the sorts of problems a high carb diet can cause but there is no question I was addicted to carbs having been brought up on them.

    On a separate point, naturally because of this work from Norway and the fact I know I have an autoimmune problem with the thyroid and possibly adrenals too I do find the connection with ME/CFS very interesting.

    If you could throw some light on this difficulty with maintaining energy whilst walking it would be very helpful.

    Best Wishes

    Pam
  16. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,220
    Likes:
    4,524
    australia (brisbane)
    if you can lower carbs enough you can go into a state called ketosis which basically means your burning lots of fat and ketones are a by product. When in ketosis your body and brain can also use ketones as an energy supply which u have 24/7, so u might find cutting carbs further can help u with energy slumps and morning headaches in blood sugar too low. Even though carbs and sugars arent in the diet the body uses a prcess called glucogenisis and can make adequat glucose for the brain from certain amino acids, glutamine being a common one, glutamine can also help with carb cravings if u get them, stir a tsp into a 1/3 glass of water and drink, cravings are gone in 5 mins as brain now has its energy supply.

    Ketosis is in an out of control in uncontrolled diabetic is a different animal as they no longer produce enough insulin which is used to drive ketones, fats and proteins into the cells for energy, and ketosis get way out of control causing dangerous increases in potassium and a few other minerals. This doesnt happen in nondiabetics who still produce adequate insulin to help move these nutrients into the cells for energy. good side effects of ketosis is that it greatly reduces apetiite, abig breakfast of bacon, eggs and sausages and most can last the whole day until dinner time.

    I think these meat pro diets are great for vitamins and minerals. fruitand vege are overated as meat contains complete protein so all essentil amino acids present, multitudes of vitamins and minerals, especially the b vitamins, folic acid, b12, iron, if u were to add green veges and fibrous veges u would get what nutrients missing
  17. Marco

    Marco Old blackguard

    Messages:
    1,279
    Likes:
    959
    Near Cognac, France
    Hi again Rich

    I'm sure we all appreciate this note of caution.

    I certainly wouldn't advocate any form of vigorous exercise for PWME until such times as the underlying pathology is known and it is confirmed that exercise is safe/desirable.

    Re glutathione supplementation I agree that it is a maintenance approach rather than a cure but then so is insulin or SSRIs and if it helps me get through the day a little better then I'll take that benefit for the time being. My only concern might be that, as with SSRIs, supplementation may lead to a downregulation of endogenous production.

    Just a few questions if you'd be kind enough to consider them :

    Assuming some of our mitochondria are still functioning, would it be beneficial to stimulate mitochondrial biogenesis by either stimulating the SIRT/PPAR pathways and/or by light exercise of muscles with a high concentration of mitochondria (such as calf muscles). Would the latter induce mitochondrial biogenesis globally or only locally?

    Is there any possibility that a combination of gluauthione supplementation plus mito biogenesis by whatever means might reach a level sufficient to overcome the vicious circle?

    I'd also be interested if you have any data on the effectiveness of the methylation protocol?
  18. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    747
    Hi, Pam.

    It's good to hear from you! You were one of the first people who was willing to try methylation treatment four years ago. I'm sorry that this treatment, together with the Myhill mitochondrial treatment, has not brought you to a full energy status, though I'm happy to hear that you have apparently experienced some benefit from it.

    I recall your history of adrenal dysfunction and your use of steroid supplementation. I suspect that it probably is true that the prednisolone supplementation causes your blood glucose level to be elevated. I suppose that you have tried lowering the dosage of prednisolone, and that you have good reason to maintain it at 5 mg per day. If it were possible to lower it somewhat, your glucose level might come down.

    I don't know what the current statuses of your methylation cycle and glutathione are. If you continue to have a partial methylation cycle block and glutathione depletion, then the following discussion may apply to your mitochondria: Glutathione depletion (a low level of reduced glutathione and a low ratio of reduced to oxidized glutathione) causes a partial block of the enzyme aconitase in the Krebs cycle in the mitochondria. Aconitase is normally responsible for converting citric acid to cis-aconitic acid and then to isocitric acid. If this enzyme is partially blocked, the ability to use either carbs or fats as fuel for the Krebs cycle becomes limited, because both carbs and fats must enter the Krebs cycle as acetyl-CoA, being converted initially to citric acid by reaction with oxaloacetic acid. If these fuels are consumed at a higher rate than they can be utilized, they will be stored as fat in the adipose cells, and this will result in weight gain. On the other hand, the cells will still be able to burn amino acids (from protein) as fuel, because some of them are able to enter the Krebs cycle downstream of aconitase, and amino acid can be converted one to another by transamination reactions.

    I'm not sure how you could improve your stamina. It would be interesting to know what your methylation/glutathione status is. If you could run a methylation pathways panel, I think it would shed a lot of light on that. If your glutathione is depleted and you have a partial block of aconitase, I think that could explain your limited stamina. This panel is offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA.

    Best regards,

    Rich
  19. baccarat

    baccarat Senior Member

    Messages:
    188
    Likes:
    80
    I agree. I went vegan for a couple of years and my condition didn't improve, it got worse. When I started to eat meat again I experienced detox symptoms (e.g. urine and stool stinking of ammonia) for a good couple of months and had some improvement in energy levels. However, I stick to rather lean meats such as turkey and chicken as I tend to put one weight rather easily.
  20. bertiedog

    bertiedog Senior Member

    Messages:
    422
    Likes:
    238
    Thanks for that Rich, I think it would be an excellent idea for me to get the panel done and will look into it.

    I have managed to drop 5mg of hydrocortisone that I had been taking the last few years in addition to the 5mg Pred since I cut out carbs between meals 2 1/2 weeks ago. I stopped 2.5mg in the first week and today I stopped the 2.5mg h/c I usually take first thing in the morning to get me up and about. (Usually I wake up for the steroid and thyroid meds around 5.30 am and go back to sleep). I have also dropped 6 mcg of T3 that I used to take around lunchtime because I started to get symptoms of too much T3 around 3 pm since going lower in carbs.

    Actually I have felt even better today apart from an initial migraine first thing probably because I walked my dog for 20 minutes yesterday evening around 7.30 pm and didn't eat anything until I had a few peanuts around 9,30 pm to sort of top up the blood sugar because I did feel it all used up so to speak. I used to have half a Ryvita with peanut butter as a 10 pm snack but have managed to drop the Ryvita.

    My blood sugar is still adapting I think because it did drop to 5.5 after a good 20 minute walk this afternoon but I had no energy at all and felt very weak so once home I ate a small piece of Cheddar cheese and later about 12 peanuts and a cup of tea. One hour later I took it again and it had jumped to 6.8. There was only about 2grams of carb in what I had eaten but my blood sugar over reacts to any food I think! Its still early days, the main changes are that I never eat carbs apart from a few nuts between meals now for the past 2 weeks whereas over the past 9 years I had cut carbs right down at meal times but always needed repeated snacks like 1/2 a no sugar Oatcake plus protein between meals. It always gave me rebound feelings of low blood sugar when it wasn't low at all.

    I am delighted that I have been able to stop these carb snacks fairly easily.

    One final thing I would like to mention that I find confusing is that I had a DEXA bone scan done a year ago and it showed I had the bones of a 30 year old despite the fact I am 63 and been on steroids since 2002 plus thyroid meds! Also my triglycerides are really low and so is my cholesterol. I only weigh around 9 stone 8 lbs and look fairly slim so I have no signs of insulin resistance at all its just the way my brain reacts to where my blood sugar is if you know what I mean! I have a feeling this is fairly common with this illness?

    Thanks for your help and your explanations. I think it does mean that my body can handle the fats and protein I eat because I have been able to do quite a bit more physically and recover quicker these past few weeks which is encouraging.

    Pam

See more popular forum discussions.

Share This Page