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!
Dr. Kerr, I presume?
Clark Ellis brings us a rare interview with British researcher Dr. Jonathan Kerr who is now living in Colombia.
Discuss the article on the Forums.

Exercise, glutathione and inflammatory response

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

  1. kaffiend

    kaffiend Senior Member

    Messages:
    166
    Likes:
    122
    California
    Following a suggestion by Mellster on another thread to discuss inflammation, I'm starting this thread with the topic of exercise/exertion, redox status, and ways to support glutathione. Since being at my worst this past winter and spring (house/bedbound), I've reduced my symptoms to very specific ones that follow exercise or heavy mental exertion. I'd almost describe it as a gremlin in my immune and autonomic systems, pulling wires and turning knobs for 48 hours after activity.

    I think looking at the normal inflammatory processes (which I don't claim to understand) provoked by exercise are an important link to understanding some parts of ME/CFS. One aspect that seems relevant from reading studies is a healthy neutrophil response, which is dependent upon glutathione. Importantly, this might be supported with supplementation of precursors other than B12 and folic acid. By the way, I've had a very good response to methyl B12 supplementation and hydrocortisone, but they are still not protecting me from a range of post-exercise symptoms that seem like a swing from being immune compromised (canker sores, sore throat) to immune over-response (wired/tired, inflammatory response/allergies, severe neurcog. problems). Several studies have been done using l-cystine and l-theanine to combat these in over-trained athletes. Such things may be useful to people with ME/CSF as well. I've posted one study below and will try to summarize a few others over the next few days.
    ----------

    Journal of Strength & Conditioning Research:
    March 2010 - Volume 24 - Issue 3 - pp 846-851
    doi: 10.1519/JSC.0b013e3181c7c299
    Original Research

    Kawada, S, Kobayashi, K, Ohtani, M, and Fukusaki, C.

    Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res 24(3): 846-851, 2010

    Abstract
    We investigated the effects of supplementation with cystine, a dipeptide of cysteine, and theanine (CT), a precursor of glutamate, on immune variables during high-intensity resistance exercise. Cysteine and glutamate are involved in the formation of glutathione, which modulates the activity of natural killer (NK) cells. In this double-blinded clinical trial, 15 well-trained men (aged 22.8 4.0 years) were divided into 2 groups: placebo (n = 7) and CT (n = 8). The placebo group was administered a powder containing cellulose (950 mg) and glutamate (30 mg), whereas the CT group was administered a powder containing cystine (700 mg) and theanine (280 mg), once daily for 2 weeks. The subjects trained according to their normal schedule (3 times per week) in the first week and trained at double the frequency (6 times per week) in the second week. Concentrations of immunoglobulin (Ig)M, interleukin (IL)-6, IL-8, and salivary IgA and the leukocyte count did not change significantly in either group. There was a significant decrease (p ? 0.05) in the NK cell activity (NKCA) in the placebo group after the second week compared with that in the CT group (placebo: 69.2 16.1% vs. CT: 101.7 38.7%). Phytohemagglutinin-induced lymphocyte blastoid transformation did not change significantly in either group. These results suggest that NKCA is not affected in a normal training schedule with or without CT supplementation. However, high-intensity and high-frequency resistance exercises cause attenuation of NKCA, which CT supplementation appears to restore. Therefore, in practical application, CT supplementation would be useful for athletes to restore the attenuation of NKCA during high-intensity and high-frequency training.
     
  2. mellster

    mellster Marco

    Messages:
    800
    Likes:
    180
    San Francisco
    Hey kaffiend,

    Thanks for the link, I will definitely give them a try as I do think proper glutathione restoration is key (btw. my post-exercise symptoms are very similar to your description). Also, this is not a popular view on the forum, but first of all - and please people don't flame me ;) - IF YOU CAN exercise (i.e. no severe issues, this is oboviously not a recommendation for someone who is house/bedbound) you should exercise (IMO), I think low-grade aerobic exercise is ideal (low-resistance and/or slow cycling for example). I haven't found a silver bullet against inflammatory responses either, but common anti-inflammatories taken before and after exercise and possibly anti-histamines might help a bit. The next best thing is good quality, 8-9 hours sleep and massage (esp. of local hotspots). If you find a silver bullet. let me know. But the reason I think it is impossible to keep the circulation going (amongst all other benefits of exercise) is that it helps clearing local inflammation points and detoxification in spite of the fact that activated cytokines might cause an overall flu-like inflammatory feeling. Definitely slow down for a while though after experiencing these reactions and maybe switch to 30 minute walks instead until feeling better. cheers
     
  3. alex3619

    alex3619 Senior Member

    Messages:
    7,678
    Likes:
    12,472
    Logan, Queensland, Australia
    Hi, if you want to discuss post-exercise issues, you can't ignore the Light's research. What is going on is far beyond just inflammation, or decreased antioxidant status. There is a specific increased production of a range of either cytokines or cell receptors. We need to understand what triggers that. Glutathione might indeed be a major part of that, but we dont know for sure yet. Both anti-inflammatories and antioxidants help.

    In relation to mellsters comments on exercise, I think this is correct for special cases. In the past I have been able to successfully exercise whlle on an experimental anti-inflammatory and antioxidant program, but even then it had to be careful. In the long run it failed though, the early successes went away and I crashed badly. However, a big part of this was that I was vegetarian at the time, and I think protein intake is crucial if you want to take this approach, and important even if you don't. If the post-exercise responses can be suppressed, then we can exercise and get benefits. Its research from the Lights and others working in the same area that will eventually figure it out, but that does not mean we can't figure some out on our own.

    On a different experimental and antioxidant program I have been able to do unlimited exercise, but the cost and side effects made it not worth it, and I had to abandon my own protocol. Running out of money and not finding information on how to decrease problems made this antiinflammatory-antioxidant-metabolic-amino program of mine difficult to follow. Please note that while on this protocol I had no PEM and full energy, a large part of the feeling of fatigue was untouched.

    While on another protocol which was based on Immunocal, and is what got me through my biochem degree, I had short episodes doing which I could do anything without consequences. During these times my full cognitive capacity was restored. They did not last however, and in time I ran into other side effects on this protocol.

    So it is possible to exercise, we just have not figured out how to reliably suppress the post-exercise issues. I for one can't wait for this to be solved, I used to be a runner and I want to do it again.

    If the post-exercise issues are not suppressed, its not just crashes you have to worry about. Its long-term muscle damage. I have so many muscles that are fubar because of this, and last time it took about 15 years for the pain to die down even after I started resting those muscles a lot and never exerting them.

    Bye
    Alex
     
  4. floydguy

    floydguy Senior Member

    Messages:
    650
    Likes:
    238
    I've mentioned this before but I don't get PEM from exercise. I have high inflammation regardless of whether I exercise or not though. I have a difficult time doing (really can't) intense exercise because I do have a low VO2 max (where does that come from). However, once I stop the intense exercise I am okay. But I am in a constant state of inflammation (read physical & cognitive agony) but exercise or activity does not seem to exacerbate it. I may be an anomaly though as the exercise researchers and CFS doctors don't get why I have the same lab results (i.e. almost non-existent NKC Activity, cytokine inflammation, high TGF Beta, etc) but don't have PEM.
     
  5. mellster

    mellster Marco

    Messages:
    800
    Likes:
    180
    San Francisco
    First of all, listen to Alex, he has done the most research and the most knowledge :) I am somewhere in between PEM/PENE and floydguy's state as sometimes I cannot attribute the inflammatory response to exercise and I don't always get PEM/PENE from exercise. Also I am less worried about damages to the muscles as the inflammatory response seems more broad flu-like rather than specific muscle pain, but it is definitely important to be careful with this (muscle twitching can also be a good indicator for overdoing). floydguy, you could be more in the FM camp if exercise does not exacerbate your general inflammation, although there is not data I think about the prevalence of low NKC activity in FM I think. But the general inflammation seems more Fibromalgia like.
     
  6. kaffiend

    kaffiend Senior Member

    Messages:
    166
    Likes:
    122
    California
    I actually don't get much in the way of muscle pain or muscle weakness. I had years of resistance training experience prior to becoming ill, so I might be able to rely on anaerobic pathways more than the average person.

    When I write inflammation, I do mean the response of pro-inflammatory cytokines, not just arachidonic acid pathways. From what I've been reading, IL-6 is one of major pro-inflammatory cytokine released from muscle. There also seems to be a large neutrophil response to exertion, which infiltrate tissues and produce ROS. If the redox status in neutrophils is poor, they are more likely to undergo apoptosis, leading to a further immune response to deal with mitochrondrial distress signals and cellular debris.

    Just to be clear on my views here, I don't find ME/CFS to be a deconditioned state (making graded exercise pointless and harmful). In my case, there seems to be an inappropriate crossover of the normal inflammatory response in the periphery to the central nervous system. The brainstem and hypothalamus (paraventricular nucleus), if they are being damaged by ROS or immune responses, are candidate places that would lead to amplification of normal stress responses. I'm thinking that understanding and reducing this normal inflammatory response will help. There's some decent evidence that cystine and theanine may do just that.

    A note on anti-inflammatory medications, I avoid NSAIDS due to the fact that they can damage the gut and increase intestinal permeability. Getting gut issues (food sensitivities) in line has been a major factor in my improvement...nothing much was helping until that started to improve.

    Edit: I meant paraventricular nucleus, not periventricular. There's an important difference.
     
  7. alex3619

    alex3619 Senior Member

    Messages:
    7,678
    Likes:
    12,472
    Logan, Queensland, Australia
    Hi kaffiend, I agree with avoiding NSAIDs. They are toxic at best, and typically not very effective. To make them effective you need the high impact NSAIDs, but this also make them more dangerous (remember Vioxx?). There are many other things that impact inflammation, its worth trying many of them as they can be cheap. Cytokines, eicosanoids and other mechanisms are involved, including changes to the nervous system (sensitization). We do not know enough to be sure what is optimal, the search continues.

    One intriguing thing about the successes I have had at dealing with inflammation and exercise is that protein and a range of aminos seem to be important. So cystine and theanine are worth a try I think if you are in the mood to experiment. I wonder what happens to NK cells on NAC though? There are so many possibilities, and few have been tried. Some years ago several Australian doctors groups informally tested different protein intake on patients. I don't think this has been published. About 1.5g of protein per kilo of lean body weight per day was the optimal result from dietary protein titration, but this was vague and imprecise at best - no biomarkers were tracked, just patient symptoms, and it wasn't a formal study. This amounts to a little over one and a half times the usual recommended protein intake. This would of course include a wide range of aminos.

    This is one reason I am unsure if high protein diets are often beneficial due to low carbs or just amino availability. I regard this as an open question.

    Bye,
    Alex
     
  8. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

    Messages:
    795
    Likes:
    293
    Czechosherlockia, USA
    I haven't been here in a while, but came here today just to see if anyone had any suggestion for "magic bullets". I see there really isn't.

    I've been back to exercising regularly and well, from weightlifting to sprints, etc., for a while this year. But lately I've had a flareup, with burning eyes, hypertension and bad insomnia (can't sleep more than 4 hours at a time). On top of that, my muscles aren't working right. For one thing, I get minor tears just from normal activity, in the quadriceps. Glutes, especially minimus and medius, are also affected. My joints are <i>loose</i>, too.

    Curiously, my upper body seems more unaffected (benching and pullups etc are just a little weaker).

    In the past months I'd been sporadically taken with drinking raw eggs - and I have now again this week got that urge. Maybe it's the glutathione connection. I just had two. Maybe I'll do 10 or so today to see if that brings about a noticeable change. (Btw, it's easy to do.)

    Wrt low O2 max, in my case that definitely seems to be related to congestion/inflammation in my lungs. If i take a deep breath on days like today, I'll cough. But since I've been sick these 3 years, I've had varying degrees of diminished breathing capacity every day.

    kaffiend: I'd guess you have a very powerful endogenous anti-oxidant capability, so the marginal increase from exercise doesn't drag you down much.

    P.S. While reading this thread today I realize I haven't had a post-exercise day of malaise for a long time, maybe over a year. So yes, I agree 100% that a person who can exercise should exercise. In fact, I think I might have gone steadily downhill without it. It's important, though, to get very recovered in between.
     
  9. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

    Messages:
    795
    Likes:
    293
    Czechosherlockia, USA
    Having delved into Paleo, then now avoiding it as well as all lo-carb, I can say that in my experience LC makes no difference. Alternatively, I can have days in a row of eating tons of carbs and that makes no difference - at least in me. But come to think of it, I hardly ever have a period of low protein intake. I'll go through 5 lbs of whey every two months or so, plus a fair amount of meat daily.

    I'm just throwing out my experience so others can compare.
     
  10. alex3619

    alex3619 Senior Member

    Messages:
    7,678
    Likes:
    12,472
    Logan, Queensland, Australia
    Hi Sherlock, back when I was vegetarian my health was crashing every two weeks and it took longer than that to recover. Crash, almost better, crash, repeat. I was heading from mostly housebound to sometimes bedbound (and mostly couchbound). Eating meat again turned it around very quickly. I am interested in hearing from vegetarians who are doing well in the long term, but I have never met one. While vegetarian I improved at first - it can give a sense of improvement, possibly because of the higher antioxidants in fruit and vege. Bye, Alex
     
  11. satori

    satori

    Messages:
    25
    Likes:
    4
    NJ
    Alex,

    What was the program that worked for you that was too expensive? Perhaps some parts of it would work for others. Thanks.
     
  12. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758

    Hi, Sherlock.

    I just want to note that raw egg whites contain avidin, which binds to biotin. Over time, consuming avidin can cause a biotin deficiency unless sufficient biotin is in the diet or supplements to compensate for the avidin binding.

    Best regards,

    Rich
     
  13. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

    Messages:
    4,113
    Likes:
    960
    Concord, NH
    What link? or do you mean article?

    GG
     
  14. alex3619

    alex3619 Senior Member

    Messages:
    7,678
    Likes:
    12,472
    Logan, Queensland, Australia
    Hi Satori, that program was my own which I developed over several years. I tested it on myself in stages, and it was loosely based on earlier work by Dr. Andriya Martinovic. Antioxidants, aminos, vitamins, minerals, a shotgun effect rather than a narrowly focussed treatment. Several current protocols are similar - I emphasized the antixodant quartet (C, E, CoQ10, Lipoic, NAC, although NAC was only used off and on) and had minerals designed to improve metabolic rate such as chromium picolinate, as well as the usual like zinc and magnesium. Omega 3 fats were also important, as was limiting but not halting intake of omega 6 fats. In particular the protocol included high dose B vitamins, but I ran into problems with this, possibly due to B6 toxicity - I am not sure of this, I was never in a position to investigate this.

    I could recompile a version of it (I have extensive notes) but at the moment I am in a legal quagmire that is dragging on way too long, which I have to put most of my focus on. I am trying to divest myself of a trust, and it turns out that isn't easy for someone with brainfog. I will post a simplified version of it if I can find it, but if I have to recompile it I will have to spend hours going through my notes.

    Two aminos that I used to use regularly are almost never discussed in ME literature - glycine and alanine. Both increase cellular survival under hypoxic conditions, which was why they were included. To get benefits from these aminos from eating meat you might have to eat a kilo a day (two pounds) which would not be good for you. I have always wanted to do more research on this protocol, but have never had the resources including my old brain function.

    A part of my protocol can be found here: http://www.me-cvs.nl/index.php?pageid=4132&printlink=true&highlight=brief

    Please note that the hypercitricemia theory was wrong and was extensively revised several times after that. The latest version has never been disproved, but is no longer about causation but about cellular complications that might drive some symptoms and is unpublished. This paper has recommendations at the end, but I no longer recommend this protocol - it is incomplete. My full protocol more closely resembles protocols by the like of Marty Pall.

    Bye
    Alex

    ps Biotin was a critical supplement in my earlier protocol, I added this after reading the comment on biotin.
     
  15. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,393
    Likes:
    4,783
    australia (brisbane)
    Alex, is it safe to say it was awhile ago u used this protocol. I say this as many would say it isnt expensive but 10 years ago plus before we were onto cheap overseas supps from the internet, these supps would have cost an arm and a leg to buy, especially in australia.

    cheers!!!
     
  16. Marco

    Marco Old blackguard

    Messages:
    1,383
    Likes:
    1,060
    Near Cognac, France
    It would be great to see this discussion continuing - perhaps outside the context of treatment only.

    On the inflammation angle, going by the literature I don't appear to fit the 'fatigue' stereotype whereby its difficult to get started in the morning and 'fatigue' is the limiting factor. In fact I'm usually up around 6.30am and do most of my net surfing and anything requiring mental exertion before lunch as post lunch I need to sleep and the afternoon and evening are progressively less productive. Subjectively what happens does not feel like fatigue. More, as the day goes on, I get a growing feeling of inflammation most usually felt as a paradoxical feeling of my head feeling simultaneously light and full/inflammed at the same time.

    My current thinking is (I reserve the right to flit around theories at will:D) that the core of the illness is a mitochondrial deficit with the possibility that this also triggers a sensory gating deficit as outlined in this thread :

    http://forums.phoenixrising.me/showthread.php?9108-ME-CFS-Autism

    For me the latter would explain the tired/wired and overload cognitive issues we have to deal with.

    I also think it would be a useful exercise to look wider than our own symptoms at genetic mitochondrial diseases; acquired mitochondrial disorders and diseases such as autism; schizophrenia; bipolar disorder; fibromyalgia etc where a mitochondrial deficit is suspected.

    One major drawback of differential diagnosis is the very thing that makes it useful for medics. The tendency to reduce the description of the disease (the symptoms) to those that differentiate it from other diseases is often at the cost of excluding symptoms that overlap with other disorders and may indicate a common underlying cause.

    Its entirely possible that a heritable predisposition to a mitochondrial deficit might manifest itself as 'different diseases' depending on genotype; developmental stage; gender; type of 'stressor' etc.

    As for magic bullets my own 'Rituximab moment' came when I discovered by accident that acetylcysteine could help me prevent PEM and heat intolerance symptoms before I new what was in the product or even less the theoretical basis of why it might help.
     
  17. mellster

    mellster Marco

    Messages:
    800
    Likes:
    180
    San Francisco
    I have good results from NAC as well but I often wake up in the morning achey (not fluey, more torso inflammation achey) and the only thing that can relieve it quickly is exercise. Also being on LDN helps prevents a lot of that inflammation but it comes with a slight cost of light sore throat and tender glands. I tried to wean off, either by taking it every other day or a lower dosage but it seems I do best staying on the LDN. Also, I have been one of the 2 people (Marg does it as well) doing the CVAC treatment (www.cvacsystems.com) and it has had tremendous influence on my well-being. I am know at a level where the pressure chamber takes you up to 20000+ feet and it is sometimes hard not to get drowsy as the air is thin and the drops are steep, and the rest of the day I am pooped and usually go to bed around 9 pm, but it gives great energy for the next 2-3 days as well as it totally gets your lymphatic system going. I recommend everyone in the US to try the CVAC. At this point though, my main goal is to get rid of the constant background inflammation (mostly torso, a bit in the head as well) and the reactions to strenuous exercise which has been proven difficult. cheers
     
  18. xrunner

    xrunner Senior Member

    Messages:
    636
    Likes:
    311
    Surrey
    Kaffiend,
    you're right about l-theanine. I used it years ago and soon after falling ill and remember that it helped reduce fatigue.
    However, as regards pem I found herbal remedies that directly address inflammation much more effective. The trouble with these is that nobody knows about their long-term effect.
     
  19. kaffiend

    kaffiend Senior Member

    Messages:
    166
    Likes:
    122
    California
    That's remarkably similar to my experience. The whole time I've been sick, I still woke up 6-6:30am and usually felt great. Then as I started to move around, the dizziness and vertigo would begin, until I was walking around in a state of delirium as if I'd just had my bell rung. About a year in, I developed tertiary adrenal insufficiency, which produced crushing fatigue at the slightest exertion, even talking on the phone. That resolved within a day of starting low-dose hydrocortisone therapy.

    I've been doing a protocol similar to what Alex describes above, but with d-ribose and few things to hopefully keep EBV and HHV-6 in check (elevated IgG titers). Right now, I feel as well as I ever have unless I try to exercise or do a lot of mental work. I'm capable of anything when I'm rested but I pay the price (although this seems to be improving since adding theanine and curcumin).

    The shotgun approach is key, keep assessing what "stage" you're in (perhaps worthy of another thread), and don't be afraid to try anything that can't hurt but might help, i.e., probiotics even in the absence of noticeable digestive issues.
     
  20. kaffiend

    kaffiend Senior Member

    Messages:
    166
    Likes:
    122
    California
    I don't know why this cluster of studies on immune function with theanine and cystine use cystine rather than NAC or l-cysteine. A lot of times, once one gets published, others just repeat the published protocols with a new manipulation because research is time-consuming and expensive. I found one old study showing different transport mechanisms for cystine and cysteine. I believe cystine is immediately reduced to cysteine but unless one has cystinuria, it probably can't hurt to supplement with a variety of sources.
     

See more popular forum discussions.

Share This Page