Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Supplements and Drugs That Reduce or Prevent PEM (Post-Exertional Malaise)

Discussion in 'Post-Exertional Malaise, Fatigue, and Crashes' started by Hip, Dec 21, 2016.

  1. Hip

    Hip Senior Member

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    List of Supplements and Drugs Which Can Reduce PEM

    Several supplement and drugs appear to be able to reduce or prevent post-exertional malaise (PEM), by either preventing PEM from physical or mental exertion occurring in the first place, or helping to relieve any PEM that has already appeared.

    PEM can be caused both by physical exertion, and also by mental exertion (such as hectic social activity). The mechanism of mental exertion-induced PEM may be different to the mechanism of physical exertion-induced PEM.

    The PEM reducers (aka "PEM busters") detailed on this thread have been compiled from other threads about ME/CFS patients' experiences with supplement and drugs that they have observed reduce PEM.



    PEM Reducer Supplements and Drugs

    The following are the supplements and drugs that ME/CFS patients have found reduce PEM:

    Creatine hydrochloride — 2 grams
    Citrulline — 1000 mg
    Branched-chain amino acids (BCAA) — 5 grams
    Co-enzyme Q10 — 800 mg to 1800 mg (this is a very high dose of Q10)
    Sodium bicarbonate (baking soda) — 2 grams (half of a level teaspoon)
    Catalase — 600 mg (taken after exercise)
    D-ribose — 5 grams, three times daily
    Cannabis — taken just as PEM begins to appear prevents PEM from fully manifesting; see the Cannabis section below
    Corticosteroids — taken before exertion can completely prevent PEM; see the corticosteroids section below

    You can try one or more of the above supplements and drugs during PEM itself, or in advance of any physical or mental exertion that you suspect is going to trigger PEM, and see if they relieve or prevent your PEM.

    Most experienced ME/CFS patients know roughly how long their PEM periods tend to last for, so will certainly notice if a supplement can dramatically shorten the severity or duration of their PEM.



    PEM Shielders vs PEM Relievers

    A PEM reducer supplement or drug may fall into one (or both) of the following two categories:

    PEM shielders — help prevent PEM from occurring in the first place. PEM shielders only work properly when taken as a preventative medication before you engage in the physical or mental exertion

    PEM relievers — mitigate the severity and duration of PEM only when taken after the exertion has occurred, where the PEM may already have begun to manifest.

    It is important to know whether a supplement or drug is a PEM shielder or a PEM reliever, because the former only work when taken before the exertion, and the latter only work when taken after the exertion.

    As an example of the difference, @hamsterman found that the corticosteroid drug prednisolone 20 mg is an excellent PEM shielder for both physical and mental exertion, but found that such corticosteroid drugs do not work at all as PEM relievers.

    Whereas @hamsterman found that BCAA, Q10, creatine and baking soda work more as PEM relievers, rather than PEM shielders.

    Though @TravelChimp said in this post that creatine works for him as both a PEM shielder, as well as a PEM reliever.

    And @SOC said Q10 works both as a PEM reducer when taken at a one-off very high dose of 2400 mg (two 1200 mg doses on the same day), but also found Q10 had some mild PEM shielding effects when taken at a dose of 800 mg daily.

    Note that this study found 3000 mg of Q10 daily for 8 months was safe.

    Cannabis appears to be a good PEM shielder, when taken just as the first signs of PEM appear. See the Cannabis section below for more details.

    Nothing however seems to be quite as powerful as corticosteroids for total PEM shielding.



    Biochemical Theory of PEM

    The above PEM reducers were discovered by various members of this forum, who observed that a supplement or drug they were taking had anti-PEM effects. Interestingly, some of these supplements (but not D-ribose, Cannabis or corticosteroids) are known to inhibit exercise-induced lactate (see the athletic exercise studies in this post); that may be their mechanism of action in fighting PEM.

    D-ribose may work by a different mechanism: by helping to replace ATP molecules that may be lost during significant exertion.

    In the theory of PEM proposed by Myhill, Booth and McLaren-Howard (briefly explained in this post), they suggest PEM is caused by the loss of ATP molecules that occurs when ME/CFS patients exercise.

    According to this theory, you only get over PEM once the body re-manufactures the lost ATP molecules, which can take many days or weeks — hence the why PEM can last for days or weeks. D-ribose speeds up the process of re-manufacturing the lost ATP molecules, thus curtailing the duration of PEM.

    Their theory also proposes that a build up of lactic acid during exercise exacerbates and worsens PEM (since lactic acid requires a lot of energy to clear from the body); so that might explain why the above supplements which reduce exercise-induced lactate are PEM relievers: they can help ME/CFS patients get over PEM much more quickly.



    Patient Accounts of The Anti-PEM Effects of The Supplements

    This post details how D-ribose powder, at the standard dose of 5 grams taken three times daily, consistently curtails PEM from its usual 3 or 4 days, down to just 12 to 24 hours, for ME/CFS patient @arewenearlythereyet.

    This post details how for ME/CFS patient @SOC, a very high one-off dose of 2400 mg of co-enzyme Q10 (taken as two 1200 mg doses on the same day) dramatically eliminated a PEM period with 24 hours, a PEM that would normally have lasted 10 to 14 days. The patient also found that 800 mg of Q10 taken daily noticeably raised their PEM threshold (see this post). Cheap sources of bulk Q10 powder are found on purebulk.com.

    This post details how regular supplementation with creatine monohydrate 10 grams daily increased energy, and allowed ME/CFS patient @TravelChimp to do much more physical exercise before the PEM was triggered; in other words, this patient found the creatine raised their PEM threshold. Not only that, but when they did get PEM by overdoing it, they noticed their PEM was reduced in severity as a result of the creatine supplementation.

    Note that creatine hydrochloride 2 grams daily may be a much better form of creatine to use than creatine monohydrate, as creatine HCl does not cause stomach aches or fluid retention (as the monohydrate form can), and also is much more water soluble and absorbable in the gut, and so you only need to take around ⅕ of the dose (so 10 grams of creatine monohydrate = 2 grams of creatine hydrochloride; ref: 1).

    Here is a thread detailing the anti-PEM effects of branched-chain amino acids (BCAAs). @Mary says later in this thread that BCAAs reduce her PEM duration from 2 days to 1 day.

    Here is a thread detailing the anti-PEM effects of sodium bicarbonate, catalase, glutathione and others. In the thread, @Mya Symons says that sodium bicarbonate taken just before exercise, and 600 mg of catalase taken just after exercise, has the best anti-PEM effect.



    Studies on these Supplements

    Athletic performance studies which demonstrate how these PEM reducing supplements also generally improve exercise performance are given in this post. These studies are also listed in Cort's excellent resource about PEM reducers found here.

    These athletic performance studies found that the very same supplements that ME/CFS patients on this forum have found prevent or relieve PEM also reduce the recovery period after athletic exercise in healthy people. Several of these studies found that the athletic performance-enhancing supplements work via neutralizing exercise-induced lactate circulating in the blood, and this is probably one of the mechanism by which they reduce PEM.



    Cannabis as a PEM Shielder

    Several ME/CFS patients have reported that Cannabis is a good PEM shielder: they find if Cannabis is taken just when the first signs of PEM appear, at the first PEM "danger signals", then Cannabis will prevent the PEM from fully manifesting.

    Cannabis seems to prevent PEM caused by both physical or mental exertion. Patients report that when they have done too much physical or mental activity, and start to sense the "danger signals" that PEM is about to appear, taking Cannabis pulls them out of the danger zone, so that they can escape PEM.

    Interestingly, some ME/CFS patients report that moderate doses of Cannabis do not produce any high at all. This observation is interesting in itself, as Cannabis will normally get people high; but the fact that in ME/CFS, moderate doses of Cannabis often do not cause any high is intriguing. And this is good news for patients who would like to benefit from the anti-PEM effects of Cannabis, but do not want to experience a high just in order to gain these benefits.

    To help ensure only moderate doses are taken, Indica Cannabis may be the best choice, rather than Sativa Cannabis. Indica has less of the THC that gets you high, and more of the CBD which acts to counter some of the effects of THC. Whereas by comparison, Sativa has more THC and less CBD.

    Of course, the legality of Cannabis varies from region to region, but this option of using moderate dose of a mild Cannabis like Indica to prevent PEM is another useful addition to the list of medications that reduce PEM.

    In terms of why Cannabis has this anti-PEM effect, this article says the THC and CBD in Cannabis can affect mitochondria: cannabinoid type 1 receptors (CB1) are found on mitochondria, and THC is an agonist of the CB1 receptor, whereas CBD is an antagonist of this receptor. So maybe that's how Cannabis helps get over PEM, by modulating mitochondrial function.



    Corticosteroids as Potent PEM Shielders

    Corticosteroids such as prednisone, prednisolone and hydrocortisone are reported to be potent PEM shielders, that when taken just before any physical or mental exertion, can totally prevent any PEM from appearing.

    But note that these drugs were found to be useless if taken after the exertion. That is, they do not help if you are already experiencing PEM from a previous period of exertion.

    But in ME/CFS these drugs should only be used occasionally, such as once a week; if they are used every day on a long term basis, this can lead to worsening of ME/CFS (possibly because the corticosteroid immune suppression may allow any underlying infections to grow).

    Some examples of corticosteroid usage as a PEM shielder to prevent PEM:

    Prednisone at a one-off dose of 20 mg or so taken 4 hours before a mentally exerting event (such as socializing). Some ME/CFS patients have vouched this works effectively and reliably (though others report ill effects from this corticosteroid drug). See this thread.

    @hamsterman found that prednisolone can work amazingly well to prevent physical exertion-induced PEM, if taken just before a physical exercise workout:
    Note that @hamsterman was using prednisolone and not prednisone as he stated in the quote above.

    But see the warning in this post, which cautions against using prednisone for any extended period of time, and warns that the PEM protective effects do not work for the whole day, they seem to wear off after about 6 to 8 hours. Prednisone is a strong drug, and has sometimes caused adverse events in ME/CFS patients.

    Hydrocortisone at a one-off dose of 80 mg or so taken 30 minutes before a mentally or physically exerting event has also been reported as very effective for preventing PEM due to physical and mental exertion:
    Correction: note that @hamsterman was using prednisolone and not prednisone as he stated in the quote above. Prednisolone has the advantage of kicking in faster than prednisone, as the following explains.

    The exact time it takes for these corticosteroid drugs to kick in after taking them orally is as follows: prednisone takes around 2.6 hours for the drug to reach peak levels in the bloodstream, whereas prednisolone takes around 1.3 hours, and hydrocortisone takes around 1 to 2 hours. Ref: 1

    So when you are taking any of these corticosteroids in advance to prevent PEM from a physical or mental exertion you are about to perform, you need to give them enough time to kick in before starting the exertion, else you "PEM shield" will not be in place.

    In terms of how long the "PEM shield" lasts, the plasma half-life of prednisone and prednisolone is 3 to 4 hours, and the plasma half-life of hydrocortisone is 2 hours.

    So once your "PEM shield" is active it will last for say one or two half-lives, ie, it may last about 4 to 8 hours for prednisone and prednisolone, and last around 2 to 4 hours for hydrocortisone.
     
    Last edited: May 1, 2018
  2. Mary

    Mary Forum Support Assistant

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    @Hip - I did a very small dose of creatine once, but was scared off of it by negative things I had read. However, I just read your post linked above where you set out the difference between creatine hydrochloride and creatine monohydrate - I never knew all that, it's great information and think I will give the creatine hydrochloride a try - Thanks for all the info! :thumbsup:
     
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  3. Hip

    Hip Senior Member

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    Yes, some of the creatine monohydrate is converted into creatinine by the action of the stomach acid on creatine, and this creatinine can have mildly toxic effects, leading to stomach cramps or fluid retention the ankles and legs (this issue can be eliminated, though, if you take creatine monohydrate on an empty stomach where there is minimal stomach acid present).

    But better still, this problem of conversion of creatine to creatinine in the stomach does not really occur at all with creatine hydrochloride, so creatine hydrochloride seems like a much better form of creatine to take.


    Creatine in all forms does raise DHT (dihydrotestosterone) though. This study found that in young men, a daily dose of 5 grams of creatine in the form of creatine monohydrate led to a 40% increase in DHT levels. Higher levels of DHT are linked to prostate problems, can exacerbate hair loss (androgenetic alopecia), and paradoxically can increase body and facial hair. So for anyone taking high doses of creatine regularly on a long term basis, you might want to consider also taking a supplement that reduces DHT, such as the herb saw palmetto, which reduces DHT by around 40%. Ref: 1

    But if you were just temporarily taking creatine during the PEM period, or on the day that you exercise, I don't think you'd have to worry about DHT.
     
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  4. Mary

    Mary Forum Support Assistant

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    Dang! I was hoping it could be something I would take regularly to extend my activity window. I don't exercise per se as I can't. My energy is very limited, roughly 3 hours of very light activity a day, with rest breaks in between, in order to avoid crashing, so that energy is used for things I have to do - grocery shop etc. I still crash a lot though.

    I just saw this, don't know if it would be worth trying in addition to the creatine - if the creatine actually helped me, I guess I would probably give something like this a try: http://www.pipingrock.com/hair-skin...0?prd=D0000J&gclid=CJisj6euhtECFVKGfgodvbML1w
     
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  5. Hip

    Hip Senior Member

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    The DHT blocker supplements in that product all look good. These DHT blockers are often used by men with male pattern hair loss, since high DHT is often the primary cause of this type of hair loss.

    But as you say, you would only need to be concerned about addressing raised DHT if you took creatine on a long term basis.
     
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  6. Mary

    Mary Forum Support Assistant

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    Thank God I have a lot of hair! ;):D:sluggish:

    Actually, if it was too much to take regularly, if it at least helped with PEM recovery or certain times when I know I have to do too much, that would be great - I will definitely be trying the creatine hydrochloride a try --
     
    Last edited: Dec 21, 2016
  7. Strawberry

    Strawberry Senior Member

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    Is there any one specific thing that I could try safely and easily? I do use the sodium bicarbonate at times, but wonder which of the other 6 would be worth trialing? And then add another one to it later?
     
  8. Hip

    Hip Senior Member

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    Judging by patients' reports, the supplements that have the most potent anti-PEM effects are probably: D-ribose and very high dose Q10. So you could try any one of those.

    For example, in one patient D-ribose 5 grams x 3 times daily routinely reduces their normal 3 or 4 day PEM down to as little as 12 hours. So that is quite a dramatic improvement.

    And a single one-off high dose of 2 x 1200 mg of Q10 seemed to virtually eliminate one patient's normal 10 to 14 day PEM, curtailing the PEM within 24 hours. So that is another potent effect.

    A daily dose of 800 mg of Q10 is reported to raise the PEM threshold (meaning you can do more physical exertion before PEM is triggered). Likewise for creatine: it raised the PEM threshold for one patient, and made any PEM that did appear less severe.

    You may have to experiment before you find the supplement(s) that suit you.



    It is possible that some of these supplements may work better as PEM preventers (ie, when taken before exercise/exertion, they raise PEM threshold, and thus help prevent the exercise from triggering PEM).

    Whereas other supplements may work better when taken once the PEM period has started, where they may help shorten the duration of PEM, or reduce the PEM severity.
     
  9. Bansaw

    Bansaw Senior Member

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    I started to take Sodium Bicarbonate after physical exercise and that's helped my muscles aching I think.
    I believe its the release of lactic acid that it seems to deal with.
    However, why does mental exertion cause PEM? What substance does mental exertion release that has to be dealt with in the human body?
     
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  10. Hip

    Hip Senior Member

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    This is a good question.

    My theory (briefly outlined in this post) is that it may be the increased brain arousal which results from mental exertion (such as face to face socializing) which then triggers PEM.
     
  11. Thinktank

    Thinktank Senior Member

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    Thanks for compiling that list Hip.

    From experience i have to say i do notice positive effects from each supplement you have listed and that's very strange because i'm overly sensitive to most supplements and medication - making me feel restless or overstimulated.

    Creatine hydrochloride:
    In my strength training days i used creatine monohydrate or creatine ethyl ester on and off.
    Not sure if it has been debunked or not but back then everyone believed creatine supplementation needed a loadup period of higher intake, a single dose does not work.
    I usually noticed an increase in strength after a week or so.

    Citrulline:
    This improves my brain fog, doesn't do much for PEM.

    Branched-chain amino acids (BCAA)
    Pre-ME i used BCAA formulas extensively. With BCAA i could add 10 - 15 more minutes to my cardio workout with ease and pump a few extra heavy reps.

    Co-enzyme Q10
    Decreases my PEM if taken the night before.

    Sodium bicarbonate
    I take alka seltzer gold. This very effectively decreases the lactic acid feeling in my muscles.
    But somehow it causes constipation, i really like to know why that happens.

    D-ribose
    Does indeed decrease my PEM slightly, but it's derived from corn which i'm allergic to. More than one or two doses daily causes a reaction.
    If anyone knows of a non-corn derived d-ribose product please let me know.

    Mental exhaustion / overstimulation is a bigger problem for me than PEM is. I've not really found a solution for that yet. Things that slightly help are high dose fish oil and magnesium malate.
    I used low dose clonazepam in the past which is very helpful for mental overstimulation but i've stopped using that.
     
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  12. Mary

    Mary Forum Support Assistant

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    BCAAs cut my PEM recovery time in half, from 2 days to 1 day. This first happened about a week after starting them. They have not extended my stamina or activity window, but continue to keep my recovery time at about a day. I've been taking them daily for about 2 years now.
     
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  13. Monarda

    Monarda

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    Bignonia capreolata, a wild vine native to the southeastern US. In the 40’s and 50’s it was a common ornamental in landscaping, even made its way to the Ohio valley and the west coast. I find it in the wild. This year I had a friend harvest, dry, and ship me some. It’s far more common in Appalachia than in my area, I didn’t have the energy to find and process it.

    I make a tea with it, delicious, an excellent tea. It’s an adaptogen, superior to Ginseng. It tones and promotes proper function of the adrenal glands (adaptogens have many other health benefits). (an excellent book… “Adaptogens – Herbs for Strength, Stamina, and Stress Relief” by David Winston and Steven Maimes) There are lots of adaptogens scattered around the globe. A common adaptogen on Amazon… Ashwagandha.

    What crossvine (Bignonia capreolata) does for me? It prevents crashes when I over do it in a minor to medium way. I’ll have a bad day or so but not a crash. It helps me recover quicker than without it. A small cup of tea everyday will help for 3 to 5 weeks then the effect weakens. I stop drinking the tea for a couple of weeks then start again. :)
     
    Last edited: Dec 21, 2016
  14. Hip

    Hip Senior Member

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    Do you think taking BCAAs daily helps prevent PEM (ie, raises the PEM threshold), or would you say that BCAAs only act to reduce the duration of PEM, once PEM has started?

    The reason I ask is that if it is only the latter, then you might save some money by only taking the BCAAs once your PEM has begun, just to reduce its duration, assuming that approach works.


    The same idea may apply to the other PEM busters too: it may be cheaper and easier to take them only once PEM has begun, in order to shorten PEM, rather than taking them all the time.

    Though if the supplement also has good PEM preventing abilities, then it may be advantageous to take it either all the time, or just on the days that you know you are going to engage in a higher level of exertion.


    If these supplements mitigate PEM by reducing exercise-induced lactic acid, then it makes sense that you may only need them when you engage in physical exertion (when the lactic acid is generated), and during the PEM period (when the body is trying to clear the lactic acid).
     
    Last edited: Dec 21, 2016
  15. Mary

    Mary Forum Support Assistant

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    The BCAAs have not raised my PEM threshold; they only act to reduce the duration of PEM, but it was huge for me. I could try taking the BCAAs only when PEM has begun, instead of all the time, and see what happens, but I'm afraid to do this. Just the thought of going back to a full 2 days or more of recovery is too much for me.

    I don't think the mechanism of action for BCAAs is reducing exercise-induced lactic acid. Here are some articles about how BCAAs can help and it's not related to lactic acid. I found the first article most interesting:

    http://www.ncf-net.org/forum/Fword.htm
    http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=41341 - this article has a very interesting paragraph which states:

    https://www.ncbi.nlm.nih.gov/pubmed/11310928
    http://jn.nutrition.org/content/136/2/544S.full
     
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  16. Mary

    Mary Forum Support Assistant

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    @Hip - what first got me looking into BCAAs was my Nutreval testing in 2010 which showed low leucine levels. It wasn't until 4 years later that I googled CFS and leucine and came up with the above research (wish I had done it sooner!)

    So perhaps a blood test would be a good indicator of who could benefit from BCAAs. I did have a blood test done a year or so to recheck my leucine etc (all the amino acids) and my levels were normal that time, but as I said I'm afraid to stop the BCAAs

    And I don't know if that blood test was the same as or as accurate as the Nutreval testing.

    Though I think I could safely cut my dose, I'm still taking almost the full dose and I think I could cut it in half, and actually will give that a try.
     
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  17. Hip

    Hip Senior Member

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    Yes, I remember reading those articles when you posted them in your BCAA threads. I agree it is certainly possible that BCAAs might reduce PEM by a mechanism other than lactic acid reduction.

    The theory and mechanism you are referring to is the "central fatigue hypothesis" — the idea that physical exercise-induced central nervous system fatigue (aka: central fatigue, which is the washed out feeling in the mind that athletes get when they train too hard) is driven by serotonin increases in the brain, and that this central fatigue is increased when the free tryptophan / BCAA ratio in the blood increases, because increases in this ratio act to raise serotonin in the brain.

    So the theory is that by supplementing with BCAA's, you lower this ratio, and thereby reduce serotonin and central fatigue.


    I just found this article on the subject: Carbohydrates, Branched-Chain Amino Acids and Endurance: the Central Fatigue Hypothesis.

    At the bottom of this article is says:
    Note that f-TRP = free tryptophan.

    So in the article they say that the idea of using BCAAs to reduce central fatigue may not be a viable one.


    They also note that eating carbohydrates greatly reduces the free tryptophan / BCAA ratio, and greatly reduces fatigue in athletes. So if this central fatigue and free tryptophan / BCAA ratio theory of PEM is right, you would expect PEM to be greatly reduced by switching to high carbohydrate meals or drinks during PEM.

    That's something ME/CFS patients could certainly try during PEM: test to see if high carbohydrate meals or drinks can reduce the duration or severity PEM.

    If they can, then it supports your central fatigue and free tryptophan / BCAA ratio theory of PEM. But if such high carbohydrate meals or drinks do not help PEM, then that would suggest that this central fatigue theory of PEM may not be a correct one.

    In the article, they cite this study on cyclists, which according to the article, found that:
    So that's a major result in reducing fatigue simply by consuming carbohydrates, which greatly reduces free tryptophan in the blood, and greatly reduces the free tryptophan / BCAA ratio.


    This article also talks about carbohydrates and tryptophan.
     
    Last edited: Dec 22, 2016
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  18. Mel9

    Mel9 Senior Member

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    Basica Active E alkalising mineral formula works well for me.
     
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  19. Mary

    Mary Forum Support Assistant

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    Interesting, @Hip. I don't have the mental wherewithal to properly digest the article you've linked (no pun intended!). Although I'm almost positive that consuming lots of carbohydrates would do nothing for my PEM. It never mattered what I ate or drank, my crashes were depressingly the same.

    I do know that my PEM duration was cut in half within about 5 days after starting the BCAAs, and has remained at that level ever since. And my leucine was low.

    So perhaps the BCAAs reduced the PEM duration by a different mechanism (although I don't have a clue what that could be).

    Where the article states:

    I'm not suaded by the fact that studies on BCAAs are limited. Any time I do any research on anything nutrition-related, there's always a caveat that studies are limited - nutritional studies are just limited period. No one's spending tons of money on them as they do on drugs.

    And when he states that there are reasons to believe that this approach may not be viable, does he give the reasons? I did made an attempt to look at the article but quickly gave up.

    So I think BCAAs are definitely worth experimenting with. They're non-toxic, affordable, and in my experience at least one would know relatively quickly whether they would be of any benefit. And if they helped someone else as they have helped me, it would be fantastic.
     
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  20. Hip

    Hip Senior Member

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    I agree. With these things, the proof of the pudding is in the eating, and if they work for you, that's the bottom line. And if they work, it means the same supplements may also help others with ME/CFS. In fact I have been experimenting with BCAAs on and off ever since I read your threads (though in my case, because I don't get PEM from physical exertion, only from mental exertion, I can't really test any of these PEM busters on myself, except for their effects on mental exertion PEM — but that may be a different sort of PEM).
     
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