The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
Discuss the article on the Forums.

POLL: Do You Get PEM From Physical Exercise? Are You Sensitive To Lactate Probiotics Or Prebiotics?

Discussion in 'Gastrointestinal and Urinary' started by Hip, May 7, 2015.

?

Do You Get PEM From Physical Exercise? Sensitive To Lactate-Producing Probiotics, Or To Prebiotics?

  1. I GET PEM FROM PHYSICAL EXERCISE, and I am SENSITIVE to prebiotics or lactate-producing probiotics

    25 vote(s)
    47.2%
  2. I GET PEM FROM PHYSICAL EXERCISE, but NOT SENSITIVE to prebiotics or lactate-producing probiotics

    24 vote(s)
    45.3%
  3. NO PEM FROM PHYSICAL EXERCISE, but I am SENSITIVE to prebiotics and/or lactate-producing probiotics

    1 vote(s)
    1.9%
  4. NO PEM FROM PHYSICAL EXERCISE, and NOT SENSITIVE to prebiotics or lactate-producing probiotics

    3 vote(s)
    5.7%
  1. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    This poll, open to ME/CFS patients, is about whether or not you get significant PEM after physical exercise, and also whether or not you are sensitive to lactate-producing probiotics and/or to prebiotics.

    By sensitive, we mean you get a significant worsening of ME/CFS symptoms when taking such probiotics or prebiotics.





    Hypothesis Underpinning This Poll

    Note: you don't necessarily need to read the following if you just want to answer the poll.

    The hypothesis being explored in this poll is: whether PEM induced by physical exercise might be caused by increases in blood lactate resulting from exercise.

    If you look at this list of microglial activation / brain inflammation promoters and inhibitors, you see that lactate is one of the promoters of brain inflammation. Lactate causes microglia to release the pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and astrocytes to release TNF-α and IL-6 (see this study).

    Thus the lactate produced from muscles during exercise could be ramping up brain inflammation (lactate in the blood does cross the blood-brain barrier), and if so, this increase in brain inflammation might be a causal factor of PEM.

    Lactate levels in the brain have been shown to increase after exercise: this study indicates that a lot of lactate is taken up by the brain during exercise (and in fact we now know that the brain can use lactate as well as glucose for energy).

    Under normal circumstances this take up of lactate may cause no problems, and beneficially supplies the brain with an alternative source of energy.

    However, if you already have chronic microglial activation and chronic inflammation in the brain as a result say of a persistent infection, this surge of lactate from exercise may conceivably increase your pre-existing brain inflammation even further, thereby leading to a worsening of ME/CFS symptoms and to PEM.

    So although blood lactate surges from exercise may be no higher than normal in ME/CFS patients, such lactate surges might dramatically ramp up inflammation if there is already chronic microglial activation in the brain (which there appears to be).

    This is the hypothesis being explored.



    To try to provide supporting evidence for this hypothesis that lactate plays a role in physical exercise-induced PEM, what we are looking for in this poll is whether those ME/CFS patients who suffer from physical PEM also tend to be sensitive to lactate-producing probiotics or prebiotics.

    Because if exercise-derived lactate is a major cause of physical exercise-induced PEM, then you might expect that patients who suffer from this physical PEM will also tend to be sensitive to lactate-producing probiotics or prebiotics. Either source of lactate may produce similar bad effects in these patients.

    So if the poll results show that most patients who get physical PEM also tend to have these lactate-producing probiotic or prebiotic sensitivities, this will help support the hypothesis that lactate released from the muscles during exercise is a cause of this PEM.

    But if the poll results show no strong relationship between suffering from physical PEM and having lactate-producing probiotic or prebiotic sensitivities, then this result would not actually negate the hypothesis as such, but would not provide any supporting evidence.
     
    Last edited: May 11, 2015
    L'engle and John Mac like this.
  2. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    Note there was slight error in setting up this poll: the first answer option should read:

    I GET PEM FROM PHYSICAL EXERCISE, and I am SENSITIVE to prebiotics and/or lactate-producing probiotics.

    I can't seem to edit it now.
     
  3. JaimeS

    JaimeS Senior Member

    Messages:
    3,192
    Likes:
    11,786
    Mid-Ohio Valley, United States
    @Hip, I am extremely sensitive to a sour (acidic!) fermented drink... trying to remember its name... eurgh, brain fog. KOMBUCHA. It makes my symptoms almost instantly worse - just a sip will do it! However, there are many probiotics that make me feel quite a bit better, some of which are the ones you mention: psyllium and Lactobacillus, the latter of which is in a probiotic I take every morning and feel improvement. I replied with the first answer, because I have had that experience... but it doesn't seem like it's the same for every pro/prebiotic you mention.

    -J
     
    oceiv likes this.
  4. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    @JaimeS
    If prebiotics and many Lactobacillus probiotics make you feel better, that perhaps suggests that you are not really sensitive to them. It may be something else in the kombucha that is causing your bad reaction to it.

    A quick check in this Wikipedia article on kombucha reveals that this fermented drink contains yeast strains such as Saccharomyces cerevisiae:
    I quickly feel really terrible if I take Saccharomyces cerevisiae (sold as EpiCor®). I get miserably depressed. I have heard other ME/CFS patients having problems with Saccharomyces cerevisiae as well.



    You can change your answer if you wish to. The poll is set up to allow this.
     
    Last edited: May 7, 2015
  5. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    How To Reduce The Amount Of Lactate Produced During Physical Exercise

    If lactate release from the muscles during exercise is a major cause of PEM, this might explain why some ME/CFS patients have found supplements such as sodium bicarbonate, creatine, citrulline, BCAA and Q10 mitigate or eliminate their physical exercise-induced PEM (see this thread). All these supplements appear to reduce lactate, as the following studies indicate:

    This study suggests that sodium bicarbonate (bicarbonate of soda) can help neutralize lactate circulating in the blood.

    This study shows that the supplement creatine reduces blood levels of lactate from exercise. Creatine hydrochloride is a good form of creatine to take, as this is more soluble and better absorbed than creatine monohydrate.

    This study found citrulline reduces lactate levels produced by exercise.

    This study found that branched-chain amino acids (BCAA) reduce lactate levels produced by exercise.

    This study found that co-enzyme Q10 reduces lactate levels produced by exercise (in myotonic dystrophy).​

    The fact that ME/CFS patients have reported that these lactate-reducing supplements mitigate or eliminate PEM arising from physical exertion supports the idea that PEM may be due (at least in part) to the lactate surge from exercise.

    So to utilize these supplements, a good PEM preventing protocol might be:

    PEM Preventing Protocol:
    Sodium bicarbonate
    ¼ teaspoon
    Creatine hydrochloride 2 grams
    Citrulline 1000 mg
    Branched chain amino acids (BCAA) 5 grams
    Q10 400 mg​

    These supplements may be particularly efficacious at preventing PEM if taken an hour or two before doing some unavoidable physical exertion.



    How To Reduce The Amount Of Lactate Produced In The Gut

    In addition to reducing the exercise-derived lactate, ME/CFS patients may well benefit from reducing the lactate arising from lactate-producing bacteria in their guts.

    Quite a few ME/CFS patients seem to be getting very good results from the taking the probiotic Clostridium butyricum (Miyarisan®), which does not itself produce lactate, and may help displace or reduce lactate-producing bacterial populations in the gut, thereby reducing the gut's contribution to blood lactate.

    See this thread: Clostridium Butyricum - A Game Changer?
     
    Theodore, oceiv, adreno and 3 others like this.
  6. JaimeS

    JaimeS Senior Member

    Messages:
    3,192
    Likes:
    11,786
    Mid-Ohio Valley, United States
    I've taken baking soda and CoQ 10. I take the latter every day, but the baking soda only when muscles hurt especially, or with PEM. It definitely lessens my symptoms.

    -J
     
    Hip likes this.
  7. Mary

    Mary Senior Member

    Messages:
    2,742
    Likes:
    6,123
    Southern California
    @Hip - thanks for all this great information! I am typing on a tablet so it's harder than my computer so will make it brief - what have you found most helpful for PEM? The bcaas are helpful but unfortunately are not the magic bullet -
     
    Hip likes this.
  8. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    If you glance at those studies, you'll see that creatine, BCAA and Q10 prevent the release of lactate from exercise (they increase what's called the lactate threshold). So for these supplements to work, I expect they will need be in your system before you perform the exercise. They probably need to be taken say 1 or 2 hours before you start your physical exertion, to sure they are properly assimilated in your body by the time you begin the exercise and muscle usage.

    Sodium bicarbonate is slightly different, in that it does not stop the release of lactate, but the study suggests it can neutralize the lactate that is already in the blood. So that means sodium bicarbonate would probably work if taken before or after exercise; but I guess that before may be better.

    Citrulline I am not quite sure about, but I think it may be another supplement that prevents the release of lactate from exercise.
     
    Last edited: May 8, 2015
    ahmo likes this.
  9. Ema

    Ema Senior Member

    Messages:
    4,276
    Likes:
    5,996
    Midwest USA
    When I tested my blood for lactate, my level was at the very bottom of the range unlike many with MECFS.

    This corresponds with my lack of PEM (I'm just M'd all the time but movement typically makes me feel better if I'm able).

    I'm also able to tolerate meds and supplements pretty easily unlike many others and am not sensitive to pre/probiotics.
     
    Hip likes this.
  10. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    I only get PEM from mental exertion (anything that excites my mind for several hours gives me PEM). It's a work in progress for me to try to find drugs or supplements that might mitigate this mental PEM.

    Each time I am about to face such mental exertion, I often take an hour or two beforehand a good dose of a supplement or drug I want to test for its possible PEM mitigating effects. But so far I have not had much in the way of conclusive results.

    Some things on my list of possible mental PEM busters (which I need to test a bit more) are: rifaximin 200 mg (an antibiotic that stays in the gut and reduces gut inflammation), erythromycin 800 mg (an anti-inflammatory antibiotic), hyaluronic acid 400 mg (a supplement which reduces microglial activation by a TLR-4 receptor mechanism, like LDN).
     
    shaya, oceiv and Mary like this.
  11. oceiv

    oceiv Senior Member

    Messages:
    259
    Likes:
    551
    @Hip What if you are sensitive to some products but not others - which answer would you choose or maybe none apply? Are you defining sensitivity as an increase in fatigue/weakness/exhaustion? Or can it also be increased symptoms in one system, like GI?
     
  12. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,020
    Actually, CB directly utilizes lactate for butyrate production. In other words, it turns lactate into butyrate. That may be one of the reasons why it has potential to be so effective for PWMEs.
     
    Last edited: May 8, 2015
    Theodore, Hip, zzz and 1 other person like this.
  13. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,812
    I've given up on yogurt, even when non-dairy. It just makes me feel wretched :(
     
    Mel9 and Hip like this.
  14. Mij

    Mij Senior Member

    Messages:
    2,269
    Likes:
    5,028
    My lactate testing was at the bottom range, I do get mental and physical PEM if I go beyond my limits.
     
    Hip likes this.
  15. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    Right, well that's even more interesting. So not only will Clostridium butyricum mop up some of the lactate produced by other bacteria in the gut, but conceivably, CB might also mop up some of the blood lactate surge released from muscles during exercise.


    One thing I could not find info on, though, is just how easily it is for lactate in the gut to pas through the intestinal lining and get into the blood stream, and vice versa. Lactate in the blood can pass through the blood-brain barrier, although not quite as efficiency as glucose can (see here), so I am assuming lactate can also cross the intestinal lining relatively easily. And given that you can get supplements like magnesium lactate, that indicates lactate is absorbed. There is some info on lactic acid absorption in the guts of sheep here.

    The testing of my lactate-causes-PEM hypothesis by this poll depends on the idea that some of the lactate made by gut bacteria gets absorbed into the blood stream.
     
    Last edited: May 8, 2015
    oceiv likes this.
  16. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    If you are sensitive to some of the regular sort of Lactobacillus-containing probiotics, then I think that would count as being sensitive.

    I defined sensitive above as being a "significant worsening of ME/CFS symptoms", ie, the sort of worsening you might experience in PEM. So provided it is one or more of your ME/CFS symptoms that significantly worsens after taking Lactobacillus probiotics, you can count that as being sensitive, for the purposes of this poll. Or if you just feel generally ghastly after taking these probiotics, you can probably count that as sensitive.

    If it is just local GI symptoms, like say a worsening of IBS for example, or some increased gut discomfort or pain, then on its own that probably shouldn't be counted as being sensitive. Although gut pain and irritable bowel are considered ME/CFS symptoms.

    But it's more the major overall ME/CFS symptoms like fatigue, brain fog, sound or light sensitivity, muscle aches and pains, joins pains, sore throat, etc that we are interested in. I understand that when people are sensitive to lactate-producing probiotics, it hits them hard. It's not just a small reaction.

    Perhaps people here that are probiotic-sensitive can give an account of what it feels like.
     
    Last edited: May 8, 2015
  17. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    A more straightforward and simple way to test if lactate is a cause of PEM would be to find some figures for the amount of lactate released into the blood during exercise, and then take this amount orally. If this oral lactate then triggered the typical sort of PEM symptoms, it would demonstrate that lactate is a cause of PEM. Though you would have to factor in the bioavailability / absorption percentage of oral lactic acid for your oral dose calculation. You can buy lactic acid quite cheaply from home brewing suppliers.
     
  18. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,020
    I don't think lactate is the only cause of PEM. But it is likely part of it.
     
  19. Hip

    Hip Senior Member

    Messages:
    9,354
    Likes:
    14,659
    Yeah, biochemistry is rarely so simple that an effect only has one cause; there are usually multiple simultaneous causal factors.

    One other exercise-derived factor that I think may very likely play role in PEM is IL-6. IL-6 is both a cytokine and a myokine. Myokines are factors released by muscles during exercise. During exercise, IL-6 levels in the blood can increase by a staggering amount: as much as 100-fold.

    Studies have shown that even in healthy people, injection of IL-6 causes fatigue and reduces the ability to concentrate, probably I think via the affect of IL-6 on brain inflammation. So if you already have brain inflammation and fatigue, as ME/CFS patients do, this IL-6 from exercise will likely make you even more fatigued. Although IL-6 does not easily cross the blood-brain barrier. Nevertheless, with such high amounts in the blood, some IL-6 will enter in the brain.

    So physical PEM might result from a combined effect of lactate plus IL-6, both of which are released in copious amounts in the blood during exercise, and both of which are pro-inflammatory.

    It's quite possible that IL-6 inhibitors might reduce physical exercise-induced PEM. See this post for a list of IL-6 inhibitors. Though you'd presumably want an IL-6 inhibitor that specifically reduces IL-6 release from muscles. Vitamin C and vitamin E inhibit such muscle-derived IL-6 (see this study).

    Or equally, you would probably want some sort of inhibitors that block the pro-inflammatory effect of IL-6 in the brain.



    Note that there are two sides to the IL-6 pathway, one which is pro-inflammatory, and another which anti-inflammatory. Normally, IL-6 released from the muscles during exercise operates on the anti-inflammatory pathway, which may help to explain why exercise is generally beneficial (in those who do not have ME/CFS, of course).

    However, I speculate in this post that something may have gone wrong in ME/CFS, such that the IL-6 released during exercise now becomes pro-inflammatory rather than anti-inflammatory, which might help explain why exercise causes PEM in most ME/CFS patients.
     
    Last edited: May 9, 2015
    Theodore and Ema like this.
  20. oceiv

    oceiv Senior Member

    Messages:
    259
    Likes:
    551
    This was exactly the debate I was having. Because system-specific symptoms can be so integral to the disease, as it is in mine.

    I understand what you mean. I ended up voting no, because some products seem great for me. It might be something other than lactate in the other bad for me products causing the ill effects.

    You might be interested in a study about Lactobacillus rhamnosus altering the function of GABA in the brain. Perhaps another explanation for ill effects from at least one probiotic. This study was about stress-related disorders, but the effect of the gut on GABA in the brain may be applicable in our PEM.

    One other thought, since the poll numbers are almost half and half between the first two answers, maybe there's a way to figure out the subset for sensitivity? Duration of illness. Severity. Types of symptoms.
     

See more popular forum discussions.

Share This Page