August 8th, 2016: Understanding and Remembrance Day for Severe Myalgic Encephalomyelitis
Jody Smith joins with other ME voices in honor of Understanding and Remembrance Day for Severe Myalgic Encephalomyelitis.
Discuss the article on the Forums.

Some ideas re Chris Armstrong's presentation at Stanford

Discussion in 'The Gut: De Meirleir & Maes; H2S; Leaky Gut' started by Richard7, Oct 26, 2017.

  1. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    Hi.

    This may take a bit to explain. But it relates to Chris Armstrong's presentation at Stanford. The one in which he explained that pwme/cfs seem to be locked into a vicious cycle.

    The steps are:
    1) we do not have enough ATP so we switch on AMP kinase;
    2) which puts our cells into an energy efficient mode that favours the use of lipids and proteins for energy;
    3) which means that they no longer have those lipids and proteins available for making enzymes and bile;
    4)which means that fats and proteins are not properly digested in the small intestine and pass through to the colon;
    5) where they change the balance of our gut bacteria leading to an increase in production of Short Chain Fatty Acids;
    6)which in turn trigger AMPK, reinforcing the cycle.

    And we do in a sense seem to have a kit to deal with this.
    1) Betaine HCL plus pepsin allow us to emulate the acid and pepsin production and release of normal people breaking proteins into peptides.
    2) Creon or another source of animal derived pancreatic enzymes can then break these proteins into small oligopeptides
    3) ox bile to break fat down into manageable globules and lipases (in the Creon) to break them down into monoglycerides and free fatty acids.

    (The creon also works on carbohydrates too but Armstrong was focussed on proteins and lipids, so I have too.)

    I think that there is a problem though. We can kind of approximate a working stomach and pancreas and gall bladder but we are not replicating the brush border enzymes that activate some of the pancreatic enzymes and turn the oligopeptides into the amino acids, dipeptides and tripeptides that we can absorb.

    (For lipids I think that the Creon and ox bile should be enough to do the job.)

    I got to thinking about this because I was playing around with Oral Rehydration Solutions to try to reduce the severity of my PoTS.

    In reading the ORS research I found that there are the usual sodium, potassium, glucose and citrate or bicarbonate solutions and others that use cooked cereal flours in the place of glucose. It seems like the cereal had an advantage when trying to rehydrate people with diarrhoeal infections that did not damage the gut, but were a disadvantage for those with infections that had damaged the gut.

    The trick to ORS is glucose sodium symporters. These transport equal numbers of sodium ions and glucose molecules into the cells and create the osmotic pressure that brings the water across from the small intestine into the body. The cereal solutions uses brush border enzymes to break the carbohydrates into the glucose needed to make the trick work without increasing the osmolarity of the solution.

    When I tried the cereal solutions on myself I found that they were indistinguishable from ORS minus glucose. Which is to say that they were of little use. I conclude from that rather unprofessional n=1 experiment (2 litres solution on 2 days) that they did not work for me, But had to read and think for a few weeks before it occurred to me that this might be because my brush border enzymes are not being produced, or not being produced in sufficient quantities.

    The normal ORS really helps with the PoTS but I have issues with having too much glucose - it makes me feel ill, makes it hard to sleep, it feels a bit like being drunk.

    So it occurred to me that it should be possible to use the same principle as ORS with sodium dependent amino transporters. So I tried it with whey protein and like the cereal based ORS it had no effect. (Even when I took it with Betaine hcl, Pepsin and Creon).

    Which lead me to read about brush border enzymes and here.

    My hope with the Betaine HCL + pepsin + oxbile +Creon combination was to digest and absorb the nutrients my body needs and to provide the right substrates to grow the right bacteria and get rid of the dysbiosis that is characteristic of ME/CFS.

    I think Chris Armstrong's presentation underlines the importance of sorting out this dysbosis.

    And the current kit has improved things, but if I am right it cannot get someone all the way.

    What I am wondering is if people who have a better handle on the biology and biochemistry are aware of exogenous sources of enzymes that can fill the role of brush border enzymes.

    Or if taking amino acids (glutamine and luecine perhaps) or something of the sort might be able to get those cells on the brush border to down regulate AMPK or at least get the lipids and aminos needed for making the brush border enzymes.

    Or if I am just very very wrong, and have misunderstood something important.

    In reading up on the above I have chiefly relied on this site for info on digestion.
    http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/index.html
     
    merylg, Ben H, Jo Best and 7 others like this.
  2. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    While not sleeping I think I just got part of an answer. Sprouts. When brewers malt barley they use the barley's own enzymes to change the storage form of carbohydrate into sugar.

    There are also storage forms of proteins, so I assume that sprouts probably contain the relevant enzymes.

    I will need to look it up tomorrow.
     
  3. Wishful

    Wishful Senior Member

    Messages:
    256
    Likes:
    340
    I haven't checked the presentation, but I'm very skeptical about digestive system dysfunction being a critical aspect of this disorder. It just seems that changes in diet should have much more effect on the symptoms than I've observed. While I've seen effects from specific dietary chemicals, there should be much more effect when switching from carb-heavy to fat-heavy or protein-heavy, or refined sugars/starches to high-fibre and complex carbs.
     
  4. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    @Wishful
    I had an appointment earlier this year with a specialist who made the observation that he knew of some people who had managed to get out of chronic fatigue syndrome by identifying allergies and avoiding allergens but he knew many more who have tried the same things and got nowhere.

    or rather improved their allergy symptoms but did not recover from chronic fatigue syndrome. from the point of view of our conversation that second group were the ones who were unsuccessful, but really both are kinds of success.

    When it comes to treatment I'm in the same situation with regard to digestion. If I just get the sort of digestion I had pre chronic fatigue syndrome that would be good, if it also improved my chronic fatigue syndrome symptoms that would be better.

    Anyway the combination of betaine HCL + ox bile + digestive enzymes is the one that I was advised to take after I did some pathology early on in my illness.

    my understanding was that it was meant to be sufficient. I was quite unaware of brush border enzymes and it wasn't until I started researching this recently that I realised that my digestive aid kit was insufficient.

    I just spent today reading up on enzymes in germinating seeds and it all seems terribly complicated but for the moment I think I'll try consuming some in the hope it will help .

    I don't suppose it can make me worse.
     
  5. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    I should add that when I became ill the idea that dysbiosis could hold you in CFS was something I was aware of. Chris Armstrong has helped provide a mechanism for this. I think it also provides a direction for action that could help prune part of the illness away.
     
    merylg and ljimbo423 like this.
  6. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

    Messages:
    1,191
    Likes:
    891
    Mackay, Aust
    I don't understand fully the OP's post or subsequent, but I did experience dramatic weight loss when I stopped all cereals and increased meat intake. Also had a lot of gallbladder/reflux etc issues until I went off the cereals. So does this fit the model? It would seem to, or have I got this wrong.
     
  7. Wishful

    Wishful Senior Member

    Messages:
    256
    Likes:
    340
    I think that allergies are unlikely to have much to do with ME/CFS. Allergies (type I and III) involve immunoglobulin. My disorder involved a type IV sensitivity, which involves t-cells and is technically not considered an allergy. ME/CFS seems to be triggered mostly by t-cell activating events.

    Allergies might make ME/CFS symptoms worse by secondary effects (extra stress on the body). I'm skeptical about claims that avoiding allergens would cure ME/CFS. The patients he referred to might have based their avoidance on the scratch test, which allergists admit is around 50% accurate (meaning that it's effectively worthless).
     
    TrixieStix likes this.
  8. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    @RustyJ Armstrong and McGregor certainly showed that the pwme/cfs they were looking at were using fat and protein rather than carbohydrates for energy. So you experience is consistent with their research.

    But in the presentation from August this year Chris Armstrong went further and explained how metabolomic change could change the gut microbiome in a way that sustained or reinforced itself. His model is summarised in these two slides.

    [​IMG]
    In the healthy person you can see bile and enzymes turning fat and proteins into fatty acids and amino acids in the small intestine. These are then absorbed and then carried away in the blood to a cell (bottom of the image).

    In the healthy cell you can see that energy mostly comes from glucose. Some energy comes from amino acids and fatty acids but most amino acids and fatty acids are used for making cell proteins and fats and enzymes and bile.

    In the image of the healthy gut you can also see that it is only carbohydrates that make it to the colon, and that a small amount of short chain fatty acids are produced to ensure intestinal health.

    [​IMG]
    In the pwme/cfs things are different. There is less bile and fewer enzymes so fats and proteins make there way to the colon which now contains new (red) strains of bacteria that increase the production of short chain fatty acids. The extra short chain fatty acids are carried through the blood to the cell where they stimulate AMPK.

    AMPK causes the cell to favour the use of amino acids fatty acids for energy, which means that the cells do not produce enough bile or enzymes to get you back into the healthy pattern.



    the slides can be found here https://www.slideshare.net/MelbourneBioanalytics/me-metabolism-and-i-by-chris-armstrong-2017
    the video is here
     
    voner, Murph and ScottTriGuy like this.
  9. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    Chris leaves that stomach out. In the stomach food is exposed to acids and pepsin. Pepsin is an enzyme that breaks protiens down into long chains of amino acids and it only works in an acidic stomach.

    I take pepsin and betaine HCL. The betaine HCL makes my stomach acidic: https://www.ncbi.nlm.nih.gov/pubmed/23980906 . I am taking things that do the jobs that my body is no longer doing, sort of like crutches or wheel chairs only internally.

    So I also take ox bile which performs that job of the missing human bile. And Creon which is a pancreatic extract containing pancreatic enzymes and lipases.

    What I do not take is brush border enzymes, these are the enzymes that are made by the cells of the small intestine.

    One of the tasks of these enzymes is to activate some of the pancreatic enzymes [​IMG]

    Pepsin from the stomach and most of enzymes from the pancrease work by breaking long chains of aminos into shorter chains of amino acids.

    According to the site that I got this information from there are some pancreatic enzymes that release individual amino acids from the ends of these chains but most of the enzymes that do this are attached to the brush border.

    This picture is of brush border enzymes that work on carbohydrates but the idea is much the same.
    [​IMG]

    So my concern is that I do not know for sure of a way to emulate the brush border enzymes.

    The thought I had after my initial post is that seeds contain many of the sorts of proteins, fats and carbohydrates that we eat and that germinating seeds are rich in the enzymes that are needed to break them down so that they can be used to build and feed a plant.

    I was rather hoping that someone who knew much more about biochemistry would jump on board and tell me why I was wrong, or how to solve the problem or something.

    I guess I should have tagged @ChrisArmstrong @JaimeS @alex3619 @bspg @MeSci and paid more attention to whomever else has a background in biology or biochemistry
     
    Learner1, ukxmrv and ScottTriGuy like this.
  10. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

    Messages:
    1,191
    Likes:
    891
    Mackay, Aust
    @Richard7, thanks for going to all that trouble. I am intrigued. Please post further progress.
     
    Learner1 and Richard7 like this.
  11. alex3619

    alex3619 Senior Member

    Messages:
    12,528
    Likes:
    35,244
    Logan, Queensland, Australia
    If Ron Davis's observation that cellular chemistry is deranged from a large blood serum protein, and we cannot be sure yet, then that would be my primary focus. Altering diet might or might not help. I was on digestive enzymes at one point, and have no need of more acid. Probiotics would probably be best if they were precursor foods, rather than bacteria. For bacteria it seems acidophilus is a poor choice for us, and bifidus might be better.

    I have never investigated brush border enzymes. These are deep topics with complex interactions. There are no easy answers. Trying various things very cautiously is something I and many patients have done many times. Sometimes it helps, usually it doesn't. Occasionally its a bad choice and results in negative symptoms.

    I do know that I can lose weight on a high protein diet without my energy declining (I am overweight). However this results in almost total loss of gastric movement for me, and that is not good.

    If you focus on short chain fats, primarily vegetable and fish, then breaking them down is not so important. They are already broken down or mostly broken down. The only way to be sure for amino acids would be to use an amino supplement. Both of these would bypass the digestion problem. There is also a long history of patients trying these. Sometimes it helps, sometimes it does not, and sometimes it makes things worse. If doing this then animal protein sources might be better as low fat portions.

    My experience with nutritionists is they are unaware of most of this. It would be good if you could find a doctor who is very much aware, and that might well be a doctor who does functional medicine. There is no guarantee such a person could be found, or that they could help.

    I do know that many CFS doctors back in the 90s tested various diets here in Australia, but I do not think they published the results. What I was told is that they found by altering dietary intake in their patients that about 1.5g/kg of body weight in protein was better. This is about double normal, but not as high as some body builders work at.

    I also know that composition of fats is as important as fat intake itself. Fish oil is both inflammatory and anti-inflammatory, and they need to be very pure or can cause gastric issues. Omega 6 polyunsaturated fats are inflammatory (though some derivatives are very anti-inflammatory) so need to be taken cautiously. Hormonally neutral fats might be better if wanting to increase digested fat intake. I have not researched these fats enough to tell you what would be very short chain though. In terms of these fats macadamia oil is highest in monounsaturated fat, but expensive, and probably longer chain. Monounsaturated fats are not processed into hormones so far as I know, but the science has moved a long way since I last investigated this. I just do not know for sure. I suspect most of the good ones would be liquid at lowish temperatures. However this is also linked to how the molecules pack.

    What I suspect is that if digestion is compromised then many tiny meals might be much better than larger ones as they are less likely to overwhelm digestion. However this would also mean that the digestive system was on all the time.

    Digestion biochemistry is badly under-researched in ME.
     
    Last edited: Oct 29, 2017
    merylg, bertiedog, MeSci and 4 others like this.
  12. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    Thanks @alex3619

    I guess this is just something I need to read into and play with.

    One pathway could be to play around with amino acids, the other to play around with enzymes.

    With digestive enzymes one concern is that I might not be producing the serine proteases that activate the pancreatic enzymes the second is that I do not appear to be producing the vast array of enzymes that do the final stage of degradation.

    I mentioned above (#2) that sprouts might be a source of enzymes. I have been searching and glancing over lots of papers I do not understand but it seems that quite a few legume contain serine proteases (but I am not sure that they are the right ones) and sprouts in general seem to contain a lot of proteases.

    And, of course, enzymes are proteins too and all of these plant based enzymes may be degraded by the pepsin in my stomach before they get to do much work.

    Well if anything terribly good or bad happens, or I get a good grip on the theory I will report it.
     
  13. alex3619

    alex3619 Senior Member

    Messages:
    12,528
    Likes:
    35,244
    Logan, Queensland, Australia
    One of the concerns with the hypometabolic research is pathways might be shut down deliberately. That might include enzymes. If we can find the trigger the other secondary issues might go away. Sigh. We need more research on so many issues.
     
    merylg, justy, JaimeS and 2 others like this.
  14. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    Yeah. That is the concern Alex.

    I noticed that Naviaux made some comment about needing to get out of the environment that was causing the CDR before stopping it. You know kill the virus (for example) before killing the cell's defence against the virus.

    One can just imagine a solution got us out of CFS/ME for a virus to kill or maimed us a few months or years later.

    I imagine you can remember how politicians and journalists in Australia entertained allegedly serious arguments in the 80s and early 90s about how we needed to spend our money on applied research that benefited us or taxpayers or something and not the pure research which was considered to be of academic interest only (ie something that academics wanted to do for fun).

    If only someone had explained that our knowledge of human physiology had holes you could throw an encyclopaedia through.
     
  15. Learner1

    Learner1 Professional Patient

    Messages:
    1,229
    Likes:
    2,040
    Pacific Northwest
    I spoke with Naviaux at the OMF Symposium. He said the game is to get rid of the cell dangers, then move all the Winter metabolism processes into summer.

    As for your brush border problem, @Richard7 , my doctor is a fan of the Australian doctor Jason Hawrelak. In the attached, he says that S. Boulardii will significantly increase brush border enzymes.

    Interesting discussion, thanks!
     

    Attached Files:

    merylg, Murph, Isaiah 58:11 and 2 others like this.
  16. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    @Learner1

    That pdf is interesting but on reflection the problem with the research Hawrelak cites is that it is research done on healthy volunteers. We are neither healthy nor volunteers.

    Well only the first is relevant, but the repetition of that expression "healthy volunteers" in the abstracts struck me.

    The only relevant mechanisms that I would expect to help us (given Chris Armstrong's model) would be something that increased our absorption of amino acids and lipids, or switched our energy metabolism over to glucose. But there may be other options.
     
  17. Learner1

    Learner1 Professional Patient

    Messages:
    1,229
    Likes:
    2,040
    Pacific Northwest
    Good point. I have the same discussion with my endocrinologist about expecting the rules of thyroid for otherwise healthy patients to apply to patients like us.
    That would be helpful, but I fear this problem is far more complex than that. It's multidimensional.:nerd:
     
  18. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    This is the lesson that I keep relearning.
     
  19. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    You have all probably heard about the way in which too much magnesium can cause diarrhoea. This is apparently caused by osmotic pressure.

    In a healthy gut salt is concentrated outside the gut and water is pulled through to join it. If you have more magnesium than you can absorb the magnesium stays in the gut and holds some water with it.

    Sorbitol and manitol are sugars that healthy people cannot absorb and can therefore do the same trick and cause osmotic diarrhoea.

    They would not be able to do this is we had the enzymes needed to break them down into absorbable carbohydrates. We would instead absorb them and they would bring their water with them.

    Lactose is only able to cause diarrhoea in who cannot break it down with enzymes expressed on their brush borders.

    Source http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/diarrhea.html

    So I expect that failure to produce the enzymes needed to properly digest carbohydrates could be a cause of diarrhoea in ME/CFS.
     
  20. Richard7

    Richard7 Senior Member

    Messages:
    536
    Likes:
    957
    Australia
    I get the complexity and multidimensionality, @Learner1 getting the gut right is not just about digestion and fermentation but peristalsis and other autonomic systems that I cannot get at.

    (Well save that I know that it is worse if my diet does not have enough choline, or if my PoTS is too severe.)

    But I do think that if we follow Armstrong's logic the obvious thing to do is to fashion a "crutch" that emulates a healthy person's digestion so that we might provide the right substrates to our gut and create the right environment for a beneficial microbiome.

    I think from looking around online that this may be possible using appropriate digestive enzymes. I have not yet seen a promising formulation as most of them seem to be designed to also break down fibre which I do not want to do.

    I am not sure this is possible, or rather I think it likely that it is not entirely possible but hope that I will be able to get close enough.

    I see this as a crutch that will get me on my feet and make life with ME/CFS easier to endure, not a cure to ME/CFS - though that would be nice too.
     

See more popular forum discussions.

Share This Page