Advances in Understanding the Pathophysiologyof Chronic Fatigue Syndrome (Komaroff, 2019)

[percyval577]

It always amaze me how much the ICC criteria are resisted here. Maybe because then some would fall out of the grid? is it fear?

Interestingly I meet the ICC only after my improvement has begun to take place, whereas before I met only the CCC [now some food sensitivity had/has become "noticible", sometimes a strange heartbeat showes up]. Complicate matters at work, I guess.

Diseases are often not strictly seperated from normal conditions. Very little decays in the teeth may be repaired by the body, mutations of cells that eventually can result in cancer take place normally. On the other hand there might be diseases like Huntington or maybe MS which show abnormality already in their begin.

It would be easily possible to interpretate our disease as an exaggerated mechanism that rather takes place normally. Why are symptoms non-specific? Because it would be a normal mechanism, only that it would have become laughable high (or low) driven. This does not say that there couldn´t built up new feelings (for sure such feelings occure).

So, in this case it wouldn´t be a surprise that there is an overlap to other diseases and to normal bad feelings. It also would easily explain why there is not only a sudden onset (mostly after viral infections) but also a gradual one (maybe e.g. after vaccination?).

I personally think that it´s a feeling-ill mechanism, and for certain, I think, there must be such a mechanism (though it has not been identified). Such a mechanism would explain the non-specificity and the wide range of symptoms, the different onsets from physiological impacts, and possibly an influence on physiological things (assuming a feedback regulation).

 

[Wishful]

I personally think that it´s a feeling-ill mechanism, and for certain, I think, there must be such a mechanism (though it has not been identified). Such a mechanism would explain the non-specificity and the wide range of symptoms, the different onsets from physiological impacts, and possibly an influence on physiological things (assuming a feedback regulation).

I was thinking last night that it's rather pointless to argue about whether it feels like fatigue or exhaustion, or whatever else, since our feelings are subjective. According to one report, we have a 'fatigue nucleus' which controls our feeling of fatigue. This likely has multiple direct inputs (neurons, hormone receptors, cytokine receptors, etc) and multiple indirect factors (blood pH, oxygen and CO2 concentration, local nutrient availability, etc), and our responses to each of these factors are as individual as a fingerprint. How our bodies respond to the outputs of this nucleus vary individually too. When ME messes up some of these factors, we're going to respond to them in different ways, and interpret the feelings in our own way. What one person interprets as fatigue, another may interpret as exhaustion or malaise or something else.

We may have a fatigue nucleus, and pain brakes, and various other bits of neural processing that form our feelings, all of which can be affected in individual ways by ME. Tests based on subjective feelings are probably going to provide fairly useless results. The wording of how the questions are asked would probably create a large bias in the results.

 

[percyval577]

I was thinking last night that it's rather pointless to argue about whether it feels like fatigue or exhaustion, or whatever else, since our feelings are subjective.

I think well that there is a regularity in normal behaviour. Beings can start to act, and after some time they might be able to have a high awareness, but then after some time the concentration declines, and if you carry on with doing you will do mistakes, regardless if you are a human, a fox, a dolphin, or even a cow (whom´s tasks are usually pretty monotonous).

You might be right, nevertheless I like to try the following scheme:

acting - exhaustion - tiredness - (sleeping) - acting - exhaustion - tiredness - ...

Assuming that this would be an intrinsic logic in animals, regardless of different concrete arrangements (slow cows vs. foxes), it might give a hint for a mechanism that could possibly be involved in our illness.

My idea would be that acting leads to a built up of synapses (because the being, if any higher, will need to learn), initially these are (in humans and ...) NMDA receptors. We also know that there is a constant flow of synapses in the brain (which is only logical, given some flexible behaviour).

Then exhaustion could be a peak on NMDAR´s (and synaptical connections), and tiredness could be disbanding of NMDAR´s (and so on). Comparable to Naviaux´s guess of a disturbed healing cycle (where different diseases may stuck at some points), we could stuck somewhere in this scheme.

We could stuck at a point before acting (a kind of sleep disease) or we could stuck at a point after acting, so this would be an exhaustion disease. And it could be explained then as to that our brain would make ever and forth new NMDAR´s.

(And in my case, I now might be compare to a long acting cow, and wouldn´d say to be exhausted, but when I was worse I might have compared to a fox after two hours of hunting or so.)


Furthermore, it is logically possible to relate this scheme to a feeling ill mechanism. However, it leads to an idea what to look for, and who knows, maybe it will prevail. In my view it´s with regard to a core of our strange illness the most plausible approach.

 

[Nanni]

I had a big picture, aha moment about this illness recently. I think that as individual as we are, with our genetic predispositions and our unique experiences we are still all governed by the same basic blueprint for a healthy body. If you damage your soft tissue the body has a whole series of responses to repair it. Same for everyone. It’s the mechanics of what the body does. For instance, 90% of a newborns neural networks will develop during the first three years of life producing a customized brain, depending on the interaction of our physiology/temperament (nature) and the environment (nurture). That’s a lot of variables but the mechanics are the same for everyone. For instance, the more the alarm system, the fight, flight, and freeze response, is activated during that critical period,the more neural networks are being activated to develop in those areas of the brain. It’s the mechanics of the brain development. I know that I have a very overdeveloped alarm system and have been very much in workaholic flight mode all my life. I say was because I can’t be a workaholic physically anymore but I can still be stressed out. There are many layers of letting go. Sometimes when I’m on this site, I can be in fight mode, fighting with the reality of this illness, like the absolutely unnerving pain I’m experiencing today. But I can also benefit from the wall I’m up against, It makes me stop and remember to breathe and then breathe again until I can get settled again. Anyway I digress, I think the hibernation theory is on to something, big picture wise. This illness maybe normal or just what the body is doing, for some of us, in order to survive. And I don’t think any of us really understand how much we stress out the body. I’ve always been a problem solver type so saying...I can do this, was my moto, Still is, to some extent, only now I know I have to acknowledge the stress and I have to do more than just use my willfulness to cope. I’m betting that, big picture wise, this illness gets back to the mechanisms for managing the healthy balance between stress and rest. It seems like there was a convergence of variables that stacked up from the top down,from the more general, a viral attack on a body that was ripe for the attack, down to the specifics of all our variations and mutations that is our uniqueness. Anyway, that was one of my 4am illuminations.

 

[Rufous McKinney]

When ME messes up some of these factors, we're going to respond to them in different ways, and interpret the feelings in our own way.

If you think about, say "headaches"...all these people get them. Don't most of us? Yet there are many many VERSIONS of headaches.

I hypothesize that there are things which can turn off or reduce the intensity of: the sickness behavior response (eg like THC).

But one is still sick.

 

[Wishful]

I hypothesize that there are things which can turn off or reduce the intensity of: the sickness behavior response (eg like THC).

But one is still sick.

The reverse hypothesis is also possible: that the sickness behaviour (or various other chronic problems) can get 'stuck' in that state, and make us feel sick, even if our bodies are otherwise functioning normally. Chronic pain seems to be a lowering of thresholds for 'feeling' pain. The 'pain brakes' can get stuck in the off state.

 

[CFS_for_19_years]

I had a big picture, aha moment about this illness recently. I think that as individual as we are, with our genetic predispositions and our unique experiences we are still all governed by the same basic blueprint for a healthy body.

If you damage your soft tissue the body has a whole series of responses to repair it. Same for everyone. It’s the mechanics of what the body does. For instance, 90% of a newborns neural networks will develop during the first three years of life producing a customized brain, depending on the interaction of our physiology/temperament (nature) and the environment (nurture). That’s a lot of variables but the mechanics are the same for everyone.

For instance, the more the alarm system, the fight, flight, and freeze response, is activated during that critical period,the more neural networks are being activated to develop in those areas of the brain. It’s the mechanics of the brain development. I know that I have a very overdeveloped alarm system and have been very much in workaholic flight mode all my life. I say was because I can’t be a workaholic physically anymore but I can still be stressed out.

There are many layers of letting go. Sometimes when I’m on this site, I can be in fight mode, fighting with the reality of this illness, like the absolutely unnerving pain I’m experiencing today. But I can also benefit from the wall I’m up against, It makes me stop and remember to breathe and then breathe again until I can get settled again.

Anyway I digress, I think the hibernation theory is on to something, big picture wise. This illness maybe normal or just what the body is doing, for some of us, in order to survive. And I don’t think any of us really understand how much we stress out the body.

I’ve always been a problem solver type so saying...I can do this, was my moto, Still is, to some extent, only now I know I have to acknowledge the stress and I have to do more than just use my willfulness to cope. I’m betting that, big picture wise, this illness gets back to the mechanisms for managing the healthy balance between stress and rest.

It seems like there was a convergence of variables that stacked up from the top down,from the more general, a viral attack on a body that was ripe for the attack, down to the specifics of all our variations and mutations that is our uniqueness. Anyway, that was one of my 4am illuminations.

Separated into readable paragraphs for those of us who can't read more than 4 to 5 lines at once. Thank you for expressing your thoughts. Hopefully there will be more to come (in readable chunks).

 

[Learner1]

I wonder how many threads must be derailed by this same debate about ME vs CFS vs SEID and whether we all have exhaustion, fatigue, malaise, neuroimmune symptoms or what, and whether we are sick according to Fukuda, ICC, CCC, or IOM criteria. Or whether we don't if we have anything that can exclude us from this disease.

Is it important to win this particular debate at a cost to whatever information was presented at the start of this or any other thread?

As pointed out by @Cort and @Mary, the significance of the Komaroff article in JAMA is that it brings long-needed attention to this illness to the general medical community from someone with credibility, and helps doctors to understand that this illness is not all in our heads and functional, somatic, or psychiatric in nature.

This should be something to celebrate!!! Wow! Attention in JAMA! Wahoo!

And, what do we do? We stomp all over it, call out our contempt for the content, the nomenclature, and even whether we are fatigued....

Truth be told, we are all individuals. None of us has the exact same disease - the same genetics, the same etiologies. the same list of symptoms, the same labs, and the same responses to treatments.

So, there is never going to be a perfect article that matches exactly each one of our illnesses. Therefore many of us will always be able to pick apart the patient selection criteria, symptoms, labs, and other data reported, because it doesn't match our specific experience with this illness.

Therefore, let's attack every thread mentioning ME/CFS or CFS if you think you only have ME or every thread mentioning ME only if you think you have CFS, or any thread that refers to fatigue, or exhaustion, or neuroimmune symptoms, or pain, or headaches... Is this what we really think is productive???

As a patient, I care about getting well. We need doctors to know about this illness/these illnesses, we need various sorts of tests and various sorts of treatments. And for this disease to be more broadly known about, so more of us can have access to doctors who are curious, willing to learn, and willing to try tests and treatments to figure out what can help us improve. So, it would seem to be productive to discuss new threads in this light and examine how news like this can help us toward the goal of more patients getting well, instead of tearing each other apart which seems a bit self-destructive as a patient community.

On my journey, it really hasn't been productive to dicker about ME or CFS or ME/CFS. None of them have gotten me tests or treatment. My doctors have found 16 other ICD10 codes that do qualify for diagnostics and treatments, which have been tremendously helpful. And, my doctors and I have also found that reading all the research articles and finding the ones that best match the description of my illness and my labs and then applying the learnings, if possible, to my situation has been driving progress. It has also been helpful to examine pros and cons of concepts in a forum like this, but that's very difficult to do if people derail each thread with debates about the correct name for the disease, the correct criteria, and the correct symptoms, which is ludicrous given the range of patients and their experiences here.

I wonder what will happen as a result of Komaroff's significant, though imperfect article... With all those views, wonder who is reading it and what conclusions they'll come to?

 

[percyval577]

... same debate about ME vs CFS vs SEID and whether we all have exhaustion, fatigue, malaise, neuroimmune symptoms or what, and whether we are sick according to Fukuda, ICC, CCC, or IOM criteria. Or whether we don't if we have anything that can exclude us from this disease.

... we are all individuals. None of us has the exact same disease - the same genetics, the same etiologies. the same list of symptoms, the same labs, and the same responses to treatments.

So, there is never going to be a perfect article that matches exactly each one of our illnesses. Therefore many of us will always be able to pick apart the patient selection criteria, symptoms, labs, and other data reported, because it doesn't match our specific experience with this illness.

After all the question what the core of our illness is can not be put aside. And without any proper understanding what the main properties are, it´s more a question of good luck to get any further clue than it is inevitable anyway.

Science must try to ask the right questions. Given the difficulty to spot the illness I find it not so unlikely that patients make major contributions. Dr Phair aka Htester said also, maybe it would be possible to establish a PR definition of PEM. If only more serious (especially "serious") people would be able to behave human like him.

I wonder what will happen as a result of Komaroff's significant, though imperfect article... With all those views, wonder who is reading it and what conclusions they'll come to?

Yes, and Komaroff ever has been very helpfull as far as I have seen.

 

[Mary]

I wonder what will happen as a result of Komaroff's significant, though imperfect article... With all those views, wonder who is reading it and what conclusions they'll come to?

Good question - it seems like this will be a drop in the bucket (okay, maybe several drops) but I think we're getting more and more drops and maybe eventually will reach a tipping point where it will suddenly be common knowledge that ME/CFS is a very real, serious and very debilitating illness, research for which has been criminally underfunded.

fwiw, I get the JAMA newsletter and got this in my inbox today ("Most Read This Week")
http://read.alerts.jamanetwork.com/csb/Public/show/axac-16sbb0--ln35o-azspmv75

Also fwiw, I think PEM (or PENE) is the hallmark of ME/CFS, and has been demonstrably proven by the 2-day CPET. Unfortunately of course most people with ME/CFS are either too debilitated to take the test or otherwise lack access, but it still is conclusive proof that we don't respond to exertion like normal people. I crashed once after watching a talk (on DVD) about cancer by Nicholas Gonzalez and the Kelly protocol. It was fascinating and I took notes, it was very intense, took a lot of mental energy for close to 3 hours. Most of my crashes are from physical exertion. But my crash felt the same, though it was from mental exertion and I am certain that if I'd done a 2-day CPET involving mental exertion instead of physical, the results would have been the same.

And of course there is the nanoneedle developed by Dr. Davis' team - I think people with ME/CFS do share a commonality (PEM/PENE) though our other symptoms vary widely, and hopefully in the near future an accessible affordable and safe means of testing for it will be available..

 

[Gemini]

Here's an article by Cort, about the JAMA article linked above:
https://www.healthrising.org/blog/2...yndrome-article-tony-komaroff-unifying-model/

@Mary Cort's article states most JAMA articles get 3-5000 views, total.

The Komaroff article is up to 46,778, that's almost 5000 per day since publication 10 days ago!

@Cort

 

[Nanni]

The reverse hypothesis is also possible: that the sickness behaviour (or various other chronic problems) can get 'stuck' in that state, and make us feel sick, even if our bodies are otherwise functioning normally. Chronic pain seems to be a lowering of thresholds for 'feeling' pain. The 'pain brakes' can get stuck in the off state.

I have wondered about that myself. Any suggestions? Sometimes I really don’t know how much I can and can’t do. I can be having a good day and over due it. Other times I’m so achey but feel like I could push myself to get to the store, and I don’t think about it but you know, I’m uncomfortable. When i first started b12 and methylation and dealt with SIBO I felt normal for a day here and there and remembered what wellness is like. So it’s confusing. I’m better but that chronic pain stuff is an obstacle.

 

[Nanni]

I wonder how many threads must be derailed by this same debate about ME vs CFS vs SEID and whether we all have exhaustion, fatigue, malaise, neuroimmune symptoms or what, and whether we are sick according to Fukuda, ICC, CCC, or IOM criteria. Or whether we don't if we have anything that can exclude us from this disease.

Is it important to win this particular debate at a cost to whatever information was presented at the start of this or any other thread?

As pointed out by @Cort and @Mary, the significance of the Komaroff article in JAMA is that it brings long-needed attention to this illness to the general medical community from someone with credibility, and helps doctors to understand that this illness is not all in our heads and functional, somatic, or psychiatric in nature.

This should be something to celebrate!!! Wow! Attention in JAMA! Wahoo!

And, what do we do? We stomp all over it, call out our contempt for the content, the nomenclature, and even whether we are fatigued....

Truth be told, we are all individuals. None of us has the exact same disease - the same genetics, the same etiologies. the same list of symptoms, the same labs, and the same responses to treatments.

So, there is never going to be a perfect article that matches exactly each one of our illnesses. Therefore many of us will always be able to pick apart the patient selection criteria, symptoms, labs, and other data reported, because it doesn't match our specific experience with this illness.

Therefore, let's attack every thread mentioning ME/CFS or CFS if you think you only have ME or every thread mentioning ME only if you think you have CFS, or any thread that refers to fatigue, or exhaustion, or neuroimmune symptoms, or pain, or headaches... Is this what we really think is productive???

As a patient, I care about getting well. We need doctors to know about this illness/these illnesses, we need various sorts of tests and various sorts of treatments. And for this disease to be more broadly known about, so more of us can have access to doctors who are curious, willing to learn, and willing to try tests and treatments to figure out what can help us improve. So, it would seem to be productive to discuss new threads in this light and examine how news like this can help us toward the goal of more patients getting well, instead of tearing each other apart which seems a bit self-destructive as a patient community.

On my journey, it really hasn't been productive to dicker about ME or CFS or ME/CFS. None of them have gotten me tests or treatment. My doctors have found 16 other ICD10 codes that do qualify for diagnostics and treatments, which have been tremendously helpful. And, my doctors and I have also found that reading all the research articles and finding the ones that best match the description of my illness and my labs and then applying the learnings, if possible, to my situation has been driving progress. It has also been helpful to examine pros and cons of concepts in a forum like this, but that's very difficult to do if people derail each thread with debates about the correct name for the disease, the correct criteria, and the correct symptoms, which is ludicrous given the range of patients and their experiences here.

I wonder what will happen as a result of Komaroff's significant, though imperfect article... With all those views, wonder who is reading it and what conclusions they'll come to?

I’m so sorry that what I shared was so misconstrued. Totally not the point i was going for. I have to air my subjective experience to get another point of view which I appreciate. Very important input. And that’s the gift of this site for me.

 

[Wishful]

I have wondered about that myself. Any suggestions?

It's one thing to have a vague hypothesis that seems to fit. It's another to know how to figure out a treatment.

For 'how much can I do safely', that's a matter of self-experimentation. We don't have nice clear numerical internal readings, so you just have to accept that you're working from vague guesses, and that the answer is going to vary day to day due to factors you aren't aware of. So, make a guess as to how much you've done and how much you might have left, and err on the side of caution. I overdid it a few days ago, and am still feeling the effects, so I have one more example to base further--hopefully wiser--judgements on.

Some treatments for ME work really well, and let you feel healthy again, and even let you believe that you've finally solved the problem...but then the treatment stops working and never works again. That's just how ME works. Our bodies seem to adapt to some treatments and return to the abnormal state, which does kind of fit the 'dauer state' hypothesis.

As for pain, have you tried LDN? It was really effective for me, but there is no 'guaranteed to work for everyone' treatment for ME, so you'd have to try it for yourself. It's such a low dosage that doctors shouldn't be too reluctant to write a trial prescription.

 

[Nanni]

It's one thing to have a vague hypothesis that seems to fit. It's another to know how to figure out a treatment.

For 'how much can I do safely', that's a matter of self-experimentation. We don't have nice clear numerical internal readings, so you just have to accept that you're working from vague guesses, and that the answer is going to vary day to day due to factors you aren't aware of. So, make a guess as to how much you've done and how much you might have left, and err on the side of caution. I overdid it a few days ago, and am still feeling the effects, so I have one more example to base further--hopefully wiser--judgements on.

Some treatments for ME work really well, and let you feel healthy again, and even let you believe that you've finally solved the problem...but then the treatment stops working and never works again. That's just how ME works. Our bodies seem to adapt to some treatments and return to the abnormal state, which does kind of fit the 'dauer state' hypothesis.

As for pain, have you tried LDN? It was really effective for me, but there is no 'guaranteed to work for everyone' treatment for ME, so you'd have to try it for yourself. It's such a low dosage that doctors shouldn't be too reluctant to write a trial prescription.

Thanks for the info. I have heard about the getting well reverting back phenomena but I guess I thought just more tweaking of a protocol or something was needed. I’m grateful to understand what’s been going on. A little depressed I guess. As far as LDN i wish... I have to take pain medication already for nerve damage from a tumor removed from my spine, the nerve root between c1 and c2. I got sick 5 years after that surgery and just after my gallbladder was removed. I do wonder about vagus nerve damage which gives me complete license to sing my heart out. Lol. Supposed to stimulate the v.n.

 

[Wishful]

There's no way to know absolutely for sure that a treatment that stops working can't be somehow made to work again, but in my experience and that of many others here, treatments stop working and won't work again. It is depressing when it stops working, but at least it showed that you can feel better: it's not permanent degradation, but rather something that can be reversed fairly quickly. We just need to figure out how to maintain the restoration of normal function.

If you haven't tried LDN, read up about it. It's supposed to work by tricking our cells to produce natural opiates, and is considered a viable option for chronic pain.

 

[Learner1]

Our biochemistry is a complex set of reactions. If inputs for a reaction are short, a bottleneck occurs.

It makes sense that if a bottleneck exists due to such a dhortahe, that adding the midding ingredient helps open it up. And, that will go splendidly until you run out of one or more of the other cofactors needed by the same reaction. That will stop the benefit.

But, if you can figure out which cofactors are imidfing and add them, you can get the reaction giing again. Voila!

Then, once that is working great, the system moves on to the next reactions in the cascade, which may have also bern bottlenecks, waiting gor the first reaction to get going. If one or more of these reactions is missing a cofactor, they won't work, but the reactions that hsve sufficient cofactors will work just fine.

This explains many of the mysteries you were expressing.

Even though there's a fairly wide tolerance for most of these reactions, it is hard to get every single nutrient we neef adequately in our diets. Take magnesium - 70% of Americans are deficient in it. That's just one nutrient.

And, when we have infections, toxins, and disease processes goung in, we have increased demands for certain nutrients - in some cases, many times what is normal.

The ME/CFS researchers have found this - amino acids, B vitamins, antioxidants, minerals, and phodpholipids have all found to have increased demand in ME/CFS.

So, the answer is to ensure one is replete in each nutrient, with an eye to which ones csn be toxic if overdone, while realixing that getting 100% of the DV is not hoing to be nearly enough in many cases.

In my case, I need 10mg B12, 350mg of B6, and 250mg of riboflavin daily, ehich are huge amounts, but I was chronically deficient until I increased to those doses. And I need 1.8-2g/kg of amino acids, far more than is recommended for a healthy person. If I get less, my total protein drops, and lab values of other things dependent on various aminos drop, too, which supports ehst Fluge and Mella found.

Testing will solve many of these mysteries and allow you more control over your destiny.

 

[Nanni]

Our biochemistry is a complex set of reactions. If inputs for a reaction are short, a bottleneck occurs.

It makes sense that if a bottleneck exists due to such a dhortahe, that adding the midding ingredient helps open it up. And, that will go splendidly until you run out of one or more of the other cofactors needed by the same reaction. That will stop the benefit.

But, if you can figure out which cofactors are imidfing and add them, you can get the reaction giing again. Voila!

Then, once that is working great, the system moves on to the next reactions in the cascade, which may have also bern bottlenecks, waiting gor the first reaction to get going. If one or more of these reactions is missing a cofactor, they won't work, but the reactions that hsve sufficient cofactors will work just fine.

This explains many of the mysteries you were expressing.

Even though there's a fairly wide tolerance for most of these reactions, it is hard to get every single nutrient we neef adequately in our diets. Take magnesium - 70% of Americans are deficient in it. That's just one nutrient.

And, when we have infections, toxins, and disease processes goung in, we have increased demands for certain nutrients - in some cases, many times what is normal.

The ME/CFS researchers have found this - amino acids, B vitamins, antioxidants, minerals, and phodpholipids have all found to have increased demand in ME/CFS.

So, the answer is to ensure one is replete in each nutrient, with an eye to which ones csn be toxic if overdone, while realixing that getting 100% of the DV is not hoing to be nearly enough in many cases.

In my case, I need 10mg B12, 350mg of B6, and 250mg of riboflavin daily, ehich are huge amounts, but I was chronically deficient until I increased to those doses. And I need 1.8-2g/kg of amino acids, far more than is recommended for a healthy person. If I get less, my total protein drops, and lab values of other things dependent on various aminos drop, too, which supports ehst Fluge and Mella found.

Testing will solve many of these mysteries and allow you more control over your destiny.

Great info. Thanks. Which tests do you think are most helpful if you have limited resources?

 

[Nanni]

is there a list somewhere about which cofactors are important for which supplements?

 

[Rufous McKinney]

The reverse hypothesis is also possible: that the sickness behaviour (or various other chronic problems) can get 'stuck' in that state, and make us feel sick, even if our bodies are otherwise functioning normally

Its possible, but does not compute here. The hibernating bear is not experiencing Horrific Internal Poisoning. Bear may come to and feel hungry, or groggy, or have slow return of muscle function...all understandable.

Is the hibernating bear's gut biota sick? Doubt it. Is the permeability of gut and brain: increased in hibernating bear? Why would it be?

Its hard for me to identify any aspect of this body which is: functioning normally.

Last night I ignored the Sickness Response Messages. I went out anyway. The level of horrible I feel today is a type of POISONED.