End ME/CFS Severe Patient Study Turns to the Mitochondria

[Paw]

Zapped, I know you're mainly responding to the rhetoric and logic of someone's specific post, but I'm interested in why emotions sometimes run so high around a topic like this. Several times I've been surprised when I share my own experiences of my own body, only to have someone angrily say it's not true -- as if I had been insisting that they apply my story to themselves.

This is an entirely different topic, but perhaps worthy of debate sometime: My guess is that some people react in such a knee-jerk way because they believe any discussion that hints of psychological or non-biological bases for our illnesses could provide fodder for critics out there who aren't particularly empathetic to our plight. Again, I'm only guessing here, but I have heard some of us basically say there's no good place for such discussion, as it could lead to blaming, less funding for research, etc. In other words, they're adhering to a political stance.

As I said earlier in this thread, my own stance is that there are countless routes to these illnesses, and the more we understand the differences and similarities of all the variables the better we'll understand possible treatment options, etc. To rule out an entire thread of investigation seems counter-productive medically, and not particularly useful politically. But that's just my opinion.

I don't have to "blame" myself in order to look back at the events that brought me to my present state. But even if I could pinpoint a bunch of things that I might have done differently (e.g., handled my stress better?), the fact remains that, right now, I am dealing with demonstrably physiological consequences. Any theories or ruminations about the past are solely for the purpose of better understanding my current maladies. I certainly don't point toward stress as a sole cause. What rings most true to me is that there was a veritable smorgasbord of factors conspiring together to make me sick, and, yes, one of those factors could certainly have been a virus.

 

[Merida]

I appreciated Cort's comment - ie that before onset of CFS I had little or no anxiety, depression, etc. There has been something about this disorder that has made me interpret my environment differently. Now, just getting off the couch is stressful.

Interesting that mice infected with Toxoplasma interpret their environment differently from normal mice. The infected mice now are attracted to cat urine, instead of being repulsed by it. This makes the infected mice more likely to be eaten, and then the Toxoplasma can complete its life cycle in the cat. Crazy S - --.

I also do not like to hear that this is may be stress induced disorder. It just makes me feel 'bad' - like I may not be a competent human who can deal with Life. We have all struggled too much to go to this type of "mindset."

I do think that we are different in some basic ways, though. Think we belong to a super sensitive group - can feel the complex energies that surround us, have way above average intuition, can sense things that are coming up, can feel others' emotions, and more. Is that true???

 

[Snow Leopard]

The problem with the "stress" hypothesis is that it is so non-specific as to be meaningless.

Many people in our society suffer from psychological stress but most do not develop ME or CFS. There are some who suffer from psychological stress or depression or anxiety some time after onset but not before. There are some who suffered from such before onset, but not while ill with ME or CFS and there are some who suffered from such before onset, during illness and even after recovering.

Unless you can predict who is likely to develop ME or CFS (or recover!) with a high specificity* based on some sort of measurement along these lines, then I am not interested in these vague "stress causes ME or CFS" hypotheses.

*By that, I mean without a huge false-positive rate.

 

[Paw]

The problem with the "stress" hypothesis is that it is so non-specific as to be meaningless.

Many people in our society suffer from psychological stress but most do not develop ME or CFS. There are some who suffer from psychological stress or depression or anxiety some time after onset but not before. There are some who suffered from such before onset, but not while ill with ME or CFS and there are some who suffered from such before onset, during illness and even after recovering.

Unless you can predict who is likely to develop ME or CFS (or recover!) with a high specificity* based on some sort of measurement along these lines, then I am not interested in these vague "stress causes ME or CFS" hypotheses.

*By that, I mean without a huge false-positive rate.

I know I've said this, but, again, I'm not invested in persuading others to share my own interest in this. But, as an open forum, anyone who is interested should be able to discuss the topic without it being mischaracterized. I don't recall anyone here advancing the hypothesis that "stress causes ME or CFS" -- a framing that, of course, would rankle nearly everyone.

And, respectfully, I can't wrap my brain around why I keep seeing the argument that most people who suffer from stress "do not develop ME." It's an argument against a position that I don't think anyone is advancing ("stress causes ME"). Not everyone exposed to herpes develops Alzheimers, but leading researchers are currently finding it fruitful to explore the possibility of viral connections.

Finally, as has been mentioned, stress has demonstrable (if not fully understood) chain reactions in the body that, if better understood, could indeed lead to new treatment insights for a variety of diseases. That, for me, is my bottom-line interest in the topic. So it's not just some sort of historical scab I life to pick at.

I do think that we are different in some basic ways, though. Think we belong to a super sensitive group - can feel the complex energies that surround us, have way above average intuition, can sense things that are coming up, can feel others' emotions, and more. Is that true???

Ha, there was a time as a young adult I might have identified with that description, but now my brain feels much less fine-tuned.

But I've long thought a comprehensive survey of wide-ranging traits like this might yield some interesting trends within our community. Just for fun though though -- not to prove psychological causation!!

 

[Merida]

@Paw
In spite of my thoughts about stress and the development of CFS, there are only two people in support group that got well - I led a large group for 13 years. One evening a young man ( 40 ish) came to the meeting and told his story. He had had 2 pages of neuro/ autonomic / fatigue symptoms, which developed following an episode of back pain after pushing a piano. Out of work several years. Found John Sarno's books ( The Divided Mind, etc) and read them. Over the course of a month he got well - no pain, symptoms gone. Now, he is head of a successful company. Says he must be careful with stress, has occasional minor relapses , which clear up quickly.

So I ordered the Sarno DVD program and we all watched it, read Sarno's books. Well, amazingly, one young woman ( age 20), who had disabled student status, listened to what the young man was saying, talked with him, read Sarno's Healing Back Pain. One month later she informed us that she was well. Raynaud's syndrome had resolved, as well as fatigue, pain, multiple symptoms.

She was well several years later, but had a minor relapse after taking a very stressful job. Quit the job, got well.

I did the whole Sarno program, but did not get well. So, I just don't know what to think. Perhaps our minds and intentions are very powerful, and are capable of healing us. The Divided Mind, by John Sarno, is worth reading. Also, there are interviews with Sarno on You tube.

 

[Merida]

One more interesting story: One year ago I went to South El Monte, CA to have a session with Grandmaster Zhou - " the Jewel of China" , " the Healer's Healer." He speaks no English, so there was an interpreter. He did a one hour ' qi gong' massage. Was very serious.

After the session I asked ( through interpreter), " why have I been sick for so long, and have so many symptoms? "
He smiled and said, " You are a kind and generous person. You gave away your energy." I was completely floored.

I then asked, "What can I do to get better and stay well? " He said, " Try to breathe."

 

[RuthAnn]

I am looking forward to this thread returning to discussion of mitochondrial issues.

 

[Merida]

Okay, does anyone have their lactate dehydrogenase values? My enzyme values are consistently 60 to 70 per cent of normal. This enzyme quantity is under strict genetic control. Lack of LDH is one of the several glycogen storage disorders - number 11, I believe. Very little research.

LDH converts lactate to pyuvate and back, as well as NAD+ to NADH and back. The pyruvate is then chemically converted to several possible compounds, which then enter the citric acid cycle, where we get our big ATP production. When oxygen is in short supply, LDH converts pyruvate to lactate, with a small amount of energy production. Of course, this is a self limiting process, as lactate builds in tissues.

It is interesting that red blood cells have no mitochondria, and depend on LDH 1 ( these are 5 main isoenzymes for LDH) to convert pyuvate to to lactate, which yields some energy. The red blood cells use none of the oxygen they carry. Thus, could an LDH deficiency affect red blood cell activity ? No research on this that I have found.

So, LDH -1 is of critical importance to red blood cells and their activity. Mitochondria are not even involved.

Parvoviruses ( like B19 - which I have) can infect the precursor cells to mature red blood cells, and cause some anemia.

The biochemical apparatus is so complex that it takes research experts to address the possibilities.

 

[RuthAnn]

Judging from the results I am having from consistently taking biotin, I am thinking I must have something wrong with biotinidase function.

Biotin is important for heme production in Complex , and if heme isn't produced it causes a severe problem in Complex IV.

http://www.ncbi.nlm.nih.gov/pubmed/17182796

BD caused heme deficiency; there was a decrease in heme content and heme synthesis, and biotin-deficient cells selectively lost mitochondrial complex IV, which contains heme-a. Loss of complex IV, which is part of the electron transport chain, triggered oxidant release and oxidative damage, hallmarks of heme deficiency. Restoring biotin to the biotin-deficient medium prevented the above changes.

Besides causing heme deficiency, one would see a build up of iron.

"Heme, the major functional form of iron, is synthesized in the mitochondria. Although disturbed heme metabolism causes mitochondrial decay, oxidative stress, and iron accumulation, all of which are hallmarks of ageing, heme has been little studied in nutritional deficiency, in ageing, or age-related disorders such as Alzheimer's disease (AD)"

I think this might set one up for chronic lung infections, as at least two pathogens that I know of replicate on iron.

Also, "Moreover, biotin-deficient cells exhibited an increased susceptibility to oxidative damage in response to stress."

 

[Zapped]

Zapped, I know you're mainly responding to the rhetoric and logic of someone's specific post, but I'm interested in why emotions sometimes run so high around a topic like this. Several times I've been surprised when I share my own experiences of my own body, only to have someone angrily say it's not true -- as if I had been insisting that they apply my story to themselves.

This is an entirely different topic, but perhaps worthy of debate sometime: My guess is that some people react in such a knee-jerk way because they believe any discussion that hints of psychological or non-biological bases for our illnesses could provide fodder for critics out there who aren't particularly empathetic to our plight. Again, I'm only guessing here, but I have heard some of us basically say there's no good place for such discussion, as it could lead to blaming, less funding for research, etc. In other words, they're adhering to a political stance.

Your reasoning sounds plausible to me. IOW, expanding it further, PWCs who pursue stress as cause might be concerned that others will think they are wimps or at least not as tough as those who don't get it yet suffer stress?

I would venture a guess that if they think stress is not key just ask them to get in the car and sit in traffic for an hour,
maybe with the radio up full tilt, while it's raining and their plane leaves in 1'10"; or physiologically, tie a rope around
their waist with the other end to a horse and have a 10" pulling contest; or lastly, mostly psychologically, have a neighbor
tell them his King Cobra got out of its Aquarium and he last saw it under their house - 3 days ago!

Any PWC experiencing such stress would no doubt crash - bad! At that point ask him/her about the
role of stress in their lives.

While the above are just illustrative exaggerations of after-the-fact stressors, I believe there is a 'tipping point' prior to CFS where
stress damages the mitochondria and from there CFS is ON! How to measure that or test it empirically has been the
subject of much debate. Electricity comes to mind but that's artificially induced. As stated earlier, the same measuring
problems exists as to identify art, pain, and other amorphous entities. Therefore, they get relegated to the 'later'
category, sic after we find the 'real' cause.

Forget a PWC; force a well person sleep in a house thinking there's a King Cobra or Black Mamba somewhere therein will
develop illnesses directly related to the time of exposure (even if s/he only thinks there's a 10' venomous reptile loose in
their house)... .

So it goes. Because we can't as yet get to these entities in quantitative form they are deferred
in favor of more reachable factors, which to date have gotten us nowhere but better treatment of
symptoms and we PWCs becoming more expert in detail on what is already known... .

 

[RuthAnn]

Another very good link to information about biotin.

http://www.ncbi.nlm.nih.gov/pubmed/26168302

Regulation of immunological and inflammatory functions by biotin.


Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear protein involved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.
KEYWORDS:

 

[Cort]

There is an important article in Advances in Virology, Vol. 2013, article 738794:, Viruses as Modulators of Mitochondrial Function by SK Anand and SK Tikoo ( Canadian researchers). " Viruses either induce or inhibit various mitochondrial processes in a highly specific manner so that they can replicate and produce progeny."
" Viruses like Herpes Simplex virus 1 deplete the host mitochondria DNA . . . "

I would sure hope that the ME/ CFS researchers would call in some of these experts.

Courtney Craig has a really interesting blog on this. Here's what she says with regard to EBV. I had no idea it could do this...

• http://www.drcourtneycraig.com/blog/2015/7/5/5-ways-viruses-declare-war-on-your-mitochondria

Intracellular Mutiny

Many viruses induce the generation of free radicals (unstable molecules with unpaired electrons) to indirectly help them survive in the host cell. Within the cell, mitochondria are especially vulnerable to increasing oxidative stress; which can overwhelm their protective mechanisms. An onslaught of free radicals damages the mitochondrial membrane making it “leaky” and subject to complete rupture.
Some viruses, like Epstein-Barre, utilize the intracellular chaos of free radicals, to thrive. Within 48 hours, EBV hijacks the cell and initiates free radicals. Latent infection can be reactivated by continued oxidative stress. These radicals activate viral genes in EBV which signal virions to bud from the cell and reactivate the infection.

 

[Cort]

The problem with the "stress" hypothesis is that it is so non-specific as to be meaningless.

Many people in our society suffer from psychological stress but most do not develop ME or CFS. There are some who suffer from psychological stress or depression or anxiety some time after onset but not before. There are some who suffered from such before onset, but not while ill with ME or CFS and there are some who suffered from such before onset, during illness and even after recovering.

Unless you can predict who is likely to develop ME or CFS (or recover!) with a high specificity* based on some sort of measurement along these lines, then I am not interested in these vague "stress causes ME or CFS" hypotheses.

*By that, I mean without a huge false-positive rate.

I really reject the idea that stress causes this illness. It just does not fit in my experience.

Both axes of the stress response in the body - the HPA axis and the ANS - on the other hand have problems in ME/CFS. I imagine that these problems contribute to the situation where small stressors - such as exercise, the wrong foods, bad things that happen - have much greater than usual effects. I don't mean those effects are debilitating necessarily but they are physically obvious and they didn't use to be. Some small thing happens, for instance, and I feel it in my body - usually in a small way and sometimes in a bigger way. That didn't use to happen.

The stress response systems don't know how to handle stuff so well anymore....

 

[Paw]

One more interesting story: One year ago I went to South El Monte, CA to have a session with Grandmaster Zhou - " the Jewel of China" , " the Healer's Healer." He speaks no English, so there was an interpreter. He did a one hour ' qi gong' massage. Was very serious.

After the session I asked ( through interpreter), " why have I been sick for so long, and have so many symptoms? "
He smiled and said, " You are a kind and generous person. You gave away your energy." I was completely floored.

I then asked, "What can I do to get better and stay well? " He said, " Try to breathe."

Wow, that's such a moving story, Merida. Amazing. I wonder if the Grandmaster's suggestion brought you some deeper breaths. I could use some of those too. Nice to have someone like that be so accepting of you and your body. Must have helped you accept yourself more.

I don't know about gi gong massage (although I've seen gi gong practice). But a few years ago a reiki master worked over my whole body -- with absolutely no touch -- and the release was so intense I was literally bawling.

One evening a young man ( 40 ish) came to the meeting and told his story. He had had 2 pages of neuro/ autonomic / fatigue symptoms, which developed following an episode of back pain after pushing a piano. Out of work several years. Found John Sarno's books ( The Divided Mind, etc) and read them. Over the course of a month he got well - no pain, symptoms gone. Now, he is head of a successful company. Says he must be careful with stress, has occasional minor relapses , which clear up quickly.

I bookmarked Sarno. Thanks, sounds interesting. But it's funny, in my case I was able to reorder my life to remove most of that chronic stress. But that was three or four years ago, and I'm still sick. I'll keep delving into possible causes and cures (including, perhaps, the divided mind), but at least it's nicer being sick with very little noticeable stress. I honestly don't know how people survive when they don't have the luxury of rearranging their lives around this illness.

 

[Paw]

While the above are just illustrative exaggerations of after-the-fact stressors, I believe there is a 'tipping point' prior to CFS where
stress damages the mitochondria and from there CFS is ON!

This "tipping point" rings true from my experience. Although I had many disparate symptoms for decades, I was churning along as usual until one day I suddenly got systemically sick and never recovered. Thought maybe I'd had a stroke. It's clear to me something physiological just broke that day.

 

[IrisRV]

PWCs who pursue stress as cause might be concerned that others will think they are wimps or at least not as tough as those who don't get it yet suffer stress?

Nope. I imagine others would think those PWCs have a very real psychosomatic illness. They have real physical symptoms originating from a mental or emotional cause. That's what you're saying, isn't it, that ME (real physical symptoms) is caused by stress (mental or emotional cause)? That makes ME psychosomatic. I don't buy it.

psychosomatic in MedicineExpand
psychosomatic psy·cho·so·mat·ic (sī'kō-sō-māt'ĭk)
adj.

1. Of or relating to a disorder having physical symptoms but originating from mental or emotional causes.

So people with genuine physical symptoms similar to ME caused by stress have a psychosomatic illness by definition. The treatment for psychosomatic/somatoform illnesses is CBT.

The focus of treatment is on improving daily functioning, not on managing symptoms. Stress reduction is often an important part of getting better. Counseling for family and friends may also be useful.
Cognitive behavioral therapy may also help relieve symptoms associated with somatoform disorders.

People with ME symptoms caused by non-psychological conditions (genetics, pathogens, injury, toxins) have ME. They do not have a psychosomatic illness. It's not caused by a mental or emotional condition.

That's not to say stress could not exacerbate symptoms in ME, or contribute to physical deterioration. It could in other illnesses, too. Psychological conditions may also arise out of having any of a number of severe or chronic illnesses. That's not causal. In those cases the stress is secondary or maybe a contributing factor, not the cause. If stress is causal in a patient, by definition the patient has a somatoform disorder, not ME.

 

[RuthAnn]

While the above are just illustrative exaggerations of after-the-fact stressors, I believe there is a 'tipping point' prior to CFS where
stress damages the mitochondria and from there CFS is ON!

Would be interested to know more specifics of the actual mechanism of the stress induced mitochondrial damage. And I suppose since we are talking about CFS, it would have to be a nonrelenting damage.

 

[Zapped]

Nope. I imagine others would think those PWCs have a very real psychosomatic illness. They have real physical symptoms originating from a mental or emotional cause. That's what you're saying, isn't it, that ME (real physical symptoms) is caused by stress (mental or emotional cause)? That makes ME psychosomatic. I don't buy it.

So people with genuine physical symptoms similar to ME caused by stress have a psychosomatic illness by definition. The treatment for psychosomatic/somatoform illnesses is CBT.

People with ME symptoms caused by non-psychological conditions (genetics, pathogens, injury, toxins) have ME. They do not have a psychosomatic illness. It's not caused by a mental or emotional condition.

That's not to say stress could not exacerbate symptoms in ME, or contribute to physical deterioration. It could in other illnesses, too. Psychological conditions may also arise out of having any of a number of severe or chronic illnesses. That's not causal. In those cases the stress is secondary or maybe a contributing factor, not the cause. If stress is causal in a patient, by definition the patient has a somatoform disorder, not ME.

Stress causes real ulcers, heart disease, and X other tangible disorders in humans. Lack of sun exposure results in certain D-3 disorders. I would not
see a doc who thinks these illnesses are soma and that the treatment is CBT... .

BTW, in the news recently has been the debate over the use of 'waterboarding', which in my mind is turning up the stress knob. However, others argue
it is 'torture' and has damaging affects, eg akin to CFS... .

 

[Paw]

IrisRv, we may be splitting hairs here, since we agree that stress sometimes may well be a contributing factor. Not speaking for anyone else, but that's all I've ever been saying.

This illness seems way too convoluted to point to any one factor as entirely causal. Even if one can establish a clear "triggering factor," that's not the same thing as a factor that's uniquely causal. Otherwise, as so many here have pointed out, why doesn't everyone exposed to that trigger find themselves debilitated by ME?

But this statement (and its context) does make me a little uncomfortable:

People with ME symptoms caused by non-psychological conditions (genetics, pathogens, injury, toxins) have ME. They do not have a psychosomatic illness. It's not caused by a mental or emotional condition.

I understand your objective is probably to make sure there's no doubt about the fact that your illness is in no way "psychosomatic." Fine. But the flip side of that statement, in effect, sets you up as a gatekeeper of a disease notorious for its diverse manifestations and causes -- and difficulty to define. Paradoxically, it could make some people feel like you're telling them precisely what you most hate others telling you: that they're not really sick (at least not in the same category that you are).

Since ME is not like, say, diabetes -- a disease fairly clearly defined by one's blood-sugar data -- it's not possible (or, I would argue, helpful) to suggest that so-and-so who is wrestling with the complexities of CFS -- trying to make sense of possible past exposures to pathogens or toxins, their genetics, their injuries, and, sometimes, yes, their psychological proclivities -- should maybe consider hanging out on some CBT forum instead of here. I know you didn't say that, but an unintended consequence of your stance could be a certain divisiveness.

Perhaps, one day, researchers will figure out how better to dichotomize these definitions. But, until then, can we go easy on the gatekeeping?

 

[RuthAnn]

The subject of this thread being mitochondrial issues and their relationship to ME/CFS of course can include stress induced damage to mitochondria, but I would think that those who wish to tie in stress induced mitochondria issues to ME/CFS should try to show the area of the mitochondria affected and the way the stress induced the sustained damage. It's easy to theorize that stress has a place in induction of ME/CFS, but that's not what this thread is about, it's about showing how mitochondria are affected so that a possible remedy can be applied.