Mitochondrial and Energy Metabolism Dysfunction in ME/CFS — Myhill, Booth and McLaren-Howard Papers

[Learner1]

So in the MBM 2012 study, it says:

Possible sources of blocking agents are byproducts of viral or bacterial pathogens, cellular debris due to oxidative damage, and some environmental chemicals. Results from molecular level fluorescence microscopy, and the identification of the blocking agents by Micro Raman Spectroscopy and Fourier Transform Infrared Spectroscopy, will be the subject of a further paper.

The paper ends saying a future paper will come out giving clinical relevance for treatment. Have either come out?

I've had 3 docs who know CFS very well tell me that there aren't really any useful tests for mitochondrial function. I took it to mean that they wouldn't really know what to do with the results if they had them.

How can we know if we're group A or B? And, how do we know what the blocking agents are? I had the Acumen test and nothing significant was stuck to my DNA. I've done a lot of detoxing. Will treating viral/bacterial pathogens help remove remaining blocks?

What's blocking? What substrates are needed? Myhill's mito cocktail helps but doesn't solve things.

And why does Naviaux say there's nothing wrong with the mitochondria? It sure seems like there is. My doctors believe that fixing the other problems will fix my mitochondria...

So, is there any clinical info to help us (and is it worth paying for any of these tests?). How do we:

1. Figure out if our mitochondria are just dysfunctional or really damaged?
2. Figure out if we're pattern A or B
3. Figure out what's blocking them
4. Find a solution to make them work do we have normal energy

Laughable, I know... But what's the status of the above?

 

[Valentijn]

I've had 3 docs who know CFS very well tell me that there aren't really any useful tests for mitochondrial function. I took it to mean that they wouldn't really know what to do with the results if they had them.

Last month I had an appointment with a clinician from a genetic mitochondrial diseases clinic, and he seemed to think there are plenty of ways to find indications of mitochondrial dysfunction. Presumably many of the same indications would be present regardless of the cause of the mitochondrial dysfunction.

And why does Naviaux say there's nothing wrong with the mitochondria?

He or others might have tested blood for genetic mitochondrial mutations. But in the case of a genetic mitochondrial disease with adult-onset, the mutations are much more likely to be in the muscles, and blood is pretty much the last place you'll find them.

 

[Learner1]

Last month I had an appointment with a clinician from a genetic mitochondrial diseases clinic, and he seemed to think there are plenty of ways to find indications of mitochondrial dysfunction. Presumably many of the same indications would be present regardless of the cause of the mitochondrial dysfunction.

Yes, I'd seen you'd been to a mito specialist and your account of the experience was similar to what I'd heard from doctors and patients at the United Mitochondrial Disease Foundation Conference I attended last year.

During the researcher presentations they had little charts showing which complex of the mitochondria were misbehaving in lab environments.

Patients were going around asking each other which complex was malfunctioning. They all knew as they'd all had the very expensive genetic testing to learn which of the 200 or so genetic mutations known to cause various primary mitochondrial diseases.

Most of the patients there had multiple affected family members and many had tragically lost children due to mito disease.

I learned about mitochondrial biopsies, where they punch holes in your thigh and see how the mitochondria are. it seemed to be the only way to know how they are doing, and its painful and not something you want to do a lot of.

After sitting through it, speaking with the doctors and patients there, and following up with a doctor who'd been there, I concluded I probably had secondary mito dysfunction as I seem to have an energy budget problem.

But I've been frustrated that no one seems to know how to produce the little charts I saw the researchers show for a real patient and notes Petri dish. The MBM charts are similar, but my doctors feel it wouldn't change my treatment even if I spent the money to do the tests... I'm already on a mito cocktail with the stuff Myhill and the doctors at the conference use.

He or others might have tested blood for genetic mitochondrial mutations. But in the case of a genetic mitochondrial disease with adult-onset, the mutations are much more likely to be in the muscles, and blood is pretty much the last place you'll find them.

That's right. Hence the muscle biopsy.

I've had cancer. Cancer cells have defective mitochondria, which can't do OXPHOS, they can only use glycolysis. Cancer is a metabolic disease, where cells under too much stress (as in Naviaux's CDR?) end up with genes that are stressed and start to mutate. Tumors are made of mosaics of differently mutated cells, depending on what for stressed most in each cell.

There is an overlap between cancer and ME/CFS. Having stressed mitochondria is not a good thing. I know my mitochondria are stressed, and don't behave like they're supposed to and I worry about getting another cancer.

I don't think I have primary mitochondrial disease, but wish there was an easier (and repeatable) test to figure out what's malfunctioning, fix it, and recheck. Obviously removing the stessors and providing an environment that encourages health will help while not adding any new stressors.

But I'm still confused by Naviaux's statements that the mitochondria are fine.

 

[ljimbo423]

But I'm still confused by Naviaux's statements that the mitochondria are fine.

My understanding of Naviaux saying that, is that he means they are not permanently damaged. Once you remove the stressor, they should work normally. Which is good news!

 

[Hip]

But I'm still confused by Naviaux's statements that the mitochondria are fine.

The mitochondria in ME/CFS probably are physically fine; that is to say, there is no inherited genetic diseases and dysfunction of the mitochondria, and in most cases, there is probably no acquired genetic damage to the mitochondria (except in Gulf War Illness, where there may be organophosphate-induced mitochondrial genetic damage).

But in spite of the mitochondria being physically fine in ME/CFS, there is evidence that some eternal factor may be blocking or down-regulating the functioning of mitochondria.

One tweet about Fluge and Mella's findings indicates these researchers think the immune system may producing anti-mitochondrial autoantibodies that are disabling the mitochondria.

So in ME/CFS, the physical machinery of the mitochondria is fine, but when these autoantibodies (which are floating around in the blood) bind on the mitochondria, it throws a spanner in the works, such that these mitochondria can no longer function properly.

An analogy would be having a car which is in perfect physical condition, but then someone sticks a potato in the exhaust pipe, and creates a blockage in the system which prevents the car from performing properly.


If you look at this thread, it details the ANT autoantibody, which targets and throws a spanner in the works of the mitochondria in patients with coxsackievirus B infections of the heart muscle.

In these viral heart muscle infections, the mitochondria are unable to perform properly, because the ANT autoantibody (triggered by the virus) attacks the mitochondria and prevents them from functioning normally (even though these heart mitochondria are physically fine).

Prof Peter Behan suggested that this ANT autoantibody (or a similar mitochondria autoantibody) might be a cause of the mitochondrial dysfunction of ME/CFS as well.

 

[Learner1]

Once you remove the stressor, they should work normally.

I'm not convinced. That may be true for some people, but I don't think its a blanket statement that applies to all. The trouble is how we can know which group we're in.

And, as 1 out of 2 men and 1 out of 3 women will get cancer and most diseases are related to dysfunctional mitochondria, it is wrong to assume all of ours are fine.

As a stage 3 cancer survivor (and I was diagnosed at 52 in the best shape of my life with extremely healthy habits) I learned that damaged mitochondria are a key feature of cancer. And currently, I'm at a high risk of lymphoma and liver cancer and working to minimize risks. And I know my mitochondria are stressed.

It would sure be nice to have a little more info to guide treatment decisions. I'd like to know the quality of my mitochondrial membranes, which complex(es) are struggling, and what, if any interventions can be made to improve things.

The good news is that mitochondria are recycled every 6-8 weeks or so. And as long as we have more good ones than bad ones, things should be ok. But there's a tipping point. We can also encourage more to grow through exercise and PQQ and we can encourage the recycling if good ones by ensuring the right ingredients are in place. We can also encourage more ATP production by ensuring the right ingredients are available for the process as well as for the building if high quality membranes.

There a lot that can go wrong and it's far from effective clinical practice...

 

[Learner1]

Prof Peter Behan suggested that this ANT autoantibody (or a similar mitochondria autoantibody)

So, where's the test and what's the treatment for that? And what would the other autoantibodies be and how do you test and treat them?

And, how do we know if, like the Gulf War veterans, we don't have organophosphates or other toxins damaging our mitochondrial DNA?

 

[Valentijn]

The mitochondria in ME/CFS probably are physically fine; that is to say, there is no inherited genetic diseases and dysfunction of the mitochondria ...

I don't think that has been proven. Existing studies have only involved blood samples, which would miss the heteroplasmic mutations more likely to be present in adult onset.

And one which did look at mitochondrial DNA from blood actually involved a lot of mutations implicated in mitochondrial disease, at about 10x the frequency found in the general public. Unfortunately the researchers in that study seemed to be working from a very short list of mutations and did not bother to consult OMIM, and retested blood to exclude an unknown number of definite disease-causing mutations that did turn up.

To know definitively if there is or isn't mitochondrial genetic involvement, we need a muscle biopsy study with well-defined ME patients.

 

[Hip]

I don't think that has been proven.

Yes, in ME/CFS, we don't know for sure whether there is mitochondrial genetic damage or not. As you pointed out on this thread, there are some claims of mitochondria genetic damage in ME/CFS, but I believe you view these claims to be quite flimsy at present.

However, we can look at this from another angle: if you look at Dr John Chia's work treating ME/CFS with interferon, this treatment was able to put many patients into full remission, for periods of up to 14 months (then most patients relapsed). That suggests that there is no mitochondria damage in ME/CFS (or at least in the subset that recovered via interferon), because if there were, you would not expect patients to go into full remission from an antiviral treatment like interferon.

And in the metabolic findings of Fluge and Mella, they found that healthy muscle cells (myoblasts), when exposed in vitro to the blood serum of ME/CFS patients, developed energy metabolism alterations, including excessive lactate secretion. So healthy mitochondria go wrong as soon as they are exposed to the blood of ME/CFS patients.

So this again supports the idea that the mitochondria in ME/CFS are likely physically and genetically in reasonably good shape, but that there is some mitochondrial blocking agent (eg an autoantibody) in the blood of ME/CFS patients that thwarts mitochondrial functioning.


If your ME/CFS was associated with organophosphate exposure, though, then I guess there might be more chance of some genetic damage to the mitochondria. My own case of ME/CFS was preceded by a major chronic organophosphate exposure.

Gulf War Illness is thought most likely to be cause by organophosphate exposure, and mitochondria genetic damage has been found in GWI.

So, where's the test and what's the treatment for that? And what would the other autoantibodies be and how do you test and treat them?

You will have to read the ANT autoantibody studies if you want details on how they tested for the ANT autoantibody in these CVB myocarditis patients. I am not sure if there are any commercially available ANT autoantibody tests. There are several anti-mitochondrial autoantibodies known, and there are likely others that are unknown.

(And it does not necessarily have to be an autoantibody in the blood that is down-regulating the mitochondria; it might be some other factor in the immune system that is responsible).

There is very little treatment for CVB viral myocarditis or the mitochondrial autoimmune attack associated with it, apart from a few antivirals that may have some benefit.

And as far as I am aware, nobody has even bothered to look whether the ANT autoantibody might be present in ME/CFS, even though this autoantibody is known to be triggered by the same chronic enteroviral infections that are found in ME/CFS.

 

[ljimbo423]

Once you remove the stressor, they should work normally.

I'm not convinced. That may be true for some people, but I don't think its a blanket statement that applies to all. The trouble is how we can know which group we're in.

You make a good point, it probably doesn't apply to all. It makes sense to me, that you, as a cancer survivor, would be more aware of the potential risks of damaged or dysfunctional mito. I didn't realize that the mito were so important in cancer.

I learn something new every day! If I remember right, from some of your past posts, you are doing an awful lot to take care of your mitochondria. The only thing that comes to mind to me rate now, is what Naviaux said about NADPH in cfs patients- LINK

The Importance of Mitochondria, Redox, and NADPH Metabolism in Chronic Fatigue.
All of the metabolic abnormalities that we identified in CFS were either directly regulated by redox or the availability of NADPH.

NADPH is derived from vitamin B-3. I get 50 mg in my multivitamin, but decided to add 15-20mg a day. It gave me really good energy during the day, but at night, I was having trouble sleeping, so I stopped it.

I think I'm going to try it again at a lower dose, because the energy it gave me was smooth and consistent, during the day, not jittery like too much caffeine.

 

[Valentijn]

So this again supports the idea that the mitochondria in ME/CFS are likely physically and genetically in reasonably good shape, but that there is some mitochondrial blocking agent (eg an autoantibody) in the blood of ME/CFS patients that thwarts mitochondrial functioning.

I don't doubt that there are other ways to get to ME/CFS symptoms. In fact, genetic mitochondrial disease simply couldn't be the sole cause, due to the vastly different prevalence rates in men and women. But I don't think it's been ruled out as a cause in a substantial number of cases.

 

[Learner1]

I didn't realize that the mito were so important in cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941741/

 

[ljimbo423]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941741/

VERY enlightening article! I had no idea of the amount of overlap between how the mitochondria in cancer cells function and how the mitochondria in cfs function.

It seems everyone could benefit from taking really good care of there mitochondria, in multiple ways. Healthy mitochondria are happy mitochondria.

 

[Learner1]

Yes, in ME/CFS, we don't know for sure whether there is mitochondrial genetic damage or not. As you pointed out on this thread, there are some claims of mitochondria genetic damage in ME/CFS, but I believe you view these claims to be quite flimsy at present.

However, we can look at this from another angle: if you look at Dr John Chia's work treating ME/CFS with interferon, this treatment was able to put many patients into full remission, for periods of up to 14 months (then most patients relapsed). That suggests that there is no mitochondria damage in ME/CFS (or at least in the subset that recovered via interferon), because if there were, you would not expect patients to go into full remission from an antiviral treatment like interferon.

And in the metabolic findings of Fluge and Mella, they found that healthy muscle cells (myoblasts), when exposed in vitro to the blood serum of ME/CFS patients, developed energy metabolism alterations, including excessive lactate secretion. So healthy mitochondria go wrong as soon as they are exposed to the blood of ME/CFS patients.

So this again supports the idea that the mitochondria in ME/CFS are likely physically and genetically in reasonably good shape, but that there is some mitochondrial blocking agent (eg an autoantibody) in the blood of ME/CFS patients that thwarts mitochondrial functioning.


If your ME/CFS was associated with organophosphate exposure, though, then I guess there might be more chance of some genetic damage to the mitochondria. My own case of ME/CFS was preceded by a major chronic organophosphate exposure.

Gulf War Illness is thought most likely to be cause by organophosphate exposure, and mitochondria genetic damage has been found in GWI.





You will have to read the ANT autoantibody studies if you want details on how they tested for the ANT autoantibody in these CVB myocarditis patients. I am not sure if there are any commercially available ANT autoantibody tests. There are several anti-mitochondrial autoantibodies known, and there are likely others that are unknown.

(And it does not necessarily have to be an autoantibody in the blood that is down-regulating the mitochondria; it might be some other factor in the immune system that is responsible).

There is very little treatment for CVB viral myocarditis or the mitochondrial autoimmune attack associated with it, apart from a few antivirals that may have some benefit.

And as far as I am aware, nobody has even bothered to look whether the ANT autoantibody might be present in ME/CFS, even though this autoantibody is known to be triggered by the same chronic enteroviral infections that are found in ME/CFS.

The immune system is definitely a part of it, but there are other factors at work that impact mitochondria. Mitochondrial membranes get damaged by oxidative and nitrosative stress, making efficient ATP production a problem. This can not only be a factor but can lead to other diseases:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382850/#!po=1.55367

https://www.ncbi.nlm.nih.gov/pubmed/24557875

 

[anni66]

I think dysfunctional adrenal hormones could have an effect and may be behind strange inflammatory symptoms. Many gradual onset pwcfs report having undergone some form of stress such as bereavement or life changing events or simply burning the candle at both ends for too long before getting CFS.. This to me sounds like they could be candidates for poor functioning adrenals before onset of CFS proper. Perhaps this is linked to the infection theory or perhaps a different route to end up at the same point (high inflammation and dysfunctional mitochondria).

...... I started thinking about adrenal and flight or fight response after seeing a David Attenborough documentary the other week. Basically this tribe hunt an antelope and don't do anything in terms of attack, rather they just slowly follow the poor beast until it just lies down and dies from exhaustion. They then do a ceremonial stab with a spear for show, but basically they have used the antelopes adrenals to kill iT. I guess the point is flight or fight response is powerful thing. I wonder if the antelope escaped what it's mitochondria would be like after that experience?

Fight or flight for too long is epigenetic -cortisol going from high to low modifies gene expression -your immune system is run down, your gut chemistry is altered, vit D is compromised due to production of the binding protein being suppressed, chronic illness becomes more likely. EBV was the trigger for my daughter' s illness, but problems with bullying at school for 2 years prior to this effectively compromised her system - the severity of her symptoms may be proportional to any damage done

 

[gettinbetter]

For those of you using D ribose
Does it make you groggy ?

 

[Deepwater]

For those of you using D ribose
Does it make you groggy ?

I've been taking D ribose for years, and it generally helps all round. I was prone to groggy spells before I started taking it and I still get them, but they are intermittent and not linked to D ribose. There are things I have found cause grogginess, though - gluten consumption and summer air pollution (damp summers particularly), so currently groggy and swimmy head.

 

[Learner1]

For those of you using D ribose
Does it make you groggy ?

No, it doesn't. I've been taking it for over a year. Perhaps you don't need it otlr your grogginess is caused by something else?

I found this on Dr. Teitelbaum's site:

Our study included patients with a diagnosis of fibromyalgia or chronic fatigue syndrome who were given ribose at a dose of 5 grams three times per day for an average of three weeks. We found the ribose therapy led to significant improvement in energy levels, sleep patterns, mental clarity, pain intensity, and well being. Of the patients participating in the study, 65.7 % experienced significant improvement while on ribose, with an average increase in energy of 44.7% and overall well being of 30%—remarkable results from a single nutrient! The only significant side effects were that 2 people felt too energized and hyper/anxious on the ribose. This is simply dealt with by lowering the dose and/or taking it with food.

 

[gettinbetter]

No, it doesn't. I've been taking it for over a year. Perhaps you don't need it otlr your grogginess is caused by something else?

It really seems to be the ribose

Who uses Magnesium and Malate along with ribose ?

 

[Learner1]

It really seems to be the ribose

Who uses Magnesium and Malate along with ribose ?

I take Designs for Health magnesium malate each morning. No complaints...