Mitochondrial dysfunction - mainstream view in CFS or not?

[peggy-sue]

Depression is a serious disorder, resulting from breakdown of biochemical pathways, there is a specific test fro measuring it - the dexamethasone supressor test, Phoenix Down.

I'm firmly in the camp that thinks mitochondrial problems are at the root of this disease. Didn't the electron micrographs Elaine de Fritas took show a virus - IN the mitochondria?

 

[voner]

Hey Rich (or anyone)...... What is Dr englander's opion on mito dysfunction?

 

[MDL]

At the most recent IACFS/ME confererence in early 2009, mito dysfunction came up a few times in the course of the talks there, but the only one who really focussed on it was Norman Booth, who presented the paper by himself, Myhill and McLaren-Howard. At least the conference committee allowed this to be presented orally, rather than being relegated to the poster session.

Hi Rich,
I presented a poster at the 2009 Conference titled "Hypothesis: Chronic Fatigue Syndrome is caused by problems of hydrogen sulfide metabolism and results in mitochondrial dysfunction". I also published a hypothesis in 2008 titled "Hypothesis: Chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism". You are familiar with the extensive paper I wrote in 2007 "Hypothesis: Chronic Fatigue Syndrome, Mitochondrial hypo-function, and Hydrogen Sulfide" prior to the publication of the abbreviated hypothesis. I also presented testimony to the federal CFSAC committee on October 28, 2008 on my hypothesis. It can be found online.

In my poster presentation at 2009 conference, I raised the questions of whether an increase in hydrogen sulfide inhibits mitochondrial utilization of oxygen and whether our bodies are using hydrogen sulfide (H2S) to seek redox equilibrium. I asked how a mitochondrial myopathy or enzyme deficiency related to sulfur metabolism might affect this proposition, as well as the effect of a possible increase in sulfate-reducing or sulfide-producing bacteria in the gut. I also suggested that diet was critical and that B-12a in the form of hydroxocobalamin (as you know, methylcobalamin was the preferred form at that time) could serve as an antidote to cytotoxicity.

Norman Booth et al's recent work, particularly relating to cytochrome c oxidase and its role in the electron transport chain (which I focused on in my work as a key mechanism), is very exciting. There is also a lot of other tremendously important work being done on unlocking the mechanisms of the mitochondria and energy which may well have pervasive effects on human disease. However, as liquid sky rightly points out, CFS/ME may not begin with the mitochondria, although the genetic predispositions we bring to the disease process are certainly tied to our mitochodrial dna.

My thinking of late has been much influenced, or I should say, reinforced by the findings of the Human Microbiome Project. There is so much focus on the gut and finally, its relationship to the brain. There is no doubt in my mind that hydrogen sulfide plays a significant role in that relationship and that the make-up of the gut bacteria, particularly those oxygen-hating anaerobic bacteria in the deeper recesses of the colon which thrive on hydrogen-sulfide, will eventually be found to play a significant role in many diseases under certain circumstances.

I don't want to give the impression that H2S is a bad thing, as it plays absolutely critical roles as a signaling molecule and neuromodulator, among others. It is all about balance. I was very pleased to see that Dr. Jamie Deckoff is attacking the diet using the specific carbohydrate approach, which targets the harmful bacteria in the gut. Did you know that Vitamin B-12 is produced by gut bacteria and serves as an antidote to H2S?

All the best,
Marian

 

[MDL]

"Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production."

As a follow on to my previous comment, this evidence pertaining to mitochondria and hydrogen sulfide is very much on point. Basically, they are restating my hypothesis and confirming it, but also elucidating the mechanism by which the hydrogen sulfide moves into the mitochondria. I think this is pretty solid ground and very important. Please see" http://www.ncbi.nlm.nih.gov/pubmed/22323590

 

[richvank]

"Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production."

As a follow on to my previous comment, this evidence pertaining to mitochondria and hydrogen sulfide is very much on point. Basically, they are restating my hypothesis and confirming it, but also elucidating the mechanism by which the hydrogen sulfide moves into the mitochondria. I think this is pretty solid ground and very important. Please see" http://www.ncbi.nlm.nih.gov/pubmed/22323590

Hi, Marian.

I'm confused by this abstract. I don't have the full paper, but the abstract seems to be saying that H2S increases the ATP output of the mitochondria. I have been under the impression that it blocks the mitochondria and causes "torpor."
Wasn't your hypothesis arguing in the opposite direction from what this abstract is reporting? Or is it a matter of how much H2S is present? When the dysbiotic bacteria in the gut are pouring out more H2S than can be catabolized by the cells lining the gut, so that it enters the blood and is excreted in large quantities in the urine, I don't think this is helping the ATP output of the mitochondria. They must be referring to smaller amounts.

Best regards,

Rich

 

[MDL]

Hi, Marian.

I'm confused by this abstract. I don't have the full paper, but the abstract seems to be saying that H2S increases the ATP output of the mitochondria. I have been under the impression that it blocks the mitochondria and causes "torpor."
Wasn't your hypothesis arguing in the opposite direction from what this abstract is reporting? Or is it a matter of how much H2S is present? When the dysbiotic bacteria in the gut are pouring out more H2S than can be catabolized by the cells lining the gut, so that it enters the blood and is excreted in large quantities in the urine, I don't think this is helping the ATP output of the mitochondria. They must be referring to smaller amounts.

Best regards,

Rich

 

[richvank]

Hi, Marian.

Did part of your post get lost?

Rich

 

[alex3619]

Depression is a serious disorder, resulting from breakdown of biochemical pathways, there is a specific test fro measuring it - the dexamethasone supressor test, Phoenix Down.

I'm firmly in the camp that thinks mitochondrial problems are at the root of this disease. Didn't the electron micrographs Elaine de Fritas took show a virus - IN the mitochondria?

Hi peggy-sue, I once asked Kenny de Meirleir about mitochondrial viruses. He said he and others had looked but had been unable to confirm it. I wonder though how easy it would be to spot if you could not properly stain the virus? Bye, Alex

 

[peggy-sue]

Electron micrographs require the sample to be "plated" with a metal, not stained, with a dye, Alex. Electron micrographs bounce electrons off the sample - not light.

 

[alex3619]

Electron micrographs require the sample to be "plated" with a metal, not stained, with a dye, Alex. Electron micrographs bounce electrons off the sample - not light.

Hi peggy sue, that is the problem. Cutting edge light microscopy with antibody fluorescent staining might well be much better. Electron microscopy is more about form, not about selective staining. When I say staining I mean antibody staining - that way you can light up specific types of viruses, athough first you would have to lyse the mitochondria. Thus we could select antibodies matching known or suspected mitochondrial viruses (I don't know of any, but hey) and they would show very well. In the convoluted interior of a mitochondria conventional electron microscopy might not be the best too. Bye, Alex

 

[peggy-sue]

Very good point, Alex!

 

[MDL]

Hi, Marian.

Did part of your post get lost?

Rich

Rich, sorry about leaving the thread hanging. I started to respond but had to run off to the airport to pick up my daughter. She is the one who was so profoundly ill with ME/CFS that she had the worst tilt table results ever recorded at a very important hospital, among other findings. If she got on an airplane, she suffered horribly for days afterwards. No longer. I am happy to report that she is flourishing, exercising at peak performance levels and about to enter graduate school, so there is hope!

 

[richvank]

Rich, sorry about leaving the thread hanging. I started to respond but had to run off to the airport to pick up my daughter. She is the one who was so profoundly ill with ME/CFS that she had the worst tilt table results ever recorded at a very important hospital, among other findings. If she got on an airplane, she suffered horribly for days afterwards. No longer. I am happy to report that she is flourishing, exercising at peak performance levels and about to enter graduate school, so there is hope!

Hi, Marian.

That's great news! Wonderful! How did she turn things around?

Best regards,

Rich

 

[MDL]

Hi, Marian.

That's great news! Wonderful! How did she turn things around?

Best regards,

Rich

It's a very long story, but basically, we did everything we could do, short of going on extensive rounds of antibiotics and antivirals. Diet was key, particularly when she gave up dairy, gluten and sugar. The biggest improvement came when she gave up dairy several years ago, along with other things she was allergic/sensitive to which were identified in the ELISA/LRA test by Dr. Russell Jaffe. She ate and continues to eat fairly simple, mostly organic food, but increased her protein intake dramatically. She also did small bits of exercise, walking down the street, then around the block-- whatever she could handle. (It is important to get oxygen flowing into the body. Even meditational deep breathing will help when you can't move.) We rid her bedroom of any possible allergen, knowing that indoor air is usually much worse that outdoor air. She did only one thing a day, then gradually added a second. She got a weekly massage for many years. She also implemented a nasal cleansing program at the suggestion of Dr. Alex Chester. We can't attribute her recovery to any single thing. It was a very slow process over six and a half years and we were often is despair, but her story, at least, has turned out well.

All the best,
Marian

 

[*GG*]

Hi, Marian.

That's great news! Wonderful! How did she turn things around?

Best regards,

Rich

I concur, that's awesome! Please share what more you can, so others can get some improvements also.

GG

PS Not even sure what country you are in, so what you are dealing with in a medical system is unknown.

 

[MDL]

Hi, Marian.

I'm confused by this abstract. I don't have the full paper, but the abstract seems to be saying that H2S increases the ATP output of the mitochondria. I have been under the impression that it blocks the mitochondria and causes "torpor."
Wasn't your hypothesis arguing in the opposite direction from what this abstract is reporting? Or

is it a matter of how much H2S is present? When the dysbiotic bacteria in the gut are pouring out more H2S than can be catabolized by the cells lining the gut, so that it enters the blood and is excreted in large quantities in the urine, I don't think this is helping the ATP output of the mitochondria. They must be referring to smaller amounts.

Best regards,
Rich

While the article requires careful reading, the findings closely track many of the points I have made in building my hypothesis; they strengthen the case for hydrogen sulfide as a legitimate focus for research into the underlying mechanisms of ME/CFS.

In broad terms, the authors appear to conclude that H2S has a positive effect under a negative condition (hypoxia), a condition which, they acknowledge, could have been caused by H2S to begin with. The fact that H2S steps in and takes over to keep the mitochondria going under stress conditions answers the very question I posed in my 2009 poster:

“Are our bodies using H2S to seek redox equilibrium, drawing on an ancient capability conserved in the mitochondria to utilize H2S as a substrate to obtain energy?”

Wang et al conclude:
“Our results suggest that H2S may function as an energy substrate to sustain ATP under stress conditions.“

Further:
“By sensing the oxygen levels in mitochondria, H2S regulates ATP production under different conditions, thereby fulfilling the roles of an oxygen sensor and a regulator of energy metabolism.” These finding may help deepen and widen our understanding of fundamental sulfur metabolism and the regulation of mitochondrial energy metabolism in eukaryotes.”

As I said, this is solid ground—and probably paradigm-shifting in terms of our understanding of how our bodies operate. To answer your question about gut bacteria, of course, they figure prominently in the calculus, although there are many ways in which H2S can be dysregulated in the body. A favorite phrase regarding H2S is "The amount counts."

Rich, I am glad you asked the questions. Knowing of your interest in sulfur metabolism, I think you will agree that this is important.

All the best,
Marian

 

[MDL]

I concur, that's awesome! Please share what more you can, so others can get some improvements also.

GG


PS Not even sure what country you are in, so what you are dealing with in a medical system is unknown.

Hi GG,
The following is something I wrote privately a couple of years ago to someone in this forum. I would add that diet and specific probiotics appropriate to your gut composition and problems, not a general formulation, are important. Glutamate is an issue for many people and is hidden in a variety of products. The vitamin and mineral supplements are a whole separate topic. The green juice I mentioned below is just one of hundreds, and it is important to know your allergies and sensitivities before diving into any diet, of which there are many. For example if you are histamine sensitive, you will want to avoid tomatoes. You may also have nasal issues--H2S isn't confined to the gut. A good dietician can help. I have recommended the Metametrix ION Profile test in the past as a baseline, but it is expensive. The CDSA is also really important. So, here's the message from two years ago:

"We live in a toxic world...

I can only tell you what I have learned the hard way. The body needs oxygen, which I believe can be diminished by H2S.

Briefly, you may want to begin by focusing on ways to reduce inflammation/free radicals in the body in order to improve your immune status. Fatigue can be caused by many things: look closely at allergies/sensitivities, yeast, mold and bacteria. You must have clean air and clean, organic food. Ha--this is not very easy! Gluten, casein and sugar are very problematic. Raw, chlorophyll-filled greens are essential. Grow your own if you can in soil rich with healthy microbes. Antibiotics and anti-fungals may be necessary (very likely, I think) depending on the results of a CDSA. If so, favor the natural remedies and make sure your physician understands something about appropriate probiotics, as antibiotics of all sorts are a double-edged sword, and could be the reason many of us are here to begin with. Your amino acids may be out of kilter. You may also lack the ability to absorb nutrients because of small intestinal bowel overgrowth. One thing that I have found incredibly helpful is to consume a fresh green juice (a couple of carrots, half a head of romaine or endive, several stalks of celery, and lots of fresh spinach) with the B-Complex vitamins to activate the natural folate. Much safer, I think. Helps with motility, often a problem in CFS, and gives trace elements as well. I use an Omega Juicer to avoid spoiling the enzymes with heat. At first you may not be able to tolerate much, but gradually you will be able to build up. Sometimes the massive doses of b vitamins and folic acid can break through the cycle, but the underlying dietary and H2S issues will likely remain- in waiting. Beyond that, there may be genetic polymorphisms to contend with, but I would start with the things you can do at home before going that complicated route. Last, I don't know the extent of your illness, but getting some fresh air each day and maybe doing a little bit of walking and deep breathing will help to regulate your autonomic nervous system and may even clear brain lesions, depending on the type of breathing- "

I hope this helps-
Marian

 

[alex3619]

Just to let people know about six months ago I found a book somewhere on mitochondria and CFS, not sure how much they look at ME. I didn't buy it as it was very expensive, and now I have misplaced the reference. This is an academic text, not a lightweight read, and has chapters on nitrosative and oxidative stress plus methylation. I wish I could recall details. If I find it again I will update this post. Bye, Alex

 

[JT1024]

Very interesting info... I definitely believe mitochondrial dysfunction is implicated in ME/CFS and Fibro.

I had recently posted this on another forum:

Mitochondrial myopathy presenting as fibromyalgia: a case report
Mishal Abdullah, Sahana Vishwanath, Amro Elbalkhi and Julian L Ambrus Jr*
J Med Case Reports. 2012; 6: 55.
Published online 2012 February 10. doi: 10.1186/1752-1947-6-55

Abstract

Introduction: To the best of our knowledge, we describe for the first time the case of a woman who met the diagnostic criteria for fibromyalgia, did not respond to therapy for that disorder, and was subsequently diagnosed by biochemical and genetic studies with a mitochondrial myopathy. Treatment of the mitochondrial myopathy resulted in resolution of symptoms. This case demonstrates that mitochondrial myopathy may present in an adult with a symptom complex consistent with fibromyalgia.

Case presentation: Our patient was a 41-year-old Caucasian woman with symptoms of fatigue, exercise intolerance, headache, and multiple trigger points. Treatment for fibromyalgia with a wide spectrum of medications including non-steroidal anti-inflammatory drugs, antidepressants, gabapentin and pregabalin had no impact on her symptoms.

A six-minute walk study demonstrated an elevated lactic acid level (5 mmol/L; normal < 2 mmol/L). Biochemical and genetic studies from a muscle biopsy revealed a mitochondrial myopathy. Our patient was started on a compound of coenzyme Q10 (ubiquinone) 200 mg, creatine 1000 mg, carnitine 200 mg and folic acid 1 mg to be taken four times a day. She gradually showed significant improvement in her symptoms over a course of several months.

Conclusions: This case demonstrates that adults diagnosed with fibromyalgia may have their symptom complex related to an adult onset mitochondrial myopathy. This is an important finding since treatment of mitochondrial myopathy resulted in resolution of symptoms.

 

[JT1024]

In addition,

XMRV Global Action posted this on Facebook:

XMRV Global Action shared Clare A. Keefe's photo.
One of the important document which has been kept in the UK National Archives, locked until 2072. One would wonder why on earth the UK would keep this information from the public? Share far and wide.