Alliance To Target Muscle Problems in Chronic Fatigue Syndrome

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Progress in the U.K.

Now this is progress. Newcastle University - the home of Dr. Julia Newton- is teaming up with a hospital (Newcastle Hospital) and two Trusts (Tyne and Wear NHS Foundation Trusts) to translate scientific research findings into treatment possibilities. These Trusts employ more than 6,000 staff and serve a population of approximately 1.4 million people. The Trusts are listed as mental health and disability trusts but the focus is going to be on common age-related chronic diseases, such as dementia and musculoskeletal disease, cancer and diseases that affect the brain.

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[/fright]It's always good when academia and medicine get tied at the hip but here's the kicker: the publicity release featured their work on chronic fatigue syndrome.

"Partnership tackles Chronic Fatigue Syndrome"

There was no downplaying the seriousness of ME/CFS. The news release stated that chronic fatigue syndrome "causes crippling fatigue, often with severe muscle pain that does not go away, and can create long-term disability." It related the case of a professional who "went from being a fully independent working mum, to becoming dependent on my partner to look after me and my 2 daughters in the space of two weeks."

Having a professional become mysteriously disabled in two weeks is not exactly a recipe for a psychological disorder.

For this to happen in the land of CBT and GET seems like pretty much of a jaw-dropper but maybe not. The ME/CFS Community is very active in the UK and Dr. Julia Newton has been doing some stunning work.

First she found that people with ME/CFS produced twenty times more acid in their muscles during exercise than normal. That little abnormality piqued Dr. Newton's interest so much that she took some muscle biopsies, grew them in the lab and then examined the biochemical changes that took place during exercise.

AMPK - Cellular Energy Regulator May Not Be Working in Chronic Fatigue Syndrome

"AMPK is a major cellular energy sensor and a master regulator of metabolic homeostasis." Zang et. Al.
Just this year Newton found greatly impaired production of an enzyme called AMP Kinase (AMPK) and a cytokine (IL-6) involved in AMPK activation. Described as a cellular energy sensor and metabolic regulator AMPK, AMPK activation switches the body from being in an energy consuming to an energy producing state.

AMPK activation has shown to have effects similar to those shown in endurance training (increased fatty acid oxidation (ATP production), glucose transport and glycogen content) as well as muscle mitochondrial gene activity.

AMPK ensures that proper ATP levels are present in our cells are. As ATP declines during say, exercise, AMPK triggers more ATP production. AMPK should, therefore, be activated in the muscles during exercise but when Newton whacked the muscle cells from ME/CFS patients with exercise, she found no evidence of AMPK activation.


AMPK is not just any enzyme. It's getting enormous attention because of the central role it plays in so many processes. One review article stated AMPK has "umpteen downstream targets whose phosphorylation mediates dramatic changes in cell metabolism, cell growth, and other functions." It's most well-known because of the role it plays in type II diabetes but is being examined in a host of other illnesses. AMPK deactivation, for instance, is believed to contribute to the muscle weakness seen in chronic obstructive pulmonary disease (COPD).

In type II diabetes AMPK deactivation contributes to "metabolically inflexible" muscles that become unable to switch between glucose and fatty acid metabolism. (Fatty acid metabolism is part of the aerobic energy cycle.) Researchers refer to the deficiencies in skeletal muscle mitochondrial capacity found in type II diabetes as "mitochondrial overload".

The mitochondria need to have oxygen to produce ATP and it appears that AMPK helps out there as well by helping to increase blood flows to the muscles. That's an intriguing connection given the reduced blood flows some studies suggest may occur in the muscles and brains of ME/CFS patients.

A thyroid connection may be present as well. Noting the similar symptoms found in low thyroid production and AMPK disorders Hardie found that thyroid treatment increased AMPK activity. Hypothyroidism appears to be quite common in ME/CFS.

An inflammation connection is present as well. Work in chronic obstructive pulmonary disease (COPD) indicates that AMPK activation releases anti-inflammatory cytokines.

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[/fleft]ME Research UK (MERUK) recently pointed out that this wasn't the first time AMPK was postulated to play a role in ME/CFS. Over ten years before Dr. Newton found AMPK problems in ME/CFS Dr. Grahame Hardie at a MERUK Workshop talk in 2003 ( "Management of cellular energy by AMPK " suggested AMPK problems might be present in ME/CFS. Hardie noted that AMPK gets (or should get) switched on when any cellular stressor (hypoxia, heat shock, glucose deprivation) that increases ATP consumption or inhibits it occurs.

Diabetes and Fatigue

Chronic fatigue syndrome is not diabetes but fatigue is one of the more disabling symptoms in diabetes. It turns out that high blood glucose slows the delivery of oxygen and nutrients to the cells.

If one woman's comment is typical post-exertional malaise may be present in diabetes as well:

"Fatigue is a constant and I have had to learn to do only what I can. I don’t push myself anymore as I pay for it dearly."
Another comment was very ME/CFS-like:

" I sleep very little now for the past 7 or eight years and simply get by with rest. My exercise is almost nil ....as I am too fatigued most of the time. I never feel refreshed or rejuvenated after doing absolutely nothing. When I arise, I feel just as tired as when I went to bed."
Several people with diabetes reported that supplements regularly used in ME/CFS and FM such as glutathione, CoQ10, B-12 and alpha lipoic acid have helped. Others, however, who found that exercise was quite helpful clearly have a different kind of illness.

From the Bench to the Bedside: Translational Medicine - At Last

It's one thing to find an abnormality. It's quite another to test for possible solutions for it. Dr. Nancy Klimas recently noted one of the pitfalls of ME/CFS research has been a lack of follow through. The IOM panel she was on found many intriguing findings that they couldn't use in their report because they were never validated. Despite a positive outcome the research for whatever reason simply stopped.

That's not happening in this case. Dr. Newton stated that the new Allliance will allow her to carry out experiments to determine if the AMPK problems found in ME/CFS can be reversed. She hopes that these experiments will ultimately form the foundation for clinical trials. She called the new Alliance "an exciting step towards that holy grail of trialing medicinal products."

Advocates have been working hard for many years in the UK and it looks like some of their efforts are paying off. Despite the years the UK government has devoted to making the conversation about ME/CFS about behavior the physiology just keeps leaking out.

When a hospital, two major Trusts and a University in the U.K. team up and use an abnormality in ME/CFS muscle physiology as an example of the breakthroughs they expect to produce, ME/CFS is clearly making strides.

Increasing AMPK Levels

Two factors - type II diabetes and obesity - are driving the interest in AMPK right now. AMPK activators are, in fact, being advertised an anti-obesity supplements.

If reduced AMPK synthesis is validated in chronic fatigue syndrome the interest in the enzyme should prove helpful. A variety of treatments that can enhance AMPK production in the laboratory have been identified. Most haven't made it clinical trials; the Clinicaltrials.gov lists studies involving metformin, resveratrol, activamp, omeprazole and fish oil but the sheer variety of possibilities is encouraging.

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[/fright]With regards to drugs two of the main classes of Type II diabetes drugs, the biguanides (e.g., metformin) and the thiazolidinediones (e.g., rosiglitazone) have been shown to activate AMPK. Metformin's ability to enhance AMPK production results in reduced glucose production in the liver and reduced insulin resistance in the muscle.

Many other possibilities exist and new ones are being published almost monthly. Just last month a mice study found that the theaflavins found in black tea increased AMPK levels, oxygen availability (VO2) and energy expenditure for 12 hours. The researchers undoubtedly slammed the mice with theaflavins and the study noted that the bioavailability of theaflavins (their ability to penetrate to the tissues) is low - but the study points to a possible future avenue of drug development.

Another recent study found that a flavinol, rutin, increased AMPK activity in obese mice by 40% (and reduced their weight). Other studies in the past six months have reported that novel complexes from marine alginate, a Chinese medicine called Jinlada, and a drug called Dibenzoylmethane (DBM) have all increased AMPK activity.

The short fasting periods and ketogenic diets Courtney Craig has found success with both appear to increase AMPK levels.

The Self-Hacked website lists an enormous number of possible AMPK enhancing compounds - all with scientific citations. Some of them include berberine, R-Lipoic Acid, Quercetin ,Glucosamine, Resveratrol, Curcumin, Extra Virgin Olive Oil, Cod liver/Fish Oil , Anthocyanins, Cannabanoids, Cinnamon, Astragalus, Reishi, Apple Cider Vinegar, Creatine, CoQ10 , Bitter melon ,Gynostemma, etc. Some such as ALA may decrease hypothalamic AMPK and increase skeletal muscle AMPK.

Some of these may be counter-productive. Berberine, for instance, increases AMPK activation by inhibiting mitochondrial functioning - thus triggering AMPK to activate ATP pathways. If exercise isn't activating AMPK in ME/CFS then berberine might not be a good idea.

Most, if not all of these studies, are focused on increasing AMPK activity in type II diabetes - an immense problem facing health systems world-wide. Whether they might assist the kind of AMPK problems found in ME/CFS, of course, is unclear. Dr. Newton is apparently working on that now.
 
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Cort

Founder of Health Rising and Phoenix Rising
Staff member
Excellent news - and practical stuff we can do now!
My only worry with that is that AMPK activation appears to be very complex and different treatments may target different parts of its pathway. It sounds like its worth giving targeted treatments a try with the proviso - that who knows? :)
 
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minkey

New Member
My only worry with that is that AMPK activation appears to be very complex and different treatments may target different parts of its pathway.
I would like the team to look at ways of increasing blood flow I think this is a huge issue . It seems that the more I do both physical and cognitively, blood flow decreses maybe blood vessels constrict/ I know someone who is on Nimodipin (spelling?) and they are able to get out and about every day- not cured but 80%
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
I would like the team to look at ways of increasing blood flow I think this is a huge issue . It seems that the more I do both physical and cognitively, blood flow decreses maybe blood vessels constrict/ I know someone who is on Nimodipin (spelling?) and they are able to get out and about every day- not cured but 80%
I've got to do a blog on Nimodopine or whatever the heck it is called. Thanks for the reminder. With the recent Fluge and Mella paper and now this blood flow issues are looking more and more like a crucial element.
 

Katie

Active Member
Yes, very exciting news. However we acquire ME eg. viral etc. I'm quite interested in the above theory regarding AMPK activation/deactivation and its involvement in the energy cycle. I've always believed something like this is going on in our systems, we're not getting enough energy into our cells (O2 transportation etc.) and we in turn feel this lack of energy throughout our body. I imagine all systems, circulatory, respiratory, digestive etc. suffer from this faulty system involving AMPK and ATP and mitochondrial energy production and blood flow/volume control. Wow, it makes so much sense. No wonder we feel so horrible. Scary too if all our cells are not functioning properly then our organs, heart, stomach, lungs, kidneys etc are not receiving the proper energy for cellular health (function). Hmmmm, I'm not as excited as I first was (I wrote myself out of my excitement) :)
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Yes, very exciting news. However we acquire ME eg. viral etc. I'm quite interested in the above theory regarding AMPK activation/deactivation and its involvement in the energy cycle. I've always believed something like this is going on in our systems, we're not getting enough energy into our cells (O2 transportation etc.) and we in turn feel this lack of energy throughout our body. I imagine all systems, circulatory, respiratory, digestive etc. suffer from this faulty system involving AMPK and ATP and mitochondrial energy production and blood flow/volume control. Wow, it makes so much sense. No wonder we feel so horrible. Scary too if all our cells are not functioning properly then our organs, heart, stomach, lungs, kidneys etc are not receiving the proper energy for cellular health (function). Hmmmm, I'm not as excited as I first was (I wrote myself out of my excitement) :)
OMG - I wrote me out of my excitement - that made me laugh :hilarious::hilarious:

Thanks!

Whatever it is - it's not going to be pretty - functionality is pretty darn low in ME/CFS and FM...I've always thought when they figure out what's going on it's going to be a little shocking! :jawdrop:
 

Katie

Active Member
I've got to do a blog on Nimodopine or whatever the heck it is called. Thanks for the reminder. With the recent Fluge and Mella paper and now this blood flow issues are looking more and more like a crucial element.
What about people with POTS? Wouldn't we be fainting all over the place? Guess I need to wait for your blog on Nimodipine.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
What about people with POTS? Wouldn't we be fainting all over the place? Guess I need to wait for your blog on Nimodipine.
I need to do learn a lot more about Nimodipine. I know one fibro doctor uses it as the basis for her treatment plan./ POTS is interesting in that it can be caused in several ways I think.
 

tatt

Well-Known Member
several of the things mentioned are things people often suggest helped their ME - I have some quercetin that I keep forgetting to take, will try doing so more regularly and go back to drinking rooibos tea.

I love Professor Newton she just quietly gets on with showing ME has physical changes
 

Sarah R.

Active Member
Such great news that a huge UK alliance is pursuing this process that is so fundamental to energy production. Cort, your excellent, understandable coverage is REALLY highlighted in comparison to the video. A million thank yous!
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Such great news that a huge UK alliance is pursuing this process that is so fundamental to energy production. Cort, your excellent, understandable coverage is REALLY highlighted in comparison to the video. A million thank yous!
Thanks Sarah...
 

agapanthus

New Member
Thank you so much for the above, Cort. So readable and easy to follow for a non scientist. I have been wanting to know the latest on Dr Newton's work and you have provided it! I often feel I am getting too old at 63 to benefit from any research as my mitochondria are naturally deteriorating, but even if so it would be wonderful to know that the next generation get some decent help.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Thanks Agapthus but please don't think that. Yes we are all getting older - particularly us boomers - but think even if you didn't get well - think if your wellness increased 50% - how great that would be.....

Given how much you're endured - think how much you would appreciate that. I think most of us could squeeze more out of a moderate (or a major) increase in wellness than most people and who knows maybe you could get most of your health back...Who knows?
 

agapanthus

New Member
Yes, Cort, thanks for reminding me to be positive. I have been ill for 10 years, and spent the last 5 trying all kinds of things to improve, and to be fair, some of them are helping - stomach in much better shape, and immune system not as ghastly as it was. I go to a lovely medical herbalist who supports me with a variety of herbs, and this has certainly improved things a bit over time.
Sometimes it feels like feeling around in the dark but it's so good to know that there is some proper science going on even in the UK and who knows where this could lead!
 

Prashanti

Member
I've got to do a blog on Nimodopine or whatever the heck it is called. Thanks for the reminder. With the recent Fluge and Mella paper and now this blood flow issues are looking more and more like a crucial element.
I have also been wondering about the blood flow issue, especially blood flow to the brain. I notice if I am tired sometimes an aspirin will wake me up to some extent. I do think that Aspirin dialates the capillaries thus increasing blood flow. Does anyone know if that's correct?
 

Merida

Well-Known Member
I have also been wondering about the blood flow issue, especially blood flow to the brain. I notice if I am tired sometimes an aspirin will wake me up to some extent. I do think that Aspirin dialates the capillaries thus increasing blood flow. Does anyone know if that's correct?
Well, aspirin is anti-inflammatory, and inflammation results in swelling. So, perhaps the aspirin is reducing swelling. Aspirin also reduces the 'stickiness' of red blood cells. So?
 

Susan S.

New Member
Very interesting. Thanks for posting.

I took an AMPK supplement from Life Extension (whom I trust for quality) for a few months and got no detectable benefit. That would make sense if my body isn't processing AMPK correctly in the first place.

However, I do a weekly IV of a modified Myers Cocktail (otherwise known as banana bags) which is all nutrients and get a weekly IM injection of B-12. The improvement is subtle, but every time I stop doing it weekly, I start going downhill in energy. The theory is that the nutrients put directly in the bloodstream, instead of being broken down in the gut, will assist the mitochondria in going through the Krebbs Cycle and thus improve ATP production. Not sure if that's what's happening, but for me, it seems to work.
 

greg hay

Active Member
I took ampk activator also. Useless.
Berberine and.ALA are best...with chromium picolnate.
I eat a high carb diet now and keeps me at a decent 7-8/10.
The extra blood glucose helping to get more glucose into cells.
Other great tools are aspirin and phosphotylserine.
I believe cortisol and cortisol spikes are the cause of poor ampk activation and therefore low cellular uptake.
Work in progress.
 

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