A possible step forward in the treatment of chronic fatigue syndrome (CFS/ME)

This sounds encouraging. I was diagnosed with CFS & FMS nearly 4 years ago. Overnight I went from working a 40-50 hour week as an intensive care charge nurse to not being able to walk to the front door (CFS affects significant numbers of nurses and teachers). I personally prefer the term 'Central Sensitivity Syndromes' as its an umbrella term for a handful of illnesses which I believe are on a spectrum rather than being independent.

Central Sensitivity Syndromes

The following research supports the hypothesis of mitochondrial dysfunction.

Chronic fatigue syndrome is a multisystem disease that causes long-term pain and disability. It is difficult to diagnose because of its protean symptoms and the lack of a diagnostic laboratory test. We report that targeted, broad-spectrum metabolomics of plasma not only revealed a characteristic chemical signature but also revealed an unexpected underlying biology.

Metabolomics showed that chronic fatigue syndrome is a highly concerted hypometabolic response to environmental stress that traces to mitochondria and was similar to the classically studied developmental state of dauer. This discovery opens a fresh path for the rational development of new therapeutics and identifies metabolomics as a powerful tool to identify the chemical differences that contribute to health and disease.

Some background info on Metabolomics

Metabolomics has several advantages over genomics for the diagnosis of complex chronic disease and for the growing interest in precision medicine. First, fewer than 2,000 metabolites constitute the majority of the parent molecules in the blood that are used for cell-to-cell communication and metabolism, compared with 6 billion bases in the diploid human genome. Second, metabolites reflect the current functional state of the individual.

Collective cellular chemistry represents the functional interaction of genes and environment. This is metabolism. In contrast, the genome represents an admixture of ancestral genotypes that were selected for fitness in ancestral environments. The metabolic state of an individual at the time of illness is produced by both current conditions, age, and the aggregate history, timing, and magnitude of exposures to physical and emotional stress, trauma, diet, exercise, infections, and the microbiome recorded as metabolic memory.

Analysis of metabolites may provide a more technically and bioinformatically tractable, physiologically relevant, chemically comprehensive, and cost-effective method of diagnosis of complex chronic diseases. In addition, because metabolomics provides direct small-molecule information, the results can provide immediately actionable treatment information using readily available small-molecule nutrients, cofactors, and lifestyle interventions. Our results show that CFS has an objectively identifiable chemical signature in both men and women and that targeted metabolomics can be used to uncover biological insights that may prove useful for both diagnosis and personalized treatment.

One thing I have learned since being a member of ATS is to look at who is funding research. The article is on PNAS which seems to be a reputable source.

Dr. Naviaux is the founder and co-director of the Mitochondrial and Metabolic Disease Center (MMDC), and Professor of Medicine, Pediatrics, Pathology, and Genetics at UCSD. He directs a core laboratory for metabolomics at UCSD. He is the co-founder and a former president of the Mitochondrial Medicine Society (MMS), and a founding associate editor of the journal Mitochondrion. He is an internationally known expert in human genetics, inborn errors of metabolism, metabolomics, and mitochondrial medicine. He is the discoverer of the cause of Alpers syndrome---the oldest Mendelian form of mitochondrial disease---and the developer of the first DNA test to diagnose it. Dr. Naviaux's lab has developed a number of advanced technologies like biocavity laser spectroscopy and mtDNA mutation detection by mass spectrometry.

Naviaux's lab is also trying to ratify the The 28th Amendment Project which gives all Americans the right to be born into a healthy environment that does not cause chronic disease.

Naviaux Lab

Another snippet which I have broken down so as to avoid a wall of text.

Hypometabolism, Dauer, and CFS.

Our results show that the metabolic features of CFS are consistent with a hypometabolic state. Sphingolipids, glycosphingolipids, phospholipids, purines, microbiome aromatic amino acid and branch chain amino acid metabolites, FAD, and lathosterol were decreased. The decreases in these metabolites correlated with disease severity as measured by Karnofsky scores.

Much research has been done on the hypometabolic phenotype in other biologic systems, including dauer, diapause, hibernation, estivation, torpor, ischemic preconditioning, ER stress, the unfolded protein response, autophagy, and caloric restriction. Dauer, which means persistence or long-lived in German, is an example of one well-studied system.

The developmental stage of dauer is a hypometabolic state capable of living efficiently by altering a number of basic mitochondrial functions, fuel preferences, behavior, and physical features. Dauer is comprised of an evolutionarily conserved and synergistic suite of metabolic and structural changes that are triggered by exposure to adverse environmental conditions. Entry into dauer confers a survival advantage in harsh conditions.

When the dauer response is blocked by certain mutations (dauer defectives), animals are short-lived when exposed to environmental stress. These mutations show that the latent ability to enter into a hypometabolic state during times of environmental threat is adaptive, even though it comes at the cost of decreasing the optimal functional capacity. Similar to dauer, CFS appears to represent a hypometabolic survival state that is triggered by environmental stress.

The metabolic features of CFS and dauer correspond to the same pathways that characterize the acute CDR and metabolic syndrome but are regulated in the opposite direction. For example, cholesterol, phospholipids, and uric acid are often elevated in the acute CDR and metabolic syndrome, but these metabolites were decreased in CFS patients. A prediction based on these findings is that patients with CFS would be more resistant to the constellation of hypertension, dyslipidemia, central obesity, and insulin resistance that increase all-cause mortality associated with metabolic syndrome, but at the cost of significant long-term disability, pain, and suffering.

To be honest I don't have the ability to critique the study as its not my area of expertise. I am keeping my fingers crossed. If anyone does have experience in this field I would value any contribution.

Thanks,

Morrad

Metabolic features of chronic fatigue syndrome

Study Q&As

a reply to: Morrad

what does the word dauer mean?

Tired of Control Freaks

a reply to: TiredofControlFreaks

It refers to Dauer larva, an alternative developmental stage of nematode worms, particularly Caenorhabditis elegans, whereby the larva goes into a type of stasis and can survive harsh conditions.

Wikipedia

Several MSM sources who reported the findings misinterpreted this as a 'hibernation state'.

a reply to: Morrad

OK - the study is a long read but interesting. I gather that the information gathered could provide for a new technique of CFS diagnostics.

The study group is small - only 89 individuals.

But alot of work still needs to be done. Cost and ease of testing etc.

I find it interesting that CFS is compared to a dauer state. And I wonder if treatment of metabolism would be considered for CFS to overcome the environmental stress. This could also have implications for other metabolism issues (ie obesity).

My guess is that the results of this study is one of those "bricks in the wall" kind of study that provides a basis for someone else to move forward with.

Note that this study still needs to be replicated by someone else to be considered "real".

Tired of Control Freaks

a reply to: TiredofControlFreaks

BTW - I love the way you presented this study and the follow-up research. Quality post. I gave you a flag for your thoughtfullness alone and you made the subject matter far more interesting than normal.

Your work is a good example to me (and I am sure others)

Tired of Control Freaks

I took a class on Metabolomics. It was interesting but I would like to find a more advanced free course, the course I took did not go in depth into it. It was meant to stir interest in the field.

Bone broth or soup made with cartilaginous beef or chicken bones is supposed to be good for stuff like fibromyalgia. So is jello. They contain substantial levels of proline and glycine and not too much cysteine and tryptophan which actually do promote inflammation if the proline and glycine levels are not high enough.

So having a little jello after your meal can help to dampen the pain. It does take a long time of eating these things to build cartilage though, it is slow but sure. Bone broth is a really good source of nutrition but takes a long time to prepare. Jello does not have all the properties of bone broth or the real bone and cartilage soups. There is another chemistry in cartilage that is very good for things like fibromyalgia. Usually metabolism insuficiencies contribute to FM

Here are a few articles.

raypeat.com...

www.jadeinstitute.com...

I have personally found that these soups and even jello do take away some sore muscles and tendons and they seem to help with the senovial fluid replenishment too. I'm not sore at all anymore, but when I tried utilizing magnesium supplements instead of these soups to control my epilepsy, I wound up with a lot of inflammation in my tendons and sore muscles after about a month. I now increased magnesium along with the soups again and lowered foods like tomatoes and oranges to get rid of the inflammation.

Thank you for your kind words. The study is small but reinforces what many CFS specialists believe to be the root cause, mitochondrial dysfunction.

I wonder if treatment of metabolism would be considered for CFS to overcome the environmental stress.

I follow Dr Sarah Myhill's work in the UK. She recommends Coenzyme Q10.

To produce ATP, mitochondria need certain essential raw materials, namely Coenzyme Q10 (CoQ10), D-ribose, L-carnitine, magnesium and vitamin B-3.

In a normal healthy person, CoQ10 can be synthesized, but it requires the amino acid tyrosine, at least eight vitamins, and several trace elements. The vitamins include folic acid, vitamin C, B-12, B-6 and B-5.

Synthesis of CoQ10 is inhibited by environmental toxins and chronic disease.

I am coming to the view that many of my CFS patients are metabolically “dyslexic” - that is to say, even when all the raw materials are available, they cannot make their own CoQ10 in sufficient amounts, and therefore levels need to be measured and supplemented.

Indeed a recent study showed a close correlation between levels of CoQ10 and severity of CFS. (“Coenzyme Q10 Deficiency in ME/CFS” by Michael Maes, et al.)

Link

Interestingly, CoQ10 has robust double blind studies which show a moderate reduction in fibromyalgia pain. Unfortunately it did not work for me pain-wise but I do take it every day on her recommendation.

Link

Very interesting indeed. But I found it all too much to understand as I have just woken up. Will re_read later and hopefully some more people have joined in on this thread.

a reply to: rickymouse

Hi rickymouse. Thanks for the links. You were one of the main contributors to my CFS thread in 2014 along with Stormdancer777 (I had a different username then). I had a break from ATS due to worsening symptoms and when I came back I couldn't remember my password and my email had changed so couldn't log on. I tried all the things you suggested in that thread.

Chronic Fatigue Syndrome and the Scandal of Medical Ignorance

It is quite easy to see from that OP two and half years ago, the cognitive decline I have experienced since then. In fact my overall level of function was 60% then and is now its around 40%. Most of my OPs now consist of quotes. Real-time continuous posting in threads on ATS is unfortunately beyond my capabilities now.

TiredofControlFreaks mentioned environmental stressors. I believe there are multiple stressors with some affecting certain individuals but not others. Many CSF sufferers try elimination of foods, processed foods, chemicals etc. Someone on a CSF forum I use makes his own supplements to avoid the fillers (bulking agents) which keep tablets' integrity. He believes the fillers are an unknown variable.

He buys organic powders and capsules and uses this encapsulation machine to make his pills.

Amazon

This guy actually ingests colloidal silver. I know that it inhibits growth on wounds and work surfaces. I thought it was poisonous. Have you read anything about taking it orally?

thank you so much for posting this. I have been reading pretty voraciously over the last 4 years about all kinds of health stuff because i my newly acquired low energy health condition and i find it strange i have never heard of or read about Metabolomics until i saw YOUR thread! Thank you!


i seemed to notice the most benefit from taking a daily combination of coq10, ALCAR, and bio PQQ as my main "stack" and taking an assortment of other supplements as i can afford them. I'm still in search of the "magic bullet" but all of these things cost alot of money and without even knowing alot of times where i should even LOOK for answers i often feel as if im just throwing money away.

Im going to start researching this aspect of MITO treatment/therapy now that i know about it.....


please do continue to share as much as you have time to. Oh,a lmost forgot....HOW in the world did you even get a diagnosis?!?!? seems to me this is the biggest hurdle since most docs dont know a dam thing about it and all the ones ive been to just tell me im depressed which is such a lazy and pathetic, not to mention OFFENSIVE, fall back diagnosis since they really dont have the knowledge to approach the thing in the first place and dont really seem interested in going down the rabbit hole with it.

as an aside....i have noticed the greatest benefit from exogenous cannabinoids and wonder if you have given any thought at all to the role the endocannabinoid system plays in the overall bigger picture of some of these energy related illnesses.


thanks again and keep this going!

a reply to: tribal

I have heard rumours that people who take statins, should also supplement with CO Enzyme 20. Can anyone expand on that?

Tired of Control Freaks

a reply to: TiredofControlFreaks

i have read that too.....its because statins deplete coq10 reserves if i remember right and the heart uses more coq10 than any other part of the body.

a reply to: tribal

Hi,

Thanks for the feedback and info. In the UK (not sure where you are), CFS was not included in medical training. In recent years medical students get a 20-30 minute session. In the US, CFS is now called Systemic Exertion Intolerance Disease (SEID) although it has not been adopted in Europe. I am not familiar with US medical training.

Your GP story is unfortunately very common. Unlike newly diagnosed depression, CFS sufferers never lose motivation, especially the motivation to get well. I would insist on a second opinion. It is very difficult having to fight with your doctor when you are very unwell.

I saw a medical physician initially who did a battery of tests which ruled out other causes for my symptoms. He made a provisional diagnosis of CFS. There was no specialised service locally so I paid to see an endocrinologist that specialised in fatigue disorders. As far as I am aware, the Canadian Consensus (Fukuda) criteria is used internationally except the US where the Oxford criteria is used (both very similar). I met all the criteria below.

Canadian criteria:



Canadian Consensus criteria

Pyrroloquinoline quinone is new to me but like you say its very expensive. Last year I tried 50 grammes of Liposomal Vitamin C per day for six months with no discernable benefit. What works for some does not work for others. The other problem is that you have to pay for quality as you have already mentioned which makes it prohibitive for many people, especially those that are unable to work.

You might find this presentation on Youtube by Richard van Konynenburg interesting. It is in 3 parts (approx 3 hours). Nutrigenomics is the study of the effects of foods and food constituents on gene expression. Richard van Konynenburg had a working hypothesis that certain gene traits ultimately lead to a biochemical cascade that causes glutathione depletion, which he believes is responsible for many of the symptoms of CFS/ME. The second video is quite advanced and I found it quite difficult to follow and absorb. If you decide to jump from session 1 to session 3 you can still follow without it being too disjointed.

The third video is the results and case studies of 30 females with CFS that were given specialist guided high supplements of sublingual hydroxocobalamin (Vit B12), tetrahydrofolate, folic acid/folinic acid, phospholipids and fatty acids. The case studies are easy to follow and very interesting.

Session 1 (approx 1hour, 20 mins)


Session 2 (approx 50 mins)


Session 3 (approx 1hour 25 mins)


I used NAC Detox regulators (N-Acetylcysteine) made by Dr's Best for a good 18 months. I was unaware of this research at the time. I took it to protect my liver as I was taking a lot of co-codamol (Tylenol 3)

This study is very interesting as well. Computer simulations based upon experimental observations of other studies.

In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

Metabolite dynamics in skeletal muscles are simulated during high intensity exercise. We take into account exercise induced purine nucleotide loss and de novo synthesis. A reduced mitochondrial capacity is assumed for CFS patients. CFS simulations exhibit critically low levels of ATP and a prolonged recovery time. Additionally an increased acidosis and lactate accumulation is observed in CFS.

There is also a research which shows gut flora to be less diverse in people with CFS. I would have to dig that out of my internet history if you want a link.

a reply to: TiredofControlFreaks

Statins are now contra-indicated with CFS and FMS as it worsens neuropathic pain.

a reply to: TiredofControlFreaks

I did a lot of research on statins when my husband was on them and what I found convinced us both that statins are one of the worst medications a person can take!

It has been a while now since he got off them, so I no longer have links, but here's some of the basic info:

They can do permanent damage to the nervous system, many people end up with excruciating pain that doesn't go away even when they stop the meds. (my husband was having a constant 'pins and needles' feeling in his feet)

Statins can actually damage the heart in ways that increase likelihood of heart attack and stroke.

The worst thing is that they interfere with the body's mitochondria (which are the cells that help us metabolize nutrients into energy), this is one reason that supplementing C O q 10 (actually Ubiquinone) is recommended...

...because statins actually 'turn off' the body's ability to make it's own C O q 10 (I have my husband on the supplement even though he is off statins, because I read the effect was permanent).

And to top it all off, we found that the pharmaceutical companies have actually 'misrepresented' cholesterol number statistics to make relatively 'safe' levels seem dangerous..

The fact is, our bodies and especially our brains actually need cholesterol for optimum functioning, so doctors should not be pushing these medications to get people to ultra low ranges..

Most of the research I found that gives accurate info about statins came out of England - the U.S. medical system is heavily indoctrinated..


OP - Sorry for off topic post, just felt I should reply with the info...
...Also, thank you for making this thread - I've suffered Chronic Fatigue/Depression, etc. most of my life.

a reply to: lostgirl

No problem. It is relevant for CFS patients who are taking or offered statins. I declined them when offered by my GP 5 years ago. Thanks for the info.