As the overall health status of individuals is captured in their metabolic state…(it’s believed) that metabolomics results embody global biochemical changes in an individual due to a disease. The Authors
Health Rising has focused a lot of attention on metabolomics studies in chronic fatigue syndrome (ME/CFS), but thus far not much attention has been paid to fibromyalgia metabolomic studies. Studies of the metabolome – the metabolic factors in the body – in fibromyalgia are pretty rare but what’s been done so far has been encouraging.
Metabolomic studies are starting to show up in fibromyalgia
Metabolomics analyses the small molecules that result from metabolic interactions or cellular processes taking place in the body. As such, metabolomics presents the possibility of uncovering physiological signatures which represent what’s happening in the cell.
A 2013 study that differentiated FM from two other chronic pain diseases (rheumatoid arthritis, osteoarthritis) was encouraging in several ways. For one, it found that osteoarthritis and rheumatoid arthritis were metabolomically similar but fibromyalgia was distinct. That made sense; all three are chronic pain conditions but osteoarthritis and rheumatoid arthritis are linked to distinct structural changes and a specific kind of inflammation. No distinct physical abnormalities, on the other hand, have defined FM. That study suggested that metabolomics might be a good fit for FM.
The authors of this study certainly think so. We don’t know exactly what is causing fibromyalgia, but it’s clear that central nervous system problems including central sensitization, over-active pain processing pathways and under-active pain inhibiting pathways are involved. Given the focus in metabolomics on analyzing the same type of very small molecules which play critical roles in nervous system metabolism and neurotransmission, the authors asserted that metabolomics is a particularly apt tool to study FM.
A 2014 fibromyalgia metabolomics study specifically examining the lipids in FM patients found increased levels of metabolites associated with the fragmentation of the lipid or fat membranes surrounding our cells. Injury to the lipid membranes is often associated with high levels of oxidative stress and further analysis indicated that other markers of oxidative stress (thiobarbituric acid and reactive substances – unpublished) are indeed present in FM. High levels of oxidative stress are also often found in chronic fatigue syndrome (ME/CFS).,
Because the metabolites involved have been linked to increased pain levels, it’s possible that the increased oxidative stress is contributing to the pain FM patients feel.
The Study
A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and control. Bontle G. Malatji, Helgard Meyer2,Shayne MasonUdo, F.H. EngelkeRon A. Wevers3, Mari van Reenen1 and Carolus J. Reinecke, BMC Neurology BMC :88, https://doi.org/10.1186/s12883-017-0863-9
This new study examined a broad range of metabolites (in urine) in people with fibromyalgia (n=18), their first-degree relatives (mother, father, sister, brother; n=11), age matched controls (n=10), and young healthy controls (n=20).
Results
Twenty-one metabolites were associated with fibromyalgia. Among those were metabolites (hippuric, 2-hydroxyisobutyric and lactic acids) associated with gut microbiome issues – an interesting finding given the gut-brain connection that’s been established in this disease.
Increased levels of D-lactic acid producing bacteria have been found in ME/CFS. D-lactic acid has neurotoxic properties which can leave you feel fatigued, irritable, cognitively challenged, etc. Because D-lactic acidosis is more common in people with dysbiosis (gut flora problems), small intestinal bowel overgrowth, and/or who have problems digesting carbohydrates, a good diet focused on reduced carbohydrates is recommended. (Because yogurt contains lactic-acid forming bacteria, kefir is probably a better choice.)
Biomarker?
Further statistical analyses narrowed the field down to the six most important metabolites (succinic acid, taurine, tyrosine, lactic acid, creatine and trimethylamine).
Just three metabolites were needed to differentiate FM patients from the healthy controls
The researchers then assessed whether the levels of these metabolites could differentiate FM patients from healthy controls; i.e. could they be a biomarker for fibromyalgia? One model (forced entry model) suggested that the levels of just three metabolites in FM patients (creatine, succinic acid & taurine) were highly diagnostic for FM (AUC=90%). That was a nice finding given the small size of the study.
Correlation statistics using symptoms the patients reported and the metabolomic findings suggested that creatine and succinic acid may be contributing to the fatigue and pain found in FM as well.
Interestingly, given fibromyalgia’s overlap with chronic fatigue syndrome (ME/CFS), and the studies suggesting energy metabolism is an issue in ME/CFS, these metabolites suggested problems with energy metabolism may be present in fibromyalgia as well. One difference, though, is that, if I’m reading the tables properly, is that most of the significant metabolites were increased suggesting, perhaps, that FM is not a hypometabolic condition.
Succinic and lactic acid are directly associated with energy metabolism. Succinic acid or succinate (as it appears in cells) is generated in the mitochondria during aerobic energy production. Once it leaves the mitochondria it performs a variety of functions including epigenetic signaling, effecting gene expression and sometimes acting like a hormone. Neurons in the brain are believed, at least at times, to use astrocyte derived lactate for energy production as well.
Taurine plays a particularly important role in a part of the basal ganglia called the substantia nigra which effects movement, reward and regulates the autonomic nervous system. The basal ganglia are best known in Parkinson’s disease which is largely caused by the death of neurons in the basal ganglia, but basal ganglia problems have also been implicated in both ME/CFS and FM. Neither FM nor ME/CFS is obviously Parkinson’s but note some of the similar symptoms (stiffness, sleep issues, decreased movement, fatigue, cognitive issues, problem with gait, depression).
The authors were focused on the neurological implications of their findings, but it seems intriguing that both exercise and energy production issues may be present in both FM and ME/CFS. People with fibromyalgia can generally exercise more than people with ME/CFS, and many studies indicate that mild exercise is helpful in FM, although most FM patients have trouble exercising vigorously. Some studies suggest problems with aerobic energy production – the main ATP producer in our cells – may be present in FM.
The succinic acid finding was putatively tied to elevated glucose levels in another metabolic disorder – diabetes. Elevated glucose (as well as pyruvate and NAD+) has been found in metabolomic studies in both FM and ME/CFS, and impaired glucose regulation and diabetes has been associated with an increased risk of chronic widespread pain in one study.
Conclusion
Metabolomics – an increasingly exciting field in ME/CFS research – is now showing up in FM as well. The results from this small study – possible gut, energy production and neurotransmitter issues – were tantalizing. The fact that just three metabolites were able to effectively separate the FM patients from the healthy controls was encouraging indeed. Now what is needed is more funding and bigger studies – both of which have been in short supply in FM. Hopefully, this study will spur more interest.
Quick question.
Are you saying that Taurine, as found in Red Bull, may be helpful to people with FM???
I used to drink it a few years ago and felt it done more for me than pain killers. Thinking I may speak with Dr (although they’ll likely lack the knowledge) and try a Taurine supplement.
Actually I took a look at Taurine ( https://www.healthrising.org/blog/2017/11/06/metabolomics-study-points-finger-energy-production-fibromyalgia/) and if I’m reading it right I think its levels were increased. One thing I’ve found with metabolomics studies is that it takes an expert to decipher the results because a high or low figure could be the result of disruption in a pathway and in itself may not be the problem.
Taurine was one of the three metabolites that successfully distinguished FM patients from healthy control but it’s levels were not correlated with any symptoms so high levels could be fine, I suppose. Another proviso is that this was a small study of a very complex field. I would be really hesitant to base any treatment plan on this study.
I guess what I as a laymen am saying is that if Taurine helps I would use it:)…
I would avoid those energy type drinks they are known to Cause profound Tachycardia & also damage to the Heart resulting in Death, one of my best
Friends almost lost his Daughter to these beverages She survived but ended up in an ICU Unit on life support from Tachycardia attacks
Taurine is used in Red Bull to help absorb the B vitamins and caffeine that provide the energy boost. I would not recommend drinking Red Bull because of the food colours flavours and too much caffeine. But taurine is helping our energy levels and specifically enhancing the absorption and effects of other supplements that help muscle relaxation and pain levels.
I’m surprised there is not more research on Taurine for the whole ME/CFS/Fibro/MCS illness family. Taurine supports mitochondria, nervous system, energy production, muscle function, metabolic syndrome, bile production and mineral absorption, and is an antioxidant. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933890/
Thanks Jen…Nice points. 🙂
I tried taurine and it made more difference than any other thing I’ve tried in 36 years of this illness (CFS and FMS).
Ha! Another taurine lover. Thanks for passing that on. I’ve never really connected taurine with FM. I have used it for MCS.
It’s interesting that taurine – according to this FM site – http://www.living-smarter-with-fibromyalgia.com/treatment-for-fibromyalgia-amino-acids.html
and according to this FM site – https://www.verywell.com/treating-gaba-and-glutamate-dysregulation-716040
GABA is a feel-good chemical found in the brain. It’s been suggested to be low in FM and ME/CFS.
Fascinating….
“…Taurine is found naturally in meat and seafood…”
Another plus from low-carb diets where one eats a lot of meat and seafoods?
“…Because D-lactic acidosis is more common in people with dysbiosis (gut flora problems), small intestinal bowel overgrowth, and/or who have problems digesting carbohydrates, a good diet focused on reduced carbohydrates is recommended…”
There are probably a whole lot more reasons as well!
As you know, a low-carb diet is one of the elements in my own lucky improvement story.
Diagnosed with CFS in ’93, POTS in ’97 and Lyme in 2008. At some point I read that Taurine might help me and started taking it. It made me so sick my PCP (a functional medicine doctor, now LLMD) told me I must have gotten a bad bottle. Hmmmm….
I’ve tried GABA, with no noticible results, but not Taurine. Does anyone know how much we should take? (I’m one of those VERY sensitive people and have had bad reactions to multiple meds, even some “natural” supplements and vitamins, so have to be cautious.) For me the chronic fatigue and depression are worse than the aches and pains of “fibromyalgia.” Thanx.
Hi,
Very similar to you, chronic fatigue worse than fibro, and now I have an autoimmune. Taurine may relax you, but it can cause insomnia too. I took it in combo with Magnesium Gycinate and Mg Malate and entire pill 75 mg. May want to buy your own empty capsules from health food suppliers and buy the smallest amount and stuff your own capsule. Seems early to tell but I am having success with CBD oil (brand CBDunlimited)…not sure allowed to mention brands. Early to tell, just few weeks. Concentration improved, depression improved, but it’s the anxiety that lifted more so, fewer deep depression days, however I keep changing amount of drops..I take just 4 drops a day. Pain, and especially neuropathy (mild but I can feel circulation) diminished. Caused insomnia, so I take in a.m. Effect on some neurotransmitters, even serotonin..forgot which ones. Hang in there!!!! Prayers.
Unfortunately, CBD oil has not worked for me.
I’ve not heard of Taurine.What is it exactly? I’ve had Fibro for 33 yrs and CFS for about 9 yrs.
Chronic Depression since I was a teen.
I agree, the pain is pretty horrible but the depression? That’s the worst. I have to say,though, that in the 24 years since my initial diagnosis of FM/CFS/ME , I think they are all so interrelated. Depression exhausts me, so I am far less active, so my body hurts, which is depressing, so I’m drained of energy….
Mass General Hospital now wants to use the TB Vaccine in Fibro they also claim to have a Genetic blood test for this condition. A Clinical Trial is to get underway soon & the blood test is available now for testing they also plan to do a complete Genome test on 250,000 People in California related to said study
Whoa! That’s fascinating. Would you happen to have a link to that? I would love to learn more.
Have you heard Prof Gottfries story in ME/CFS. He used another vaccine to cure his and others ME/CFS. He had to keep taking it continuously.
https://www.healthrising.org/blog/2015/11/21/gottfries-chronic-fatigue-syndrome-story/
Good review, Cort.
Jeez, I posted that upcoming MGH TB vaccine here multiple times, was disparaged by all! Google “FM/a test” by Epicgenetics, a lot of us passed test and have been waiting years for FDA approval and MGH trial. Assesses blood cytokines and chemokines unique to FM.
This is the company: https://fmtest.com. I didn’t have the test done, though, because my insurance doesn’t cover it and it was going to be $900 out of pocket. Too rich for my blood!
“…given fibromyalgia’s overlap with chronic fatigue syndrome (ME/CFS), and the studies suggesting energy metabolism is an issue in ME/CFS, these metabolites suggested problems with energy metabolism may be present in fibromyalgia as well. One difference, though, is that, if I’m reading the tables properly, is that most of the significant metabolites were increased suggesting, perhaps, that FM is not a hypometabolic condition…”
Yes! I have been hypothesizing for a while now, as you know, that ME/CFS may well involve dysfunctions at the cellular level itself, whereas in FM, the metabolic disturbances are a result of simple and crude distortions in muscle tissue itself, specifically the fascia, so that micro-vessels are crushed amidst all those horrible lumps, knots and corrugations that hands-on therapists have been well able to feel all along. Crucial flows, for energy inbound and waste disposal outbound, are restricted. This is amply sufficient cause for all these Metabolomics study outcomes.
I think this is the big failure of FM research – failure to concentrate on actual biomechanical disruptions in favour of the downstream consequences including the CNS sensitisation. I say the CNS is sensitized because of real and constant pain which is a consequence of real biomechanical dysfunction. If anything, I say that FM patients have ended up blocking out a lot of the constant pain from all over because the CNS cannot handle the overload. There is always a focus on a specific location, which is the worst one. Of course when a hands-on therapist starts exploring, the pain at the spot of exploration is “through the roof”. This is not “CNS sensitization” at all, but very real “raw injury” in the tissue.
Muscles have also long since responded to CNS signals in response to pain, to “relax” – part of FM is that muscle fibres, probably actually fascia, are “stuck” in the tensed condition for biomechanical / biochemical reasons. Of course the CNS burns out when its desperate signals to muscles, are ineffective.
I am slowly reversing these vicious “causes and effects” backwards. Once I had reached a certain level of de-toxification, muscles were starting to actually “come free” as a result of stretching and hands-on therapy; the next stage has been Feldenkrais lessons, which are wonderful in re-training muscles everywhere to “let go”. But I do not believe that any of this would work without the de-tox in the first instance, addressing the bio-chemical initial causes.
Sorry, I meant to say “Muscles have also long since CEASED TO respond to CNS signals in response to pain, to “relax”…
I agree with you . I have been suffering from fibromyalgia for 10 years and I have many lumps in my back and I think this all occurred due to metabolic problems. And there comes a time when the CNS no longer supports the load. I never thought that CNS sensitization would be the beginning of everything, but a consequence of diseased muscles
If I understand the paper correctly, succinic acid was up in FM patients? Is that correct?
If so, that may point to some interesting things:
In https://en.wikipedia.org/wiki/Succinic_acid I find:
* “Effect on the liver and retina
Succinate signaling often occurs in response to hypoxic conditions.”
-> I suspect local strong hypoxic conditions due to too much constriction in hair vessels in exerted tissue for quite some time. This may be another lead.
* Under “Effect on the kidneys
Succinate serves as a modulator of blood pressure by stimulating renin release”
-> I fail to understand it, but renin is related to blood volume (more should be good for us?) but also constricts vessels further (bad, especially in combination with insufficient NO?)
* It’s also involved in inflammation and immune regulation.
But the main thing is IMO this:
“Ischemia reperfusion injury
Succinate accumulation under hypoxic conditions has been implicated in the reperfusion injury through increased ROS production.[8][28] During ischemia, fumarate is formed from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle.[28] Fumarate overflow results in the production and accumulation of succinate through reverse activity of SDH. Upon reperfusion, succinate is rapidly oxidized leading to abrupt and extensive production of ROS.[8] ROS then trigger the cellular apoptotic machinery or induce oxidative damage to proteins, membranes, organelles etc.”
I’m a “believer” of strong oxidative stress and ischemic reperfusion injury (which is highly inflammatory) since some time. This may point to a culprit.
If I understand this one correctly, too much fumarate may block the “flow” or conversion of succinate to fumarate as too much of the end product typically inhibits the conversion process. If too much succinate is formed that can not be converted to fumarate (due to too much already) then excess electrons from the Krebs cycle are converted to peroxide/ROS generating strong oxidative stress. This can be improved by “throwing out” succinate and fumarate (fumarate not mentioned in the paper).
From where is it indicated the potential too much fumarate comes? Too much purine/protein breakdown. See https://en.wikipedia.org/wiki/Urea_cycle
The urea cycle converts poisonous ammonia to urea and… fumarate… generating excess fumarate potentially disrupting the all important Krebbs cycle both generating massive amounts of ROS and potentially disrupting mytochondrial energy production at (roughly) the same time.
In a previous blog about metabolics you discussed the low to very low amount of proteins in the blood plasma of ME patients if I recall well. This was believed to be the case due to massive gluconeogenesis breaking down proteins for generating additional glucose to feed to glycolysis to convert the glucose to pyruvate and lactate, mostly occurring under again hypoxic/anaerobic conditions.
This leads me one step further: both glycolysis and the urea cycle potentially “eat” plenty of ATP/oxygen/calories. If pyruvate and lactic acid are too plentiful it cannot be consumed as energy source fast enough. Lactic acid is formed because too much pyruvate (from glycolysis) is not good. Too much lactic acid increases blood acidity too much leading to among others CNS agitation/problems. And too much ammonia in the blood is plain poisonous. So all three components must be reduced out of the blood stream.
For upcycling pyruvate/lactic acid it costs 4 ATP to convert it back to glucose, while glycolysis delivered only 2 ATP to the exercising tissue. Removing ammonia costs another 3 ATP (see https://en.wikipedia.org/wiki/Urea_cycle). So deriving glucose from proteins in an anaerobic way costs plenty of ATP.
The liver is the one converting both pyruvate, lactic acid and ammonia to less harmful products. In addition the liver is also the one recycling key anti-oxidants such as glutathione (needed badly for reducing ROS damage). It also is a general detoxifier. According too https://courses.lumenlearning.com/boundless-ap/chapter/blood-flow-through-the-body/ “The liver consumes about 20% of total body oxygen when at rest, so the total liver blood flow is quite high.”
That’s in healthy people. In people with reduced blood volume (FM/ME) that percentage likely is higher. Add above mentioned recycling and detoxification during exercising and it could easily reach over 30 to 35%… …compared to the blood flow of healthy people. As our blood flow may be quite a bit less then this 100% that refers to healthy people, during exercising blood flow to the liver may take an extremely large portion of our total blood flow. As total blood flow likely already is reduced quite a lot this leaves very low blood flow to the rest of the body, somewhere less than half of what it should be… …causing lack of oxygen in those parts… …causing prolonged anaerobic functioning leading to more gluconeogenesis/glycolysis, anaerobic functioning, lactic acid, increased load of the liver, less blood and oxygen for the rest of the body and less NO (more ROS equals less NO and depleted proteins equals to less NO too) further constricting the “non-essential” blood vessels such as those to skeletal muscle… … leading to a long lasting derailed blood and oxygen flow and plenty of toxic byproducts and hours to days of trickling down side-effects.
If this view were correct, there might be a good side too: it could mean that mitochondrial functionning may be relatively fine from Acetyl-CoA to succinate (in the Krebs cycle). That is the part taking up the oxygen IMO (as it is there where CO2 is released).
Indeed! Your insights are amazing. By “too much constriction in hair vessels” you mean vessels as thin as a hair, I presume. Micro-vessels.
And you are describing a “vicious circle” of effects, a feedback loop that makes the same things steadily worse, each acting and reacting on the next thing in the loop. This is what I have thought for a long time, about FM.
And there are certainly multiple feedback loops, again and again we are discovering another element that has such an effect, such as what you are now saying about succinate. And pyruvate, lactic acid and ammonia – and the liver, and the blood flow. And the CNS. Causing a vicious circle of even deeper anaerobic dysfunction, which increases yet again, the toxic byproducts.
And quite possibly it is toxic byproducts that are causing the myofascia ground substance to lose its lubricant property, which results in stuck muscle strands, in which micro vessels are trapped – and there we have another feedback loop.
I believe people get FM when a mixture of exposures create a tipping point where this vicious circle begins. Stress meaning muscles inappropriately tensed already. An infection and / or poisoning with a toxic element, commencing hypoxia in the muscle tissue and myofascia ground substance, and overwhelming the liver. An operation for whatever reason, where the myofascia is cut through and some vital equilibrium is disrupted. All the foregoing is true of me (the infection was guardia and the toxin was cadmium, which is diabolical in its effect on the renal system).
I think it is urgent for FM research to stop focusing on tiny elements of what is actually a big, inter-connected syndrome with multiple elements, at least several of which need to be addressed simultaneously if the patient is to get any help. I do not believe there will ever be a single magic bullet drug or substance which reverses FM by interfering with one single known imbalance. There are multitudes of imbalances, and no single one of them is “the” single trigger for all the rest.
And all research must start from the point that actual biomechanical deformation, resulting in real pain, evidently palpable to hands-on practitioners long since, is present, and it is misleading nonsense to focus on the CNS as “causative”.
hi Phil,
“By “too much constriction in hair vessels” you mean vessels as thin as a hair, I presume. Micro-vessels.”
-> Is hair vessels a wrong translation of mine? I indeed mean the tiniest blood vessels. Are they called micro (blood?) vessels?
“there are certainly multiple feedback loops”
-> I currently see both FM and ME as a mixture of underlying vulnerabilities (for example genetic defects, inherited easy inflammation, strong weakness to certain pathogens, having really small lungs…) with some sort of trigger(s) (and with it the environment you live in and your personal health history) and a memory mechanism.
That memory mechanism could be the sum of increasing permanent damage and nasty feedback loops that are “as good as permanent but could potentially be undone and reversed under ideal circumstances”.
I feel that (the very difficult thing of) reversing some of those feedback loops won’t create full recovery as your personal weaknesses keep dragging on your health and permanent damage won’t disappear. I say this as I feel that when I try and roll back some of those mechanisms there is improvement but far less than what I feel there should be. Rolling back these loops has to be done day after day as they keep creeping back.
“I think it is urgent for FM research to stop focusing on tiny elements of what is actually a big, inter-connected syndrome with multiple elements…”
-> This type of research is very challenging in medical research. It’s near impossible to both find funding and publish findings if one can’t provide a strict research protocol and extract convincing statistics out of the experiments. The Pace study worked around this problem by using statistics in a way they should never be used but that ain’t a real option…
Having plenty of isolated dots researched first and connected bit by bit later is the slow way of what you desire. It’s slow, but skipping this faze is full of problems. If just they would increase spending so we get more well researched dots faster…
I don’t believe my pain sensitivity is increased neither, rather the opposite.
I once had a nasty interaction of meds that was very good at pain killing (but with very strong side effects). I noticed several times I had cut myself only after seeing traces of blood around the house. Then I saw that I had cut myself and could “detect” some pain in that zone. The FM pain however remained clearly present but much less than without this nasty interaction of already nasty meds on their own.
Also, many things described as very painful by healthy people are quite mild to me. That indicates reduced pain sensitivity. Other person could be different…
Thanks, Dejurgen.
I hadn’t heard the term “hair vessel” before but I understood immediately what you probably meant.
Your experience and judgement are so close to mine. Yes, “…there is improvement but far less than what I feel there should be. Rolling back these loops has to be done day after day as they keep creeping back…”
Absolutely, the amount of time I devote to self-help activities, in a normal person, would produce a top-level athlete (and I regarded myself as a top-level athlete in my pre-FM days – I am just as dedicated now, but merely to try and converge my condition on that of a normal well person).
I am glad you agree too that the assumption that we are “over-sensitive to pain” is the opposite of the reality. We are actually numbed to the chronic pain that exists everywhere in our bodies as a result of very real hypoxicity and adhesion-deformation of muscle tissue – and the reason for our extreme reaction to a significant stimuli like an impact or pressure, is that the pain really truly is extreme – not that our CNS is “over-reacting”. It is just that the stimuli “cuts through” the general numbness. The same is true for individual locations of heightened pain – I always seemed to have a “pinched nerve” on one side or the other of my neck – or in my pectoral area – or lower back – which was making me wince and writhe – and it was always nonsense that this was “over-sensitivity”, it was the worst pain “cutting through” the numbness. Then there was the horrible frequency with which I had an actual torn muscle – a calf or hamstring or quad. I believe these are more painful for someone with FM, not because of a heightened CNS alone, but because the muscle tissue is already hypoxic and riddled with adhesion-deformations.
And the CNS is dysfunctional because of the constant overload from this, not dysfunctional in itself.
I too have become aware of cutting myself after noticing blood on surrounding surfaces! I have also had ugly bruises for which I have no recollection of the impact that caused them. Someone else notices a bruise and asks “how did you do that”? And I don’t know!
By the way, is your first language German? I would very much appreciate if you could get the attention of Dr Robert Schleip and his colleagues at Ulm University, who are leading fascia researchers. I have had no luck. It is wrong that “fascia researchers” for nearly 2 decades, seem to have done no looking at FM yet. If you take their hypotheses about the problems at one or two locations in some patients, being due to a fascia dysfunction at those locations, and extend the hypothesis to “the fascia in the whole body”, you have an excellent explanation for FM.
Sorry Phil,
I know less than twenty words of German, can’t help you with that. But the good doctor should be able to read English well as near all publications are written in English.
Most scientist chose to not react to unsolicited mails, so that’s likely the problem.
Wow….
I so embrace the idea that hypoxia and blood vessel problems could be key in these diseases. Thanks for the tour de force…
Remember I’m still an amateur with a ME brain, crude ideas and plenty of ifs and buts. On the other hand, Pace and the Lancet haven’t set the bar for quality research that high neither…
Now I am trying to extract useful information out of this preliminary model in order to make better health choices. So far health is going in the good direction, but that is by no means proof of anything. Still it would be wonderful if I could get steady and growing improvement out of a model based approach. The path is still very long, difficult and prone to setbacks. The next big “test” will be how well I recover from this years flu vaccination. Last year it cost me over 4 months of near inescapable decline.
Now I hope to have a month of milder and temporally reduction in health. If so, I can continue to relearn basic stuff like cooking a meal or reading a book without the letters blurring and floating around (thanks god for computers paired with big screens and huge sized fonts!). It’s ironic how I manage some very few complicated things better than most utterly basic tasks ;-).
As a side node on the anaerobic/liver connection: it (if it were to be even remotely of value) may give clues why both a keto diet and a seemingly opposite vegan diet seem to benefit different patients.
The fat in the keto diet is hard on the liver, but that load is temporary. Resting after meals could do a lot. The low blood glucose levels should hamper anaerobic capacity. When tissue hasn’t cleaned up this could be problematic (part of keto-flu?) and could remain troublesome for many patients. Later lower anaerobic capacity should deliver a slight advantage as there is less anaerobic waste to clean up. The biggest advantage however could be the very low amount of (glucose derived) pyruvate in keto-patients blood and tissue. It would provide quite a buffer before concentrations become problematic and needed to be recycled by the liver. Moreover, as pyruvate likely isn’t supplied in large quantities to mitochondria in keto-patients and pyruvate is an excellent food source for mythochondria it should be cleaned out of the blood stream quite fast.
The vegan diet on the other hand is one of the more alkalic diets. That would lower rest acidity of vegan-patients blood and tissue. That should provide quite a sizable buffer to absorb bursts of lactic acid production and reducing the need of the liver to go all in to prevent acidosis. If (the science is not settled as to if it is possible or not) lactic acid could be used as a source of energy for heart and brains, then the waste product once more could be converted to a useful source of energy. The buffering effect would be important here as there is no need to use it at an impossible rate in a oxygen challenged environment. Just my two cents thought on another contradiction. Still needs some more work.
“…clues why both a keto diet and a seemingly opposite vegan diet seem to benefit different patients…”
Again, thanks for the excellent, convincing hypothesis. That very point had intrigued me for a long time. I know a woman who has improved spectacularly from FM, on a “Fruitarian” diet, which is similar to Vegan. Yet for me it was a Ketonic one.
But can it be “only the liver connection”? Is there not more to the whole story about these diets? I have been convinced that forcing the body to burn fat for energy, by depriving it of carbs, produces less toxins than carb-based energy (which toxins the body has a reduced ability to clear out). Maybe if the Vegan-dieter is still burning carbs for energy, some other mechanism enables quicker clean-out of the post-exercise toxins?
“I have been convinced that forcing the body to burn fat for energy, by depriving it of carbs, produces less toxins than carb-based energy”
-> Under ideal conditions carb base energy production only produces H20 and C02 as waste so it doesn’t need to. Going too anaerobic however does. Also, many anti-inflammatory diets go low on sodium and animal based protein. Proteins always produce some toxic waste that need to be handled. If protein is broken down for using its glucose contend to be used in an anaerobic manner then it could get pretty dirty…
“But can it be “only the liver connection”? Is there not more to the whole story about these diets?”
-> Sure there is more to it. I’ll just try to find common ground between seemingly opposed views. I believe there is much to be gained by doing so. It could cast more light on some deeper lying causes and make choices easier and more adapted to individuals.
I believe maintaining a relative flat level of blood sugar is important. Many vegan diets do well at this, containing plenty of fiber. The fruitarian diet may be more challenging here. In my experience big portions of fruit can let spike blood sugar (my senses, not measured). Does your friend happen to eat many small portions around the day rather then some few big ones?
I also believe one needs to be well hydrated around the day in order to keep blood volume constant enough. Vegetables and fruit are basically “bags of slow water” plus slow nutritional ingredients (fruit however has intermediate glycemic index due to containing lots of sugar mixed with lots of fiber). This provides more spread hydration as there is a wet mass in the bowel for a long time (including overnight).
I did find this that may be in favor of a frutarian diet https://en.wikipedia.org/wiki/Fructolysis:
“It appears that fructose is a better substrate for glycogen synthesis than glucose and that glycogen replenishment takes precedence over triglyceride formation.”
-> This would allow for faster restoring important glycogen stores in muscle cells. During strong anaerobe muscle functioning it is easy to see muscle glycogen stores completely depleted. This may sound good in order to reduce future anaerobic functioning but if your cells find no other way they may go all in on breaking down proteins for glucose and use that anaerobically. That would be pretty dirty and be in line with the low amounts of amino acids found in ME patients blood in metabolic studies. That leaves few proteins for body construction/maintenance. It would get even worse if, lacking sufficient proteins in local blood to break down, the body would start to break down cells to extract proteins from it. Breaking down (muscle)cells to use its protein happens during starvation. But if no source of anaerobic energy is found nearby and aerobic energy production can’t meet demand, do cells see it much different then starvation? If such thing would happen, it would provide quite a basis for micro cellular muscle damage and inflammation in FM…
Note: using large quantities of fructose has *plenty* of significant disadvantages but when done very well it may provide a positive benefit to cost ratio.
“Elevated glucose (as well as pyruvate and NAD+) has been found in metabolomic studies in both FM and ME/CFS, and impaired glucose regulation and diabetes has been associated with an increased risk of chronic widespread pain in one study.”
In the almost 25 years I’ve dealt with FM, I have also been told I’m pre-diabetic. Diet changes and exercise made no difference, my numbers are consistent. Where can I find more information/studies about this so I can share with my doctor?
FM has many proposed causes and pathophysiologies. People get focused on their own theories IMO, both us and researchers. Maybe these studies will point in more productive directions.
I’ve found many things upregulate my fibro pain, pointing me to the CNS, and no body therapies have helped. Cipro family drugs, now with a black label finally, I could have told them years ago, really increased my pain. Nootropics, acting on CNS, also are awful for me.
Hi Steven,
For me I do not put into doubt that a large or likely the largest part of FM patients can have an oversensitivation of the CNS and pain centra. I see however that a significant subgroup of patients (including me) becomes less sensitive to “general” pain and thus do not find myself in the “almost axioma” that FM equals to oversensitivation and that researching and correcting this oversensitivation is the answer to FM.
In fact, my physical therapist tells me that pain is the only signal that one should never be able to block. One can block noise and other things according to her, but even partially blocking pain would be a bad thing according to her. Pain has always an alarm function to her.
While having increased pain thresholds may sound nice to a chronic pain patient, it may indeed be not that good. It for example allowed me to push through at moments that all parts of my body were in pain. At that moment the pain should have grounded me. However I managed to push even some deeper until I started losing all strength and even started increasingly losing control over my muscles. That grounded me, but it has cost me dearly. So having your body increasing pain levels or generating oversensitivation if you keep ignoring pain could make more sense?
Anyhow, let us suppose that oversensitivation multiplies the intensity of felt pain by a factor of three. That would still require huge amounts of base pain or “physical non CNS induced” pain wouldn’t it? Taking the origin of that “base” pain away still would make a lot of sense. I think it’s that that people like Phil, I and others try to communicate.
For people with an oversensitised CNS the combination of researching “base pain” causes and oversensitivation mechanisms should multiply the improvement in pain levels.