New paper: Aerobic Energy production and lactic acid excretion inhibited in severe ME

[Countrygirl]

The Aerobic Energy Production and the Lactic Acid Excretion are both Impeded in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Mark Vink*

Access to the full paper is here:

https://sciforschenonline.org/journals/neurology/JNNB-1-112.php

Abstract
Background: In this study the muscle bioenergetic function in response to exercise in severe ME was explored to see if the underlying metabolic problem in ME, responsible for the severe difficulties with trivial exercise, and the severe loss of muscle power, could be discovered.

Methods: Inorganic phosphate, creatine kinase and lactate were measured in a former Dutch National Field Hockey Champion, who is now a patient bedridden with severe ME, before and 5 minutes after very trivial “exercise”, from which his muscles needed 12 hours to recover.

Results: Inorganic phosphate and creatine kinase were both normal, however, lactate after this trivial exercise was very high, and further testing showed that a second batch of lactic acid was excreted after the same exercise with a 6-fold delay, showing that the lactic acid excretion was impaired and split into two. And this was delayed up to 11- fold by eating closer to the exercise.

Conclusion: This study found that in severe ME, both the oxidative phosphorylation and the lactic acid excretion are impaired, and the combination of these two is responsible for the main characteristic of ME, the abnormally delayed muscle recovery after doing trivial things. The muscle recovery is further delayed by immune changes, including intracellular immune dysfunctions, and by lengthened and accentuated oxidative stress, but also by exercise metabolites, which work on the sensitive receptors in the dorsal root ganglions, which in severe ME are chronically inflamed, and are therefore much more sensitive to these metabolites, which are produced in high quantities in response to trivial exercise, which for ME patients, due to the underlining metabolic problem, is strenuous exercise. And a similar problem is most likely responsible for the abnormally delayed brain recovery after doing trivial things.

This study also shows that the two metabolic problems are the result of an impaired oxygen uptake into the muscle cells or their mitochondria and in combination with the Norwegian Rituximab studies, which suggest that ME is an autoimmune disease, it is suggestive that antibodies are directly or indirectly blocking the oxygen uptake into the muscle cells or their mitochondria.

Keywords
Myalgic encephalomyelitis; Chronic fatigue syndrome; Exercise; Muscle fatigue; Muscle pain; Lactate; Lactic acid; Immune dysfunction; Inorganic phosphate; Creatine kinase

 

[Sasha]

Seems a bit of a generalisation from a single patient, but interesting. How does this tie in with the Staci Stevens etc. work? New finding or consistent?

 

[Marco]

Rare to see this kind of single case study write-up outside of psychiatry journals.

 

[SOC]

This could be a very valuable observation. I hope someone follows up with a real research study. It could go some way to explaining PEM, a critical step in improving our functionality and QOL.

However, I am appalled at the poor quality of the science demonstrated in the Conclusion. If the author didn't have sufficient research training to understand that you cannot extrapolate from one case to the entire patient population, the reviewers and editors should have informed him. The only conclusions that can be drawn should be about "this case of severe ME". Then a hypothesis could be proposed and suggested for further research.

The intentions of the author are probably very good and I applaud him for that. It's important, though, that we don't accept poor quality research whether it harms us or appears to benefit us. We want the truth about our illness, not various people's personal beliefs, directing diagnosis and treatment.

 

[Jonathan Edwards]

It seems that the author was the case.

 

[Sidereal]

The participant, i.e. the writer of this article, i.e. me, is a patient who has been bedridden with severe ME for more than 10 years, after Graded Exercise Therapy caused a severe relapse from which I haven’t recovered so far. I was diagnosed with ME by 2 knowledgeable primary care physicians who in the absence of a diagnostic test for ME/CFS, used the 1994 Fukuda [33] and the Canadian Consensus Criteria [34] to diagnose the disease, and the diagnosis was later confirmed by a consultant neurologist and by using the International Consensus Criteria [2].

Prior to falling ill with pneumonia, which triggered my ME, I was fit and well, was hardly ever ill and was very sporty. I do not smoke, and hardly ever drink alcohol. I have a brown belt in judo; I’m a former Dutch national field hockey champion, captain of my team; I ran marathons (PB: 3.05), half marathons (PB: 1.19), and competed in quarter triathlons.

I do not have a history of an autoimmune disorder, MS, psychosis, major depression, heart disease, thyroid-related disorders or any other chronic illnesses apart from ME, I had a very happy childhood, no childhood traumas, I’m not a perfectionist, I do not suffer from anxieties, mental health problems were excluded by a consultant psychiatrist and there are no confounding factors influencing my ME.

 

[SOC]

Mark Vink*

Family Physician/GPwSI, Soerabaja Research Center, The Netherlands

The participant, i.e. the writer of this article, i.e. me, is a patient who has been bedridden with severe ME for more than 10 years, after Graded Exercise Therapy caused a severe relapse from which I haven’t recovered so far.

So the patient and researcher (not a wise combination -- lack of objectivity) is a family physician as well as a former field hockey champion? I suspect he has never written a real research paper and is simply basing his format on research papers he has seen, but is unaware of the principles behind solid scientific research.

I would rather this was written up as an informative article rather than a pseudoscientific research paper. I blame the editors of this journal for presenting this interesting information as if it were legitimate scientific research. They should know better. There are a number of ways to present interesting observations that could lead to valuable research. It is neither necessary nor ethical to present such information as scientific research in research paper format.

Again, I hope someone with research training and the necessary resources follows up on this interesting observation, but I'm far from ready to accept that this one case allows us to draw conclusions about ME in general.

 

[Grigor]

I'm proud of my fellow Dutchman and hope there will be a follow up by someone with research training.

 

[jimells]

Maybe it's not suitable for an evidence review, but I sure appreciate the author's efforts. The idea of patients conducting research from their beds stands in stark contrast with the feeble efforts of the NIH and CDC.

 

[Dolphin]

I just read the paper.

There isn't that much new data in it.
Just Table 1:

and then some other data on lactic acid as he measured it on a few different days at lots of time points.

So, the abstract should have been a lot different if one is just going on the reported data.

But it could also be looked at as being a review. So it is interesting enough to be told/reminded about various other studies that have been published.

The author is not now able for any phone calls along with being exhausted for 12 hours by very short walks walks to the toilet so clearly is in a bad way. So I congratulate him on getting a paper done and thank him for the effort it must have taken. He thanks his parents for typing out his "speech memos" so thanks to them for their help.

 

[Dolphin]

The results are spread over a little more than one page (starts end of page 3, ends start of page 5) so one could skip to them if one isn't so interested in the background and his thoughts.

 

[sillysocks84]

http://scholarscompass.vcu.edu/etd/3629/

The lactic angle is interesting because many of us go on to develop mast cell problems. Mast cells can effect many body systems: skin, respiratory, circulatory, brain and even reproductive. The link above goes to an article that shows that lactic acid sets off masts cells. So does the lactic acid problem come before the mast cell degranulation issue, or can mast cell degranulation come first causing lactic build up? Because I always thought a vaccine sparked mine, which seems immunological... unless something is at play i dont understand yet. Anyone? This is interesting most of the time when I walk I get that lactic acid feeling in my legs. And in my arms when I barely exert myself. Hmmmm

 

[sillysocks84]

"When oxygen is unavailable or the Krebs’ cycle is inhibited, the body shifts its energy production from the Krebs’ cycle to the Embden Meyerhof pathway of glycolysis, a very inefficient way of making energy.

As well as producing far less energy, glycolysis also produces lactic acid as a byproduct. Increased lactic acid is a common acidotic condition that can be caused by a variety of metabolic problems. "

The mitochondria are what needs oxygen to carry out the kreb cycle. So again, can mast cells degranulation somehow suffocate mitochondria. Is it caused by a "microcellular allergy so to speak?"

 

[alkt]

just googled lactic acid studies in patients with m.e. because this post reminded me of something i have read some time ago. the medical world have known about it for some time strangely i remember vaguely that the lactic acid build up did not contribute to muscular pain.?

 

[sillysocks84]

http://nutritionreview.org/2013/04/krebs-cycle-intermediates/

Link for above

 

[sillysocks84]

Our nerves can induce mast cells to leak histamine and other chemicals. I remember reading somewhere that vagus nerve stimulation inhibited mast cell degranulation in cats. Hypothetically, the histamine coming from masts due to injured, sick, or infected nerves would be causing inflammation overdrive which would limit oxygen uptake for that area, effecting mitochondria and thereby inhibiting the kreb cycle. Ok time for a rest.

 

[sillysocks84]

http://drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure

@alkt This has an explanation for lactic acid causing our pain.

"Problems arise when the system is stressed. If the CFS sufferer asks for energy faster than he can supply it, (and actually most CFS sufferers are doing this most of the time!) ATP is converted to ADP faster than it can be recycled. This means there is a build up of ADP. Some ADP is inevitably shunted into adenosine monophosphate (AMP -1 phosphate). But this creates a real problem, indeed a metabolic disaster, because AMP, largely speaking, cannot be recycled and is lost in urine.

Indeed this is the biological basis of poor stamina. One can only go at the rate at which mitochondria can produce ATP. If mitochondria go slow, stamina is poor.

If ATP levels drop as a result of leakage of AMP, the body then has to make brand new ATP. ATP can be made very quickly from a sugar D-ribose, but D-ribose is only slowly made from glucose (via the pentose phosphate shunt for those clever biochemists out there!). This takes anything from one to four days. So this is the biological basis for delayed fatigue.

However there is another problem. If the body is very short of ATP, it can make a very small amount of ATP directly from glucose by converting it into lactic acid. This is exactly what many CFS sufferers do and indeed we know that CFS sufferers readily switch into anaerobic metabolism. However this results in two serious problems - lactic acid quickly builds up especially in muscles to cause pain, heaviness, aching and soreness ("lactic acid burn"), secondly no glucose is available in order to make D-ribose! So new ATP cannot be easily made when you are really run down. Recovery takes days!

When mitochondria function well, as the person rests following exertion, lactic acid is quickly converted back to glucose (via-pyruvate) and the lactic burn disappears. But this is an energy requiring process! Glucose to lactic acid produces two molecules of ATP for the body to use, but the reverse process requires six molecules of ATP. If there is no ATP available, and this is of course what happens as mitochondria fail, then the lactic acid may persist for many minutes, or indeed hours causing great pain."

So why are our mitochondria failing all of a sudden and producing lactic buildup and other issues? Is it because of mast cells? Why are mast cells malfunctioning. What triggered your disease? Perhaps something sent out mast cells into overdrive. I know what triggered mine. Does the mitochondria weakness make our nerves jumpy? I suppose injured nerves could be the cause in some cases.

For my case I think it is mast cells were triggered effecting my mitochondria trying to keep up but getting bogged down from histamine. Mitochondria overworking led to lactic buildup. I think my case involves my body trying to rid the vaccine...adjuvant or something else in the vaccine who knows...our triggers will not all be the same. We have to think of our trigger and ask ourselves, how does that fit into the body's disfunction. It is effecting all of our mitochondria Dr. Myhill believes, but why are your mitochondria being effected? Mine are most likely mast cell degranulation due to vaccine.

 

[Sasha]

I thought I saw Mark Van Ness say (in his talk at Bristol on YouTube? Not sure) that lactic acid is very mild and isn't what's causing the muscle pain. I think he was saying that it's the acid produced as a by-product of aerobic functioning that's the problem (from carbon dioxide not getting cleared fast enough?).

I've got zero understanding of biology so I might be talking rubbish.

 

[Mij]

It's the CO2 that is the "potent acid", "carbonic acid is very uncomfortable and toxic to the system"

anareorbic exercise = produces lactic acid which is a "gentle acid" that does not produce muscle pain.

Video- explanation starts at around the 20:00 minute mark.

 

[panckage]

I think it's interesting that he 'recovered' within 12 hours. I'm not sure if it's PEM that he's measuring but quite a few members have been skeptical the person has ME when they recover that quickly after exertion.

Glad to know that I am not such an outsider as a couple members have made me out to be