Exercise Intolerance: Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)

[Inara]

The lower leg (calf) is usually used because that is the most common place to find SFN, if your SFN is caused by poor circulation.

So if a skin biopsy shows SFN in the lower AND upper leg (and a QST shows SFN in the hands), the SFN is not caused by poor circulation?

 

[Inara]

And certainly is well-documented in its association w/ exercise intolerance (including studies demonstrating how this works).

Would you link? This is new to me, so I can learn.

I believe this is because the pain symptoms helped them quickly get to a SFN diagnosis. Whereas someone (like me) w/ just fatigue, well, the docs just don't know what to do w/ you.

The same here.
Do I understand you correctly that you say some with SFN present mainly with pain, others mainly with fatigue and/or PEM? Where do you have that from?

QST and skin biopsy show SFN, but I don't have pain. That's why it was questioned that I can have SFN, but it was tested standardly along with dysautonomia diagnostics.

 

[Pyrrhus]

So if a skin biopsy shows SFN in the lower AND upper leg (and a QST shows SFN in the hands), the SFN is not caused by poor circulation?

SFN in the lower leg/feet and forearms/hands is consistent with poor circulation, since the lower leg/feet and the forearms/hands are the parts of the body that are furthest away from the heart/spine - but there can be many other possible explanations for the SFN as well.

SFN in the upper leg might indicate a cause other than poor circulation.

Hope this helps.

 

[Crux]

@Learner1 ,

It seems to irk people when I bring up possible deficiencies when some symptoms match, so here goes anyway.
This may be N/A for you as well, but ...

I've had paresthesia for years , calcium deficiency turned out to be the cause, even when it was not low in blood serum.

Chemo. drugs and some antibiotics can lower calcium. High phosphorus intake can as well. many causes.

https://www.ncbi.nlm.nih.gov/books/NBK279022/

 

[Oliver3]

I am not a doctor but know many people with diabetic neuropathies, to compare their „fatigue“ to me/cfs is ridiculous by all means, this has nothing to do with their pain and that their struggle is real, it only is NOT very relevant to me/cfs and its cardinal symptom PEM.

Apart from that I have severe SFNP and have been in contact with specialists around the world for it: they all say the same thing: It is at very best contributing factor for PEM and even „fatigue“ - one you want to treat if you can obviously, it will definitely make you feel better in many aspects, it will not get your muscle out of a deficient glucose and oxygen utilisation state though, there is even some evidence for this (re cultured musclecells of me/cfs patients show this defiency - without any nervous system derived blood circulatory constraints).

Is this why hbot works for some?
Isn't there an altitude sickness drug for intercranial hypertension too that helps deliver oxygen into the muscles.
Could some of this be because of dysregulated breathing patterns. Blowing off too much co2. Have you heard of the Bohr effect? The less c02 gas there is through hypoventilation, the more fatigued you are.
I'm not saying it's causative but would that drug or smthg like buteyko at least help deliver oxygen by improving a better affinity between oxygen and c02

 

[andyguitar]

Is this why hbot works for some?

Could be.

 

[Oliver3]

Could be.

Seem to remember Robert phair saying hbot could help shunt trytophan out of the cell.
Also interestingly, I've heard freedivers say that breath holding, vastly increasing breath holding times stopped their autoimmune diseases

 

[Learner1]

@Learner1 ,

It seems to irk people when I bring up possible deficiencies when some symptoms match, so here goes anyway.
This may be N/A for you as well, but ...

I've had paresthesia for years , calcium deficiency turned out to be the cause, even when it was not low in blood serum.

Chemo. drugs and some antibiotics can lower calcium. High phosphorus intake can as well. many causes.

https://www.ncbi.nlm.nih.gov/books/NBK279022/

Good point. How did you figure out calcium was low?

this why hbot works for some?

HBOT is at pressure which can push oxygen further into capillaries.

Seem to remember Robert phair saying hbot could help shunt trytophan out of the cell.

Yes, it is the solution to the IzdO2 metabolic trap.

 

[Oliver3]

Good point. How did you figure out calcium was low?
HBOT is at pressure which can push oxygen further into capillaries.
Yes, it is the solution to the IzdO2 metabolic trap.

Is it hbot that is the solution or just opening up the capillaries? From what I know of buteyko. The classical method opens up the capillary bed throughout the body

 

[Crux]

Good point. How did you figure out calcium was low?

It's funny, some folks on reddit were commenting about leg cramps. One guy was recommending calcium.
I had been using lots of mag. oil and potassium.

Then I read about it. Couldn't believe my numb feet, insomnia, anxiety, etc., may also be due to it. 10 years ago I had numb lips, B12 seemed to help.

Some of these symptoms have been since childhood. suspect genetic cause. sluggish parathyroid? serum calcium only as low as 9mg/dl. normal range : 8.8 - 10.2 mg/dl varies per lab

I haven't read about it improving VO2, but I can climb stairs easily now. Much less fatigue.

 

[Oliver3]

Wonder if anyone can provide an insight on this. Deffo related to blood flow.
I've had a crash recently, not helped by the change in weather.
I had intense pressure in the ribs, the stomach, bruising developed there, or leakage from a vein. It got so bad, I went to the hospital with chest pain.
As usual, high BP but no NHS issues. Clear bloods etc. Even when I was laid down and my BP a 130/ 80 I felt that malaise, like my blood is compartmentalised and pressurised. The fight flight reaction is kicking in every time I stand, presumably to get blood where it needs to be, but which feels it might kill me.
To cut a long story short, I'm s musician and had the chance to work with a drummer for three hours.
I want sure if I could survive it but I'm so fed up I decided to go.
I took my BP meds and then added 150 mg of aspirin. Within ten mins, I felt oxygenated, fight or flight calmed lots.
Obviously it wasn't perfect and after the three hours I was exhausted but I feel better than usual.
I know heparin is used in ling covid, and there's the idea that micro clots are forming in ling covid.
So the short question is. Are blood thinners used to help m.e. patients..warfarin, or even just aspirin and garlic.
I didn't feel like I was wearing a diving suit to walk around in.
I've had my calcium score done on the last 4 years and my arteries are clear. My bp is hugely mobile, which worries me. Is thinning the blood a potential therapy to get oxygen further into the body. ( My platelets are already normal btw)

 

[andyguitar]

I had written about a month ago that I felt better on blood thinners twice while given in the hospital over the last 10ish years. I ran into mentions here about the Berg hypercoagulation theory, read up on it, and made an appt. with a functional medicine doctor that has mentioned it as something he investigates and treats.

I had my appt. almost a month ago and he ordered a slew of labs. Low and behold, my D-dimer was over-range and my Fibrin Monomer was positive. I don't begin to understand all this, as even though I understand well enough when it comes to the body, this is something I've never studied before. But it is odd that I feel better on anti-coagulants and now my labs show hypercoagulation.

I think the next thing we will be doing is all the infectious labs to see if and what hidden infections I may have, and then begin treatment for that. From what I understand, I will most likely be on Heparin injections for 6 months while the antibiotics do their thing.

The answer is yes and here is a sample. I suggest you put "heparin" into our search box.

 

[Oliver3]

The answer is yes and here is a sample. I suggest you put "heparin" into our search box.

Thanks for that andy

 

[minimus]

Isn't there an altitude sickness drug for intercranial hypertension too that helps deliver oxygen into the muscles?

@Oliver3 The drug is diamox. Paul Cheney would occasionally prescribe it to some of his ME patients, finding that it symptomatically seemed to relieve chronic pressure headaches in some cases.

Interestingly, as part of his annual clinical exam, Cheney would have his ME patients fully exhale and then hold their breath for 30 seconds, measuring their oxygen saturation levels with a finger pulse oximeter. He found that all of his patients had normal (98-99%) oxygen saturation prior to breath hold, but that many of them would barely desaturate after breath hold - dropping only a few percent.

He prescribed diamox to me in the mid-2000s and while I was on it, he noted that my oxygen desaturation improved substantially, dropping by ~15% during breath hold, compared to only 5-6% pre-diamox. I think my exercise capacity improved while I was on diamox, though that was a long time ago. In contrast, mestinon worsened my exercise intolerance during a 3-month trial of it, even though my iCPET by David Systrom showed me to be in the “high-flow” subset of ME patients who often clinically benefit from mestinon.

After the Naviaux paper on metabolomics in ME patients was published, Cheney adopted the view that ME is probably a protective metabolic state, that we have switched from aerobic to anaerobic metabolism because we are deficient in antioxidant defenses. He found that his patients had abnormally low levels of SOD, catalase, and glutathione synthase. Strangely, he found that a 6-day course of artesunate - the anti-malarial drug - increased SOD and catalase to normal levels in his ME patients, which is why he recommended it for a while.

Cheney eventually stopped prescribing diamox because he feared greater oxygen desaturation also increased aerobic metabolism, and with it the production of dangerous reactive oxygen species, though he never tested this theory. I have occasionally toyed with the idea of trying diamox again, especially since my muscle fatigability has become so disabling in recent years.

 

[Oliver3]

@Oliver3 The drug is diamox. Paul Cheney would occasionally prescribe it to some of his ME patients, finding that it symptomatically seemed to relieve chronic pressure headaches in some cases.

Interestingly, as part of his annual clinical exam, Cheney would have his ME patients fully exhale and then hold their breath for 30 seconds, measuring their oxygen saturation levels with a finger pulse oximeter. He found that all of his patients had normal (98-99%) oxygen saturation prior to breath hold, but that many of them would barely desaturate after breath hold - dropping only a few percent.

He prescribed diamox to me in the mid-2000s and while I was on it, he noted that my oxygen desaturation improved substantially, dropping by ~15% during breath hold, compared to only 5-6% pre-diamox. I think my exercise capacity improved while I was on diamox, though that was a long time ago. In contrast, mestinon worsened my exercise intolerance during a 3-month trial of it, even though my iCPET by David Systrom showed me to be in the “high-flow” subset of ME patients who often clinically benefit from mestinon.

After the Naviaux paper on metabolomics in ME patients was published, Cheney adopted the view that ME is probably a protective metabolic state, that we have switched from aerobic to anaerobic metabolism because we are deficient in antioxidant defenses. He found that his patients had abnormally low levels of SOD, catalase, and glutathione synthase. Strangely, he found that a 6-day course of artesunate - the anti-malarial drug - increased SOD and catalase to normal levels in his ME patients, which is why he recommended it for a while.

Cheney eventually stopped prescribing diamox because he feared greater oxygen desaturation also increased aerobic metabolism, and with it the production of dangerous reactive oxygen species, though he never tested this theory. I have occasionally toyed with the idea of trying diamox again, especially since my muscle fatigability has become so disabling in recent years.

Thank you, that's interesting. When I'm unwell sometimes my ox say can be low but interestingly, as you point out, sometimes at 99 percent and it felt like the oxygen wasn't getting taken up into the muscle

 

[Consul]

Not sure where to put this so i will try here since its also from an article on invasive cardiopulmonary exercise testing.

In Corts new article (linked below) he references to researchers that suggest LC patients muscle fibers are depleted of enzymes responsible for activating aerobic activity.

So im just wondering if they could mean PDH here? Fluge et al 2016 found evidence that this enzyme is reduced(downregulated?) in me/cfs patients. But i think the idea here is that this occurs because theres a problem with oxygen delivery to the cells, so its the body adapting to metabolic stress, So in that case the arrow points back to e.g blood clots or something like that messing with the oxygen delivery, the lack of enzymes would then just be a secondary phenomenon.

Probably im misunderstanding something but i will ask anyway.

Read here for proper context
https://www.healthrising.org/blog/2021/11/19/heart-failure-muscles-long-covid-chronic-fatigue/

 

[GlassCannonLife]

I was told to monitor my heart rate and stay within my energy evelope as well to avoid triggering PEM.

I find this recommendation strange - I've seen it in a few places. I get PEM regardless of what my heart rate does. It very rarely goes above 100 and I have PEM all the time - I can lie on my back and use my laptop for a little bit and cause PEM if I do it too long.

@sometexan84 you mentioned people getting lowered RBCs - is this as a result of SFN over time? Do you have any papers you would like to share on that? I wonder if that's why some people on discord found they had increased haemoglobin/haematocrit (also RBCs? Not sure - was all just 2nd hand reports from mitoMAN) when they used ARA-290. Could it be normalising this issue..? I've never heard of it before though and the papers on ARA don't mention this being an issue, or that it can be corrected by addressing the SFN.

 

[Pyrrhus]

I find this recommendation strange - I've seen it in a few places. I get PEM regardless of what my heart rate does.

The recommendation to stop activity when your heart rate is too high, in order to prevent PEM, does not imply that the high heart rate causes PEM. It merely uses the elevation in heart rate as a convenient sign that you may be over-exerting yourself. It's not a perfect sign, but it's helpful for those who tend to "accidentally" do too much.

 

[GlassCannonLife]

The recommendation to stop activity when your heart rate is too high, in order to prevent PEM, does not imply that the high heart rate causes PEM. It merely uses the elevation in heart rate as a convenient sign that you may be over-exerting yourself. It's not a perfect sign, but it's helpful for those who tend to "accidentally" do too much.

Yeah I understand that, I'm just saying it's not very useful when you're in a situation like mine, where you often do too much while your HR is never above 90 (or it even stays in the 50s the entire time and it still overexterts you).

I have learnt to manage this myself, but if you are early on in your illness you can easily overdo it by thinking that you can judge if you're doing too much or not based on HR.

 

[livinglighter]

find this recommendation strange - I've seen it in a few places. I get PEM regardless of what my heart rate does. It very rarely goes above 100 and I have PEM all the time - I can lie on my back and use my laptop for a little bit and cause PEM if I do it too long.

I think the general rule for staying under 100 relates to PEM caused by physical activity. PEM caused by cognitive activity could be a different matter based on what you identify happening without the use or much physical effort. We can also get PEM from emotional expenditure. I was recently told it’s because the same metabolic pathways are used during all exertion.

Some of us, including me, find cognitive effort more taxing then physical activity and vice-versa.