New Book about Thirst in ME/CFS

[Aidan Walsh]

On the blocked blood vessels point: there are a couple of studies showing that people with pots who were found to have a compressed vein in their pelvis or abdomen sometimes found that their pots resolved when the vein was stented. I can dig out the studies if anyone is interested.

@crussher or anyone else, do you have thoughts on using the WHO homemade oral rehydration solution (half teaspoon salt plus 6 teaspoons sugar per litre of water) vs normalyte/dioralyte? As you say in your talk, normalyte isn't available in the UK and dioralyte is very expensive if you want to drink multiple litres per day

Yes, would be a good thing to post the blocked vein studies of Nutcracker on here in POTS which I believe is another label name for Syncope, thanks

 

[Donsboig]

Oh and also any theories as to why the renin-angiotensin-aldosterone system might be messed up in pots/me patients?

 

[Donsboig]

Here are the two papers I know of linking vein compression to POTS:

https://pubmed.ncbi.nlm.nih.gov/35620060/

"We describe three patients with concomitant POTS, EDS, and MTS. Although abdominopelvic vasculature evaluation can be difficult via conventional imaging techniques, we present the use of novel dynamic contrast-enhanced magnetic resonance angiography with Differential Subsampling with Cartesian Ordering (DISCO) and four-dimensional flow magnetic resonance imaging to aid vasculature evaluation and the diagnosis of MTS. Two patients underwent left common iliac vein stenting to treat MTS, experiencing significant improvement in their POTS symptoms and quality of life."


https://pubmed.ncbi.nlm.nih.gov/32757696/

"Objectives: Some patients with postural orthostatic tachycardia syndrome (POTS) demonstrate improved dysautonomic symptoms following treatment for pelvic venous insufficiency (PVI). This study assessed the prevalence of significant left common iliac vein (LCIV) compression in POTS patients.

Methods: Radiologists retrospectively reviewed CT images of pelvic veins for 216 women (191 with POTS and 25 age-comparable controls).Quantitative vascular analysis identified percent-diameter compression of the LCIV by the right common iliac artery. Significant LCIV compression was defined as >50%.

Results: Significant LCIV compression was found in 69% (131/191) of females with POTS versus 40% (10/25) in controls. The hypothesis that venous compression and presence of POTS are independent was rejected (p = .005).

Conclusions: Significant LCIV compression was noted in a majority of female POTS patients, suggesting that incidence of iliac venous obstruction may be higher than the general population. Patients with POTS and symptoms of PVI may benefit from assessment for venous outflow obstruction."

 

[crussher]

Oh and also any theories as to why the renin-angiotensin-aldosterone system might be messed up in pots/me patients?

Two German researchers, Scheibenbogen and Wirth, have suggested why this might be happening.

This is my summary as to why. Regarding home-made ORS, I'm afraid I can't advise as have no experience. Hopefully someone else can help with that.

Extract from my book:

"However, a range of recent papers by two German researchers, Prof. Carmen Scheibenbogen and Dr. Klaus Wirth, offer another compelling hypothesis for the downregulation of the RAA axis in ME/CFS. In a series of three papers, Wirth & Scheibenbogen posit a convincing ‘big picture’ thesis for the whole pathophysiology of ME/CFS, from the brain, to the endocrine, cardiac and vascular systems, right down to sodium-potassium pump cellular exchange. Their work could represent the most dramatic breakthrough in ME/CFS research to date and is essential reading for anyone interested in understanding the complexities of the illness.[1],[2],[3] I will not focus on all of their ideas here but will limit my discussion to their views on the RAA axis suppression within the illness.

In essence, Wirth & Scheibenbogen believe that central to the illness’ pathophysiology is both a chronic vasoconstrictive state and a chronic impairment among vasodilatory functions. This situation is caused by autonomic changes (in the form of excessive sympathetic tone) and Beta2-adrenergic autoantibodies, both of which lead to the diminished functionality of Beta2-adrenergic receptors, which are particularly responsible for vasodilation. The result of this is poor blood perfusion and systemic hypoxia in the organs and musculoskeletal systems. As normal vasodilatory function is impaired, the body tries to rectify this state of affairs by enlisting emergency ‘back up’ vasodilatory systems, primarily through the activation of the KKS (Kallikrein-Kinin-System) and the release of bradykinin, a powerful vasodilator. While the activation of the KKS represents the body’s attempt to rectify the chronic hypoperfusion, it comes with its own serious side-effects. In particular: i) the vasodilators are powerful enough to cause vascular microleaks leading to the transfer of extracellular fluid into the interstitial space and ii) as the KKS system naturally opposes the actions of the RAA axis, it downregulates the latter thereby increasing salt and water excretion. Under this hypothesis, we therefore have two possible reasons for the emergence of a hypovolemic state in ME/CFS: the actual leaking of blood from extracellular fluid into the interstitial space and an explanation for the significant blunting of the normal RAA axis response to preserve adequate salt & water balance. From the second of these, therefore, we have a compelling potential explanation for the RAA axis downregulation that has so perplexed ME/CFS researchers. It is particularly important to note that, for Scheibenbogen and Wirth, this RAA axis downregulation will become even more pronounced during episodes of post-exertional malaise during which all of the central mechanisms within the illness will necessarily flare up. This episodic deterioration can also explain why ME/CFS patients often note that their thirst is at its worst during periods of post-exertional malaise, as during those times solute loss will increase."

---

[1] Scheibenbogen and Wirth, ‘A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors’, 2020.
[2] Scheibenbogen and Wirth, ‘Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)’, 2021.
[3] Scheibenbogen, Wirth and Paul, ‘An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome’, 2021.

 

[Murph]

@crussher I find your hypothesis credible and important.

I remember dong a 24h urine test once and needed to use extra bottles beyond the enormous one they'd given me. I showed up in the path lab with like 10kg of old soda water bottles full of urine!

I still drink a lot of water but I've bascially given up on straight water. I add sodium pretty much all the time now. Sometimes I add potassium too. It helps but I still drink an awful lot.

One medication i've been given that helps is vasodrine. It was prescribed by ths guy:

He convincingly argues low blood volume causes feelings of anxiety in mecfs. But doesn't recommend drinkng huge amounts. He recommends salt. In that video he says to add "as much as you can stomach" (30 min mark)

 

[Aidan Walsh]

@crussher I find your hypothesis credible and important.

I remember dong a 24h urine test once and needed to use extra bottles beyond the enormous one they'd given me. I showed up in the path lab with like 10kg of old soda water bottles full of urine!

I still drink a lot of water but I've bascially given up on straight water. I add sodium pretty much all the time now. Sometimes I add potassium too. It helps but I still drink an awful lot.

One medication i've been given that helps is vasodrine. It was prescribed by ths guy:

He convincingly argues low blood volume causes feelings of anxiety in mecfs. But doesn't recommend drinkng huge amounts. He recommends salt. In that video he says to add "as much as you can stomach" (30 min mark)

Murph, was this a 24-hour collection of urine for cortisol or the test for Nutcracker Syndrome (ACR) Albumin Creatinine Ratio?

Also, it is 8 hours Supine urine while asleep then 16 hours in upright position it is also called the Orthostatic Proteinuria test. Another test is in the urine looking for blood, I think with urine color dipsticks?

 

[Murph]

Murph, was this a 24-hour collection of urine for cortisol or the test for Nutcracker Syndrome (ACR) Albumin Creatinine Ratio?

Also, it is 8 hours Supine urine while asleep then 16 hours in upright position it is also called the Orthostatic Proteinuria test. Another test is in the urine looking for blood, I think with urine color dipsticks?

can't remember! i think they had a look at some electrolytes etc. Other than volume it didn't raise any alarms if I recall correctly.

 

[Aidan Walsh]

Here are the two papers I know of linking vein compression to POTS:

https://pubmed.ncbi.nlm.nih.gov/35620060/

"We describe three patients with concomitant POTS, EDS, and MTS. Although abdominopelvic vasculature evaluation can be difficult via conventional imaging techniques, we present the use of novel dynamic contrast-enhanced magnetic resonance angiography with Differential Subsampling with Cartesian Ordering (DISCO) and four-dimensional flow magnetic resonance imaging to aid vasculature evaluation and the diagnosis of MTS. Two patients underwent left common iliac vein stenting to treat MTS, experiencing significant improvement in their POTS symptoms and quality of life."


https://pubmed.ncbi.nlm.nih.gov/32757696/

"Objectives: Some patients with postural orthostatic tachycardia syndrome (POTS) demonstrate improved dysautonomic symptoms following treatment for pelvic venous insufficiency (PVI). This study assessed the prevalence of significant left common iliac vein (LCIV) compression in POTS patients.

Methods: Radiologists retrospectively reviewed CT images of pelvic veins for 216 women (191 with POTS and 25 age-comparable controls).Quantitative vascular analysis identified percent-diameter compression of the LCIV by the right common iliac artery. Significant LCIV compression was defined as >50%.

Results: Significant LCIV compression was found in 69% (131/191) of females with POTS versus 40% (10/25) in controls. The hypothesis that venous compression and presence of POTS are independent was rejected (p = .005).

Conclusions: Significant LCIV compression was noted in a majority of female POTS patients, suggesting that incidence of iliac venous obstruction may be higher than the general population. Patients with POTS and symptoms of PVI may benefit from assessment for ve

thank you One thing it is clear nutcracker plays a major role in orthostatic intolerance, when the Doctor woke up in recovery her symptoms were gone the first time, 3 months later her body rejected the procedure she had to have her kidney removed.

One woman they found her pelvis had veins the size of sausages she did not have nutcracker syndrome she had Pelvic Compression Syndrome. POTS, Syncope, Orthostatic Intolerance OI are all different named LABELS

 

[Shanti1]

@crussher Thanks for your great work on this common and sometimes distressing symptom. When I was at my worst I drank about 8L of water a day, now I'm at about 3-4L.

In regard to this part of Wirth & Scheibenbogen's theory:

As normal vasodilatory function is impaired, the body tries to rectify this state of affairs by enlisting emergency ‘back up’ vasodilatory systems, primarily through the activation of the KKS (Kallikrein-Kinin-System) and the release of bradykinin, a powerful vasodilator.

I looked for a blood test for bradykinin, but it doesn't look like there are any commercially available, probably due to the extremely short half-life.

I wonder if a very low dose of a bradykinin receptor agonist, such as Icatibant would be helpful?
It is injectable, hard to get ahold of, and very expensive, so we probably won't find out anytime soon.

Maybe there are some plant compounds that could be used.

 

[Aidan Walsh]

Here are the two papers I know of linking vein compression to POTS:

https://pubmed.ncbi.nlm.nih.gov/35620060/

"We describe three patients with concomitant POTS, EDS, and MTS. Although abdominopelvic vasculature evaluation can be difficult via conventional imaging techniques, we present the use of novel dynamic contrast-enhanced magnetic resonance angiography with Differential Subsampling with Cartesian Ordering (DISCO) and four-dimensional flow magnetic resonance imaging to aid vasculature evaluation and the diagnosis of MTS. Two patients underwent left common iliac vein stenting to treat MTS, experiencing significant improvement in their POTS symptoms and quality of life."


https://pubmed.ncbi.nlm.nih.gov/32757696/

"Objectives: Some patients with postural orthostatic tachycardia syndrome (POTS) demonstrate improved dysautonomic symptoms following treatment for pelvic venous insufficiency (PVI). This study assessed the prevalence of significant left common iliac vein (LCIV) compression in POTS patients.

Methods: Radiologists retrospectively reviewed CT images of pelvic veins for 216 women (191 with POTS and 25 age-comparable controls).Quantitative vascular analysis identified percent-diameter compression of the LCIV by the right common iliac artery. Significant LCIV compression was defined as >50%.

Results: Significant LCIV compression was found in 69% (131/191) of females with POTS versus 40% (10/25) in controls. The hypothesis that venous compression and presence of POTS are independent was rejected (p = .005).

Conclusions: Significant LCIV compression was noted in a majority of female POTS patients, suggesting that incidence of iliac venous obstruction may be higher than the general population. Patients with POTS and symptoms of PVI may benefit from assessment for venous outflow obstruction."

The more I look into vascular issues the more I find for Nutcracker Syndrome it also comes with APS, MSAS, MALS & Pelvic Compression Syndrome even in Men as well countless have all of the above diagnosed. The Doctor GP Patient author also had the latent TB from Birth

 

[Aidan Walsh]

The announcement from the OMF on the 1st of the month is about their clinical trials double-blinded the Video is now in their Newsletter

 

[Aidan Walsh]

Two German researchers, Scheibenbogen and Wirth, have suggested why this might be happening.

This is my summary as to why. Regarding home-made ORS, I'm afraid I can't advise as have no experience. Hopefully someone else can help with that.

Extract from my book:

"However, a range of recent papers by two German researchers, Prof. Carmen Scheibenbogen and Dr. Klaus Wirth, offer another compelling hypothesis for the downregulation of the RAA axis in ME/CFS. In a series of three papers, Wirth & Scheibenbogen posit a convincing ‘big picture’ thesis for the whole pathophysiology of ME/CFS, from the brain, to the endocrine, cardiac and vascular systems, right down to sodium-potassium pump cellular exchange. Their work could represent the most dramatic breakthrough in ME/CFS research to date and is essential reading for anyone interested in understanding the complexities of the illness.[1],[2],[3] I will not focus on all of their ideas here but will limit my discussion to their views on the RAA axis suppression within the illness.

In essence, Wirth & Scheibenbogen believe that central to the illness’ pathophysiology is both a chronic vasoconstrictive state and a chronic impairment among vasodilatory functions. This situation is caused by autonomic changes (in the form of excessive sympathetic tone) and Beta2-adrenergic autoantibodies, both of which lead to the diminished functionality of Beta2-adrenergic receptors, which are particularly responsible for vasodilation. The result of this is poor blood perfusion and systemic hypoxia in the organs and musculoskeletal systems. As normal vasodilatory function is impaired, the body tries to rectify this state of affairs by enlisting emergency ‘back up’ vasodilatory systems, primarily through the activation of the KKS (Kallikrein-Kinin-System) and the release of bradykinin, a powerful vasodilator. While the activation of the KKS represents the body’s attempt to rectify the chronic hypoperfusion, it comes with its own serious side-effects. In particular: i) the vasodilators are powerful enough to cause vascular microleaks leading to the transfer of extracellular fluid into the interstitial space and ii) as the KKS system naturally opposes the actions of the RAA axis, it downregulates the latter thereby increasing salt and water excretion. Under this hypothesis, we therefore have two possible reasons for the emergence of a hypovolemic state in ME/CFS: the actual leaking of blood from extracellular fluid into the interstitial space and an explanation for the significant blunting of the normal RAA axis response to preserve adequate salt & water balance. From the second of these, therefore, we have a compelling potential explanation for the RAA axis downregulation that has so perplexed ME/CFS researchers. It is particularly important to note that, for Scheibenbogen and Wirth, this RAA axis downregulation will become even more pronounced during episodes of post-exertional malaise during which all of the central mechanisms within the illness will necessarily flare up. This episodic deterioration can also explain why ME/CFS patients often note that their thirst is at its worst during periods of post-exertional malaise, as during those times solute loss will increase."

---

[1] Scheibenbogen and Wirth, ‘A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors’, 2020.
[2] Scheibenbogen and Wirth, ‘Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)’, 2021.
[3] Scheibenbogen, Wirth and Paul, ‘An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome’, 2021.

@crussher, a vasoconstrictive state to me sounds 100% like compressed veins in Nutcracker syndrome. I saw one woman today her MRI Contrast showed she has a renal vein compression between her spine & the aorta not between the aorta & the SMA Vein

 

[crussher]

Have written blog for Health Rising about my experience and which summarises my book, available here.

 

[Mary]

@crussher - thanks for letting Cort publish your blog, thanks for freely sharing your book and thanks for writing so very clearly! Too often scientific articles look like mumbo jumbo to me, they're hard for me to make sense of, but your writing is very clear and intelligible.

 

[crussher]

@crussher - thanks for letting Cort publish your blog, thanks for freely sharing your book and thanks for writing so very clearly! Too often scientific articles look like mumbo jumbo to me, they're hard for me to make sense of, but your writing is very clear and intelligible.

Ah thank you, Mary, for those kinds words. I have the exact same feeling about 'mumbo jumbo' and always try to make my writing as clear as possible.

 

[Mary]

@crussher - one last thing. I don't have hypovolemia - I'm not abnormally thirsty. But, fwiw, I tend to crave salt in general - would prefer salty things to sweet things, and when I'm crashed (PEM) I definitely crave salt - will always have popcorn with salt for lunch, it's the only time I do that.

And one other anomaly - I often will feel hungry when I'm actually thirsty, especially after lunch. I'll find myself being quite hungry half an hour after lunch, and if I make the mistake of eating then, tend to pack on the pounds. But if I remember that I might actually be thirsty and drink a glass of water instead of eating then, my "hunger" for food goes away.

I don't know if the above has anything to do with your book, but am just throwing it out there for the heck of it -

 

[crussher]

@crussher - one last thing. I don't have hypovolemia - I'm not abnormally thirsty. But, fwiw, I tend to crave salt in general - would prefer salty things to sweet things, and when I'm crashed (PEM) I definitely crave salt - will always have popcorn with salt for lunch, it's the only time I do that.

And one other anomaly - I often will feel hungry when I'm actually thirsty, especially after lunch. I'll find myself being quite hungry half an hour after lunch, and if I make the mistake of eating then, tend to pack on the pounds. But if I remember that I might actually be thirsty and drink a glass of water instead of eating then, my "hunger" for food goes away.

I don't know if the above has anything to do with your book, but am just throwing it out there for the heck of it -

Oh, I think the salt craving is really common for ME patients!

You might have a slight reduction in blood volume? The thirst isn't triggered until you have 280ml plasma drop (that's 10% of total plasma volume) but a lot of ME patients have just a 50 ml or 100 ml drop, and so they wouldn't feel unusually thirsty as a result. It's a possibility anyway. Certainly the salt wasting thing is so central to the illness that craving salt makes a lot of sense. I crave it easily myself too.

 

[kushami]

Oh and also any theories as to why the renin-angiotensin-aldosterone system might be messed up in pots/me patients?

Dr Satish Raj has pondered this topic in regards to POTS.

“Renin-aldosterone paradox and perturbed blood volume regulation underlying postural tachycardia syndrome”
https://pubmed.ncbi.nlm.nih.gov/15781744/

I think he also speculates a bit in the questions section of this video lecture, which starts at the 50 min mark. (You can probably skip the main part of the lecture if you have already read the paper above.)

Understanding blood volume and hemodynamics in POTS (video)

Please forgive me if he doesn’t … I watched it a while ago and might be misremembering.

Edit: Just found that Cort has written a nice article on this topic:
https://www.healthrising.org/blog/2...onic-fatigue-syndrome-pots-renin-aldosterone/

 

[MeSci]

Having had dental treatment, involving removal of teeth and replacement of dental fillings, I no longer have hyponatraemia, and my blood pressure is completely normal!

I had been taking desmopressin for hyponatraemia since 2000, and Nebivolol for high blood pressure since approx December 2014. Before the Nebivolol I took an ACE inhibitor, which severely worsened my hyponatraemia and landed me in hospital.

I have reported it here:
https://www.s4me.info/threads/diarrhoea-caused-by-too-much-desmopressin.36981/#post-521077

I paid about 10 times more to have white fillings instead of the probably-toxic mercury ones, which would have been virtually free.

I wonder how many people have had these problems due to mercury fillings?

I still have ME.

CORRECTION

The desmopressin was for excessive urination (polyuria), but I also had hyponatraemia, which was worsened by the initial blood pressure drugs (ACE inhibitors).

I think that's right - getting foggy!

 

[ruben]

I did have my Mercury fillings removed some years ago. No change to my ME/CFS.