• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Narrowed Small Blood Vessels Linked to Fatigue in ME/CFS - HealthRising

raghav

Senior Member
Messages
809
Location
India
Narrowed Small Blood Vessels Linked to Fatigue in ME/CFS

https://www.healthrising.org/blog/2...-vessels-arterioles-chronic-fatigue-syndrome/

The Gist
  • Using a non-invasive approach (Endo-Pat) featuring a blood pressure cuff and a finger monitor, German researchers assessed the functioning of the small blood vessels called arterioles.
  • The arterioles, which are located between the arteries and the capillaries, regulate blood flows by producing nitric oxide, a blood vessel dilator.
  • The study assessed something called a “reactive hyperemia index” (RHI). An RHI below 2 is considered a cause for concern. It suggests that damage to the endothelial lining to the blood vessels has occurred, which is blocking the flow of blood. Endothelial dysfunction is often the first sign of cardiovascular disease.
  • The small study found that about 50% of people with ME/CFS had low RHI’s. Attempts to find a metabolic or immune cause including B2 adrenergic antibodies were unsuccessful, however.
  • A small substudy involving 6 patients with increased levels of B2 adrenergic antibodies, however, did find that immunoadsorption resolved the small blood vessel issues in 5 of them.
  • Dr. Scheibenbogen reported that another small follow-up immunoadsorption study has produced similar results to the first one. (The first one produced excellent results in a subset of patients.)
  • Three studies using the Endo-Pat technology have been done in ME/CFS – two have found endothelial dysfunction and one has not.
  • Larger studies are needed to validate this study’s intriguing finding indicating that narrowed small blood vessels in large subset of people with ME/CFS may be reducing blood flows to the tissues.
  • Other studies, but not all, have found reduced blood flows to the brain and/or muscles in ME/CFS. David Systrom’s large studies indicate that reduced oxygen delivery (i.e. energy) to the muscles is present in this disease.
  • Systrom believes three factors – one of which involves the microcirculation – may be causing the oxygen delivery problem.
  • As endothelial dysfunction is found in many diseases, it cannot by itself explain what’s causing the fatigue and exertion problems in ME/CFS. Wirth and Scheibenbogen have proposed impaired blood vessel functioning that results in dramatic increases in pain and fatigue producing vasodilators is present in ME/CFS. They are working on a second hypothesis they believe may explain the energetic problems in ME/CFS.

Cause?
What might be causing it is another matter. Factors like high blood pressure and high blood glucose have not been found in ME/CFS. High levels of lipoproteins, oxidative stress and inactivity have been.


Nitric oxide synthase – the study suggested that the small blood vessels in a significant subset of ME/CFS patients may not be producing enough NO.
Systrom proposed the oxygen delivery problem could be caused by mitochondrial issues, hyperventilation and problems with the oxyhemoglobin dissociation curve – and/or microcirculatory problems. This small German study suggest the microcirculatory problems might be a big deal for a large subset of patients. Its results suggested that reduced nitric oxide production by the endothelial lining of small blood vessels (arterioles) was at least, in part, contributing to the fatigue and other symptoms in about half of the ME/CFS study group.

Because endothelial dysfunction can occur in many diseases, if it’s present in ME/CFS other factors must come into play that produce fatigue, post-exertional problems, etc. (The “Blood Vessel Crunch” describes a blood vessel hypothesis that is unique to ME/CFS. The authors, Wirth and Scheibenbogen, are working on the second part of that hypothesis which seeks to explain the energy production problems in this disease.)

While the lab results couldn’t uncover why the small blood vessel shutdown was occurring, a small immunoadsorption trial which reversed the small blood vessel problems, suggested that the problem could in the immune system, and possibly in antibodies that affect the beta adrenergic receptors found on the small blood vessels. Much larger studies, of course, are needed to validate their findings, and it should be noted that Montoya’s study did not find evidence of endothelial dysfunction. Dr. Scheibenbogen reported that a small, second as yet unpublished immunoabsorption ME/CFS study had results similar to the first one.

The study did not report on natural NO boosters but several natural substances (L-Citrulline, L-arginine, niacin) are reportedly able to increase nitric oxide levels. I have no idea if they would work in ME/CFS or not but at least with me, niacin (Vit B-3) can temporarily provide small boosts to cognition and oddly enough, given its rather stimulating properties, be relaxing.

Lastly, the EndoPat is typically used to assess the risk of cardiovascular disease. The study results suggested that half the study group might be at increased risk. While no studies have verified that this is so, the combination of arterial stiffness, low grade inflammation, and high levels of oxidative stress has been hypothesized to put people with ME/CFS at increased risk of cardiovascular diseases.
 
Last edited:

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Thanks for posting @raghav I was very interested as I’ve had great improvements lately by taking tetrahydrahydrobiopterin (Kuvan) which is needed for arginine to make NO. Still, I got some NO test strips by Humann And found my NO was low.

With further investigation, this seems to be related to NOS uncoupling which promotes high peroxynitrites which impair mito complex I and damage mito membranes, as well as decreasing antioxidants reserves, increasing product of superoxide and hydrogen peroxide radicals.

Hoping the scientists look into this.
 
Last edited:

andyguitar

Moderator
Messages
6,595
Location
South east England
I found another really interesting paper by the same person
Looks like the researchers are onto something @wabi-sabi , Para 3 of the introduction is worth thinking about. It says "Removal of these autoantibodies by IgG apheresis led to a rapid improvement in most patients" Sounds good. Is this the "Something in the blood" that is causing symptoms?
 

Strawberry

Senior Member
Messages
2,107
Location
Seattle, WA USA
"Removal of these autoantibodies by IgG apheresis led to a rapid improvement in most patients"

I think Cort's article mentioned the IgG removal too, at about 20,000 USD if I remember right. Pricey, but inspiring. Although if my memory serves me right, they assume it isn't the antibodies? I guess the cell trend test didn't reflect the sickness level of the patient in the way that would have explained that. I don't know though, poor understanding and poor memory. Anyway, that article grabbed my attention in a big way. I actually texted a portion of Cort's article to my daughter yesterday, here is the exact quote I sent her:

The possible presence of stagnant hypoxia in ME/CFS and POTS provides yet another clue that oxygen delivery in ME/CFS and related diseases may be a problem. Stagnant hypoxia occurs when the oxygen content of the blood is normal, but the blood is moving too slowly to deliver sufficient amounts of blood to the tissues.

I've had my doctor's office take me on "walks" twice (about 1-2 blocks), and I get out of breath to where I can't talk any more, but my blood ox always hold steady at 97 or 98%. So IMHO it could be either thick blood, or narrowed arteries. Either way, it could explain much. Not sure if it explains some of my earlier muscle symptoms (I wound up doing a bit of searching yesterday looking for symptoms but couldn't find my specific muscle issue) but worth having a doctor try to put the puzzle pieces together.

Hopeful!
 

wabi-sabi

Senior Member
Messages
1,458
Location
small town midwest
@andyguitar I'm not sure if these autoantibodies are the same as Dr. Davis's something in the blood or not. As I recall(hopefully) Dr. Davis's tests were done with PMBCs and I just don't know if PMBCs have M3 or B2 receptors to react with autoantibodies. Also, I think I remember someone saying the 'something in the blood" was about the size of an exosome. Again, I don't how the size of exosomes compares to antibodies.

As I understand it, the something in the blood is affecting cellular metabolism (which has lots of unpleasant effects), but this paper is talking about something that affects the blood vessel walls and therefore oxygen delivery (which also has lots of unpleasant effects). The conclusion makes it sound as though the authors feel that PwME have more risk for heart diease than others, based on the blood vessel problems.
 

andyguitar

Moderator
Messages
6,595
Location
South east England
I've had my doctor's office take me on "walks" twice (about 1-2 blocks), and I get out of breath to where I can't talk any more, but my blood ox always hold steady at 97 or 98%.
Yeah I've heard that a few times- blood ox does not change when patient exerts themselves.
Also, I think I remember someone saying the 'something in the blood" was about the size of an exosome. Again, I don't how the size of exosomes compares to antibodies.
The paper you posted @wabi-sabi is quite a long one, as are the references so it might take a while to get a handle on it, but it's well worth careful study. It's the one I am talking about not the one @raghav put up.
"Removal of these autoantibodies by IgG apheresis led to a rapid improvement in most patients"
Makes a change for research to come up with a treatment. And that is the really interesting thing here.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
I think Cort's article mentioned the IgG removal too, at about 20,000 USD if I remember right. Pricey, but inspiring. Although if my memory serves me right, they assume it isn't the antibodies? I guess the cell trend test didn't reflect the sickness level of the patient in the way that would have explained that. I don't know though, poor understanding and poor memory. Anyway, that article grabbed my attention in a big way. I actually texted a portion of Cort's article to my daughter yesterday, here is the exact quote I sent her:

I've had my doctor's office take me on "walks" twice (about 1-2 blocks), and I get out of breath to where I can't talk any more, but my blood ox always hold steady at 97 or 98%. So IMHO it could be either thick blood, or narrowed arteries. Either way, it could explain much. Not sure if it explains some of my earlier muscle symptoms (I wound up doing a bit of searching yesterday looking for symptoms but couldn't find my specific muscle issue) but worth having a doctor try to put the puzzle pieces together.

Hopeful!
It may be worthwhile to look into depletion if nitric oxide and/or BH4 which may contribute to these issues.

IVIG and/or Rituximab are alternatives to plasmapheresis. They have helped my autoimmune POTS.
 

dreampop

Senior Member
Messages
296
The irony is vasodilators tend to make my pots worse.

I'm wondering if there are any drugs or herbs that dilate the small blood vessels, but leave the larger ones alone.
 

toyfoof

Senior Member
Messages
1,173
Location
Sedona, AZ
"Removal of these autoantibodies by IgG apheresis led to a rapid improvement in most patients"

The science of this paper is way over my head, but the descriptions of how their theory presents in ME/CFS symptoms — particularly as laid out in Table 5 — really resonate with me.

Does anybody know if having the quoted procedure is a “one and done” type thing, where the autoantibodies removal is permanent, or would it need to be done over and over because the autoantibodies come back?
 

MonkeyMan

Senior Member
Messages
405
Does anybody know if having the quoted procedure is a “one and done” type thing, where the autoantibodies removal is permanent, or would it need to be done over and over because the autoantibodies come back?

Great question. Wish I knew the answer! (If the results are permanent then I'm sure a lot of us would try this procedure, expenses be damned!)
 
Last edited:

MonkeyMan

Senior Member
Messages
405
I think I found the answer in the paper about the 10 patients who received the treatment (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854315/)

"3 of these patients had long lasting moderate to marked improvement for 6–12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening."

So $20,000 for a treatment that has a 3 in 10 chance of producing long-term improvement. :(
 
Last edited:

andyguitar

Moderator
Messages
6,595
Location
South east England
Does anybody know if having the quoted procedure is a “one and done” type thing, where the autoantibodies removal is permanent, or would it need to be done over and over because the autoantibodies come back?
As the patients were treated not that long ago we will have to wait and see.
So $20,000 for a treatment that has a 3 in 10 chance of producing long-term improvement. :(
The chances might be much better than that as the diagnosis of me/cfs is not that precise, so some of the subjects might not have had it. There is something in the back of my mind about this type of treatment when it comes to how long it lasts. Cant bleeding remember!!