Reduced Endothelial Function in ME/CFS–Results Open-Label Cyclophosphamide Intervention Study

Learner1

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Seems the were looking to improve endothelial function due to reduced nitric oxide.

There are easier ways of going about this without using a mitochondria damaging toxic drug like cyclophosphamide.

"Cyclophosphamide leads to persistent deficits in physical performance and in vivo mitochondria function"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507312/

Low NO can be tested with Humann test strips:

https://shop.humann.com/products/ni...YcaOKvKnRoC_MUQAvD_BwE&variant=19861378072687

This Berkeley Life NO booster product can increase NO, as well as others;

https://www.pureformulas.com/nitric...u1sdijuXWw6WZucxTK92SbYVZP0HDr7RoCaQwQAvD_BwE

Additionally, many of us have a deficit of tetrahydrobiopterin (BH4) and increasing it can cause the body to make more NO.

https://www.pulsus.com/scholarly-ar...portance-of-tetrahydrobiopterin-bh4-4879.html


These are cheaper approaches as well.
 

Diwi9

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I think this study was more of a rule-out study and found this the most interesting observation:
The lack of correlation between symptom improvement and changes in endothelial function could imply that reduced endothelial function, although present in a subgroup of ME/CFS patients, does not relate directly to the underlying pathomechanism of the disease.
 

msf

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Yeah, this is a knock-on effect, or at least is in my case. I used to have symptoms that would suggest changes in endothelial function after exercise (such as dull pain in the extremities, which I assume is caused by reduced circulation), but since I have solved what I assume to be the energy issues (see my thread on Chinese skullcap), these knock-on effects no longer occur.
 

Pyrrhus

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Just to clarify:

This study used two techniques to measure endothelial dysfunction:
  • Flow-mediated dilation (FMD)
  • Post-occlusive reactive hyperemia (PORH)
There are many different types of endothelial dysfunction in blood vessels, and FMD appears to only measure the ability of arteries (not veins) to dilate in response to nitric oxide (not in response to autonomic nerves).

PORH is a broader measure of endothelial dysfunction, which looks at microvascular tissue and may take into account input from the nervous system, but this broader approach might also make the resultant data harder to interpret.

Although it is important to note that both techniques produced significant and interesting findings, neither technique is intended to measure the activity of autonomic nerves that control dilation of veins.
 
Last edited:

Pyrrhus

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Authors:
Kari Sørland1,2*, Miriam Kristine Sandvik3, Ingrid Gurvin Rekeland1,4, Lis Ribu2, Milada Cvancarova Småstuen2, Olav Mella1,4 and Øystein Fluge1,4

Full abstract:
Sørland et al 2021 said:
Introduction:
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide.

Methods:
This substudy to the open-label phase II trial “Cyclophosphamide in ME/CFS” included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18–65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30).

Results:
Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5–13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7–21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343–4,334) vs. healthy individuals 1,886 p.u. (range 808–8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls.

Conclusions:
Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.