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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, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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Pentoxifyllihe increased my fatigue and also caused bleeding from my bottom. So did not try a second dose. I took Trental 400 mg PR (Prolonged release) tablet. I could not get the 100 mg tablet.
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.
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.
Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice
Cheng‐Cheng Li
Wei‐Xiang Chen
2020
Abstract
Aims
Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated.
Méthode
To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated.
Results
Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration.
Moreover, NR administration significantly reduced glial activation around the Vessels.
Conclusion
Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.
This may explain why nicotinamide riboside helps so much some of us.
Why is NR so costly ?
The CellTrend POTS test would be helpful. My blood got sent from California to Germany so the test could be done.
Beyond these specific antibodies, a lot of patients have had other antibodies causing all sorts of weird symptoms, so you might look into some of the antibodies on this list collected from patients here on Phoenix Rising and see if you have any of the symptoms that relate to any of the antibodies before pursuing any of the tests.
Additionally, EBV is notorious for triggering all kinds of antibodies, and other herpes viruses and other infections can do so too. So if you find antibodies, you'll want to be sure that you don't have an infection quietly creating more. I didn't think I was sick for about 3 years, just fatigued but had multiple chronic infections that my immune system wasn't doing a good job of fighting. Fighting all of these issues has been tremendously helpful. I am off my MCAS meds and have greatly reduced my POTS meds and the Rituximab is responsible for this progress.