Redefining ME/CFS: Toward a Progressive Immunovascular Syndrome (PIVS)

[Gala]

Hi again,

I've finally decided to stop taking valacyclovir (Valtrex) because it was triggering significant neuroinflammatory symptoms. After discussing it with my doctor, we've agreed to start with LDN, and once the inflammation is better controlled, we'll consider reintroducing valacyclovir.

In the meantime, I've been working on simplifying and prioritizing the most relevant supplements for our condition, organizing them by functional areas from most to least critical. I believe that before targeting infections or trying to stimulate the mitochondria—which are in a state of near-hibernation as a survival mechanism—it’s best to begin by restoring epithelial tissues (intestinal and pulmonary), reducing inflammation, and repairing the endothelium.

Here's the summary table—I'd appreciate your feedback on whether you think there's any important supplement missing.
Thanks so much!

D (Digestive)
Restore intestinal and pulmonary epithelium
Glutamine
Zinc carnosine
Butyrate
Probiotics
Bovine colostrum
Lactoferrin
Vitamins D3 and A
NAG (N-Acetylglucosamine)
Aloe vera
Hyaluronic acid
Collagen with silica
Fucoidan

I (Inflammation)
Control inflammation and support detoxification
Luteolin
Quercetin
Curcumin
Omega 3 + Astaxanthin
Resveratrol / Pterostilbene
Baicalin
NAC
PEA (palmitoylethanolamide)
Melatonin
Antihistamines

V (Vascular)
Repair endothelium and improve blood circulation
Nattokinase / Lumbrokinase
Arginine
Coenzyme Q10
Vitamin C
Ginkgo biloba
1-MNA

A (Anaerobics)
Target anaerobic pathogens: viruses and bacteria thriving in low-oxygen environments
Monolaurin
Andrographis
AHCC
Olive leaf extract
Berberine
Lysine

 

[cfs since 1998]

Hi again,

Hi Gala. Not sure if it was posted aleady but a news article was just published about a South Africa research group working on the hypothesis of direct infection of endothelial cells by viruses. It seems congruent wth your hypothesis.

https://iol.co.za/weekend-argus/new...e-shocking-link-between-mecfs-and-long-covid/

I've finally decided to stop taking valacyclovir (Valtrex) because it was triggering significant neuroinflammatory symptoms. After discussing it with my doctor, we've agreed to start with LDN, and once the inflammation is better controlled, we'll consider reintroducing valacyclovir.

I've also had a negative experience from valacyclovir. The side effects it has produced has bewildered me as they are paradoxically the same symptoms as ME/CFS, especially the neurovascular ones. What symptoms have you experienced? I'm taking it again anyway and hoping I can tolerate it if I work up the dose gradually. I was wondering if you have shared what dose you took and how long you took it?

I was considering switching to famciclovir but did a search of various ME/CFS patient groups and there are negative experiences with that one as well.

In the meantime, I've been working on simplifying and prioritizing the most relevant supplements for our condition, organizing them by functional areas from most to least critical. I believe that before targeting infections or trying to stimulate the mitochondria—which are in a state of near-hibernation as a survival mechanism—it’s best to begin by restoring epithelial tissues (intestinal and pulmonary), reducing inflammation, and repairing the endothelium.

Here's the summary table—I'd appreciate your feedback on whether you think there's any important supplement missing.
Thanks so much!

Consider pentoxifylline for microcirculation?

Also interested in your thoughts on metformin. Seems like it can be good for us but there might be a few negative aspects.

 

[Gala]

Hi Gala. Not sure if it was posted aleady but a news article was just published about a South Africa research group working on the hypothesis of direct infection of endothelial cells by viruses. It seems congruent wth your hypothesis.

https://iol.co.za/weekend-argus/new...e-shocking-link-between-mecfs-and-long-covid/


I've also had a negative experience from valacyclovir. The side effects it has produced has bewildered me as they are paradoxically the same symptoms as ME/CFS, especially the neurovascular ones. What symptoms have you experienced? I'm taking it again anyway and hoping I can tolerate it if I work up the dose gradually. I was wondering if you have shared what dose you took and how long you took it?

I was considering switching to famciclovir but did a search of various ME/CFS patient groups and there are negative experiences with that one as well.


Consider pentoxifylline for microcirculation?

Also interested in your thoughts on metformin. Seems like it can be good for us but there might be a few negative aspects.

Muchas gracias por su respuesta.

I’ve only been taking Valaciclovir at 2 g/day for 15 days (half the dose during the first week), but I decided to pause it after noticing that my GGT levels had risen above 100, along with a worsening of several symptoms: increased dizziness, irritability, headache, sensitivity to noise and light, inability to stand upright, and heightened stiffness and numbness in my hands and feet. It truly felt like the worst stage of the illness.

It has long been known that COVID causes significant endothelial damage, and later studies showed similar findings in ME/CFS, just like with Pretorius' microclots. Thanks to Long COVID, research into our condition has progressed by decades — we were moving at cruising speed, and now we’ve hit the accelerator.

The study you shared, which I had actually come across a few days ago, proposes a very compelling hypothesis to explain why the endothelium becomes damaged. It’s not just that the inflammation caused by fighting the virus harms it — but that the virus itself may have the ability to directly infect and persist within endothelial cells, driving them into a senescent “zombie-like” state that fuels chronic inflammation and microclot formation. Thank you for sharing it — it really adds depth to the understanding of this mechanism.

The point is, the endothelium appears to be a far more critical organ than previously thought, with connections to areas like the gut microbiota and intestinal barrierheal the battlefield first — repairing both epithelial and endothelial membranes — and control inflammation to avoid excessive damage when we finally confront the pathogens (via medical treatments or antiviral supplements).

I'm particularly interested in exploring LDN, sulodexide, Hemovas, and pentoxifylline, among other potentially useful treatments such as ivabradine or fludrocortisone. However, all of these are prescription-based medications and may carry greater risks of adverse interactions, so the DIVA protocol (which has turned out to be quite a nice acronym) does not currently include pharmaceutical treatments. I haven’t yet read much about metformin, but I’ll look into it — thank you for the reference.

I’m going to add NAC, lysine, PEA (palmitoylethanolamide), melatonin, and antihistamines, all of which I find interesting and potentially helpful for supporting immune regulation, inflammation control, and symptom relief — and many of which I already take.

 

[pamojja]

I'm following your developing thoughts with interest, since my ME/CFS developed with the onset of real CVD only. An 80% stenosis at my abdominal aorta from PAD, and walking disability. It's been barely noticeable already 2 years before, starting with a myopericarditis.

Could get rid of the walking disability in 2015, 3 years earlier of symptoms of COPD, and 3 years later PEMs ceased. All through comprehensive lifestyle changes and Orthomolecular supplementation. LDN too. Therefore, I can add some from personal experience overcoming it.

I'd appreciate your feedback on whether you think there's any important supplement missing.
Thanks so much!

D (Digestive)
Restore intestinal and pulmonary epithelium

Sadly, only did a microbiome test after my main remission. And a very unusual outcome, in that it was more diverse than 90% tested, by ubiome. Actually had twice as much butyrate producer microbes, as in healthy tested, in my microbiome.

On your list, vitamin D2, K2 and A, I dosed high (while monitoring blood levels; overshooting 25(OH)D to 135 ng/ml, through additional sunshine, correlated with remission of PEM). Everything else, not so much. But what's definitely missing, and I took in copious amounts, are soluble fibers. Resistant potato starch, inulin, glucomannan, beta-glucan, acacia, apple pectin, etc. Though I ate fermented foods every day, none of those bacteria showed in my microbiome.

With the COPD, and therefore pulmonary epithelium too, only a few months break at the south Indian sea helped. Many lung-function supporting Ayurvedics there (haridra, vasaka, dashamoola, pushkarmoola, etc.), as well as an unplanned strong fever for one whole month (probably typhoid; otherwise no fever for the last 25 years).

I (Inflammation)
Control inflammation and support detoxification

High dose ascorbic acid worked like any prescription antihistamine for me. I would definitely add boswellia and, if available, guggulu extracts to that list.

For detoxification, definitely liver support, like (phosphatidyl) choline (ie. organic eggs) and milk thistle.

V (Vascular)
Repair endothelium and improve blood circulation

Ascorbic acid at therapeutic high doses (above 6 g/d; I took in average 25 g/d for 16 years now) right away improved circulation and gradually my walking disability. Arginines or for example things like CoQ10, Gingko Biloba were important too. But progress easily undone by the COPD.

Maybe a coincidence, but after reading this article: https://knowledgeofhealth.com/the-m...l-molecule-20-years-before-cholesterol-drugs/ I trialled up to 5 g/d of chondroitin sulfate. Correlating with my final remission of the walking disability.

A (Anaerobics)
Target anaerobic pathogens: viruses and bacteria thriving in low-oxygen environments

Lysine at 6 g/d.

I didn't use carnosine (beta-alanine instead), butyrate, colostrum, lactoferrin, NAG, hyaluronic, fucoidan, PEA, prescription antihistamines, lumbrokinase, 1-MNA (3 g/d of B3 vitamins instead), AHCC (other mushroom extracts instead). Some things like ptherostibene, resveratrol, berberine or nattokinase in low doses only.

And I want to remind, that due to biochemical individuality, everyone's response to supplements might be different. Therefore, always good to start low dose, and increase gradually across weeks, months and years.