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.

 

[wabi-sabi]

I've finally decided to stop taking valacyclovir (Valtrex) because it was triggering significant neuroinflammatory symptoms.

I'm glad to hear it! I mean that you stopped, not about the neuropathy.

That's an awful lot of supplements to sort out which are helping you are which aren't doing anything. Are you starting these all at once or little by little?

 

[Rufous McKinney]

from early life probably play a role too. I personally had constant gastrointestinal discomfort as a child.

I had severe food allergies starting at age one. My mother said it was because they fed me peas at age two months. Well, EVERYBODY was told to feed the babies food FAR too early back in the 1950s.

 

[Gala]

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.



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).



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.



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.



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.

Thank you very much for your contributions. Interestingly, I've been taking supplements for knee cartilage—chondroitin and glucosamine—for many years, and I had already told the gastroenterologist that I noticed they worked very well for my gut. I'm going to study all the supplements you mentioned in depth to continue completing the table.

 

[Gala]

I'm glad to hear it! I mean that you stopped, not about the neuropathy.

That's an awful lot of supplements to sort out which are helping you are which aren't doing anything. Are you starting these all at once or little by little?

Thank you so much! Regarding the DIVA supplement table, my initial goal is to highlight the most effective supplements for each of the areas mentioned—definitely not to suggest that all of them need to be tried, haha. I need to make that point clear.

The next step is to create a short guide featuring a selection of the most relevant supplements—a kind of “must-have” list (as long as it's ensured that there are no contraindications with other medications, supplements, or pre-existing conditions. That’s why it’s essential for each person to follow up with their doctor).

 

[Gala]

I’ve just finished a diagnostic guide for ME/CFS with the tests I consider most relevant, organized by priority and including approximate prices (based on 2025 rates in Spain, in euros). I’d really appreciate your feedback and suggestions—thank you so much!

 

[pamojja]

I'm going to study all the supplements you mentioned in depth to continue completing the table.

I forgot, but definitely would add magnesium too. It just does so much, and somehow would fit in all of your 4 categories. Already deficient in the majority of the population.

(as long as it's ensured that there are no contraindications with other medications, supplements, or pre-existing conditions. That’s why it’s essential for each person to follow up with their doctor).

Many, like me, have been unlucky finding such a doc, who would even consider medical history, know enough about supplements, or even contraindication of medications, nor do blood tests unfamiliar with. As you outline in the next post, that's exactly how I've been able to address all underlying health issues.

Found at least a GP doing part of the lab-tests, I suggested. Some additional paid out of pocket. With this it was possible to identify all areas to be addressed (almost everything, in my case), and in the course of over a decade monitoring worsening or improvements to be related to trialled interventions. With the advantage that lab-tests register, what otherwise is felt only years latter. Of course, self-education about all supplements is needed.

I’d really appreciate your feedback

Glucose profile: I would add at least a few 1-hr postprandial glucose (prediabetes is oven not caught without), C-peptide or insulin for calculating insulin resistance. Hb1Ac.

Thyroid: free T3 (the only low in my case).

B-vitamin: Serum values might become useless, as soon as supplementing. Since measuring unmetabolized forms too. MMA or Transcobalamin would be more accurate for B12.

Cortisol: an additional 24 hrs urine cortisol test might give a larger picture.

Erythrocytes vitamins and minerals: I had to substitute with whole-blood tests, since some not available (like the important magnesium).

 

[wabi-sabi]

I’d really appreciate your feedback and suggestions—thank you so much!

You are putting a huge amount of energy into this!

What are you trying to gain by making this guide instead of using the guide on the Bateman Horne website? I'm not trying to discourage your effort- just encourage good use of resources. You are doing work that other people have already done and your energy might be better spent building on their work instead of reinventing it or creating something entirely new that only you can do.

https://batemanhornecenter.org/wp-c...-MECFS-Clinician-Coalition-V1-Feb.-2021_2.pdf

 

[Oliver3]

I’ve just finished a diagnostic guide for ME/CFS with the tests I consider most relevant, organized by priority and including approximate prices (based on 2025 rates in Spain, in euros). I’d really appreciate your feedback and suggestions—thank you so much!

View attachment 56040

I didn't know that berberine attacked microbes that thrive in hypoxic environment s.
When I started taking berberine I felt oxygen oxygenated. Could that be why?

 

[cfs since 1998]

I didn't know that berberine attacked microbes that thrive in hypoxic environment s.
When I started taking berberine I felt oxygen oxygenated. Could that be why?

Are you still taking berberine Oliver?

 

[Wayne]

I'm not trying to discourage your effort- just encourage good use of resources. You are doing work that other people have already done and your energy might be better spent building on their work instead of reinventing it or creating something entirely new that only you can do.

Hi @wabi-sabi – I’ve had some of the same thoughts myself.

@Gala, I wonder if you’re open to talking about the paradigm behind your work. As Wabi said, your approach overlaps with a lot of existing ME/CFS research, even though you’ve given it a fresh framing. -- Just to mention — I started rambling on paper, it wasn’t coming together, so I had AI help tidy it up. I gather you’re using AI too, so I hope you don’t mind.

For me, the traditional biomedical angle is valuable, but it can also be limiting. My focus has been to look “outside the box” — toward simple, low-cost interventions that may not fit the mainstream medical model but can still make a real difference. Many get overlooked because they don’t have big profit potential: ozone, HBOT, lymphatic drainage, structural alignment work, CSF flow therapies, energy-based approaches, etc.

I’ve long believed that disrupted electrical signaling, neurological imbalances, and immune dysregulation are major drivers for many of us. When I combine gentle interventions — acupuncture, detox practices, energy balancing, lymphatic drainage, EMF reduction, intermittent fasting, mHBOT, and therapeutic enemas (the last two being huge for me) — I can often shift from 25% functionality in the morning to 75% a few hours later.

Here’s an example (edited from THIS POST). A couple of months ago, I went through a brutal 6–8 week stretch where repeated sound-triggered startle responses sent my nervous system into overdrive. None of my usual tools worked — until I remembered castor oil packs, which I’d used years ago. I rubbed castor oil over my solar plexus, put on an old T-shirt, and used a hot water bottle for warmth.

Within half an hour, my body started to let go, I fell asleep, and woke feeling calmer and clearer. Repeating it brought more relief. Such a simple, inexpensive step — yet it helped restore balance between my sympathetic and parasympathetic systems. And probably did wonders for my immune system as well.

In that linked post, there’s an amazing story about Velma, who used a castor oil pack to (within minutes) “untwist” abdominal trauma from a surgery she'd had 23 years earlier, and which had given her major problems. I've actually come to believe "untwisting" or "unwinding" various traumas we've been exposed to are a major key for many of us. Balancing the Cortices Technique has been very helpful for me in this regard.

That’s the core of my paradigm: instead of chasing a single “holy grail” cure, I’ve built a toolbox of (many) small, practical things that help me unwind underlying imbalances and keep my functionality much higher. We’ve been conditioned to think only expensive, rigorously tested interventions are worth trying — but in reality, many intuitive, low-cost approaches can be surprisingly effective.

My approach to living with ME/CFS reflects something I’ve learned about life in general: people will always have problems, many with no long-term or “perfect” solutions. Part of the art of living is to do the best we can with the options we have — and be grateful for what we’re able to attain, no matter how small or seemingly trivial.

Managing ME/CFS well may not return us to 100%, but being able to regularly (almost daily) go from 25% to 75% functionality has been nothing short of transformative for me.

@Artemisia @Blair42 @kurt

 

[Oliver3]

Are you still taking berberine Oliver?

I am yes. And added nac and astralagus.
Still helps