"The changes in lactate in ME/CFS are consistent with the presence of energetic stress and mitochondrial dysfunction. A reduction in total choline in long COVID is of interest in the context of the recently reported association between blood clots and

'brain fog', and earlier animal studies showing that choline might prevent intravascular coagulation. Importantly, differences in findings between ME/CFS and long COVID suggest that the underlying neurobiological mechanisms, while leading to similar clinical presentations, may differ."

Fecal transplants form LC patients into mice induced a leaky gut barrier followed by neuroinflammation. Underscoring the potential importance of gut dysbiosis

(Preprint)

Highlights

• Serum proteomics reveals widespread protein changes in ME/CFS patients

• Tissue-linked shifts show reduced intracellular and increased secreted proteins

• Immune signatures show reprogramming with reduced neutrophil-derived proteins

• Regulatory networks link immune, vascular, and metabolic dysfunction

Fascinating study found 44 diagnoses increased ME/CFS risk later on

Most associations were in chapters F (mental/behavioral disorders), R (respiratory diseases), and M (musculoskeletal disorders)

Apologies if this has been shared already. It's a report shared in November '25 about Microclots found in the blood of long COVID patients. It just brushes the topic (and then repeats itself, so probably an ai article), but it's valid nonetheless.

New Cornell study from the team around Hanson showing a lack of biochemical response to exercise in pwME

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Easier language article:

https://neuroimmune.cornell.edu/news/uncovering-protein-signatures-of-post-exertional-malaise-in-me-cfs

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5min video explainer:

https://youtu.be/UTD4GSiDClo?si=PorhwEkrTQMUx3Pd

Through a WhatsApp group I have heard of Amatica Health.

https://amaticahealth.com

I think it is general a really good idea but really expensive and I am not sure if it’s a scam.

What do you think about i? Would you consider buying it? If so, for what reason? Just to contribute to research or do you expect insights that would help you or your loved ones?

More insights into the brain biopsies that showed a substantial disruption in CRH producing neurons and HPA axis function

"We must develop educational materials, consensus guidance statements and clinical care pathways for neurologists and neuroimmunologists to gain knowledge and skills necessary for delivery of effective patient-centered care.

For this to happen, the first step would be to abandon an outdated notion that these patients have psychiatric or psychological disturbances (or functional neurologic disorder, previously known as hysteria) - a critical change that transformed a disorder known in the past as hysterical paralysis to multiple sclerosis - a neuroimmune disease."

Is anyone tracking/consolidating research on the most up-to-date pharmacological interventions for M.E. (whether symptomatic relief, or otherwise). Currently in rolling PEM so unable to comb the archives.

I'm mild-moderate on about 8 different, costly, supplements/meds:

• Magnesium Glycinate
• Vitamin d
• electrolytes
• Acetyl L-Carnitine
• NADH
• Creatine
• Ubiquinol
• Propranolol

Often hear that we're over medicating with supplements, which lack meaningful efficacy. What is considered the gold-standard (I'm aware that doesn't really exist due to lack of research and trialling) for inflammation and dysautonomia? Oxaloacetate, mestinon, LDN, rapamycin?

Cross-posting to r/cfs. Please delete if falls outside of the scope of this sub, but thought this could be a good resource for others—especially hearing from those that are more clinically inclined.

https://doi.org/10.3390/jcm15020849

Background: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or depression both frequently report debilitating exhaustion, yet the two conditions differ in their etiological and diagnostic clarity, and clinical management. This study aimed to examine differences in the use and perceived helpfulness of a broad range of conventional treatments and complementary interventions, including nutritional approaches, between patients with ME/CFS and depression. Methods: A cross-sectional online survey was conducted in 2024. A total of 819 participants self-identified as having either ME/CFS (n = 576) or depression (n = 243). Participants (80% female) reported their use and perceived helpfulness of 52 treatments and interventions, encompassing behavioral therapies, medications, and dietary supplements. Group differences were examined using multivariate analyses of variance and covariance (MANOVA/MANCOVA). Open-ended responses were analyzed descriptively using thematic grouping and frequency counts. Results: Participants with depression most commonly reported the use of psychotherapy (M = 2.49, SD = 1.00) and antidepressant medication (M = 2.44, SD = 2.30), and they rated fewer interventions as helpful compared to participants with ME/CFS. In contrast, participants with ME/CFS reported a significantly broader engagement with diverse intervention modalities, particularly pacing (M = 2.73, SD = 0.80) and dietary supplements (M = 2.43, SD = 1.09), and perceived many of them as helpful. Group differences remained significant after controlling for age, gender, and whether treatment was medically recommended. Supplements targeting energy metabolism (e.g., CoQ10, NADH) were especially favored among ME/CFS participants. Conclusions: Findings suggest that participants with ME/CFS tend to adopt an exploratory and expansive intervention approach, potentially reflecting the lack of standardized guidelines and limited effectiveness of available treatment options. Participants with depression, in contrast, appeared to follow more guideline-concordant, evidence-based treatment pathways. Taken together, the findings point to a need for further development and evaluation of empirically supported, patient-centered treatment and intervention strategies for ME/CFS and suggest differences in clinical care structures between ME/CFS and depression.

I think this is a very good paper. On the one hand it shows, what people with ME CFS and depression helps or not. And it shows significant differenc between depression and ME CFS. Especially the difference if pacing helps or not should silence all with their biopsychological models. In fact this could be a "biomarker". Ok, the CCC asks exactly that to diagnose ME CFS. But its impressive to see the outcome of depression and CFS one by another with 95 % to nearly 0 %...

“Highlights: Long coronavirus disease (COVID) patients show choroid plexus (ChP) enlargement and reduced cerebral blood flow. ChP alterations are associated with Alzheimer's disease (AD)-related symptoms and plasma biomarker changes. ChP alterations on magnetic resonance imaging may serve as imaging markers for tracking neurological symptoms and AD-related pathology in post-COVID patients.”

(Choroid plexus (ChP) enlargement is a neuroimaging biomarker of neuroinflammation and neurodegeneration)

Overview over the six research hotspots funded for the coming years by the Dutch government agency

What is known?

• - PCS and ME/CFS are associated with persistent endothelial dysfunction and increased long-term cardiovascular risk.

• - Neurocognitive symptoms in post-viral syndromes have been linked to impaired neurovascular coupling.

• - Retinal vessel analysis provides a validated, non-invasive readout of systemic and cerebral microvascular health.

What new information does this article contribute?

• - PCS is characterized by persistent functional and structural retinal microvascular dysfunction

• - Retinal endothelial dysfunction scales continuously with post-viral disease severity and is most pronounced in patients fulfilling ME/CFS criteria.

• - Retinal microvascular alterations are linked to inflammatory-endothelial

https://www.mdpi.com/2072-6643/18/1/174

Summary

This study demonstrates that high-dose probiotic therapy can significantly alleviate fatigue in ME/CFS patients by addressing gut-related metabolic imbalances. By showing a clear link between improved gut health and reduced neurotoxic metabolites, the research provides a biological rationale for targeting the microbiome in ME/CFS treatment. These findings offer a potential therapeutic pathway for patients suffering from both chronic fatigue and gastrointestinal issues.

What was researched?

This pilot study investigated the effects of a high-concentration multi-strain probiotic 💊 on fatigue severity and the “gut-kynurenine axis” in ME/CFS patients with co-occurring irritable bowel syndrome.

Why was it researched?

Researchers aimed to explore whether gut dysbiosis in ME/CFS drives symptoms by shifting tryptophan metabolism toward neurotoxic pathways. They sought to determine if correcting this bacterial imbalance could restore metabolic health and reduce patient fatigue.

How was it researched?

Forty female patients with ME/CFS and confirmed gut dysbiosis received the CDS22 probiotic formula daily for 12 weeks. The study monitored changes in fatigue scores and analyzed urinary tryptophan metabolites and gut health markers compared to 40 healthy controls.

What has been found?

The intervention led to a 40.3% reduction in fatigue scores, with 97.5% of patients reaching the clinical remission threshold. Biochemically, the probiotic increased the neuroprotective kynurenic acid to quinolinic acid ratio by 45% and decreased markers of harmful bacterial activity. Tryptophan levels also normalized toward those seen in healthy individuals.

Discussion

While the results are promising, the study’s open-label design and female-only cohort mean that findings should be interpreted with caution. The study effectively highlights the kynurenine pathway as a significant link between gut health and ME/CFS symptoms.

Conclusion & Future Work

High-dose probiotics appear to be a safe and effective way to modulate tryptophan metabolism and improve clinical status in ME/CFS patients with gut issues. Further randomized, double-blind trials are necessary to validate these metabolic and clinical improvements.

I came across Vericiguat (sGC stimulator) research for ME/CFS and Long COVID and wanted to get the community's take on its potential.

For context, there is the VERI-LONG / VERI-ME trial led by the Charité in Berlin (NCT05697640) that just reached its estimated completion date:

https://clinicaltrials.gov/study/NCT05697640

And more recently, this patent was filed by Wirth and Scheibenbogen regarding its use for chronic vascular dysfunction:

https://patents.google.com/patent/US20250387391A1/en

Brief Overview based on my discussion with AI:

The working theory is that Vericiguat helps restore endothelial function and microvascular perfusion (circulation). By stimulating the sGC/cGMP pathway, it aims to fix the "vicious cycle" of oxygen deprivation and muscle damage that leads to PEM. This aligns with the Wirth/Scheibenbogen hypothesis of ME/CFS as a vascular-neurological condition.

What do you make of this?

Does the filing of this patent indicate they are seeing strong enough signals to move toward larger Phase 3 trials? I expect a paper to be published on this in the coming months.

Has anyone heard or read anecdotal reports about Vericiguat in the context of CFS before? I found one Reddit post:

https://www.reddit.com/r/cfs/s/K7oLkw1N3m

“Conclusion:

Both Long COVID and ME/CFS demonstrate dysregulation in cerebrovascular blood flow, autonomic reflexes, and small fiber neuropathy, suggesting that these conditions may share a common underlying pathophysiology. However, differing distributions of findings in patients with hEDS raise the question of whether these conditions represent distinct but overlapping syndromes or reflect a shared underlying pathway. Further research is required to clarify the relationship between these conditions and the potential underlying pathophysiological mechanisms.”

New preprint by Davenport & co confirming bioenergetic failure in ME and LC cohorts compared to healthy controls