Metformin Intervention Trial Targeting Post-Exertional Malaise (PEM) in ME/CFS
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| Format: | Recurso digital |
| Langue: | anglais |
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2025
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| _version_ | 1866901632517668864 |
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| author | Eshuis, Erik |
| author_facet | Eshuis, Erik |
| contents | <p>This preprint presents the <em>Metabolic Reset Program for ME</em> (MRP–ME), a systems-based framework designed to clarify and modulate the metabolic mechanisms underlying post-exertional malaise (PEM) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PEM is conceptualized as a maladaptive metabolic attractor state characterized by impaired AMPK activation, early lactate accumulation, mitochondrial inefficiency, reduced oxygen extraction, and autonomic instability.</p> <p>MRP–ME proposes a safe, low-intensity intervention centered on metabolic stabilization, combining low-dose metformin as a pharmacological AMPK activator with non-destabilizing strategies for circadian alignment, micro-movement, redox support, and microvascular optimization. The framework generates explicit, falsifiable physiological predictions—reduced lactate response, improved autonomic resilience, shorter PEM duration, and enhanced day-to-day stability.</p> <p>A corresponding randomized controlled trial (RCT) design is outlined, focused on metformin repurposing as a first-step mechanistic test of PEM modifiability. This approach aligns directly with current repurposing calls and biobank-supported ME research infrastructures.</p> <p>MRP–ME aims to establish a precise experimental foundation for metabolic intervention studies in ME/CFS.</p> <p><strong>Positioning note<br></strong>While metformin is also being evaluated in pragmatic post-COVID platform trials (e.g. RECLAIM), the present preprint describes a conceptually independent trial framework. It is explicitly centred on post-exertional malaise (PEM) as a system-level phenomenon, using PEM-based stratification, intervention rationale, and outcome logic that differ fundamentally from platform-based post-COVID studies.</p> <p>Conceptual provenance and conditions for use of the trial framework are documented separately (see Zenodo DOI: <a href="https://doi.org/10.5281/zenodo.17922679" target="_blank" rel="noopener">https://doi.org/10.5281/zenodo.17922679</a>).</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_17886420 |
| institution | Zenodo |
| language | eng |
| publishDate | 2025 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Metformin Intervention Trial Targeting Post-Exertional Malaise (PEM) in ME/CFS Eshuis, Erik Myalgic Encephalomyelitis ME/CFS Post-Exertional Malaise Metabolic dysregulation AMPK activation Mitochondrial dysfunction Lactate metabolism Oxygen extraction Autonomic dysfunction Metformin Energy Metabolism Energy Metabolism/immunology Pyruvate dehydrogenase (PDH) <p>This preprint presents the <em>Metabolic Reset Program for ME</em> (MRP–ME), a systems-based framework designed to clarify and modulate the metabolic mechanisms underlying post-exertional malaise (PEM) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PEM is conceptualized as a maladaptive metabolic attractor state characterized by impaired AMPK activation, early lactate accumulation, mitochondrial inefficiency, reduced oxygen extraction, and autonomic instability.</p> <p>MRP–ME proposes a safe, low-intensity intervention centered on metabolic stabilization, combining low-dose metformin as a pharmacological AMPK activator with non-destabilizing strategies for circadian alignment, micro-movement, redox support, and microvascular optimization. The framework generates explicit, falsifiable physiological predictions—reduced lactate response, improved autonomic resilience, shorter PEM duration, and enhanced day-to-day stability.</p> <p>A corresponding randomized controlled trial (RCT) design is outlined, focused on metformin repurposing as a first-step mechanistic test of PEM modifiability. This approach aligns directly with current repurposing calls and biobank-supported ME research infrastructures.</p> <p>MRP–ME aims to establish a precise experimental foundation for metabolic intervention studies in ME/CFS.</p> <p><strong>Positioning note<br></strong>While metformin is also being evaluated in pragmatic post-COVID platform trials (e.g. RECLAIM), the present preprint describes a conceptually independent trial framework. It is explicitly centred on post-exertional malaise (PEM) as a system-level phenomenon, using PEM-based stratification, intervention rationale, and outcome logic that differ fundamentally from platform-based post-COVID studies.</p> <p>Conceptual provenance and conditions for use of the trial framework are documented separately (see Zenodo DOI: <a href="https://doi.org/10.5281/zenodo.17922679" target="_blank" rel="noopener">https://doi.org/10.5281/zenodo.17922679</a>).</p> |
| title | Metformin Intervention Trial Targeting Post-Exertional Malaise (PEM) in ME/CFS |
| topic | Myalgic Encephalomyelitis ME/CFS Post-Exertional Malaise Metabolic dysregulation AMPK activation Mitochondrial dysfunction Lactate metabolism Oxygen extraction Autonomic dysfunction Metformin Energy Metabolism Energy Metabolism/immunology Pyruvate dehydrogenase (PDH) |
| url | https://doi.org/10.5281/zenodo.17886420 |