Fan et al. (2025)
- Authors: Jin Fan, Jiao Jiao, Hai-Qing Chang, Dong-Ling Zhong, Xiao-Bo Liu, Juan Li, Ling-Min Chen, Rong-Jiang Jin, Xi Wu.
- Institutes: Chengdu University of Traditional Chinese Medicine, Chengdu, China; various affiliated clinical and research institutes.
- Publisher: Journal of Translational Medicine
- Link: PubMed
Summary
This review provides a vital update for patients and clinicians by validating ME/CFS as a biological, multisystemic illness. By explicitly stating that Graded Exercise Therapy (GET) should be avoided, it aligns with modern safety standards and protects patients from potential relapse. The research emphasizes that while we do not yet have a “cure,” focusing on mitochondrial health and pacing can help manage the condition, and the strong link found between ME/CFS and Long COVID is likely to accelerate the development of new diagnostic tools.
What was researched?
This comprehensive review systematically analyzed current diagnostic criteria, underlying biological mechanisms, and management strategies for ME/CFS. The researchers evaluated both pharmacological and non-pharmacological interventions to provide updated clinical guidance, particularly in light of the overlap between ME/CFS and post-acute COVID-19 syndrome (Long COVID).
Why was it researched?
ME/CFS has gained renewed scientific attention due to its rising global prevalence and its significant physiological similarities to Long COVID. Despite this, clinical guidance has historically been scarce or potentially harmful; therefore, this study aimed to synthesize recent advances in pathophysiology—such as neuroinflammation and mitochondrial issues—to improve diagnostic accuracy and patient care.
How was it researched?
The authors conducted a systematic literature review across major scientific databases, including PubMed, Web of Science, Embase, and the Cochrane Library. They analyzed studies published from the inception of the databases through August 2025, focusing on diagnostic frameworks, pathophysiological evidence, and the efficacy of various treatment modalities. The review included an assessment of standard clinical practices versus emerging biomedical interventions.
What has been found?
The study confirmed that while definitive biomarkers are still lacking, diagnosis should rely on established clinical criteria focusing on post-exertional malaise and cognitive dysfunction. Central pathologies were identified as immune dysregulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. Effective management strategies highlighted include activity pacing and Traditional Chinese Medicine (TCM), while pharmacological approaches focus on mitochondrial support, antioxidant therapies, and immunomodulatory treatments. Importantly, the review found that Graded Exercise Therapy (GET) is contraindicated due to its potential to cause patient harm, and the experimental substance CP003 💊 is currently being evaluated for its safety and effectiveness in treating fatigue.
Discussion
The authors discuss the ongoing challenge of diagnosing a condition that relies primarily on subjective symptom reports rather than objective blood tests. They highlight that while cognitive behavioral therapy (CBT) can be a helpful adjunctive tool for coping, it is not a curative treatment. A major point of discussion is the necessity of moving away from outdated “one-size-fits-all” exercise recommendations in favor of individualized, symptom-oriented care.
Conclusion & Future Work
The researchers conclude that ME/CFS is a complex multisystem disease requiring a multidisciplinary management approach that respects individual patient limits. Future research should prioritize the discovery of objective diagnostic biomarkers and the development of combination therapies that target multiple disease pathways simultaneously. The authors also suggest integrating digital health technologies to better monitor patient energy levels and symptoms in real-time.