Mantle et al. (2025)
- Authors: David Mantle, Joan Carles Domingo, Beatrice Alexandra Golomb, Jesús Castro-Marrero.
- Institutes: Pharma Nord (UK) Ltd., Morpeth NE61 2DB, Northumberland, UK; Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain; Department of Medicine, UC San Diego School of Medicine, La Jolla, CA 92093, USA; Research Unit in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID, Division of Rheumatology Research, Vall d’Hebron Hospital Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
- Publisher: International Journal of Molecular Sciences
- Link: DOI
Summary
This review consolidates scientific evidence showing that ME/CFS, Long COVID, Fibromyalgia, and Gulf War Illness are not entirely separate, but share fundamental biological problems related to cellular energy production (mitochondrial dysfunction), chronic inflammation, and immune system irregularities. By grouping them as “low-energy disorders,” the paper reinforces their biological basis and suggests that treatments targeting these core issues could be broadly effective. The authors highlight coenzyme Q10 (CoQ10) 💊 as a promising intervention, as it directly supports cellular energy production and fights oxidative stress, with some existing studies showing it can reduce key symptoms like fatigue and pain. This provides a scientific rationale for exploring CoQ10 further and encourages a more unified research approach to finding treatments for this cluster of debilitating conditions.
What was researched?
This paper reviewed the scientific evidence for overlapping symptoms and shared biological mechanisms across four distinct conditions: Gulf War Illness (GWI), Fibromyalgia (FM), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Long COVID. The authors investigated the common pathologies to establish a rationale for potential therapeutic strategies, particularly focusing on the role of coenzyme Q10 (CoQ10) supplementation and stem cell therapy.
Why was it researched?
These chronic, disabling disorders affect millions of people worldwide but remain poorly understood, lack objective diagnostic biomarkers, and have few effective, approved treatments. By identifying the shared biological underpinnings, researchers hope to illuminate the disease processes and pave the way for developing targeted therapies that could potentially benefit patients across all four conditions, addressing a significant unmet medical need.
How was it researched?
This study was a literature review. The authors analyzed and synthesized findings from a wide range of existing research papers to compare and contrast the clinical symptoms and known biological abnormalities in GWI, FM, ME/CFS, and Long COVID. They specifically searched for common pathways related to cellular energy, immunity, and inflammation, and also reviewed clinical studies on potential treatments that target these pathways.
What has been found?
The review confirmed that these four disorders share a core set of symptoms, including debilitating fatigue, post-exertional malaise (PEM), cognitive dysfunction (“brain fog”), widespread pain, and sleep disturbances. Furthermore, it identified several common underlying biological mechanisms, such as mitochondrial dysfunction, oxidative stress, inflammation, immune dysregulation, a disrupted gut-brain axis, and accelerated cellular aging (telomere shortening). The paper presents a strong rationale for the therapeutic use of coenzyme Q10 (CoQ10) 💊, which has been shown in some studies to improve fatigue and pain by addressing several of these shared pathologies, particularly mitochondrial dysfunction and oxidative stress.
Discussion
The authors highlight that the extensive overlap in both symptoms and biology raises the question of why these conditions are classified as four separate disorders. They point out that the lack of specific biomarkers and objective diagnostic criteria complicates research and clinical care, leading to difficulties in diagnosis and the development of effective treatments. The authors state that this is the first review to summarize these specific shared mechanisms across all four illnesses and connect them to the therapeutic potential of CoQ10 and stem cell therapy.
Conclusion & Future Work
The authors conclude that GWI, FM, ME/CFS, and Long COVID can be collectively understood as a group of “low-energy associated disorders” with shared pathophysiological features. They propose that supplementary CoQ10 is a rational therapeutic approach for managing these conditions due to its role in improving mitochondrial function and reducing oxidative stress. The paper calls for large-scale, rigorous randomized controlled trials to fully understand the benefits of CoQ10 and to establish effective dosing protocols for these complex illnesses.