** This page is a continued work in progress***
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness, that is still not fully understood.
The issue that arises is that due to the pathology of ME/CFS not being fully understood, that many people both in the medical community and the general public continue to misunderstand the illness and even continue to question whether it’s real or not. Which is incredibly unhelpful to patients suffering from this illness.
Studies so far have been small and sparse, because there is very little funding for ME/CFS compared with other illnesses. Some statistics show that ME/CFS is funded only 5-10% relative to what it should be.
Some theories currently put forward the idea that it’s a stress response illness, with post-viral dysfunction being the most common reason for the onset of symptoms. Other theories point towards a gut-biome dysfunction but it’s still unclear what is a initial cause and what is a symptom.
It’s estimated between 5 – 9 million people suffer from this illness, and with the current evidence from studies and expert medical specialists, the illness is clearly real but what is the evidence so far?
- Abnormal muscle biopsies
- Possible Blood Biomarkers
- Cytokine Elevation in Cerebral fluid
- Brain activity differences
- Immune Abnormalities
- Mitochondrial abnormalities
- Impaired Oxygen delivery
- Gut Biome dysfunction
Abnormal Muscle Biopsies
https://www.nature.com/articles/s41598-020-75406-w
In a 2020 study, the study concluded that CFS skeletal muscle cells show similar dysfunction in mitochondrial respiration as PBMCs. The inability of CFS cells to utilise glucose as a fuel source to the same extent as healthy controls results in decreased mitochondrial respiration at both basal and maximal levels. The study suggests that CFS is a multi-tissue disease.
Possible Blood Biomarkers
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02893-9
A systematic review of potential biomarker studies concluded that several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of the illness.
Cytokine Elevation in Cerebral fluid
https://www.pnas.org/doi/10.1073/pnas.1710519114
A 2017 study found that 17 cytokines were associated with severity in ME/CFS patients. Thirteen of these 17 cytokines are primarily proinflammatory.
It built upon a previous study (https://pubmed.ncbi.nlm.nih.gov/23570606/) that identified leptin in cytokine panels being correlated with fatigue severity in ME/CFS.
Immune Abnormalities
https://www.cell.com/cell-reports-medicine/pdfExtended/S2666-3791(23)00602-X
This 2024 study announced that multiple lines of evidence implicate the dysregulation of classical monocytes in ME/CFS. They claimed that it may be a consequence of prolonged exposure to an inflamed environment in ME/CFS, which can alter cellular metabolism and functions. Their observations suggested that ME/CFS patients experience continual improper recruitment of monocytes to one or more tissues.
Mitochondrial abnormalities
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02533-3
A 2021 study concluded that the results from their study supported a model of deficient ATP production in ME/CFS, compensated for by upregulation of immediate pathways upstream of Complex V that would suggest an elevation of oxidative stress.
Impaired Oxygen delivery
https://pubmed.ncbi.nlm.nih.gov/10545311/
In this small 1999 study(20 CFS patients and 12 control), muscle oxygen delivery was measured post exercise and post oxygen re-saturation.
The results were that time constant of oxygen delivery was significantly reduced in CFS patients after exercise. Oxidative metabolism was also reduced by 20% in CFS patients, and a significant correlation was found between oxidative metabolism and recovery of oxygen delivery.
Gut Biome Dysfunction
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00029-X
This 2023 study highlights the fact that ME/CFS patients have substantial gut microbiome dysbiosis, and a correlation of low F. prausnitzii to severe fatigue symptoms.
Current Issues
The issues confounding many of the ME/CFS studies is twofold ;
Lack of funding leading to smaller studies; There is a notable lack of research funding for ME/CFS which prevents anyone from doing large scale studies which could come to more clear conclusions.
Lack of a conclusive biomarker blood test; The issue many studies find is that without such a test, it’s impossible to know whether their CFS patients definitely have CFS. They can only group them by symptoms and specialist diagnosis. So they could be looking at a range of conditions instead of one, leading to a lack of conclusive evidence or even contradictory evidence.
So the most important step really is to focus on these two issues so that much larger studies can be done and conclusive evidence can be obtained.
Once the pathology of ME/CFS is fully understood, a cure is much more likely to be found, not to mention preventative measures can be put in place to reduce the number of people who acquire this illness in the first place.
