Research has not yet been able to confidently determine the cause or causes of ME/CFS, but several factors associated with the disease have been identified.
More research is required to determine whether these biological abnormalities are the “primary drivers of disease or secondary effects resulting in chronic illness“.
Infections
Research suggests that infection with microorganisms – such as bacteria, viruses and fungi – may trigger ME/CFS. One study showed that people with a history of infection are more likely to have an ME/CFS diagnosis.
This is supported by a survey by the European ME Alliance, which surveyed 11,000 people with ME/CFS and found that 58% of respondents associated the onset of their ME/CFS with an “infectious disease”.
It is also important to note that people with long COVID – chronic illness following a COVID-19 virus infection – have reported symptoms similar to those associated with ME/CFS. In fact, some people with long COVID also meet ME/CFS diagnostic criteria.
Additionally, in some medical coding systems such as the ICD-10 5th edition, ME/CFS – recorded as “benign myalgic encephalomyelitis” – is included within the code for “post-viral fatigue”.
Immune system dysfunction
While there is evidence that the immune system is disrupted in ME/CFS, it is difficult to pin down what that disruption is, or even to identify a single universal problem.
ME/CFS shares some features of autoimmune illnesses – diseases in which the immune system attacks the body’s healthy tissues. However, the findings are inconsistent, and there is insufficient evidence to classify ME/CFS as an autoimmune disease.
Genetics
Research has found that participants with ME/CFS are more likely to have a family history of the illness.
Studies also suggest that the interaction between the environment and our genetics could play a role in ME/CFS. This interaction could affect how our body turns genes on and off, which is also called epigenetics. For example, genes associated with energy production – known as metabolic regulation – have been found to be epigenetically modified in people with ME/CFS.
One important question is why ME/CFS happens in some people but not in others, and research studies continue to look for differences in the genes that may explain this.
Hormonal imbalance
Research has identified that there may be differences in levels of hormones – signalling molecules essential for regulating many different processes throughout the body – between people with ME/CFS and healthy control subjects. There may also be differences in hormones by disease severity, and between men and women with ME/CFS.
Mitochondrial dysfunction
Research strongly suggests that people with ME/CFS have a disruption in the mitochondria, which are small structures in the body that are responsible for energy production.
Although not yet conclusive, evidence suggests that there may be both problems in energy production pathways, and structural faults in the mitochondria themselves.
Such problems seem to be exacerbated when the mitochondria are under stress.
Environmental factors
Environmental factors have also been linked with the onset of ME/CFS, and these include stress. The Centers for Disease Control note that people with ME/CFS often report physical or emotional stress before they become ill, as well as exposure to toxins such as pesticides and heavy metals like cadmium.
