Last May, a team of researchers led by Braeden Charlton and including ME Research UK-funded researcher Associate Professor Rob Wüst published a pre-print paper, which made a case against deconditioning as a primary cause of ME/CFS symptoms.
What is deconditioning and why is it often brought up in the context of ME/CFS?
Deconditioning is the decline in physical function of the body that occurs as a result of physical inactivity, including bed rest, and can adversely affect muscle mass and strength. Importantly, deconditioning is generally reversible and can be largely prevented with interventions such as maintaining a minimal activity level and following an exercise plan.
Controversially, there are frequent claims, especially from some who doubt the physical nature of ME/CFS, that ME/CFS symptoms result primarily from deconditioning and that those with the disease fear exercise, hence graded exercise therapy (GET) and cognitive behavioural therapy (CBT) have previously been recommended as treatments for the disease. However, the NICE 2021 guideline for ME/CFS explicitly cautions against offering GET to people with ME/CFS, and CBT is stressed to be offered only to allow those affected to manage their symptoms, improve their functioning and reduce the distress associated with having a chronic illness and not as a cure or a treatment.
The ME/CFS community and researchers often push against the deconditioning theory for the following reasons:
- Harm caused – The controversial PACE trial, which influenced prior ME/CFS guidance and led to widespread claims that GET and CBT were beneficial treatments for ME/CFS, was later found to major methodological concerns. Many people with ME/CFS report worsening of symptoms following attempts at GET and/or CBT. This falls in line with post-exertional malaise (PEM), the hallmark feature of ME/CFS, being the delayed worsening of symptoms following minimal physical or mental exertion.
- Physiological differences – Results from 2-day cardiopulmonary exercise test (CPET) studies repeatedly show response patterns that distinguish individuals with ME/CFS from both healthy controls and individuals with other fatiguing conditions.
The pre-print paper
Note: A pre-print is a paper that has not yet been peer-reviewed. The peer-review process aims to assess the validity and quality of articles for publication. Therefore, findings should always be
Braeden Charlton, Associate Professor Rob Wüst and the team compared exercise responses and skeletal muscle alterations in 24 healthy individuals who observed 60 days of strict bed rest to 26 people with ME/CFS, 25 people with long COVID, and 30 healthy controls who had fully recovered from COVID.
Unlike bed-rested healthy individuals who displayed muscle atrophy (wasting) across all types of muscle fibres, people with ME/CFS and long COVID only showed a selective type of muscle atrophy. Side note: Another research team later suggested that this means skeletal muscle in ME/CFS may not “rest” fully due to individuals suffering cramps and fasciculations (muscle twitches) related to certain differences on a biochemical level.
The pre-print also suggested that data related to VO2 max (maximum amount of oxygen that a person can utilise during intense exercise) suggested that “physiological impairments distinct from inactivity drive reduced exercise capacity in patients.”
Braeden Charlton, Associate Professor Rob Wüst and the team conclude that the findings “challenge the notion that deconditioning is the primary driver of reduced exercise capacity in long COVID and ME/CFS.” Rather, they state that the “observations suggest intrinsic skeletal muscle abnormalities contribute to limited exercise capacity, including reduced capillary supply relative to muscle fiber (sic) size and mitochondrial impairments.”
Caveat – it should be noted that team does not completely exclude the contribution of physical inactivity to the skeletal muscle alterations observed in the patient groups, however state that the results “indicate that physical inactivity alone is insufficient to explain the skeletal muscle changes in patients.”
The paper does however acknowledge certain limitations, including:
- The researchers did not induce physical inactivity in the patients with long COVID and ME/CFS, but mentioned that “Patients are typically more sedentary because PEM because PEM worsens both their symptoms and skeletal muscle abnormalities”
- There was also likely self-selection bias leading to over-representation of patients with milder symptoms “as they volunteered to travel to the laboratory for multiple occasions and undergo a maximal exercise test”, which means the results are “not directly applicable to home-bound patients.”
How is this topic related to astronauts?
The data for the bed rest cohort was from the AGBRESA study (organised by the European Space Agency (ESA), the National Aeronautics and Space Administration (NASA), and the German Aerospace Center (DLR)) in which 24 healthy people under went 60 days of strict bed rest for investigations involving spaceflight simulation. The AGBRESA study found that despite daily 30-min centrifugation (spinning to mimic gravity), 60-day bed rest resulted in multi-system deconditioning in participants. Yet, despite this deconditioning, the space study participants displayed different physiological patterns to the individuals with long COVID and ME/CFS in the aforementioned study. In other words, the results from the disease cohorts did not present a primary picture suggesting deconditioning.
