Overview
Chronic fatiguing illnesses such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, and Long COVID are becoming a major global health challenge. They cause severe personal and social strain and have no proven, widely effective treatments. Although these conditions have different names, they share many symptoms: long-lasting fatigue that doesn't improve with rest, worsening of symptoms after activity (post-exertional malaise), difficulties with thinking ("brain fog"), poor sleep, and widespread pain. Increasing evidence shows that these illnesses also share similar underlying biological problems. These include ongoing inflammation, problems with the autonomic nervous system (which controls automatic body functions), poor function of the blood vessels, and reduced energy production in cells.
Whole-Body Cryotherapy (WBCT) is emerging as a promising non-drug treatment that may help break these cycles. WBCT involves very short, controlled exposure to extreme cold (around -110°C to -160°C). This triggers a rapid response across the nervous, immune, and metabolic systems. The cold acts as a powerful stimulus, encouraging the body to reset imbalanced systems. A session briefly narrows blood vessels and then causes them to widen again, improving blood flow and supporting healthy vessel function. WBCT also appears to reduce inflammation, lower oxidative stress, and improve parasympathetic ("rest-and-recover") nervous system activity.
Early studies in ME/CFS and related conditions are encouraging. Small trials have reported reduced fatigue, clearer thinking, and better autonomic regulation after a course of WBCT sessions, with good safety. Research has also shown changes in blood-brain barrier proteins after WBCT, suggesting it may help repair "leaky" barriers that can drive symptoms in ME/CFS and Long COVID.
By acting on inflammation, blood flow, and nervous system balance at the same time, WBCT could offers a scientifically grounded and potentially transformative approach in understanding the mechanism behind observed treatment effect.
Description
Chronic fatiguing illnesses such as ME/CFS, Fibromyalgia, and Long COVID share strikingly similar symptom profiles: persistent fatigue, post-exertional malaise, cognitive impairment, unrefreshing sleep, autonomic dysfunction, and widespread pain. Increasingly, research demonstrates that these symptoms arise from overlapping biological disturbances involving systemic inflammation, autonomic dysregulation, endothelial impairment, and disrupted cellular energy production. These processes are thought to reinforce one another, creating a self-sustaining cycle of physiological stress that maintains chronic illness.
Whole-Body Cryotherapy (WBCT) offers a biologically plausible intervention that can interrupt these pathological loops. Brief exposure to extreme cold triggers a rapid multisystem response across neurovascular, immune, and metabolic pathways. Evidence suggests that WBCT enhances autonomic balance, improves microvascular function through vasoconstriction-vasodilation cycling, reduces oxidative stress, and stimulates anti-inflammatory signalling. Preliminary clinical work, including studies in ME/CFS, shows reductions in fatigue, improved cognitive clarity, and better autonomic regulation following multi-session cryotherapy. Early mechanistic findings, such as changes in blood-brain barrier proteins like claudin-5, further support WBCT's potential to modulate barrier integrity and downstream neuroimmune activity.
The present study is therefore designed as a pilot feasibility investigation to determine whether a fully powered mechanistic trial is achievable. The protocol includes four groups: healthy controls, ME/CFS, Fibromyalgia, and Long COVID each completing ten WBCT sessions over two weeks, with comprehensive pre- and post-intervention assessments.
Central to this study is establishing whether recruitment, retention, and completion of intensive multidimensional outcome measures are practical within this population. Alongside feasibility assessment, the study will explore changes in symptom burden using validated clinical surveys, and will collect objective data on sleep, physical activity, and mitochondrial and immunometabolic function through biospecimens. These exploratory measures will provide essential estimates of variability, acceptability, and sensitivity to change, all of which are required to refine the design of a future randomised controlled trial.
The multi- \& trans-disciplinary integration of patient-reported outcomes, wearable-derived physiological data, and advanced cellular and molecular assays provides a coherent mechanistic framework for understanding WBCT's multisystem effects. If participants can be successfully recruited, retained, and assessed, the findings will offer both practical and scientific justification for progression to a larger, definitive study capable of evaluating therapeutic efficacy.
Eligibility
Inclusion Criteria:
- The study will recruit 40 adult participants (aged 18-65 years) divided across four groups: 10 healthy controls, 10 individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 10 individuals with Fibromyalgia, and 10 individuals with Long COVID.
The relatively small group size is appropriate for a pilot feasibility study, where the primary aim is to assess recruitment, retention, tolerability of the intervention, and the practicality of completing the proposed outcome measures.
The sample size reflects the exploratory nature of the study, current resource availability and funding, and the intensive intervention schedule requiring ten visits over a two-week period. In addition, there is limited UK-based evidence regarding participant responses to whole-body cryotherapy within these clinical populations, further supporting a cautious, feasibility-focused sample size.
Exclusion Criteria:
- The primary physical risks relate to exposure to extreme cold during whole-body cryotherapy and minor discomfort associated with blood sampling. To mitigate these risks, all participants will undergo a structured medical screening using a standard WBCT medical questionnaire to identify contraindications (e.g. uncontrolled hypertension, cardiovascular disease, circulatory disorders such as Raynaud's disease, cryoglobulinaemia, severe respiratory disease, or claustrophobia). Individuals meeting exclusion criteria will not be enrolled.
