Thermoregulation: Heat and Cold Effects in ME/CFS
1 Hochecker et al. 2025 — Whole-Body Hyperthermia Treatment in ME/CFS (0.55)
Full Citation:: Hochecker B, Matt K, Scherer M, Meßmer A, von Ardenne A, Bergemann J. Heat vs. Fatigue: Hyperthermia as a Possible Treatment Option for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Mol Sci. 2025 Jun 1;26(11):5339. (Hochecker et al. 2025) DOI:: 10.3390/ijms26115339 PMID:: 40508148 PMCID:: PMC12154023 Published:: 2025 Study Design:: Pilot study, within-subject pre-post design Sample Size:: n=9 ME/CFS patients (38±10 years; 7F, 2M); n=6-9 healthy controls for comparison Key Findings:
- Autophagy: LC3-II levels decreased by 17.84% after WBH (p=0.0065); ME/CFS basal levels 20.01% higher than healthy controls
- Mitochondrial respiration increased significantly: basal +66.60% (p=0.0040), ATP production +61.41% (p=0.0023), maximal +97.88% (p=0.0071), spare capacity +112.35% (p=0.0086)
- mRNA: HSPA5 (HSP70) increased 48.33%; IL-10 increased 37.33%
- Hypothesis: WBH restores oxygen supply via improved blood flow, reducing hypoxia-induced autophagy and enhancing mitochondrial function
- All 9 participants showed responseConclusion:: Whole-body hyperthermia improves cellular autophagy and mitochondrial function in ME/CFS patients, possibly by restoring oxygenation via improved blood flow. Thermal therapy may benefit ME/CFS without triggering PEM. Limitations:: Very small sample (n=9); no standardized symptom measures; treatment conditions not fully standardized (some patients couldn’t tolerate full protocol); only immediate effects measured (no follow-up). Certainty: 0.55
2 Stanculescu et al. 2021 — Heat Stroke Mechanisms Comparison with ME/CFS (0.65)
Full Citation:: Stanculescu D, Sepúlveda N, Lim CL, Bergquist J. Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurol. 2021 Dec 13;12:789784. (Stanculescu et al. 2021) DOI:: 10.3389/fneur.2021.789784 PMID:: 34966354 PMCID:: PMC8710546 Published:: 2021 Study Design:: Narrative review Key Findings:
- Shared mechanisms between heat stroke and ME/CFS: splanchnic vasoconstriction/hypoxia, gut permeability/leaky gut (40-67% ME/CFS with elevated LPS antibodies), endotoxemia, systemic inflammation (IL-6, TNF-α, NLRP3 inflammasomes), CNS dysfunction/neuroinflammation, endothelial-cell injury, mitochondrial dysfunction, heat shock protein deficiency
- Transcriptomic overlaps: heat stress downregulates respiratory chain genes, switches to glycolysis, reduces ATP production, increases oxidative stress—similar patterns in ME/CFS PBMCs
- Predisposing factor overlaps: pre-existing inflammation/infection, viral reactivation (EBV, CMV), immune suppression, cumulative stress, microbiome disturbances, female predominance
- Suggests therapeutic opportunities from heat stroke research: gut barrier repair, anti-inflammatories, anticoagulation, HSP inductionConclusion:: Heat stroke and ME/CFS share multiple pathophysiological mechanisms involving gut permeability, endotoxemia, systemic inflammation, and vascular dysfunction. Lessons from heat stroke research may inform ME/CFS understanding and treatment. Limitations:: Narrative review (no systematic methodology); no new primary data; speculative connections. Certainty: 0.65
3 Cambras et al. 2023 — Skin Temperature Circadian Rhythms and Endothelin-1 (0.60)
Full Citation:: Cambras T, Castro-Marrero J, Zaragoza MC, Díez-Noguera A, Alegre J. Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation. Int J Mol Sci. 2023;24(5):4835. (Cambras et al. 2023) DOI:: 10.3390/ijms24054835 PMID:: 36902264 Published:: 2023 Study Design:: Case-control study Key Findings:
- ME/CFS patients exhibit modifications in circadian rhythm of skin temperature
- Circadian rhythm alterations associated with endothelin-1 levels (p < 0.01)
- ET-1 levels associated with temperature rhythm stability and amplitude
- Self-reported symptom questionnaires correlated with ET-1 and temperature rhythm disruptions
- Suggests vascular tone dysregulation mediated by ET-1 underlies thermoregulatory abnormalitiesConclusion:: ME/CFS patients have disrupted circadian skin temperature rhythms linked to endothelin-1 levels and vascular tone dysregulation, providing a potential biomarker for thermoregulatory impairment. Limitations:: Sample size not clear in available information; causality not established (ET-1 as marker vs. driver). Certainty: 0.60
4 Soejima et al. 2015 — Waon Therapy (Infrared Sauna) for CFS (0.50)
Full Citation:: Soejima Y, Munemoto T, Masuda A, Uwatoko Y, Miyata M, Tei C. Effects of Waon therapy on chronic fatigue syndrome: a pilot study. Intern Med. 2015;54(3):333-338. (Soejima et al. 2015) DOI:: 10.2169/internalmedicine.54.3042 PMID:: 25748743 Published:: 2015 Study Design:: Pilot clinical trial, pre-post design Sample Size:: n=10 consecutive inpatients with CFS Intervention::
- Waon therapy (far-infrared dry sauna at 60°C for 15 minutes)
- Followed by 30 minutes rest under blanket outside sauna
- Frequency: once daily, 5 days/week for 4 weeks (20 sessions total)Key Findings:
- Perceived fatigue significantly decreased after therapy (not at 2 weeks)
- Negative mood (anxiety, depression, fatigue) significantly improved after therapy
- Performance status significantly improved after therapy
- Pain levels and vigor did not change significantly
- No adverse effects reported during therapyConclusion:: Waon therapy may be a useful and safe treatment for CFS, improving fatigue, mood, and performance status without triggering PEM. Limitations:: Very small sample (n=10); no control group; open-label; no blinding; short duration (4 weeks); no follow-up after treatment. Certainty: 0.50