Thesis Using the Thermal Power of Light to Affect Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2025, Hochecker

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Using the Thermal Power of Light to Affect Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Hochecker, Barbara

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and poorly understood multisystem disease with an unclear cause and pathophysiology. Diagnosis remains difficult due to the absence of specific biomarkers, so the condition must be identified based solely on clinical symptoms, which vary greatly between individuals in both type and severity. Alongside the primary symptom of debilitating fatigue, patients commonly experience cognitive impairments such as memory and concentration problems, muscle and joint pain, non-restorative sleep, dizziness, and a phenomenon known as post-exertional malaise (PEM), where even minor physical or mental exertion leads to a significant worsening of symptoms. These symptoms often result in severe disability, with some patients confined to bed and unable to participate in normal daily life.

For decades, ME/CFS has been largely neglected by the medical and scientific communities, leading to a lack of knowledge and the absence of causal treatments. Current therapeutic approaches focus only on symptom management, typically involving medications or behavioral therapies designed to help patients adapt to their limitations and possibly regain some level of activity.

This thesis explores the potential of hyperthermia—an artificially induced elevation of body temperature—as a novel treatment option for ME/CFS. Hyperthermia has long been used in cancer therapy and has also demonstrated positive effects in treating severe depression and arterial hypertension, although the underlying cellular and molecular mechanisms remain poorly understood.

The study is divided into three parts. The first part compares key cellular processes—autophagy and mitochondrial function—in peripheral blood mononuclear cells (PBMCs) from healthy individuals and ME/CFS patients. The results show elevated autophagy and increased mitochondrial activity in ME/CFS patients compared to healthy controls. The second part consists of an ex vivo hyperthermia experiment in which PBMCs and fibroblasts from both healthy donors and ME/CFS patients were exposed to one hour of heat at 39°C. This treatment increased autophagy and slightly reduced mitochondrial function. Additionally, gene expression related to these processes was analyzed.

The third part is an in vivo study in which nine ME/CFS patients underwent a one-hour whole-body hyperthermia session using water-filtered infrared-A radiation, raising their core body temperature to 39°C. Unlike the ex vivo results, the in vivo treatment reduced the previously elevated autophagy levels in ME/CFS patients back to normal and enhanced mitochondrial function. Since the in vivo results more accurately reflect the effects on the whole organism, they are considered more relevant for evaluating the therapeutic potential of hyperthermia.

The observed differences between ex vivo and in vivo responses provide a foundation for developing a new hypothesis regarding the pathophysiology of ME/CFS, which is discussed in the thesis. Overall, the results suggest that hyperthermia may be a promising treatment strategy for ME/CFS, capable of normalizing dysregulated cellular processes and improving energy metabolism.

Web | PDF | Konstanz, Univ., Doctoral dissertation | Open Access
 
Woo thermal whatever aside, more seahorse done on mixed PBMC which is impossible to interpret due to differences in oxidative metabolism between different subpopulations.

It does serve some purpose. In directly contradicting the 2017 Tomas paper (more basal respiration, not less) it seems to reiterate that these measurements in these cells ultimately reflect labile confounding factors.
 
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2.2.4 In vivo Hyperthermia
A total of nine ME/CFS patients participated in this study (Table 17). The ME/CFS patients were medically diagnosed using the diagnostic criteria of the Canadian consensus criteria [26] and the Furkuda criteria [24]. In addition, the severity of the disease was assessed using the Bell scale [159].
Hyperthermia treatment was performed on medical recommendation and not for this study. The patients agreed to donate blood for research purposes before and after the therapy.
Since no healthy donors underwent whole-body hyperthermia, the data can only be compared with those of healthy donors without therapy. For mitochondrial function, the data from this ex vivo study were used. In the case of autophagy, the data from this study were not comparable as the test was performed one day after blood collection (appendix Figure A60). [160,161]
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Just a side observation on that Table 17.

It's good to see the individual markers for the ME/CFS participants. Individual markers could help with interpretation when the number of participants is small, for example allowing preliminary evaluation of confounders such as BMI and age.

But the detail (sex, exact age and illness severity) given in Table 17 is surely highly identifying? The clinic is probably mentioned, so there is information about location. Age bands would be useful enough.
 
Struggling to read much this evening, but I wondered about the severity of the ME/CFS subjects in the in vivo hyperthermia trial.

My personal reaction to heat varies enormously in relation to the current severity of my ME and also the autonomic components at the time. In general I love a warm bath, but when at my more severe, when I have more marked issues with regulating my body temperature and when I have most orthostatic issues, having a bath was not an option as it makes all my symptoms much worse and makes me feel very ill (I don’t know if this could have been limited by matching the water temperature to my body temperature). At such times showering is my only option, but very limited largely because of orthostatic issues but also requires continuous adjustment of the water temperature to avoid over heating.

At such times I suspect any hyperthermia would be a very negative experience accompanied by a worsening in my ME, immediately worsening any current symptoms and also triggering subsequent PEM.
 
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