Cold therapy for Cancer


Cold therapy has been practiced for centuries, employing diverse techniques and applied to various medical conditions, including cancer [1]. However, in modern medicine clinical trials exploring the use of cold exposure for cancer treatment remain scarce.

Recently, researchers from Karolinska Institutet demonstrated promising outcomes in animal models, along with their clinical relevance, indicating that cold-induced activation of brown adipose tissue may have a tumor-suppressive effect [2].

These findings suggests that cold therapy could potentially have a significant impact on cancer treatment, emphasizing the need for further investigation in this area of research.

Anticancer effects of cold exposure in mice

Cancer cells have a distinct metabolic program compared to healthy cells, characterized by uncontrollable growth and a notable hunger for sugar. They consume large amounts of glucose to fuel their energy and metabolic needs.

On the other hand, brown fat, also referred to as brown adipose tissue or BAT, also utilizes a significant amount of blood sugar to generate heat and maintain body temperature when the surrounding temperature decreases sufficiently. This process, known as non-shivering thermogenesis, is not associated with the muscle activity of shivering. 

Seki and his colleagues exposed animal cancer models to cold in order to create a competitive environment for glucose distribution and examine its impact on tumor growth [2].

The researchers engineered mice developing various types of solid human tumors, including colorectal, breast, pancreatic, liver cancer, fibrosarcoma and melanoma. These mice were subjected to a temperature of 4°C to activate their BAT, subsequently monitoring both blood glucose uptake and tumor growth.

As a result, after just a few weeks of such cold exposure, significant anti-tumor effects were observed. Tumors exhibited up to 80% slower growth rates, appeared to be less invasive, and the overall survival significantly extended compared to the littermates kept at thermoneutral 30°C.

Cold-induced BAT thermogenesis in mice leads to tumor suppression by competing for the supply of circulating glucose. (Adopted from Chen & Kang. Signal Transduction andTargeted Therapy 2023. Fig.1) [3]

Interestingly, mice exposed to cold experienced decreased blood sugar levels, with glucose primarily accumulating in BAT and being barely detectable in tumors. Removing BAT or administering a high-glucose diet during cold exposure led to the restoration of tumor growth. These findings support the hypothesis that reducing blood sugar through cold-induced BAT activation is one of the key mechanisms behind the observed anticancer effects.


Cold exposure effects in humans

Cold exposure has been employed in a number of clinical trials, primarily assessing BAT activity and how it may influence weight loss in adults. It’s been shown that cold exposure consistently activate BAT inducing thermogenesis and increasing in energy expenditure [4].

Additionally, research into the potential benefits of the Wim Hof Method® [5], a meditation practice involving breathing techniques and cold exposure, has garnered significant attention in recent years. Developed by Wim Hof, a Dutch motivational speaker and renowned for his ability to endure prolonged periods of extreme cold, the method has primarily been investigated for its effects on stress, metabolism, and inflammation. One the studies has demonstrated cold-induced BAT activation and thermogenesis in both Wim Hof and his twin brother, revealing no significant difference between them. These findings suggest that a lifestyle involving frequent exposure to extreme cold may not impact BAT activity. Moreover, the study highlighted that the breathing technique employed by both brothers during the cold exposure experiment might contribute to heightened heat production compared to classical non-shivering thermogenesis [6].

Researchers from Karolinska Institutet also detected cold-induced BAT activation in healthy volunteers. But most importantly, they reproduced some of their findings observed in mice in clinical settings by studying a cancer patient. They recruited a young individual with Hodgkin’s lymphoma who was between chemotherapy cycles. The patient was subjected to mild cold at a tolerable temperature (22°C) for one week, resulting in activation of brown fat and a significant decrease in glucose uptake in the tumor [2].

Mild cold-induced BAT activation and decrease in glucose uptake in the tumor in a Hodgkin’s lymphoma patient. (Adopted from Seki Nature 2022. Fig.6) [2]

The need for further investigation and clinical trials

The human pilot study from Karolinska Institutet [2] not only confirmed the clinical significance of their findings observed in mice but also introduced a concept for a potential new cancer therapy. Further clinical trials, recruiting a large number of patients, are needed to evaluate the potential benefits of cold exposure across different tumor types, stages, and treatment approaches. Technical parameters such as the degree and duration of cold exposure require thorough testing to determine the optimal settings. Additionally, the trials should investigate the influence of cold exposure on the immune system, potential resistance development, and its efficacy in older patients, considering the higher incidence of cancer in this demographic.

In conclusion, with continued research, cold exposure could emerge as a valuable addition to the cancer treatment arsenal, offering new avenues for improving patient outcomes.

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