Hyperthermia and Fever
Here is a link to the hyperthermia presentation:
Fever is a natural immune response to harmful and life-threatening infections. Conversely, blocking fever can be deleterious because fever evolved as a defense against infection. Fever works by causing damage to pathogens and infected cells while sparing healthy cells.
Many potential pathogens can survive and function over a wide range of temperatures cooler than their optimum. However, temperatures slightly higher than the optimum can damage infectious species. Some modes of action include proteins, enzymes, membrane lipids, RNA, and DNA. Specifically, hyperthermia disrupts DNA synthesis in the cells of pathogens and "host" cells.
Fever may create equal harm to pathogens and healthy tissue, at least in the short term. However, our tissues have repair and recovery pathways that are part of our physiology. Pathogens do not have this ability. Instead, they depend upon replication to proliferate. When a single cell in our body is destroyed from hyperthermia, disease, or even exercise, it is repaired or replaced. When a single pathogen is destroyed, it loses all ability to sustain and repair. Also, our tissue does not signal an attack response from our immune system, but pathogens do.
In the case of pathogens, if they can "hide" from immunity or hyperthermia, they survive or thrive through replication. But this is seldom the case. Root canals are an example of an area where pathogens can "hide" and then replicate there and spread and replicate elsewhere. Also, hyperthermia-induced artificially rather than through a fever may not globally increase body temperature. In this instance, the pathogen "escapes" the impact of the internal temperature change.
Thus,
If our tissue is damaged or destroyed by fever/hyperthermia, it will be repaired.
If a pathogen is present, fever or hyperthermia will reduce its population.
Immunity will also reduce pathogen populations.
Pathogens tend to be more susceptible to fever/hyperthermia.
If the pathogen burden is sufficiently reduced, the immune system can control or eliminate it.
According to Scientific American,[i] "Fever is an elevated temperature of the human body that is substantially beyond the normal range. Normal body temperature fluctuates daily from about one degree below 98.6 degrees Fahrenheit to one degree above that number. Lower body temperatures usually occur before dawn; higher temperatures occur in the afternoon."
However, even a slight increase in temperature, especially at nighttime, may indicate a low-grade chronic infection. Night sweats signify a slightly elevated nighttime temperature as this is the time when core body temperature is below the normal value. Chris Wilson, M.D., surgeon lieutenant of the Royal Navy, describes his long journey with Lyme disease in an article titled "my years with Lyme disease."[ii] He stated, "Constant pain, feeling permanently hung over, being unable to stand properly, and soaking erstwhile sleep partners, courtesy of night sweats, did not augur well for relationships."
Tuberculosis (TB) is historically known to cause night sweats. It is an ancient disease that has affected mankind for over 4,000 years.[iii] It is a chronic disease caused by the bacillus Mycobacterium tuberculosis and spreads from person to person through the air. TB usually affects the lungs but can also affect other body parts, such as the brain, intestines, kidneys, or the spine. Symptoms of TB depend on where in the body the TB bacteria are growing. For example, pulmonary TB may cause symptoms such as chronic cough, pain in the chest, hemoptysis, weakness or fatigue, weight loss, fever, and night sweats.
Scientific American further explains that "the hypothalamus, which sits at the base of the brain, acts as the body's thermostat. It is triggered by floating biochemical substances called pyrogens, which flow from sites where the immune system has identified potential trouble to the hypothalamus via the bloodstream. Some pyrogens are produced by body tissue; many pathogens also produce pyrogens. When the hypothalamus detects them, it tells the body to generate and retain more heat, thus producing a fever. Children typically get higher and quicker fevers, reflecting the pyrogens' effects on an inexperienced immune system."
However, this temperature regulation is not what causes our internal temperature to be "normal." Our physiological reactions are what set our internal temperature. The hypothalamus works to regulate our normal temperature. Sweat is most likely the regulatory system initiated by the hypothalamus. Thermoregulation of body temperature is a more complex interplay between physiological reactions. It is a balance between heat production and heat dissipation. Heat is generated or absorbed internally as a byproduct of any metabolic process. Heat absorption is an endothermic process, while exothermic processes cause heat production. The balance between these two reaction types set the core body temperature of approximately 98.7°F
Fever can help fight infection, but sometimes it can climb too high for the body's good. For instance, internal body temperatures above 105 degrees °F expose proteins and body fats to direct temperature stressors. This heat distress can threaten the integrity and function of proteins accustomed to the body's usual temperature variations and low-grade fevers. As a result, cellular stress, infarctions, necrosis, seizures, and delirium are the potential consequences of prolonged, severe fevers.
The receptor environment at the hypothalamus is designed to put limits on fevers. In rare instances in which the hypothalamus malfunctions, the result is typically low body temperature, not elevated.
The fever never occurs in isolation from other immune responses. In this sense, it is symbiotic. Higher temperatures speed up reactions. One type of reaction is the production and action of "acute phase reactants" that are part of innate immunity. Therefore, fever provides three benefits:
1. Temperatures above normal are hostile to the survival of pathogens.
2. Elevated core or localized temperatures speed up physiological reactions, including those associated with immunity.
3. Higher body temperatures reduce blood viscosity and provide more blood flow.
Focal Infection and Focal Temperature
Chronic infections cause many chronic diseases. Those chronic conditions localized to specific tissue are caused by "focal" or localized infections. The temperature to which pathogens at the infected site are actually exposed is currently unknown.[i],[ii] However, it is almost certainly higher than that of the blood entering the infected site since heat is generated at the inflammatory site. For example, studies assessing the temperature of inflamed atherosclerotic plaques have found temperatures up to 4°F higher than core temperature.[iii] Sources of localized heat include,
Surprisingly high physiological temperatures of up to 50°C (122°F) are generated very locally. This was elucidated by measuring mitochondrial temperatures using temperature-sensitive dyes.[vii]
High Infection Rate at Lower Temperatures
An area with an exceptionally high infection rate is the sinus. U.S. adults with diagnosed sinusitis are about 30 million, or 12% of this population. In addition, the number of people with a constantly runny nose or the "sniffles" is substantially higher. At least two factors drive this nasal "pandemic." 1. The nasal cavity is cooler than other tissue because of high airflow from the cooler ambient air, and 2. the oral cavity close to the sinus often suffers from low-grade chronic infections. The following clinical testimonial provides context to this issue:
"My bloodwork revealed an underlying infection of some kind. I was recommended the MyPeriopath, on the hunch it could be a mouth infection. I did that and had some harmful pathogens in my results. I found a new dentist in my area that includes cone scans, and low and behold; they found an infection in tooth #15 on the top. It had a crown from many years ago but had NOT had a root canal. The infection is pretty bad and even pushed into my sinus. Crazy, considering I have had zero pain in that tooth or sinus."
Nasal hyperthermia irrigation dramatically reduces rhinitis.[viii] Local nasal hyperthermia or inhalation of heated water vapor is a home remedy for various rhinitis disorders such as the common cold and allergic rhinitis. Inhaled heated vapor treatments and saline solution nasal irrigation reduce the effect on inflammatory mediator production in nasal secretions.
Treatment of perennial allergic rhinitis by local hyperthermia is a study demonstrating the value of hyperthermia.[ix] The authors state, "Due to the cooling produced by airflow, the temperature of nasal turbinates[1] varies between 88 and 95°F. This low body temperature range enables the development of rhinoviruses, the main agents of the common cold." Ninety-five patients with documented perennial allergic rhinitis were treated with local hyperthermia of the nasal passages in a formal clinic trial. Treatment and results were,
One series of three 30-minute insufflations of humidified air at 109°F was applied at two hr. intervals.
In the active treatment group, patients were free of symptoms: one week after treatment, 75%, and one month after treatment, 68%, respectively.
In the placebo group, patients were free of symptoms after treatment: at one week, 28%, and at one month, 17%.
The placebo group experienced the same device but with room-temperature air.
This important experiment from 1982 clearly shows that hyperthermia alone, without fever and the associated immune response, is a safe and effective treatment for allergic rhinitis and, by extension, other temperature-vulnerable pathogens.
Fever
Donohoe Chiropractic weighs in on the value of a fever not lowered with antipyretic treatment.[x]
The rising body temperature kills many microorganisms and curbs the growth and replication of others. This is because viruses and bacteria grow best at temperatures lower than the human body.
Higher body temperatures decrease blood serum levels of iron, zinc, and copper, all of which are needed for bacterial replication. As these minerals are reduced in the bloodstream, bacteria are starved.
Increased temperature causes lysosomal breakdown and auto-destruction of cells, thus preventing viral replication in infected cells.
Heat increases white blood cell formation and motility, thus facilitating the immune response. As a result, the white blood cells, which destroy the invaders, get where they are needed faster and do their job more efficiently.
Phagocytosis (cellular clean-up) is enhanced, and the production of antiviral interferon may be augmented.
Donohoe illustrates that reducing fever is often harmful. A study of adults with colds found that aspirin and acetaminophen suppressed the production of antibodies and increased cold symptoms, with a trend toward longer infectiousness. In a study of children with chickenpox, acetaminophen prolonged itching and the time to scabbing compared to placebo treatment. In test-tube studies, therapeutic levels of aspirin suppressed the ability of human white blood cells to destroy bacteria. Another study found that a host of pain relievers, including aspirin and ibuprofen, inhibited white-cell production of antibodies by up to 50 percent.
Although fever and sickness symptoms are regulated in different brain regions, both are inhibited by antipyretic drugs (e.g., NSAIDs and acetaminophen). However, NSAIDs, particularly ibuprofen, have more anti-inflammatory properties than acetaminophen and may carry additional risks of promoting infection.[xi]
On the flip side, fever is beneficial in patients with meningitis. Notably, a fever greater than 40°C did not indicate a poor prognosis, but all children presenting with hypothermia died, according to one study.[xii]
Many peer-reviewed reports show how reducing fever worsens outcomes. A sample of these studies includes:
Sickness behavior in feverish children is independent of the severity of the fever - an observational, multicenter study.[xiii]
Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection.[xiv]
A study from Japan found that the frequent administration of antipyretics to children with bacterial diseases led to the worsening of their illness.[xv]
A Finland study of 102 children with salmonella gastroenteritis showed a significant negative correlation between the degree of fever and the duration of excretion of organisms.[xvi] Children with a fever greater than 40°C had the shortest duration of bacterial excretion, whereas those without fever had the most prolonged duration.Fever has a favorable influence on the length of the infectious disease.
This review article provides many illuminating facts.
"Non-steroidal anti-inflammatory drugs (NSAIDs) have an optional prescription status that has resulted in frequent use, particularly for the symptomatic treatment of fever and non-rheumatic pain. However, in 2019, a multi-source analysis of complementary pharmacological data showed that using NSAIDs in these indications (potentially indicative of an underlying infection) increases the risk of a severe bacterial complication, particularly in lung infections."
"First, the clinical observations of the French Pharmacovigilance Network showed that severe bacterial infections can occur even after a short NSAID treatment, and even if the NSAID is associated with an antibiotic."
"Second, appropriate studies that overcame bias converged and confirmed the risk.
"Third, experimental in vitro and in vivo animal studies suggest several biological mechanisms, which strengthens a causal link beyond the well-known risk of delaying the care of the infection (immunomodulatory effects, effects on S. pyogenes infections, and reduced antibiotics efficacy)."
"Therefore, in case of infection, symptomatic treatment with NSAIDs for non-severe symptoms (fever, pain, or myalgia) is not recommended, given a range of clinical and scientific arguments supporting an increased risk of severe bacterial complication." 17
JianFeng Chen works at China's Shanghai Institute of Biochemistry and Cell Biology. His team studied how immune cells travel from a blood vessel to the site of an infection. His team found that a fever gives the cells a superpower that speeds up that trip.[xvii]
How does this work? Increased temperatures reduce viscosity allowing for more blood flow. This is in addition to the antibiotic effect of the elevated temperature and the recruitment of immune cells. The Chen group also showed that T lymphocytes, the viral killer cells of the immune system, become produced at higher levels during fever and infection.
Hyperthermia Treatment and the Sun
Sunlight will increase core body temperature. Infrared light, the most abundant form of light waves in sunshine, increases the temperature of any substance with which it interacts. That is why you feel a tremendous warming effect from sunlight. The primary mechanism is surface and internal heating caused by the infrared light and not from warm air interacting with your skin.
Sanatoriums are well known for their healing benefits. These facilities are usually situated high in the mountains where sunlight, including warming infrared light, is not attenuated by the dense atmosphere's lower levels. H. I. Bowditch argued for the curative powers of "pure air and sunlight," recounting the story of a 30-year-old woman he had treated for tuberculosis. "We directed that she should sit out on this piazza every day during the winter unless it were too stormy," he wrote. "The balmy influences exerted on her by the daily sun and air bath was so grateful her breathing became much easier after each of them.[xviii]
Fever vs. Hyperthermia
Fever and hyperthermia share many mutual benefits. Fever may be superior to an artificially induced elevated core temperature mainly by recruiting more immune cells. Importantly, fever is self-limiting and well-controlled. With fever, unlike hyperthermia, body temperature is well regulated by a hypothalamic set-point that balances heat production and loss. Natural fever regulates temperature that will not climb relentlessly and does not exceed an upper limit of 42°C (106.7 F).
Fever seldom causes harm, especially long-term damage. Fever does not frequently exceed an upper range of 40°C (104°F), a temperature proved not to be injurious to tissue. Children, when sick, often run a higher temperature compared to adults. About 20% of children seen in the emergency room have temperatures over 40°C, and they usually make a full recovery. If there is morbidity or mortality, it is due to the underlying disease. The associated fever may well be protective.[xix]
Hyperthermia as a treatment is well studied but seldom applied. A PubMed search reveals 44,000 medical peer-reviewed publications that include "hyperthermia" in the title. There is even a journal on hyperthermia titled "the international journal of hyperthermia. Most hyperthermia studies are on Cancer therapy. Also, in most instances, elevation in temperature is induced locally, for example, just in the tumor area. In these instances, the local temperature is substantially higher than that produced by fever. A better approach to matching what happens in a fever is to induce an elevated core temperature globally.
"Hyperthermia: How Can It Be Used?" is the title of a representative article.[xx] The authors state, "Hyperthermia (HT) is a type of cancer treatment along with surgery, radiotherapy, chemotherapy, and gene and immunotherapy. In oncology, HT uses an external heat source to increase tissue temperature, kill cancer cells, or impede their growth. The term 'hyperthermia' applies to several heat application techniques that are implemented in addition to other cancer treatments (particularly chemotherapy and radiotherapy)."
"There are three types of HT treatment predominantly used to treat cancer. Each requires applicators in contact with or in the patient's proximity for heating. Heating can be achieved using different types of energy, including:
microwaves;
radio waves; and
ultrasound."
"However, the energy source will depend on the cancer type and location. The temperature used will also vary. HT is rarely used alone and can be combined with other cancer treatments. When combined with other treatments, improved survival rates have been observed."
"High temperatures, as most studies revealed, cause direct injury to cancerous cells and sensitize the cells to other treatment modalities, and augment radiation and chemotherapy with minor or no injury to normal tissues. Hence, HT is generally used as an adjuvant treatment for cancer." HT treatment temperatures range between 40–48°C (104 - 118°F), and the temperature is maintained at a treated site for one hour or more."
"Because of the consequences high temperature may have on tissues, one can refer to use temperatures >50°C (>122°F) as coagulation, 60–90°C (140 - 194°F) as thermal ablation, and >200 °C as charring. Ablation or high-temperature HT is defined as the direct implementation of chemical or thermal therapies to a tumor to reach annihilation or significant tumor destruction."
"The curative capacities, treatment outlay, technical problems, and evidence of efficacy vary depending on the HT approach. While treatment of tumors with HT has been applied since the time of the ancient Greeks, this technique has been opposed due to certain limitations. These include:
failure to heat the target without damaging the nearby cells;
difficulty achieving homogenous heat dispersion throughout the tumor; and
inherent problems with targeting invisible micro-metastases."
Heating human tissue with high intensities of microwaves, radio wave, and ultrasound is far from natural. The most natural form of heating is infrared light. Studies on infrared light to induce an artificial fever are few. One study in the International Journal of Hyperthermia does document infrared light treatment.[xxi] The authors explain,
"Among the different methods of whole-body hyperthermia (WBH), the energy transfer with infrared radiation seems to have established itself as a relatively simple procedure. However, the infrared systems differ concerning the used spectrum of radiation. In the case of water-filtered infrared radiation, infrared A (760 - 1400 nm) is the focal point of heat radiation. This radiation penetrates deep into the skin up to the capillary area of the dermis."
"Eighty treatments of patients in an advanced stage of cancer (40 male, 40 female) were performed with a WBH device with infrared radiation. Extreme WBH was combined with induced hyperglycemia and relative hypoxemia for 83% of the patients with chemotherapy. The body-core temperature was measured rectally or vesically. The objectives of the thermal control were a low rate of side effects and a quick rise of the body-core temperature concerning the condition of the patient's skin. The mean duration of the rising phase (37.5 -41.6°C; 99.5 - 106.9°F) was 87 min.
This study aims to assert the safety of this mode of inducing hyperthermia. In this regard, it was a success. However, no conclusions were drawn regarding the approach's efficacy on the existing cancers. Studies on actual outcomes are sparse and usually involve complementary treatments, not just infrared light-induced hyperthermia.[xxii]
The National Cancer Institute does recognize hyperthermia as a viable treatment. "Hyperthermia is a treatment in which body tissue is heated to as high as 113°F to help damage and kill cancer cells with little or no harm to normal tissue. Hyperthermia to treat cancer is also called thermal therapy, thermal ablation, or thermotherapy." Infrared light as a facilitator of hyperthermia is not explicitly listed. However, they refer to "placing the entire body in a heated chamber or hot water bath or wrapping with heated blankets." Heating is an inferior way to increase core temperature compared to intense infrared treatment because heating involves conduction. In contrast, infrared light heats as deeply into tissue as it can penetrate.
Infrared Light Hyperthermia Conclusion
In combination with red light treatment, infrared light is the best way to apply hyperthermia, either systemically or locally.
Infrared and red light provides:
Antioxidants to ensure electrons (energy) are provided to the KREBS cycle (healing);
Elevated temperatures speed up reactions - of both destruction and repair;
Elevation in temperature stimulates the production of immunity (cytokines);
High temperatures are hostile to most pathogens;
Our tissues have repair mechanisms for any damage created by the natural heating of infrared light, while pathogens may not have such means.
"Go out into the light and warmth of the glorious sun, you pale and sickly ones, and share with vegetation its life-giving, health-healing power."
- The Health Reformer, May 1, 1871
[1] Turbinates are small structures inside the nose that cleanse and humidify air that passes through the nostrils into the lungs.
[i] LeGrand EK, Day JD.. Self-harm to preferentially harm the pathogens within: non-specific stressors in innate immunity. Proc R Soc B 2016;283:20160266. [ii] Stankov S. Definition of inflammation, causes of inflammation and possible anti-inflammatory strategies. Open Inflamm J 2012;5:1–9. [iii] Casscells W, Hathorn B, David M. et al. Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet 1996;347:1447–51. [iv] Van De Parre TJL, Martinet W, Verheye S. et al. Mitochondrial uncoupling protein 2 mediates temperature heterogeneity in atherosclerotic plaques. Cardiovasc Res 2007;77:425–31. [v] Tan AM, Huang YQ, Qu SS.. Determination of the respiratory burst of polymorphonuclear leukocytes by microcalorimetry. J Biochem Biophys Methods 1998;37:91–4. [vi] Nogueira-Machado JA, Mares-Guia ML, Lima e Silva FC. et al. Calorimetry: a highly sensitive technique for evaluating the effect of IL-2, IFN-γ and IL-10 on the response of peripheral blood mononuclear cells. Thermochimica Acta 1999;327:57–62. [vii] Chrétien D, Bénit P, Ha H-H. et al. Mitochondria are physiologically maintained at close to 50°C. PLoS Biol 2018;16:e2003992 [viii] Georgitis JW. Nasal hyperthermia and simple irrigation for perennial rhinitis. Changes in inflammatory mediators. Chest. 1994 Nov;106(5):1487-92. doi: 10.1378/chest.106.5.1487. PMID: 7956408. [ix] Yerushalmi, Aharon, Sergiu Karman, and Andre Lwoff. "Treatment of perennial allergic rhinitis by local hyperthermia." Proceedings of the National Academy of Sciences 79.15 (1982): 4766-4769. [x] https://www.donohoechiropractic.com/benefits-of-fever/, accessed 01/10/2023. [xi] Micallef J, Soeiro T, Jonville-Béra A-P.. Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection. Therapie 2020;75:355–62. [xii] Wong VK, Hitchcock W, Mason WH : Meningococcal infections in children: a review of 100 cases. Pediatr Infect Dis J, 8: 224-227,1989. [xiii] Corrard F, Copin C, Wollner A. et al. Sickness behavior in feverish children is independent of the severity of fever. An observational, multicenter study. PLoS One 2017;12:e0171670. [xiv] Micallef J, Soeiro T, Jonville-Béra A-P.. Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection. Therapie 2020;75:355–62 [xv] Sugimura T, Fujimoto T, Motoyama T, et al : Risks of antipyretics in young children with fever due to infectious diseases. Acta Paediatr Japanica, 36:375-378, 1994. [xvi] El-Radhi AS, Rostila T, Vesikari T : Association of high fever and short bacterial excretion after salmonellosis. Arch Dis Child, 67: 81, 1992. [xvii] C. Lin et al. Fever promotes T lymphocyte trafficking via a thermal sensory pathway involving heat shock protein 90 and α4 integrins. Immunity. Vol. 50, January 2019, p. 137. doi:10.1016/j.immuni.2018.11.013. [xviii] https://www.theatlantic.com/health/archive/2020/03/tuberculosis-sanatoriums-were-quarantine-experiment/608335/, March 21, 2020. [xix] El-Radhi, A. Sahib. "The role of fever in the past and present." Medical Journal of Islamic World Academy of Sciences 109.408 (2011): 1-6. [xx] Behrouzkia Z, Joveini Z, Keshavarzi B, Eyvazzadeh N, Aghdam RZ. Hyperthermia: How Can It Be Used? Oman Med J. 2016 Mar;31(2):89-97. doi: 10.5001/omj.2016.19. PMID: 27168918; PMCID: PMC4861392. [xxi] Wehner, H., A. Von Ardenne, and S. Kaltofen. "Whole-body hyperthermia with water-filtered infrared radiation: technical-physical aspects and clinical experiences." International journal of hyperthermia 17.1 (2001): 19-30. [xxii] Zhou L, Zhang M, Fu Q, Li J, Sun H. Targeted near infrared hyperthermia combined with immune stimulation for optimized therapeutic efficacy in thyroid cancer treatment. Oncotarget. 2016 Feb 9;7(6):6878-90. doi: 10.18632/oncotarget.6901. PMID: 26769848; PMCID: PMC4872755
[i] https://www.scientificamerican.com/article/what-causes-a-fever/, accessed 01/06/2023. [ii] Wilson CJ. My years with lyme disease. BMJ. 1999 Sep 4;319(7210):649. doi: 10.1136/bmj.319.7210.649. PMID: 10473502; PMCID: PMC1116513. [iii] Zaman K. Tuberculosis: a global health problem. J Health Popul Nutr. 2010 Apr;28(2):111-3. doi: 10.3329/jhpn.v28i2.4879. PMID: 20411672; PMCID: PMC2980871.
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