**1. Introduction**

The circadian rhythm of humans and other living beings had intrigued scientists and philosophers since antiquity. While its first known manifestation was the sleep-wake cycle, over the centuries additional body functions were identified as being controlled by the circadian rhythm. This chapter explores the relationship between human body temperature and our circadian rhythm, which turns out to be one of interdependence. The existing literature is reviewed with a particular emphasis on the health-related effects triggered by disruptions in the diurnal body temperature oscillations. The chapter concludes by offering possible future research avenues that could lead to the development of clinical tools such as mortality prediction models, sepsis early-warning systems and chronotherapy approaches to night shift work-associated disorders and psychiatric illnesses, all based on monitoring body temperature variations.

### **2. Human body temperature: An evolving story**

Human body temperature had been of interest to ancient healers [1–4]. In more recent times, the German physician and researcher Carl Reinhold August Wunderlich became known as the father of clinical thermometry for his pioneering application of a thermometer to measure a precise body temperature. In his 1868 seminal paper [5], Wunderlich used over a million axillary temperature readings from over 25,000 patients to established the first normothermia average point of 37°C, with the upper limit of normal being 38°C. To date, we still use these numbers as a reference standard. Since human body temperature continues to be regarded as an important screening and prognostic tool in modern medicine, further efforts had taken place to establish normothermia ranges and determine the factors that influence body temperature measurements, as was recently review by our group [6].

An important difference in normothermia exists between what are regarded as core body temperature measurement sites (e.g., rectal and transurethral) and the non-core sites such as oral, axillary, or tympanic. The former yield higher temperature measurements than the latter, likely due to heat-dissipating processes like convection occurring at the body surface. **Figure 1** (adopted with modifications and permission from Geneva et al. [6]) illustrates this difference using data from 36 unique peerreviewed studies. Further, age is a known major determinant of human body temperature, where a decline in temperature is observed as we get older, which is featured in **Figure 2** (adopted with modifications and permission from Geneva et al. [6]). Some studies have shown that body temperature also depends on the subject's sex due to the change in body temperature among pre-menopausal women based on when the measurement is taken with regards to their menstrual cycle [5, 7–9]. In addition, the seasonal environmental temperature itself appears to influence our body temperature – a large study of over 93,000 emergency department patients demonstrated that on average human body temperature is lower by 0.2°C (using temporal artery thermometers) in the winter compared with the summer [10]—a statistically significant difference albeit a small one. Certainly, medical illnesses such as infections, malignancies, thyroid disorders, among many others, can strongly affect our temperature as well.

#### **Figure 1.**

*Human body temperature of healthy volunteers classified by measurement site. Adapted with modifications and with permission from Geneva et al. [6] Figure 1B.*

*Human Body Temperature Circadian Rhythm in Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.1003852*

#### **Figure 2.**

*Human body temperature of healthy volunteers classified by age and measurement site. Adapted with modifications and with permission from Geneva et al. [6] Figure 1C.*

Interestingly, the 37°C normothermia average standard had been challenged by several research groups including Obermeyer et al. [11], Diamond et al. [12] and Corsi et al. [13], where a lower non-core average body temperature of 36.6°C, 36.1°C and 36.71°C were reported, respectively. While these findings were based on diverse cohorts and constituted only a point-in-time observation, Protsiv et al. [14] carried out a longitudinal study, where the measurements were adjusted for age, weight, height, and for some data sets for time of the day as well. By combining data from Civil War Union Army veterans covering 1860–1940, the National Health and Nutrition Examination Survey I covering 1971–1975, and the Stanford Translational Research Integrated Database Environment covering 2007–2017, Protsiv et al. discovered a curious trend of steady body temperature decrease at a rate of 0.03°C per birth cohort, leading to a difference of 0.56°C between males born in the 19th century and adult males today; for females, the total decrease was smaller — 0.32°C. Speculative explanations for this discovery centered around two major factors. First, there had been a decrease in metabolism as each new generation is believed to be significantly more sedentary than the prior and most homes are heated in winter and cooled in the summer, thus decreasing the human body basic metabolic rate expenditures. Second, the prevalence of fever in the human population induced by chronic inflammation had declined with the advent and widespread use of antibiotics, vaccines, and non-steroidal anti-inflammatory drugs.

In conclusion and knowing that we currently live in the era of personalized medicine, it is necessary to point out that ultimately, no matter what the population-wide average body temperature is, each person has their own baseline body temperature, which may be several standard deviations above or below the population average. This is illustrated by measured intrapersonal standard deviation of 0.32°C [12] and 0.39°C to 0.4°C [15] in healthy adults, while the range of measured interpersonal body temperatures in the same research studies spanned 2–3°C. This realization prompted several researchers to propose that "one size does not fit all" as it comes to normal body temperature [12, 13]. The definition of normothermia is further complicated by the fact that even within the same organism body temperature changes in a cyclic manner with a period of approximately 24 hours – the circadian rhythm of body temperature, which is the focus of the next chapter section.
