Volume 8 (will be Vol 7 on site)


A lack of properly functioning circadian rhythm can lead to
various sleeping disorders, as well as issues related to the
absence of zeitgebers—environmental signals like light,
temperature, or food that cue the body to adapt its processes
accordingly (Chaix, 2016). For example, “While blind
individuals do have a pathway in the brain that functions as
their body clock, roughly half of blind individuals experience
non-24-hour sleep-wake rhythm disorder, during which their
sleep cycles get later every night, jumps around, or results in
waking up later in the day” (Reddy, 2023). 

This process is just one of many that is controlled by the
circadian rhythm, stressing its importance. The circadian
rhythm is able to function because of the influence of
zeitgebers. Because of the many bodily processes influenced
by the circadian rhythm, the manipulation of zeitgebers and
timing of treatments along with them is being researched as a
method of treatment for various illnesses and infections via
the immune system. Additionally, lifestyle changes that utilize
the timing of the circadian rhythm can lead to better overall
health; the circadian rhythm is even being taken into
consideration for cancer treatment in a practice called
“circadian medicine or chronotherapy” (Dose, 2023). The
importance of the circadian rhythm and its ability to be
manipulated through zeitgebers has led discoveries about its
influence over immune response efficiency.

Practical Applications of The Circadian Rhythm
Erin Ford

 Abstract
The Circadian Rhythm is a cycle within the body that controls multiple biological processes such as the sleep-wake cycle, body
temperature, hormone releasing, and digestive system. The circadian rhythm is widely theorized and understood to be
developed because of the daily cycle of light and dark. This can be attributed to sunlight serving as the primary source of food
for photosynthetic organisms, causing a cycle within the organism that causes food to be processed during the hours of
daylight and a period of fasting during the night. Recent research has suggested that disruptions in this rhythm can lead to
various issues within the body. However, there have been advancements in the applications of the circadian rhythm in the
areas of the immune system and infection; exercise and sleep; digestion and food-processing; and cancer and treatments.
This paper explores the fundamental mechanisms of the circadian rhythm and the impact on human health in various areas,
advocating for practical applications of this profound biological cycle.

Introduction to the Circadian Rhythm and Its
Importance
The circadian rhythm can be defined as the internal clock that
controls feelings of awakeness and sleepiness in response to
the 24 hour cycles of light and dark from the environment.
The importance of the circadian rhythm cannot be
understated, as the proper functioning of this cycle is crucial
for everything from memory consolidation, eating habits, and
digestion to body healing, temperature, and hormone release
(Reddy, 2023). These processes ensure that your body is
able to function normally. 

An example emphasizing the importance of the circadian
rhythm is the release of melatonin and cortisol, a process
necessary for the proper functioning of the sleep wake cycle
and even further, the proper functioning of the brain.
Melatonin is a hormone that is released from the pineal gland
to induce sleepiness in response to a lack of light while
cortisol is a hormone that promotes alertness in response to
the presence of light (Reddy, 2023). This occurs because of
the suprachiasmatic nucleus (SCN) of the hypothalamus, the
region of your brain that controls homeostasis. In the
presence of light, the retinal cells within the eyes will perceive
this light and transmit this information via the optic nerve. The
optic nerve then activates the SCN, producing a signaling
molecule called GABA (gamma-amino-butyric acid), inhibiting
the release of melatonin. In essence, the light perceived by
the optic nerve causes the body to send out signals through
the SCN, preventing the release of melatonin so that the
feeling of sleepiness goes away during the day. The opposite
occurs when there is no longer light: the retinal cells
recognize the lack of light and inhibit the SCN, preventing the
release of GABA and initiating the production of melatonin
and inducing sleepiness (Reddy, 2023).The proper
functioning of the circadian rhythm for this process is
essential because a lack of/excess melatonin could cause the
body to not be able to sleep at night or a feeling of tiredness
during the day. Lack of sleep can even affect mood, learning
ability, and social cognisance (Sleep Deprivation, 2022).



Timing and the Immune System
One of the systems the circadian rhythm can be used to
control and improve is the immune system. The circadian
rhythm is responsible for the timing of expression of many
proteins; some of these are important for the initial response
for the immune system. One such protein is REV-ERBα: this
protein is a key part of the immune system because it
“regulates transcription of inflammatory genes in
macrophages” (Ruan, 2021). These macrophages are the
lymphocytes that are responsible for removing unfamiliar and
potentially harmful entities in the body. Another example is
Nuclear receptor RORγt which is “a master regulator for the
development of IL-17-producing T helper cells (TH17 cells),
an important immune cell type for autoimmunity” (Ruan,
2021). T helper cells are essential for activating other cells
within the immune system, such as those required to
eliminate infected cells and foreign bodies. Additionally, the
circadian rhythm controls the acquisition of lymphocytes. For
example, the amount of B and T lymphocytes in circulation
oscillates along with the rest and activity cycle, with
increased numbers in the rest phase. The more lymphocytes
in circulation, the more effective the immune response will be
and the faster the recovery. The control the circadian rhythm
has over these processes make the manipulation of
zeitgebers a viable option for the treatment of infections. For
example, light and dark cycles are used to increase T and B
cells within a patient because of their peak during the rest
phase. The lack of light acts as a zeitgeber to initiate the rest
phase, leading to the increase in production of these cells.
This leads to an increased immune response from the patient
and a better chance of recovery from the infection (Ruan,
2021). By placing the patient in a room with low light and
initiating this rest phase of the circadian rhythm, more white
blood cells can be produced. This timing along with the
circadian rhythm can contribute to the immune system’s
ability to fight off an infection. 
 
Exercise and the Circadian Rhythm
The timing of daily activities such as eating and exercise
along with the circadian rhythm can result in more efficient 

bodily processes such as exercise and digestion. As light and
dark cycles are important in the moderation of lymphocytes,
the timing of daily activities--like eating or exercising--can
improve the effectiveness of various bodily processes.
Research has demonstrated that blood pressure, body
temperature, hormone levels, and heart rate variability are all
controlled by circadian variation (Dose, 2023). With these
physiological features being integral to sport performance,
timing exercise with the optimal levels of these factors can
increase effectiveness of exercise and peak performance
during periods of exercise. Conversely, misalignment can be
detrimental to effectiveness of sleep cycles: “Night exercise
causes a phase delay of the onset of dim-light melatonin”
(Wang, 2022). As a result, exercise before bed is not
recommended because it can block the production of the
hormone that induces the feeling of tiredness and it is
advised that physical activity take place slightly earlier in the
day. Therefore, a better sleep schedule can be obtained
based on the timing of exercise with consideration of the
circadian rhythm. This better sleep schedule leads to all of
the benefits associated with more sleep, such as improved
immune response to possible pathogens (Ruan 2021). This
indicates that consideration of the circadian rhythm in the
timing of exercise can not only improve the quality of the
exercise but also improve other necessary functions such as
sleep and digestion.

Effective Digestion and The Circadian Rhythm
Similar to the timing of exercise, the timing of meals with
consideration of the circadian rhythm can also result in a
healthier lifestyle. For example, “insulin mediates the phase
adjustment of the circadian rhythm of the tissues related to
food in mice” (Wang, 2022). This process is important for
tissue function which, in turn, assists in digestion and
absorption of nutrients and aligning the stomach’s circadian
rhythm with meal times. Hence, the timing of meals with
respect to the circadian rhythm can affect the efficiency of
meal processing. Recent research supports this idea: in a
study describing how the circadian rhythm controls pathways
related to metabolic processing, researchers found that these
pathways begin to increase when eating is anticipated. This
is a temporary effect that declines after a few hours (Chaix.
A, 2019). These results indicate that having a scheduled
eating time every day can assist in the absorption of nutrients
because the body will always be prepared to process food
during that time. Furthermore, deviating from this schedule
would mean consuming a large amount of nutrients when the
body is not prepared to process it, and, as a result, leads to a
less efficient digestive process. This supports the argument
that “the consumption of a larger portion of caloric intake
during the first half of wakeful hours may be preferred for
better blood glucose regulation and weight control“ (Dose,
2023). Essentially, after a large period of fasting, or sleep, the
body has had a long period of time to prepare for the next
meal and because of this, the circadian rhythm has ensured
that the proper pathways are prepared. Cumulatively, the
timing of meals alongside the circadian rhythm results in
more efficient digestion and leads to better absorption of the
nutrients necessary for other processes within the body.

Figure 1.   A diagram explaining the processes controlled by the
circadian rhythm as well as the factors controlling it. Cycle zoomed

in on previous page. Obtained from an overview article by Ana
Amiama-Roig and others.

Brain Matters・Volume VII      48



Chronotherapy and Cancer Treatment
The circadian rhythm’s applications are not only exclusive to
day to day life but also have significance within the medical
field. The timing of the circadian rhythm can be used to
increase effectiveness of cancer treatments and the overall
quality of life in cancer patients. The time of day when cancer
treatments are administered can affect how much of the dose
can be tolerated and the side effects experienced by the
patient. An example of this was a study done with mice that
found “the same dose of an anticancer drug became lethally
toxic only when administered at certain times of day,
whereas at other times of day, a 10-fold increase in dose was
tolerated”(Ancoli-Israel, 2005). These results seem logical
when considering the amount of processes that are
controlled by the timing of the circadian rhythm. Certain
proteins being made at specific times may help the body
process the drugs or could cause unpleasant interactions
leading to side effects of the drug. If the circadian rhythm
dependent proteins that cause unpleasant interactions are
made mostly within the first hours of waking, then the
majority of this interaction can be avoided by taking the drug
treating the cancer later in the day. Other research focusing
on cancer patients has shown that the quality of life of the
patient increases significantly when chronotherapy is used.
Administration of the drug during the morning was compared
with administration during the evening and it was found that
during the morning hours patients experienced “milder
nausea, and less vomiting in those receiving the
chemotherapy in the evening” (Ancoli-Israel, 2005). The
reduction of these unpleasant side effects leads to the patient
feeling better physically, which in turn leads to “better
psychosocial adaptation (including better social relations,
less feeling of loss of independence, less anxiety, less
depression, and less somatic discomfort) than patients
receiving traditional therapy” (Ancoli-Israel, 2005). It is then
likely that chronotherapy plays a part in the patient having
fewer side effects and better quality of life during treatment.
 

Chronotherapy is an effective treatment method because of
the difference between the circadian rhythms followed by
cancerous and noncancerous cells. According to Benjamin
Dose “Chronotherapy aims to exploit these differences in
circadian rhythms by administering treatments at times when

cancer cells are most vulnerable, and healthy cells are least
vulnerable, thereby reducing toxicity and enhancing efficacy”
(Dose, 2023). This strategy ensures that the cancer treatment
can be administered at a time when it will be the most
effective and when the healthy cells will be least affected
which is what causes the minimized side effects. This kind of
thinking may extend beyond cancer treatment and to other
more common medications with adverse side effects. If other
medications can be found to be more effective or have
reduced side effects at certain periods of the circadian
rhythm, then the same benefits as those from chronotherapy
can be obtained.

Conclusion
To summarize, the circadian rhythm is a very powerful
process in the human body that has a great deal of control
over the different processes in the body; therefore, it is
important to consider the circadian rhythm when carrying out
certain processes, such as fighting off an infection. For
example, more lymphocytes are produced during the rest
phase which is initiated by a lack of light. The use of light and
dark cycles can then be used to increase the amount of
lymphocytes in circulation, which could increase the immune
response to an infection. It is also important to consider the
circadian rhythm in everyday habits such as when to eat or
exercise. Exercising before bed can delay the release of
melatonin and can lead to a worse night of sleep.
Additionally, eating at the same time everyday can help the
body process the caloric intake better because the circadian
rhythm causes the proper digestive proteins to be produced
at that same time each day. Furthermore, because the
circadian rhythms of cancerous and noncancerous cells
differ, the timing of cancer treatments to when cancerous
cells are most vulnerable and noncancerous cells will be least
affected by the treatment. This can lead to a decrease in
unpleasant side effects, increase in effectiveness and overall
better treatment experience for the patient. These
applications emphasize how important the circadian rhythm
truly is and further research may reveal even more
applications of this complex system leading to new
treatments and even more ways to live a healthier lifestyle.

Re ferences
1. Amiama-Roig, A., Verdugo-Sivianes, E. M., Carnero, A., &
Blanco, J. R. (2022). Chronotherapy: Circadian Rhythms and
Their Influence in Cancer Therapy. Cancers, 14(20), 5071.
https://doi.org/10.3390/cancers14205071 
2. Chaix, A., Manoogian, E., Melkani, G., ,and Satchidananda
P(2019). Time-Restricted Eating to Prevent and Manage
Chronic Metabolic Diseases. Annual Reviews.
https://www.annualreviews.org/doi/10.1146/annurev-nutr-
082018-124320
3. Chaix, A., Zarrinpar, A., & Panda, S. (2016). The circadian
coordination of cell biology. The Journal of cell biology,
215(1), 15–25. https://doi.org/10.1083/jcb.201603076
4. Dose, Benjamin, et al. Timeteller for Timing Health: The
Potential of Circadian Medicine to Improve Performance,
Prevent Disease and Optimize Treatment.
Frontiers, 27 Mar. 2023, www.frontiersin.org/journals/digital-
health/articles/10.3389/fdgth.2023.1157654/full.



5. Reddy S, Reddy V, Sharma S. Physiology, Circadian
Rhythm. [Updated 2023 May 1]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2023 Jan-.
Available
from: https://www.ncbi.nlm.nih.gov/books/NBK519507/
6. Ruan, W., Yuan, X. & Eltzschig, H.K. Circadian rhythm as
a therapeutic target. Nat Rev Drug Discov 20, 287–307
(2021). https://doi.org/10.1038/s41573-020-00109-w 
7. Sonia Ancoli-Israel, Chapter 103 - Sleep and Fatigue in
Cancer Patients, Editor(s): Meir H. Kryger, Thomas Roth,
William C. Dement, Principles and Practice of Sleep
Medicine (Fourth Edition), W.B. Saunders, 2005, Pages
1218-1224, ISBN 9780721607979,
https://doi.org/10.1016/B0-72-160797-7/50110-5. 
(https://www.sciencedirect.com/science/article/pii/B07216079
77501105)
8. Wang, J., Shen, L., Zhang, Y., Shen, B. (2022). Circadian
Rhythm and Personalized Exercise. In: Shen, B. (eds)
Translational Informatics . Springer, Singapore.
https://doi.org/10.1007/978-981-16-9162-1_6
9. “What Are Sleep Deprivation and Deficiency?” National
Heart Lung and Blood Institute, U.S. Department of Health
and Human Services, 24 Mar. 2022,
www.nhlbi.nih.gov/health/sleepdeprivation#:~:text=Sleep%20
deficiency%20is%20linked%20to,adults%2C%20teens%2C
%20and%20children. Accessed 17 Nov. 2023. 

Brain Matters・Volume VII      50