CIRCADIAN RHYTHMS AND METABOLISM

Written By:
ALEXANDRA MERRILL
ADRIA BUCHELI
CAITLIN CERECERES
JESSICA KINSEY

The role of circadian rhythms exists as a fascinating phenomenon that occurs in all life
forms; including animals, plants, fungi, and cyanobacteria. According to Huang et al, authors of
Circadian rhythms, sleep, and metabolism, these internal rhythms are collectively defined as
the physical, mental and behavioral changes that follow a roughly 24-hour cycle, responding
primarily to light and darkness in an organisms environment. 1 Robert Smith, author of
Metabolism and Circadian RhythmsImplications for Obesity, specifies that circadian
rhythms occur endogenouslythat is, they are of internal originin the suprachiasmatic nucleus
(SCN) of the hypothalamus. 2 The National Institute of General Medical Sciences explains that
the biological clock is a group of interacting molecules in cells that help drive the circadian
rhythm. This cycle influences many bodily functions such as the sleep and wake cycle, body
temperature, and hormone release. 3 Recently, researchers have discovered that circadian
rhythms also play a critical role in metabolism.
As reported by the Salk Institute of Biological Studies in the article entitled Powerful
link between circadian rhythms and metabolism, circadian rhythms regulate metabolism by
mediating the activity of important enzymes and transport processes required for amino acid
regulation, drug and toxin metabolism, cholesterol, glucose, and glycogen metabolism, and the
citric acid cycle. A study performed on mice cells revealed that there are two cellular switches,
EV-ERB and REV-ERB, that are essential for normal sleep and wake cycles, eating cycles,
and the metabolism of food. This discovery presents a strong relationship between circadian
rhythms and metabolism in that, upon further investigation, it may assist in the reversal of
pathologies, disorders, and other complications associated with the disruption of circadian
rhythms. 4

According to Laposky et al, authors of Sleep and circadian rhythms: Key components in
the regulation of energy metabolism, metabolic homeostasis relies on the accurate and
collaborative circadian timing within the differentiated cells and tissues of the body. Research
indicates the various problems that can arise if circadian rhythms become misaligned. The
occurrence of circadian desynchronization can lead to insomnia, short-term memory loss,
creativity and learning issues, weight loss or gain, diabetes, suppressed immunity, increased
blood pressure, insulin resistance, and risks of heart disease and cancer. Sleep disorders can
further exacerbate other chronic illnesses such as heart disease, Parkinsons disease, Alzheimers
disease, multiple sclerosis, gastro-intestinal tract disorders and kidney disease. 5
Moreover, research performed by the Salk Institute of Biological Studies has revealed
that shift work is majorly linked to circadian desynchronization. Doctors, nurses, and emergency
personnel are most susceptible to desynchronization due to alterations in the fixed 24-hour cycle.
These shift workers may work through the night, which is the natural time to be asleep, and sleep
through the day. As a result of highly irregular sleeping and eating schedules, shift workers are at
a much higher risk of developing diseases. In a study performed on mice, researchers purposely
threw off their circadian rhythms by putting them through 10 weeks of 20-hour light-dark cycles
instead of the optimal 24-hour cycle. After just six weeks, the mice gained weight, demonstrated
less flexibility, and were impulsive behaviorally. 4 This study alone shows that the around-theclock lifestyle that many, if not most, humans lead can result in a disruption in metabolism and
ultimately cause serious health effects.
Circadian rhythm disorders are discovered upon the examination of the various
symptoms associated with them. In the article, Circadian Rhythm Disorder Symptoms, Doctors
Mary Cataletto and Gila Hertz write that symptoms may include difficulty initiating or

maintaining sleep, non-restorative sleep, daytime sleepiness, headaches, poor concentration, and
gastrointestinal distress. 6 According to the Sleep Disorders Health Center, after symptoms are
recognized, a diagnosis can be determined through an assortment of specialized tests. First, a
doctor will review the patients symptoms and medical history, and then a physical exam is
administered. The doctor may use a sleep log to diagnose circadian rhythm disorders. The sleep
log shows the sleep and wake cycles of the patient while in his or her usual sleeping
environment. The patient is required to keep a diary describing the previous nights sleep. The
doctor may also conduct a sleep study to monitor the patient while he or she is asleep in order to
detect changes in the sleep and wake cycle. Sleep studies measure levels of oxygen, the number
of times a patient stops breathing, and how often a patient snores. Another test that can be used
for diagnosis of circadian rhythm disruptions is an imaging study, such as a CT scan or MRI.
These tests check for neurological diseases, among other factors. The Epworth Sleepiness Scale
is a useful tool for assessing sleep patterns. This tool may be used in order to determine the sleep
patterns of a patient by rating situations they encounter while sleeping. Also, an actigraph is used
as a motion sensor that is worn on the patients non-dominant wrist for approximately one week
to measure sleep and wake cycles. 7 Aside from specialized tests, Naturopath Connect notes that
blood tests may be used to rule out underlying conditions such as diabetes, hormone
imbalances, chronic fatigue syndrome, adrenal fatigue syndrome, or other coexisting chronic
conditions. Even with the various tests that may be performed by a doctor or medical assistant,
there are many online tools that give individuals the opportunity to perform self-assessments in
order to evaluate the condition of their sleep and wake cycles. 8
The evolution of technology has simplified the assessment and treatment of
circadian rhythm disorders. The Actiwatch, designed by Philips Respironics, is an actigraph unit

most commonly used to assess patients with a variety of different sleep complaints and may also
be used as a therapy or follow-up tool. Its range of usability includes a variety of people, such as
the elderly, newborns, and patients with hypertension, depression, and schizophrenia. The device
records the sleep patterns of a patient for approximately 7-10 days in order to generate a
representative sample of sleep and wake behaviors. The Actiwatch system is easy to use, only
requiring about 1 to 2 minutes of uploading time. Once the patient has worn the Actiwatch for
the appropriate amount of time, the device is returned to the clinic prior to a follow-up visit.
After evaluation of the Actiwatch data, the clinician reviews the sleep activity with the patient,
informs them of any malfunctions in their sleep patterns, and discusses what can be done to
improve their condition. 9 After the proper diagnosis of circadian dysrhythmias, adequate
nutritional treatment and behavior alteration may be implemented to alleviate the symptoms and
complications that occur as a result of the disruption.
As previously discussed, circadian rhythms are essential to the health and functioning of
human beings, therefore disruptions can be detrimental. Fortunately, with the appropriate
nutritional treatment, humans are able to retrain their internal clocks to follow a rhythmic cycle
of mental, physical, and behavioral patterns fit for daily and nightly activities. According to
Tahara and Shibata, authors of Chronobiology and nutrition, the concept of retraining ones
biological clocks is referred to as entrainment. 10 The Merriam-Webster online dictionary
defines entrain, as the ability to determine or modify the phase or period of. 11 Tahara and
Shibata note that there are several methods of entraining biological clocks including: light,
temperature changes, exercise, drugs, and food. However, research has found that other than
light, food is the most entrainable factor. This is a monumental notion, given that the

consumption of food is also essential to life. With food, humans are able to entrain their
biological clocks. 10
Scientists have termed this concept as chrono-nutrition, the idea that chronobiology and
nutrition correlate. Extensive research has tested foods ability to entrain biological clocks and
found that by understanding the circadian rhythms of the digestive system and its metabolic
activities, the ideal timing of food intake can be determined. 10
Tahara and Shibata analyzed a collection of studies performed on nocturnal rodents that
have similar biological patterns to humans in order to gain insight on this theory. Researchers
studied the internal clocks responsible for the eating activity of mice and rats. They found that
feeding in the daytime causes Food Anticipatory Activity (FAA). FAA arouses food-seeking
behavior approximately three hours before feeding time. The internal clock for feeding, called
the Food Entrainable Oscillator (FEO), signals the onset of FAA. FEO functions as a separate
clock from the suprachiasmatic nucleus (SCN) of the hypothalamus, which receives light signals
from the retina. 10 This is to emphasize that internal feeding clocks have individual roles set apart
from the master biological clock, further demonstrating the importance of the relationship
between time and food intake.
During the study on mice, researchers identified multiple metabolic transporters that are
controlled by circadian regulation. These transporters are critical to the metabolism and
absorption of nutrients. The following were identified: sodium/glucose co-transporter 1 (SGLT
1), H(+)/peptide co-transporter 1 (PEPT 1), glucose transporter 2 (GLUT 2), glucose transporter
5 (GLUT 5), and the sodium-potassium pump. Researchers were able to entrain SGLT 1 and
PEPT 1 in rats with a regular feeding schedule. In addition, the intestinal enzyme sucrase was
found to follow circadian patterns, exhibiting peak activity before feeding time. 10

Along with metabolic activities, means of absorption are also controlled by circadian
regulationmore specifically, the absorption of glucose, peptides, and lipids. Studies have
reported increased glucose and water absorption in the small intestines of rats during the
nighttime when compared to daytime. Researchers also found that the absorption of sodium
chloride is under circadian control. In addition, mice with defective clock genes showed irregular
feeding rhythms, obesity, lower insulin secretion, decreased peptide transportation, and abnormal
FAA. 10 Evidence suggests that when there are disruptions in circadian rhythms, malabsorption
may occur.
Furthermore, nutrition-related findings were reported when observing mice under
conditions that manipulated their circadian rhythms. Researchers noted differences in activity of
mice kept in normal day-night (light in the daytime, dark at night) environments versus mice that
were kept in dim-lit environments during the nighttime. Mice that were kept in dim-lit
environments during the nighttime consumed more food in the daytime and gained weight, while
mice kept in normal day-night environments demonstrated normal food intake during the
daytime and weighed less. From this, it is assumed that keeping a dark sleep environment at
night is conducive to maintaining normal circadian rhythms. In another study, researchers
controlled for the scheduled food intake of mice on a high-fat diet and compared them to mice
that fed during the night. The mice on the scheduled feeding, high-fat diet showed an increase in
obesity, glucose intolerance, hypertriglyceridemia, hyperinsulinemia, and hyperleptinemia when
compared to mice that fed during the night. Although research has shown that feeding at night
can disrupt circadian rhythms, this implies that high-fat diets can be even more disruptive and
should be avoided. Lastly, a study on meal timing and portioning was performed on mice. In
comparison to mice fed a large breakfast and small dinner, mice fed only breakfast demonstrated

increased weight gain, hyperleptinemia, hyperinsulinemia, and reduced expression of betaoxidation genes. 10 Evidence suggests that the largest meal of the day should be breakfast,
followed by smaller meal portions throughout the day.
In light of research, food has proved to be a highly entrainable factor in restoring
disrupted circadian rhythms. Presumably, several steps can be taken to maintain efficient
metabolism and absorption of nutrients. These include: following a timely eating schedule
throughout the day; eating the largest meal at the beginning of the day, not before bedtime;
consuming foods lower in fat; determining a preferred bedtime and adhering to it consistently;
avoiding late-night meals; and maintaining a dark sleep environment. 10 With planning and
consistency, these initiatives can prevent the disruption of biological clocks and improve the
quality of life.
EatRight Ontario provides nutritional tips for shift workers or others prone to circadian
dysrhythmias. First, dietitians suggest that individuals should practice portion size control. Those
under shift work may eat two large, high-calorie meals per day that can prompt weight gain.
Dietitians advise that snacks be consumed in between meals to satiate hunger and prevent overeating. Drinking plenty of fluids is critical in preventing dehydration. EatRight Ontario
recommends that shift workers eat according to the time of day, not according to the time of their
shifts. As the author writes, If you start work in the afternoon, have your main meal in the
middle of the day, rather than in the middle of your shift. If you're working nights, eat your main
meal before your shift starts, preferably between 5 and 7 p.m. 12 Those working late night shifts
are urged to reduce caffeine intake. Caffeine remains active for up to eight hours, so shift
workers should consume caffeinated beverages before or early in their shifts to avoid difficulties
sleeping. As an alternative, decaffeinated coffee and tea are favorable options. For improved

mood and sleep, light exercise before or during shifts can be beneficial. Some ideas may include
a brisk walk or a few minutes of stretching during breaks. As stated previously, diets high in fat,
including sugary and fried foods, should be avoided to prevent indigestion and lethargy. Lastly,
to encourage healthier food choices, shift workers should take advantage of packing nutritious
snacks and meals at home. 12 As challenging as it may be to work night shifts and maintain
optimal sleeping and eating patterns, these suggestions provide practical ways for individuals to
thrive in most work conditions while encouraging a lifestyle that promotes natural circadian
rhythms.
Doctor Daniela Jakubowicz, founder of the Circadian Rhythm Diet, proposes the Big
Breakfast Diet. Although the Big Breakfast Diet is a fad diet, it utilizes many of the concepts
learned from research to overall support the relationship between how the foods individuals eat
can influence the functioning of their circadian rhythms. Doctor Jakubowicz advises individuals
to consume foods high in fat and calories early in the day in order for the body to transform it
into long-lasting energy. The Circadian Rhythm Diet advocates protein, fats, and carbohydrates
for breakfast; protein, vegetables, and fruits for lunch; and fruits and vegetables only for dinner.
A sample breakfast might include a small whole-grain muffin, a slice of ham, and a hard-boiled
egg. Lunch might consist of a chicken breast, a salad, and an apple. Finally, dinner might contain
broccoli, grapefruit, carrots, and a banana. Various snacks throughout the day might consist of
yogurt or raisins. 13
In conclusion, it is evident that circadian rhythms play an important role in the
maintenance of life. Circadian rhythms influence sleep and wake cycles, hormone release, body
temperature, and metabolism. A small disruption in circadian rhythms can have extreme
consequences. Disruptions may occur as a result of shift work, pregnancy, time zone

adjustments, medications, and changes in routine. A variety of tests may be used to diagnosis the
diseases and disorders associated with circadian rhythm disruptions. Sleep logs, sleep studies,
CT scans, MRIs, and the Actiwatch are among the various tests and tools administered by a
doctor in order to evaluate the sleep patterns of individuals. In addition, research has shown that,
with regards to the metabolism and absorption of nutrients, nutritional guidance is key to
restoring circadian rhythms. Lastly, appropriate measures can be taken to prevent circadian
dysrhythmias such as following a timely eating schedule, consuming a diet low in fat, eating the
largest meal of the day at breakfast time, adhering to a consistent bedtime, and reducing caffeine
intake. By taking these steps, humans have the unique ability to recover their circadian rhythms
and enhance their quality of life.

References

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