How the Circadian Rhythm Affects Sleep, Wakefulness, and Overall Health

Dr. Nina Mikirova

Life on earth has evolved under the daily rhythm of light and dark. Metabolic, physiological and behavioral processes exhibit 24-hour rhythms in most organisms, including humans.

Light, one of the most powerful environmental cues, enables the organisms to adapt to the 24-hour light-dark cycle. Photic signals (signals from light) are delivered from the eye to the brain and mediate the synchronization of the circadian clock system.

This regulation is driven by a small region in the anterior hypothalamus of the brain, known as the “circadian clock”. This clock spontaneously synchronizes with the environmental light-dark cycle, thus enabling all organisms to adapt to and anticipate environmental changes. As a result, the circadian clock actively regulates sleep and wakefulness to occur in synchrony with the light-dark cycles. Indeed, our internal clock is our best morning alarm clock, since it shuts off melatonin production and boosts cortisol secretion and heart rate 2-3 hours prior to awakening.

Previously, humans tended to conduct their daily activities according to the sun’s cycle: rising at sunrise and going to bed at sunset. The internal circadian clock and sleep-wake homeostasis regulate and organize human brain function, physiology and behavior so that wakefulness and its associated functions are optimal during the solar day, and so that sleep and its related functions are optimal at night. The circadian clock influences hunger, digestion, sugar and fat metabolism, hormonal secretions, body temperature and mood.

Disturbed circadian rhythms are known to be closely related to many diseases, including sleep disorders.

Sleep disorders include chronic insomnias, which are associated with an internal clock that runs slower or faster than the normal sleep phase syndrome, periodic insomnias, due to disturbances in light perception (non-24-hour sleep-wake syndrome and sleep disturbances in blind individuals), and temporary insomnias, which are due to social circumstances (jet lag and shift-work sleep disorder).

According to the Centers for Disease Control and Prevention and the Institute of Medicine of the National Academies, insufficient sleep has become a public health epidemic. Approximately 50-70 million adults (20 years or older) suffer from some disorder of sleep and wakefulness, hindering daily functioning and adversely affecting health and longevity.

Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g. shift work and jet-lag) has led to the development of new types of agents called chronobiotics, of which melatonin is the prototype. The term ‘chronobiotic’ is defined as a substance capable of shifting the phase of the circadian time system, thus regulating circadian rhythms. Melatonin administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from delayed sleep phase syndrome, such as with jet-lag and shift-working.

Melatonin is synthesized from the amino acid tryptophan and is secreted in high amounts into the blood only in darkness (nighttime) by the pineal gland. Humans typically initiate sleep shortly after the rise of melatonin levels and awaken shortly after the fall of melatonin levels. The best quality sleep occurs at night when melatonin levels are high.

Daily melatonin production decreases with age, and in several pathologies, attaining its lowest values in Alzheimer’s dementia patients.  Due to decreased melatonin production, about 45% of dementia patients have severe disruptions in their sleep-wakefulness cycle.

Cardiac rhythm, melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels?

Light is the primary stimulus to the disruption of melatonin rhythms. Melatonin production in humans decreases when people are exposed to light at night. Since melatonin shows potential to decrease the growth of a variety of tumors, it is possible that lowered serum melatonin levels, caused by exposure to light at night, increase tumor development.

It has been estimated that about 20% of working persons have an occupation in a shift work system, including health service employees and policemen, among others. The shift work causes conflict with the “biological clock” because of required working hours. Cancer is the second leading cause of death in industrialized countries like the United States, where a significant number of workers engage in shift work, making a hypothesized relation between light exposure at night and cancer risk relevant.

Observational studies support an association between night work and cancer risk. The potential primary culprit for this observed association is the lack of melatonin, a cancer-protective agent whose production is severely diminished in people exposed to light at night.

Environmental lighting powerfully alters release of melatonin, which typically peaks in the middle of the night: a profound melatonin reduction was observed in humans after 2 weeks of intermittent nightly exposure to light.

Thus, novel hypotheses were generated, proposing that the diminished function of the pineal gland might promote the development of breast cancer in humans. One of the initial theories hypothesized that melatonin suppression may lead to an increase in levels of reproductive hormones, particularly estradiol, thereby increasing the growth and proliferation of hormone-sensitive cells in the breast. Observational studies have supported that theory, indicating that women in occupations that expose them to light at night do experience a higher risk of breast cancer, and blind women, who do not have the ability to experience lower melatonin levels because of their lack of receptivity to light, have a lower incidence of breast cancer.

Studies fairly consistently report meaningful increases in breast cancer risk among postmenopausal women exposed to shift work. Two retrospective studies of flight attendants with occupational exposure to light at night linked the employment time to an increased risk of breast cancer.

Two nationwide record linkage studies and a retrospective case–control study associated night work with an approximately 50% higher risk of breast cancer.

Finally, the Nurses’ Health Study, the only prospective study published that evaluated the association, observed a positive association of extended periods of rotating night work and breast cancer risk. In this study, night work was defined as the total number of years during which the nurses had worked rotating night shifts with at least three nights per month, in addition to days and evenings in that month. During 10 years of follow-up, 2441 cases of breast cancer were documented among the 78,562 women in the study. A positive association between the numbers of years a woman had worked on rotating night shifts and breast cancer risk was observed.

Among postmenopausal women, the relative risk for breast cancer, controlling for all the major risk factors for breast cancer, was moderately increased after 1–14 and 15–29 years of rotating night shift work, and was further increased for those nurses who worked the night shift for 30 or more years, with similar risks for premenopausal women. Thus, in summary, observational studies seem to support the hypothesis that night work increases the risk for breast cancer.

Light at night and other cancers

Only a few observational studies have addressed the relationship between shift work and cancers, other than breast cancer. One study reported an increased risk of colorectal cancer in female radio and telegraph workers. Another study did not report the risks for colorectal cancer among the female Icelandic flight attendants, but described an elevated risk for tumors of the lymphatic system.

The Nurses’ Health Study was used to explore the association between night work and colorectal cancer; 602 women were diagnosed with incident colorectal cancer during the 10 years of follow-up. In these women, those who worked 15 or more years on rotating night shifts were at a higher risk of colorectal cancer than were women who never worked rotating night shifts.

Cancer-Protective Effects of Melatonin

In recent years, an overwhelming amount of research has been devoted to exploring the cancer-protective properties of the hormone melatonin. Today, many of the cancer-preventative properties of melatonin have been fairly well-described, and evidence from experimental studies strongly suggests a link between melatonin and tumor suppression.

Some of the mechanisms by which melatonin has been shown to protect against cancer are:

1. Melatonin is believed to increase the expression of the tumor-suppressor gene p53. Cells lacking p53 have been shown to be genetically unstable and thus more prone to tumors.
2. In vitro studies support that melatonin has been shown to halt the spread of cancer for a variety of tumor cells.
3. Reports show that melatonin exhibits a growth-inhibitory effect on endometrial and ovarian cancer cell lines, Lewis lung carcinoma, prostate tumor cells, and intestinal tumors.
4. Several clinical trials confirm the potential of melatonin, either alone or in combination with standard therapy regimens, to generate a favorable response in the treatment of human cancers.

Daylight saving time shifts: leave clocks alone.

Many people, including myself, intensely dislike Daylight Saving Time. Frequent complaints are the inconvenience of changing many clocks and adjusting to a new sleep schedule. For most people, this is a mere nuisance, but some people with sleep disorders find this transition very difficult. Indeed, there is evidence that the frequency of auto accidents increases and work productivity decreases as people adjust to the time change.  There is no proof that it saves energy.

In many developed countries, including Russia, daylight saving time was cancelled and clocks are not moved back and forward. There is one example of the effect of daylight time shift on the incidence of acute myocardial infarction. To identify acute myocardial infarction incidence on specific dates, researchers used the Register of Information and Knowledge about Swedish Heart Intensive Care Admission, a national register of coronary care unit admissions in Sweden. They found an elevated incidence ratio of 1.039 (95% confidence interval, 1.003-1.075) for the first week after the spring clock shift forward.

Given the evidence from experimental studies supporting the ability of melatonin to slow the growth of cancer, it is theorized that exposure to light at night not only has an impact on breast cancer risk, but also may increase the risk of other cancers, primarily through the melatonin pathway. This has been posed previously without much further attention from the scientific community, but most recent evidence from observational studies supports such a link.

How to Get Better Sleep, Naturally

1. Turn off all electronics 1 hour before bed.
2. Make your sleeping room as dark as possible. Get black-out curtains and cover up all light sources (alarm clocks, phones, nightlights).
3. Limit caffeine intake (especially in the late afternoon and evening).
4. Take an Epsom salt bath before bed. Magnesium has a calming effect on the body and brain.
5. Do not exercise within 2 hours before going to bed. Exercise increases cortisol levels, which can keep you awake.
6. Limit stress-inducing activities 2 hours before bed. This can vary by person, but could include activities such as: watching the news, doing job-related work, playing video games…etc.