Today’s hectic lifestyle has resulted in a large number of people with altered circadian rhythm sleep disorders. Sleep disorders affect all aspects of life; including school and work performance as well as a person’s mental and emotional health. Working or driving with a sleep debt decreases alertness and response time, which can lead to injury or even death. A large number of people have resorted to the use of sleep aids, both prescription and over-the-counter; however, the use of these sleep aids can contribute to the problem by negatively altering the body’s normal circadian rhythm.

Circadian rhythm, meaning “around the day” and also called the biological clock, is an internal clock that is synchronized with the rotation of the earth and light/dark cycle lasting approximately 24.5 hours. Entrainment is the result of the continual circadian rhythm adjustment that occurs within the human body from environmental time cues, mainly the presence or absence of light. Body temperature, heart rate and blood pressure, the release of hormones, alertness, energy, mood, and weight gain are affected by the body’s circadian rhythm. The circadian rhythm also has an impact upon the effectiveness of certain medications; this is the reason why some medications have instructions as to the specific time they must be taken.

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Chronobiotics are any substance, including many prescription medications and dietary supplements that influence and alter the body’s circadian and circannual rhythms (“around the year”). Prescription sedatives, sleeping pills, antidepressants, and stimulants are chronobiotics and all affect the body’s normal circadian rhythm. Coffee is a chronobiotic when used to increase alertness and prevent the onset of sleep. Over-the-counter sleep aids and “alertness” preparations alter the normal functioning of the circadian rhythm, which can lead to even more difficulty in sleeping or staying awake.

The most common chronobiotic is the hormone melatonin, which was first discovered in 1958. All mammals, including humans, secrete melatonin as a response to changing light levels which in turn regulates internal circadian and circannual rhythms. Darkness cues an increased production of melatonin, while light cues a decreased production of the hormone. The amount of melatonin secreted and the sensitivity of melatonin receptors in the body changes during the day, with the highest sensitivity at dusk and dawn.

Melatonin is especially important for the onset of sleep, but it is also necessary for the proper functioning of our cardiovascular, immune, endocrine, and metabolic systems. Cued by darkness, melatonin levels rise which decrease body temperature, heart rate, blood pressure, pupil size, and alertness; all normal body states during sleep. The presence of light reverses this process, resulting in awakening and alertness.

Melatonin acts as a sedative and chronobiotic; it lowers anxiety, decreases pain, prevents inflammation, and has antioxidant effects. Alterations in normal levels can lead to the development of mood and behavioral disorders, and can also affect body weight. People with severe depression have reduced melatonin levels, an unsynchronized circadian rhythm and severe sleep disturbance.

Melatonin is also secreted by other tissues and organs in the body; this melatonin acts as an antioxidant, scavenging free-radicals and decreasing the risk for the development of cancer. Melatonin also prevents premature death of normal cells while destroying tumor cells. Melatonin is necessary for normal bone health and immune function, and detoxifies potentially harmful chemicals. Melatonin also enhances the action of other drugs or hormones in the body.

While circadian rhythm is a daily fluctuation, circannual rhythm meaning “around the year,” plays a role in seasonal affective disorder (SAD) and seasonal weight gain. A clock gene has been identified, which determines an individual’s sleep pattern. Circadian rhythm sleep disorders are the loss of synchronization between internal and external rhythms of the sleep-wake cycle. People with non-synchronized circadian rhythms have difficulty sleeping at night, followed by extreme sleepiness during the day.

Sleep disorders are very common, with almost half of the population experiencing occasional insomnia and one-tenth of the population experiencing chronic insomnia. Before a sleep disorder diagnosis is made, other causes of sleep disruption should first be ruled out by your doctor. Circadian rhythm sleep disorders (CRSD) are made up of a number of altered sleep/wake syndromes:

24-hour Circadian Rhythm Cycle

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A person affected with this sleep disorder will sleep for normal amounts of time and have good sleep quality, but their sleep time is not synchronized with normal or desired times.

Non 24-hour Circadian Rhythm Cycle

People affected with this sleep disorder will sleep and awaken either earlier or later each day; their sleep/wake pattern is very irregular.

Delayed Sleep-Phase Pattern

A person with this sleep disorder will go to sleep late and awaken late, and is more common in adolescents. These people are unable to fall asleep even if they try; this results in excessive daytime sleepiness (EDS).

Mild Phase-Delay

The delay of sleep onset is less than 3 hours from normal sleep time.

Advanced Sleep-Phase Syndrome

A person with this sleep disorder falls asleep early and rises early. This disorder is most common among the elderly.

Time Zone Change Syndrome

Better known as jet lag, this sleep disorder is the result of traveling across more than two time zones. Symptoms are worse when traveling east, which advances the sleep cycle; than when traveling west, which delays the sleep cycle. The best way to deal with jet lag is to try to adjust your sleep/wake schedule before you travel.

Shift Work Sleep Disorder (SWSD)

The severity of SWSD is related to how often the changes occur, how large the changes are, and how many counterclockwise changes there are that advance your sleep schedule. The circadian rhythm becomes unsynchronized and is not allowed enough time to reset itself to the new sleep/wake time. Daytime sleep is short and unrefreshing, but insomnia occurs when trying to sleep. A sleep-debt builds up and the person is excessively tired and unable to remain alert while working at night.


Blindness prevents the normal light/dark synchronization which results in severe circadian rhythm alterations.

Circadian rhythm sleep disorders cause other circadian rhythm problems: abnormal changes in body temperature and hormone production, nausea, an overall feeling of illness, irritability, and depression. There is an increased risk for the development of cardiovascular and gastrointestinal diseases, and circadian rhythm disruption has been linked to an increased risk for the development of cancer.


Melatonin is used as a chronobiotic to realign the body’s circadian rhythm, but has a narrow window of time when it should be taken; if it is not taken at the correct time, the sleep/wake problem will become even worse. The most effective time to take melatonin is either at dusk or dawn; depending upon when you want to sleep. Other treatments for sleep disorders are altering the sleep/wake pattern until the schedule is normal and bright light therapy.

Melatonin has been found to be of value in the treatment of many other diseases and disorders. Cancer patients who received melatonin during chemotherapy and radiation had less toxic effects from the treatments, and survival rates and overall ability to function both increased in people with advanced cancer. When melatonin is given prior to surgery, anxiety and pain is decreased, especially in the first day following surgery. Melatonin also helps to readjust and improve the sleep-wake cycle, which is commonly disrupted after surgery.

Melatonin protects neurons in the brain, and has been found to be effective in preventing the progression of cognitive dysfunction in people with Alzheimer’s disease. Melatonin also helps to reduce “sundowning,” where people affected with Alzheimer’s do not sleep at night due to circadian rhythm disruption. When melatonin is given to people following traumatic brain injury, the amount of brain damage is decreased, along with a reduction in inflammation and the number of infections. Melatonin increases the effectiveness of the drugs used to treat traumatic brain injury while also decreasing the drugs’ toxic effects.

When used as a treatment for chronic fatigue syndrome, melatonin improves motivation, activity, and concentration and was found to significantly improve fatigue levels. Melatonin levels normally decrease with age, which results in loss of circadian rhythms. Sleep fragmentation in the elderly can be successfully treated with melatonin.

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Melatonin is being used for cancer prevention, to treat osteoporosis, and to increase the effectiveness of some medical therapies, while decreasing the toxic effects of the drugs. Scientific studies are also being done to determine the effectiveness of melatonin in the treatment of headache disorders, especially migraines and cluster headaches.

Side effects of melatonin are headache, sleep pattern changes, confusion, low body temperature, sedation; increased heart rate; nausea and vomiting, loss of appetite; rash and itchiness; and decreased levels of the hormones progesterone, estradiol, and luteinizing hormone. Most side effects are mild, and will usually diminish or disappear over time. Melatonin has no known food interactions, and no known effects on lab test values.

Melatonin should not be taken with:

anticoagulants (including herbs that act as anticoagulants)




central nervous system depressants (including herbs that act as sedatives)

DHEA (dehydroepiandrosterone)





Who should not take melatonin

There are some people who should not take melatonin; these include children, women who are pregnant or breastfeeding, people who have kidney, liver or heart disease, autoimmune diseases, depression, central nervous system disorders, and Parkinson’s disease. Serious side effects from melatonin have not been reported, but effects from taking melatonin over a long period of time still needs to be studied. Melatonin should only be supplemented under your doctor’s supervision.

Melatonin can be found as a dietary supplement in most health food stores, and is supplied as tablets, extended-release capsules, or in an injectable form when used for cancer treatment. Preparations of melatonin are unregulated at this time; amounts are not standardized, and may be contaminated. Only synthetic forms of melatonin should be taken.

Melatonin occurs naturally in some foods, but the amounts are not high enough to influence circadian or circannual rhythm. Serotonin, a neurotransmitter, is the precursor of melatonin, and plays a role in sleep-wake cycle, appetite and gastrointestinal health, mood, depression and obsessive compulsive disorder. There are many foods containing serotonin, but serotonin in food does not cross the blood-brain barrier and is not effective as a chronobiotic in this form.

Tryptophan, an essential amino acid obtained from the diet, is a precursor of serotonin and the B-complex vitamin niacin. The pineal gland in the brain then converts serotonin to melatonin in response to external light cues. Tryptophan is present in high amounts in all protein derived from meat, and is necessary for normal growth and development. Other foods containing tryptophan are chickpeas, chocolate, cottage cheese, dried dates, eggs, oats, mangoes, sesame, pumpkin, and sunflower seeds, peanuts, spirulina, milk, yogurt. Contrary to popular belief, the amount of tryptophan found in turkey is no higher than the amount found in other meats. High doses of tryptophan may cause sedation as well as nausea and vomiting.

Many chronobiotic medications are used to promote sleep or wakefulness, but these drugs may lead to behavioral changes, “hangover,” dependency, and withdrawal symptoms. These chronobiotics can have a negative effect upon the circadian rhythm, causing a rebound effect that makes it even more difficult to fall asleep once the medication is discontinued. Some medications commonly used to treat insomnia are benzodiazepines, antidepressants, and other sedatives. Current research is focusing upon new chronobiotics derived from melatonin in an effort to avoid the negative side effects of medications used to treat insomnia.

A number of melatonin agonists have been approved for use or are in various phases of clinical trials. An agonist is a substance that mimics the body’s own regulatory function, by binding to the cell receptor and stimulating normal function. Since melatonin has a short half-life, scientists have developed prolonged release formulations to provide melatonin throughout the sleep period to maintain sleep throughout the night. These new melatonin agonists are synthetic formulations of melatonin with a longer half-life than natural melatonin. All of the following medications have shown to be effective in improving sleep quality.

Rozerem (ramelteon)

Has been approved by the Food and Drug Administration for use in the United States. Rozerem reduces the amount of time needed to fall asleep and increases the length of sleep, and is especially effective for treating insomnia in the elderly. Balance, mobility or memory are not affected if an elder gets up during the middle of the night. Side effects are mild; and Rozerem has no affect upon alertness, there is no “hangover,” and no withdrawal symptoms.

Valdoxan (agomelatine)

Is an antidepressant in the final phase of approval for clinical use in the United States. Valdoxan improves sleep in people with depression; this then improves the depression symptoms. This drug is effective for the treatment of SAD and may also be useful in treating seasonal weight gain. Valdoxan is tolerated well, with no behavioral changes, no dependence, and no “hangover.” Valdoxan needs safety studies to determine the effect of its use over a long period of time.

Circadin ™ (prolonged-release melatonin 2 mg)

Has been approved by the European Medicines Agency for the treatment of insomnia. Melatonin is released over a period of 8 to 10 hours, and is used for the short-term treatment of insomnia in people 55 years and older.

Phase III trials have been completed for the newest drug, tasimelteon. LY 156735, beta-methyl-6-chloromelatonin, S-20098 are other melatonin agonists that are currently being studied for effectiveness in treating insomnia.

Alteril™, Melatrol™, Restaid™, and Somulin™ are just a few of the 150 sleep aids available over-the-counter; these preparations contain adequate and safe amounts of natural ingredients that are associated with sleep-promotion. Always check with your doctor before adding a sleep-aid, especially if you have other medical conditions or are taking prescription medications.


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