FEATURE The Sleep-Wake Cycle and Jet Lag Trekking across time zones can disturb the body’s natural rhythms, but melatonin may ease some effects of traveling. By W. STEVEN PRAY, PH.D., R.PH., Professor of Nonprescription Products and Devices, School of Pharmacy, Southwestern Oklahoma State University,Weatherford, OK Our natural tendency to adapt to a 24.5- to 25.5-hour day helps explain the minor jet lag when a person flies three to four time et lag is one of many disorders of the sleep-wake cycle. zones to the east, where residents begin the sleep cycle 3–4 hours One characteristic these daily rhythms, known as circa- earlier than the traveler’s time Jdian rhythms, share is that they are partially controlled zone.2 The Californian flying to by one or more biological clocks.1 Circadian rhythms recur New York enters a time zone that is three hours later, with bedtime in daily cycles roughly every 24 hours. at 11 pm, which is 8 pm in The circadian clock in mammals is centered in the hypothalamic region California.3 known as the suprachiasmatic nucleus. This hypothalamic regulatory center THE ROLE OF ZEITGEIBERS ensures that the mammal’s behaviors and physiological responses are in harmony with the external environmental cycle of the sun. People generally Zeitgeiber is the term reserved function best when light and dark recur every 24 hours, allowing us to for the external environmental sleep, awaken, and eat at predictable times. clues we use to help us adapt to each day’s 24-hour time progres- CIRCADIAN CYCLE sion. Zeitgeibers include the rising Researchers have performed isolation studies in which volunteers and setting of the sun, time of undergo long-term isolation from light-dark cues in the environment and meals, activities of people around from all other human contact. They eventually lose track of time in the real us, and various social activities. world, going to sleep and awakening whenever they feel the need. When Individuals who have lost their people respond to their internal circadian clock, they create an artificial day vision often experience difficulty for themselves that lasts 24.5–25.5 hours. Since each day consists of only 24 adapting to the constraints of the hours, this phenomenon answers the question of why people find it easy to 24-hour daily cycle; this reinforces stay awake an extra hour or two, but very difficult to go to sleep an hour or the importance of visual cues in two earlier. establishing the internal clock. COMMUNICATION MARCH/APRIL 2000 13 JET LAG such as exercise, light therapy and BRIGHT LIGHT THERAPY melatonin to combat jet lag. Of the millions of travelers who Bright light therapy may play a role in jet across time zones each year, as Melatonin is not yet approved the treatment of jet lag. Bright light many as 80% report sleep disrup- by the FDA as safe and effective can actually shift the phase of the tions.1 Jet lag was first reported in for any use. Nevertheless, people sleep-wake cycle in humans, which 1931 by pioneering aviators Wiley are using it and it is sold in many results in resetting of the circadian Post and Harold Gatty after a U.S. pharmacies. In Canada, it was clock.9 If the subject is exposed to transmeridian flight of 8 days and pulled off the market a number of bright light in the evening, melatonin 16 hours.5 years ago, pending further research secretion is delayed; if bright lights are on safety and efficacy. The most well-known sign of jet suddenly turned on in the middle of lag is a slowly declining sleep Melatonin is secreted by the the night, melatonin production disturbance, occurring on the first pineal gland. A tryptamine deriva- immediately starts to drop.The night in 60%–70% of those who tive, melatonin is a chronobiotic hypothesized action of bright light is crossing a time zone, but only in medication, one of a group of through direct suppression of pineal 30% by the third night.6 Other active compounds capable of gland function. Light therapy is known symptoms also have been attrib- performing chronomodulation.8 to help such conditions as delayed uted to jet lag: dyspepsia or Melatonin secretion varies accord- sleep phase syndrome, seasonal affec- constipation (perhaps a result of ing to the season of the year. tive disorder, and seasonally related changing meal times), depression, During the summer, when daylight bulimia.Though the use of bright light disorientation, and lessened ability is long and darkness is short, mela- in jet lag is not well defined, some to estimate time, space and tonin is secreted for only a short authorities suggest that if applied in distance.6 period. However, during winter, the morning at the destination, it when daylight is short and dark- Frequent fliers who suffer might depress endogenous melatonin ness long, melatonin secretion is chronic sleep disruptions often correspondingly longer.9 In secretion to more quickly regulate the develop malaise, irritability, and 5 animals that live in regions with person to the new sleep-wake cycle. impaired performance on tasks great seasonal changes, melatonin requiring attention. In addition, plays a large role in triggering Our bodies are conditioned to menstrual cycles become irregular seasonal behavior such as hiberna- work in synchrony with the zeit- in females with recurrent jet lag.6 geibers of our home location. Body tion or breeding. Although Some symptoms attributed to jet seasonal secretion is also seen in functions that undergo daily rhyth- lag are actually due to being humans, man is not a seasonal micity (e.g., hormone secretion, confined in an airplane. These animal; any role in the human body temperature, intrinsic alert- include ophthalmic and nasal irri- would rely mainly upon daily ness) vary in a predictable manner tation, muscle cramps, nausea and changes in melatonin secretion.9 as the day proceeds. The major abdominal distention, headache, Melatonin secretion in humans is factor causing jet lag is discoordi- edema in the legs and feet, and low during the first three months nation of the body’s normal dizziness.1 They usually disappear after birth, but increases. It peaks fluctuations with the normal daily shortly after the flight is termi- at ages 4–7 and then drops progression due to a rapid shift in nated.1 slowly.10 The average amount time zones.4 produced by a male adult is 30 ROLE OF MELATONIN The human internal clock resets micrograms daily.11 Each person’s fairly slowly. If the person travels The patient leaflet describes one secretion pattern is unique and can eastward, the internal clock resets possible intervention to prevent jet be reliably reproduced day to day. at a rate of about one hour per day; lag, preadaptation prior to depar- Typically, melatonin secretion rises adaptation to westbound travel ture.7 However, much preliminary from a low basal level (perhaps 10 occurs at a rate of about 90 minutes research has been conducted on pg/mL) at about 10 pm, reaching a daily. potentially valuable treatments peak at 2–4 am (perhaps as high as 14 COMMUNICATION MARCH/APRIL 2000 120–140 pg/mL) and declines to be that people taking continual intersemester vacation. In this case, the basal level by about 8–9 am.12 doses of melatonin will experience sleep disturbances may last as long The morning decline occurs rebound sleeplessness upon with- as 10 days after arrival in India, whether or not a person actually drawal. Until long-term use is and also may last as long as 10 sleeps during the night. Individual proven safe, pharmacists should days after returning to the United advise to limit melatonin use to a differences in the times of the peak States. and trough may determine few days. whether one is considered a DOES DIRECTION OF TRAVEL MAKE WHAT TO DO ABOUT JET LAG “morning” or “evening” person. A DIFFERENCE? Many years ago, there was no Melatonin’s sedative effect One can predict what type of such thing as jet lag. When people accounts for its use in insomnia (in wished to travel across the country, sleep disturbance will occur, a dose of perhaps 2 mg daily). It the trip took weeks in covered depending on the direction of may be helpful in jet lag, in which wagons or on horseback. Even in flight and the time at the destina- the endogenous sleep cycle must the early part of the 1900s, travel tion. For instance, if a flight is from change to correspond to the desti- across several time zones may have west to east, and if it crosses three nation.6 In one study, patients taken longer than one week. time zones, as from California to traveling east from San Francisco Florida, the person arrives in a to London (eight time zones) expe- However, with the invention of Florida time zone that is three rienced a decrease in jet lag when high-speed jets, people began to hours later. If the person normally given 5 mg of melatonin daily notice that travel across time zones goes to bed at midnight in starting three days prior to depar- caused problems going to sleep or 10 California and tries to go to bed at ture. The dose was continued for staying awake at the destination. midnight in Florida, he or she will four days after arrival.12 In another probably lie awake sleepless for study involving crossing of eight WHAT DETERMINES THE SEVERITY several nights since midnight in time zones, a 10 mg dose helped OF JET LAG? prevent sleep disruptions and Florida is 9 pm California time.