Circadian clock in humans

Does Travelling Affect the Clock?

Circadian clock in humans

The circadian clock is an important mechanism within all living organisms, from plants to mammals. The primary circadian clock in mammals is located in the suprachiasmatic nucleus (SCN), within the hypothalamus. The SCN exerts its effects throughout the body by producing daily rhythms in core temperature, plasma melatonin and adrenaline, and the sympathetic nervous system. During the daytime, the body clock facilitates physical and mental activity by raising body temperature and plasma adrenaline, so harmonising with our behaviour and environment. In the evening these variables are lowered in preparation for sleep (Zanello, 2000). At the same time, plasma melatonin levels rise and contribute to the increase in fatigue. In the second half of the night, the body clock is responsible for preparing the body for waking by reversing these changes. The synchronisation between the environment and body clock is produced in several ways. Firstly, bright light directly stimulates an individual and suppresses melatonin secretion, so removing its hypnotic effect. Secondly, bright light and melatonin can independently adjust the phase of the body clock. Light signals falling on the retina between 5am and 11am, just after the temperature trough, advance the body clock, and those falling before the trough between 9pm and 3am delay it. The size of the shift is related also to the logarithm of light intensity, domestic lighting producing changes of up to two hours (Benloucif , 2005). Melatonin ingestion in the morning produces a delay, and in the afternoon and early evening an advance, of the body clock; however, the detailed times of ingestion of melatonin to produce the largest phase shifts are not as clearly known as for light (Mills, 1978). This is how the human body functions with a circadian rhythm. Here is a diagram of this important mechanism;

What evidence is there that travelling affects the clock?

There has been extensive research on the effect that travelling has on the circadian rhythm in humans. When individuals travel through rapid time zone transitions, dissociation occurs between endogenous and exogenous components with the endogenous rhythms, which take some time to adjust to the new time zone. Travelling in an Eastward direction (advancing the sleep cycle) makes it more difficult for the circadian rhythm to adapt to, and there is less effect on the circadian rhythm when travelling in a Westward direction (delays the sleep cycle) (Nicholson, 1970). The cause of travelling on the circadian rhythm is external which causes the timing of other circadian body rhythms, including body temperature and melatonin secretion to be altered. Light can reset the circadian clock in accordance with the phase response curve, and the timing of light input can advance or delay the circadian rhythm. It is also thought that entraining the circadian rhythm may be effected by the direction of the light, light coming from below, has a worse effect than light entering our eyes from above (Newman et al, 2003).

Research on the Circadian Rhythm

There have been numerous studies involving real flight and simulated time zone transitions. There are many advantages of simulated time changes performed in an isolation unit. The experiments are cheaper and the clock adjustment can be accomplished immediately and will cause less apprehension on the participants than with a real flight. However, stress, as well as the time zone change itself, might be a component of real flights and it is possible that they will have to be isolated from the rest of the community in an artificial way that might modify the process of adaptation(Siegel et al, 1969).

Measurements of sleep stages were made upon a number of participants before and during recovery from flights in both eastward and westward directions. An increase in the amount of REM sleep and a decrease in its latency after the westward flight were especially marked during the first half of sleep; the opposite changes were seen after a flight to the east (Endo et al, 1978). Further, experiments in which flights to the north and south were taken resulted in much less marked and only transient changes that the authors attributed to fatigue (Endo et al, 1978).

Hauty and Adams (1966) performed a set of experiments that compared the response of subjects to one of three conditions; a flight to the east, a flight through a similar number of time zones to the west, and a flight for a similar distance and duration but southwards. They found that all flights produced an increase in fatigue, a decrement in performance in a number of psychometric tests and changes in temperature, respiratory and cardiovascular rhythms during the first day after flights; however, normal rhythms were recovered by the second post-flight day after the southward flight. By contrast, after the other two flights, the rhythms remained phased more appropriately to pre shift than post shift time for from 4 to 8 days. Gerritzen and Strengers (1974) have obtained similar results in their study which controlled the intake of food and fluid and controlled posture. Their results argued that an endogenous rhythm is involved, even though the alterations of light and dark and social rhythms are still present.

Participants in temperature studies had their rectal temperatures taken continuously whilst they remained calm and awake. It was found that the average human adult's temperature reaches minimum at about 5am which is about 2 hours before habitual wake time. However, variation was great among normal chronotypes. Another study showed the circadian changes in rectal temperature in a group of 8 participants undergoing first an eastward shift through six time zones and then, 18 days later, a westward return journey (Klein, Wegmann et al, 1972). The initial effect after both journeys was that the rhythm was inappropriately phase. This effect was transient and adaptation seems to have been complete by about day 8.

There has been early research into circadian rhythms that suggested that when people were isolated from external stimuli like timekeeping and daylight, they preferred a day closer to 25 hours. Early researchers determined the human circadian rhythm to be 25 hours or more. Research involved participants being allowed to turn a light on or off depending on whether they awake or when they wanted to sleep. They found that the electric light in the evening delayed the participants circadian phase However, the effect of indoor electric lights was not made aware to the researchers. In the evening, participants were also allowed to keep electric lighting on. The researchers thought that a resetting effect on the circadian rhythms of humans would not have an effect by a number of 60W bulbs. It has also been shown by more recent research that adults have a built in day, which averages just over 24 hours. It has been found that people attain their best quality sleep during their chronotype determined sleep periods. It has also been found that indoor lighting does affect circadian rhythms (Cromie, 2007).

There have been a number of studies that have found that during the day, a short period of sleep such as a power nap or siesta does not have any effect on normal circadian rhythm. However, it was found that this could improve productivity and decrease stress (Pilcher, 2001). It has also been suggested that timing of medical treatment in coordination may significantly reduce drug toxicity and increase efficacy. An example of this is with appropriately timed treatment with angiotensin converting enzyme inhibitors (ACEi), there may be a reduction in nocturnal blood pressure and benefits in left ventricular remodelling (Rolston, 2007)

Melatonin has many roles in plants, animals and microbes, such as an antioxidant and interaction with the immune system. Melatonin importantly form part of the signal that regulates the sleep wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin secretion can be measured in the saliva or blood at about 9pm during in dim light melatonin onset (DLMO). DMLO and midpoint in time have been used as circadian markers of the presence of the hormone in the blood or saliva. Laberge et al (1997) analysed a sequence of urine samples for the presence of the melatonin metabolite 6-suphatoxymelatonin (aMT6s), which were taken throughout the morning to measure melatonin offset. This study confirmed the frequently found delayed circadian phase in healthy adolescents.

There has been recent research by Benloucif et al (2005) that found that melatonin phase markers were more highly correlated and more stable with the timing of sleep than the core temperature minimum. It was also found that sleep and melatonin offset were more strongly correlated with the various phase markers than sleep onset. This research indicates that the declining phase of the melatonin levels were more reliable and stable than the termination of melatonin synthesis and that melatonin offset may be the most reliable marker.

There has been some research into the concept of a 28 hour day. If we were required to live on a 28 hour hour day, we would be required to stay awake for 19-20 hours and sleep for 8-9 hours. The 28 hour day builds on the fact that the week of seven days at 24 hours and a week of six days at 28 hours both equal a week of 168 hours. There would be a unique light/dark pattern for each day on this system. Kleitman (1938) and Dijk and Czeisler (1995) conducted experiments into this concept. Participants were enforced on 28 hour sleep wake cycles for one month. They were put in constant dim light and had other time cues suppressed. They found that sleep wake episodes were uncoupled from the endogenous circadian period of about 24.18 hours. Researchers were able to assess the effects of circadian phase on aspects of wakefulness and sleep, including sleep latency and other functions. They concluded that the circadian clock resets itself daily to the 24 hour cycle of the Earth's rotation.

What are the negative effects of travelling on the circadian rhythm?

Flight across more than three time zones produces a problem because the body clock adjusts its phase only slowly, about one or two hours per day under normal circumstances. Until adjustment has occurred, the normal matching between the body clock and the environment will be lacking. Individuals will initially feel tired during the new daytime and yet unable to sleep well during the new night. The negative effects of the body trying to adjust to the new time zone as quickly as possible can cause levels of poor concentration and effectively a bad mood.

Long term effects from disruption to the circadian rhythm are believed to have adverse health consequences on peripheral organs outside the brain. The development of cancer may also be increased with the suppression of melatonin production. There are a number of negative health problems that are associated with disturbances of the human circadian clock. Two of these disorders are called seasonal affective disorder (SAD) and delayed sleep phase syndrome (DSPS) (Sinert et al, 2006)

Negative effects are often seen when there has been a disruption to our circadian rhythm. The effects from travelling can be symptoms such as fatigue, disorientation and insomnia. Symptoms can take over several days to resolve. However, in some patients, such as the elderly it can take them over a few weeks or months to resolve their rhythms as they readjust to the time zone (Martino, 2008).

What treatments are there to reduce the effects of travelling on the clock?

There are many reasons as to why it is important to reduce the effects of travelling on the circadian rhythm. Individuals such as the military or civil air crew who are repeatedly flying to one time zone to another can have the most problems with circadian rhythm disruption. There has been some research on reducing the effects of travelling to the circadian rhythm in athletes. World class sportspersons must travel widely for international competitions and sports camps. As a result, they will suffer from circadian desynchronisation if they fly across several time zones to the east or west. The rhythmicity due to the body clock is of direct relevance to athletes. Muscle strength, adrenaline secretion, short term maximal power output, and self chosen work rate are all greatest at about 6pm; and at about this time also is the highest speed for mental performance involving reaction time and manual dexterity, and the perceived exertion for a given amount of exercise is least. Most personal best performances are set at this time. This, coupled with attempting activities at a time perceived by the body clock as being night, will result in poorer training schedules and even competition results. For competitors at the international level, most results indicate a poorer performance, a feeling of lethargy, and a general loss of motivation. When athletes are travelling they are recommended to concentrate on their behaviour during travel itself. They should train in the days immediately after the flight and on methods to promote adjustment of the body clock. Dehydration and stiffness should be avoided during the flight, and the times of taking naps and meals should be adjusted to the new time zone. Training programmes should be devised with the consideration that some of the new daytime will correspond to night in the time zone just left and that the athlete or games player will also be suffering from the effects of sleep loss (Waterhouse et al, 1998).

There is evidence that the control of circadian rhythms in physiological and performance variables is affected by age. The extent to which this is due to nerve cell decay in the suprachiasmatic nuclei of the hypothalamus-the site of the body clock-has not been determined. Older subjects show reduced amplitude and a tendency towards morning in their circadian cycles. Pronounced effects of age are not evident in the rhythms of workers habituated to nocturnal shift systems due to their coping mechanisms. Even so, it seems that they are more suited chronobiologically to morning shifts and to phase advances than to night shift regimens (Jiva, 2002).

As older people tend to be responsible for crucial business decisions after long haul flights, it is recommended that important meetings are scheduled for hours of day when jet lag is likely to be minimised or the traveller has had time to adjust to the new time zone. The body clock adjusts more easily to a phase delay than to a phase advance and so circadian rhythm disruption is not so severe on travelling westwards compared with eastwards. It is possible that older people are less disadvantaged on travelling eastwards because of their earlier acrophase (Evans et al, 1972; Klein & Wegmann, 1979). Symptoms also tend to last longer the older the person. It is possible that the lower amplitudes of their physiological rhythms and their more sedentary lifestyle place elderly people at a disadvantage but this has not been confirmed. It is unclear if the poorer adjustment is indicative of an inability to alter lifestyle, the body clock, or a combination of both (Jiva, 2002).

Through extensive analysis and experimentation there has been support for the use of melatonin as a remedy for circadian rhythm disruption on long haul flights. Participants taking melatonin reported less disruption and took less time to recover from their shift across 12 time zones. They also reported that they were less tired during the day and required less time to establish a normal sleeping pattern and reach their normal level of energy. This particular study suggests that melatonin may operate by retaining the endogenous circadian rhythm (Mills et al, 1978).

Conclusion

It has been discussed that the presence of a circadian clocks is very important in humans, and is affected by travelling across different time zones. Previous research on the difference in circadian rhythm disorder after westward and eastward flights has been based on the hypothesis that lengthening the natural circadian rhythm is easier than shortening it, and therefore eastward flights generally cause fewer disturbances than westward flights (Alluisi & Chiles, 1967). Further research is needed on the dose response characteristics of melatonin to optimise its effect in alleviating jet lag. Overall the results support the use of melatonin for alleviating circadian rhythm disorder and tiredness after long haul flights and indicate further investigations necessary to maximise the positive effects of melatonin.

To summarize, there are many reasons as to why people would want to reduce the effects of different time zone transitions. If a traveller is planning on staying in any time zone for a long time, the traveller would be advised to try to adapt to it as quickly as possible, and if a traveller is planning on staying in any time zone for a short time and then a return home, they would be advised to remain adapted to the home time zone. Finally if the traveller was undertaking a series of time zone shifts, they could either attempt to adapt to each in turn or to synchronize their rhythms to home time (Conroy, 1971; Klein & Wegmann, 1979).

To conclude, travelling does effect the circadian rhythm in humans in different ways depending on the direction and change in time zone transition. However, by using the advice and in some cases drugs to help the body adjust to the new time zone, this will reduce the negative effects upon the circadian rhythm.

References

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