Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Health consequences of shift work and implications for structural design


The objective of the study was to perform a literature review on the health consequences of working rotating shifts and implications for structural design. A literature search was performed in June 2012 and a selection of the most relevant peer-review articles was included in the present review. Shift workers are more likely to suffer from a circadian sleep disorder characterized by sleepiness and insomnia. Shift work is associated with decreased productivity, impaired safety, diminished quality of life and adverse effects on health. Circadian disruption resulting from rotating shift work has also been associated with increased risk for metabolic syndrome, diabetes, cardiovascular disease and cancer. This article summarizes the known health effects of shift work and discusses how light can be used as a countermeasure to minimize circadian disruption at night while maintaining alertness. In the context of the lighted environment, implications for the design of newborn intensive care units are also discussed.


In the United States and Europe, 15 to 20% of all full-time wage and salary workers work alternative shifts.1 Evening shifts, which fall between 1400 hours and midnight, are relatively common, accounting for 4.6% of work. Shifts that include night work, such as night shifts and rotating shifts, are most prevalent, however, and account for 6.4% of all full-time wage and salary workers.1

Shift work, in particular that which includes night work, requires that the worker invert his/her activity-rest cycle. As a result, shift workers are more likely to suffer from shift work disorder, a circadian sleep disorder characterized by sleepiness and/or insomnia. Shift work disorder is associated with decreased productivity, impaired safety, diminished quality of life and adverse effects on health. Moreover, circadian disruption resulting from rotating shift work has also been associated with increased risk for metabolic syndrome, diabetes, cardiovascular disease and cancer.

The present review paper summarizes the recent scientific literature on the health effects of circadian disruption associated with working rotating shifts and discusses some non-pharmacological countermeasure options. Understanding these effects makes it possible to design lighting solutions that will aid in diminishing the negative effects of shift work on many types of workers, including nurses and doctors who work in various hospital settings.

Circadian rhythms

The Earth rotates around its axis and as a result, all creatures exposed to daylight on Earth experience 24-h cycles of light and dark. Biological rhythms are self-sustaining oscillations with a set of species-specific characteristics, including amplitude, phase and period. Living organisms have adapted to this daily rotation of the Earth by developing circadian rhythms (circa=about; die=day), which are rhythms that repeat approximately every 24 h.

Circadian rhythms are generated endogenously and are aligned with the environment by exogenous factors. It is widely known that in mammals, circadian rhythms are regulated by an internal biological clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus of the brain.2 The SCN are self-sustaining oscillators that maintain their daily activities for weeks when isolated and cultured. The SCN in humans have a natural period that is slightly greater than 24 h. Environmental cues can reset and synchronize the SCN daily, ensuring that the organism’s behavioral and physiological rhythms are in synchrony with the daily rhythms in its environment. The light/dark cycle is the main synchronizer of the SCN to the solar day.2 Light/dark information is received by the eye and reaches the SCN via the retinohypothalamic tract.

Circadian oscillations in most human cells are a result of a small group of clock genes inside the cell nuclei creating interlocked transcriptional and post-translational feedback loops. These cellular oscillators are synchronized to the biological clock located in the SCN. Neural and hormonal stimuli transmit time information from the master clock to these peripheral clocks. To accomplish this, the SCN communicate with neuronal targets such as endocrine neurons, autonomic neurons of the paraventricular nucleus of the hypothalamus and the sub-paraventricular zone in the hypothalamus. The SCN control the release of melatonin through the autonomic nervous system of the paraventricular nucleus. Melatonin is a hormone produced by the pineal gland at night (onset occurs in the early evening, 2 h before sleeping) and under conditions of darkness. Melatonin is believed to act as the main internal synchronizer of the peripheral clocks with the SCN and among themselves by transmitting time information from the master biological clock to the peripheral clocks. Maintaining the sequential and phase-relation ordering of the various circadian rhythms from molecular to behavioral levels is crucial for coordinated function throughout the human body. As discussed below, chronic desynchrony between the master biological clock and peripheral clocks (or circadian disruption), which can be experienced by rotating shift workers, can impact health and well-being.

Lighting characteristics affecting circadian rhythms

Light is formally defined as optical radiation reaching the human retina that provides visual stimulation. All current light sources and light meters are calibrated based on the characteristics of light that affects our visual system. There are five important characteristics of light for both the human visual and circadian systems: quantity, spectrum, timing, duration and distribution. The neural machinery in the mammalian retina provides light information to both the visual and circadian systems, but the two systems process light differently.3 Rods, cones and a newly discovered photoreceptor, the intrinsically photosensitive retinal ganglion cells,4 participate in circadian phototransduction (how the retina converts light signals into neural signals for the biological clock). The quantity of polychromatic ‘white’ light necessary to activate the circadian system is at least two orders of magnitude greater than the amount that activates the visual system. The circadian system is maximally sensitive to short-wavelength (‘blue’) light, with a peak spectral sensitivity at around 460 nm,5, 6, 7 while the visual system is most sensitive to the middle-wavelength portion of the visible spectrum at around 555 nm.3 Operation of the visual system does not depend significantly on the timing of light exposure, and thus responds well to a light stimulus at any time of the day or night. On the other hand, the circadian system is dependent on the timing of light exposure.8, 9 Light after the minimum core body temperature (CBTmin) will advance the timing of the biological clock (that is, promote earlier bedtimes) and light before the CBTmin will delay the timing of the biological clock (that is, promote later bedtimes). CBTmin typically occurs about 1.5 to 2 h before natural awakening. In addition, while the visual system responds to a light stimulus very quickly (in ms), the duration of light exposure needed to stimulate the circadian system can take minutes.3 For the visual system, spatial light distribution is critical for good visibility. It is not yet well established how light incident on different portions of the retina affects the circadian system, although one study showed that light reaching the lower retina was more effective in suppressing melatonin than light reaching the upper retina.10 It is also important to note that the short-term history of light exposure affects the sensitivity of the circadian system to light; the higher the exposure to light during the day, the lower the sensitivity of the circadian system to light at night (LAN), as measured by nocturnal melatonin suppression11 and phase shifting.12

Shift work, LAN and cancer risk

In 2007, the International Agency for Research on Cancer classified shift work that involved circadian disruption as ‘probably carcinogenic to humans’.13 This conclusion was based on data from animal studies, which show that light exposure during the dark period that leads to acute melatonin suppression and/or circadian disruption is associated with the development and growth of tumors. Although the International Agency for Research on Cancer decided that data from animal models was sufficient to conclude that there was a causal link between shift work and circadian disruption resulting from exposure to LAN, they felt that the epidemiological evidence for the carcinogenicity of light during the daily dark period was limited.

There are two parallel theories concerning the relationship between shift work, LAN exposure and hormone-related diseases such as breast cancer. One theory focuses on LAN as a disruptor to normal melatonin hormone production at night. A second theory focuses on the negative health effects of light-induced circadian disruption.

Melatonin, LAN and cancer

The hormone melatonin is synthesized by the pineal gland at night and under conditions of darkness in mammals.14 The synthesis and release of melatonin follow a robust circadian rhythm and are highly governed by the light/dark cycle. Substantial laboratory evidence supports an important role for LAN in cancer etiology through the melatonin pathway. Carillo-Vico et al.15 have shown that melatonin participates in various physiological processes, including immune system functions. Since the early 1980s, evidence from experimental studies suggests a link between melatonin and tumor suppression. Melatonin can prevent damage to DNA, and DNA that is not repaired can mutate and initiate cancer.16, 17 Reports show that melatonin is oncostatic in a variety of tumor cells: in vitro studies, although not entirely consistent,18 indicate that both pharmacological and physiological doses of melatonin reduce the growth of malignant cells of the breast19, 20, 21, 22, 23 and other tumor sites.24, 25, 26, 27, 28

Blask et al.29 showed that exposure to different levels of white fluorescent light during the 12-h dark phase resulted in a dose-dependent suppression of melatonin in rats bearing rat hepatomas or human breast cancer xenografts. Further, they showed that exposure to increasing levels of white light resulted in dose-dependent stimulation of tumor growth and linoleic acid uptake and metabolism. Relatively low light levels suppressed nocturnal melatonin in these rats. Blask et al.29 also showed that human nocturnal melatonin signals inhibit activities such as linoleic acid uptake that are associated with human breast cancer growth and that this effect is diminished by ocular exposure to bright, white LAN. They exposed women to 2800 lux of white light at eye level, which resulted in an 40% reduction of melatonin levels in blood compared with darkness. Perfusing tumors bearing human breast cancer xenografts with this melatonin-depleted human blood resulted in increased linoleic acid uptake in the xenografts, which is related to increased cancer growth.29 Although this landmark study is limited to an indirect relationship between melatonin and cancer growth rates, melatonin depletion might also have important implications for cancer development.30

Circadian disruption and cancer

A person whose rhythms are synchronized to diurnal activity by a light/dark cycle and their social activities must undergo phase readjustment when forced to adapt to a new light/dark cycle (or sleep/wake cycle, in the case of night-shift workers). The SCN and peripheral clocks will readapt to the new light/dark cycle, but it requires several days for a complete phase shift. Moreover, the timing it takes for each of the different peripheral clocks to re-entrain to the new light/dark cycle varies, as different clock genes respond faster to the changes than others.31 As a result, an internal desynchronization occurs between the SCN, which is faster to readjust to the new light/dark cycle, and the peripheral clocks, as well as among the different peripheral clocks. This internal desynchronization (or circadian disruption) affects the entire body, including sleep efficiency, alertness and physical and performance efficiency. More importantly, it is believed that this internal desynchronization affects cell metabolism and proliferation.32 In fact, Filipski et al.33, 34 showed that tumor growth was faster in mice subjected to repeated alteration of light/dark cycles (chronic jet lag), resulting in a severe alteration of activity and CBT rhythms. In humans, lower morning urinary melatonin levels, which are more likely to be experienced by night workers, have been associated with an elevated breast cancer risk.35 Moreover, Fu and Lee36 demonstrated that the disruption of clock gene function might increase cancer risk because clock genes may help maintain important cell repair mechanisms, such as the apoptosis of damaged cells. You et al.37 showed that Per2 expression was arrhythmic in breast tumor cells, while a rhythm of Per2 expression was found in healthy mammary tissues by Metz et al.38

Shift work and cancer risk

Observational studies suggest that shift work is associated with an increase in breast and colorectal cancer risk, potentially linked to melatonin suppression by exposure to LAN. A Finnish record linkage study first reported a significant excess of breast cancer cases among the 1577 female cabin attendants who were followed for 26 years.39 This increased risk was most prominent after 15 years on the job. A second record linkage study from Iceland, which used employment time of female flight attendants as a surrogate exposure, reported similar findings: an increased breast cancer risk after 15 years on the job.40 A third record linkage study in Norway assessed breast cancer incidence in female radio and telegraph operators with potential exposure to LAN.41 Among the 2619 predominantly postmenopausal women who were followed for 30 years, an increased risk for breast cancer was described even after adjustment for age, calendar year and year of first birth. The risk for breast cancer was highest in women aged 50 years or over who were in the highest cumulative shift work exposure category (versus no shift work).

In 2001, three studies were published that adjusted their risk calculations for reproductive history.42, 43, 44 The smallest study, a case–control study with 813 breast cancer cases and 793 controls, assessed details on sleep patterns and habits, lighting characteristics of the subject’s bedroom in the 10 years before diagnosis, and lifetime occupational history.43 The main findings of the study were a positive and statistically significant association between shift work that included night work (starting work after 1900 hours and leaving work before 0900 hours) and breast cancer as well as a 13% increase in risk per additional year having worked at least one night shift per week. The authors also described a modest increase in breast cancer risk among women who reported not sleeping during the period of the night when nocturnal melatonin levels are typically the highest, indicating that women with the brightest bedrooms (that is, likely the highest exposure to LAN) had an increased risk of breast cancer development. All results were adjusted for parity, first-degree family history of breast cancer, oral contraceptive use and recent (within the past 5 years) discontinued use of hormone replacement therapy. The second study, a large, population-based case–control study, investigated breast cancer risk among Danish women 30 to 54 years old who worked predominantly at night.42 Women were considered to work predominantly at night when they had been employed for at least 6 months in one or more of the trades in which at least 60% of the females had nighttime schedules. The authors of the study identified 7035 women with breast cancer and reconstructed their individual employment histories back to 1964 by record linkage with the files of the nationwide pension fund. After adjustment for reproductive history (age at birth of first and last child and number of children) as well as socioeconomic status, women who worked at night for at least 6 months had a 50% greater risk for breast cancer. The authors further noted a positive trend with increasing duration of work at night (no P-value was reported). The third of these studies utilized data from the Nurses’ Health Study.44 The increased risk associated with extended periods (30 or more years) of rotating night work was 36%, after controlling for known breast-cancer risk factors. The risk increased with a greater number of years on shift work. Finally, a meta-analysis summarizing current observational studies of night workers including several studies of flight attendants, suggests a 50% increased risk of breast cancer associated with night work.45

It has also been shown that patterns of night-shift work may be a variable associated with breast cancer risk. Hansen and Stevens46 found a significant increased risk for breast cancer in nurses who work rotating shifts after midnight compared with those who work permanent day shifts. Those who worked evenings, however, were not at higher risk than day shift workers. Of all the rotating shift patterns investigated, Hansen and Stevens46 found that the highest breast cancer risk was observed for long-term day–night rotating shifts. These results are consistent with those from Lie et al.47 who showed a significant increased risk of breast cancer in nurses who worked at least 5 years with 6 or more consecutive night shifts per month. These two studies suggest that breast cancer risk may be proportional to the number of consecutive night shifts worked.

A few studies failed to show a relationship between rotating shifts, which may be associated with increased melatonin suppression or circadian disruption and breast cancer risks. Pesch et al.48 investigated the association between night work and cancer risks in a German population-based case–control study and found that having ever done shift work was not associated with an increased breast cancer risk compared with women who have only worked day shifts. Similarly, Pronk et al.49 investigated the association between shift work and breast cancer risk in a population-based, prospective cohort study of women in Shanghai, China and found no link between breast cancer risk and night-shift work.

Animal studies suggest that the antiproliferative effect of melatonin is not limited to breast cancer.50, 51, 52, 53 The few previous epidemiological studies that have addressed the relationship between shift work and cancer other than breast cancer suggest an elevated cancer mortality related to shift work.54, 55 Tynes et al.41 reported an increased risk of colon and rectum cancer in their cohort of female radio and telegraph workers. Rafnsson et al.40 did not report risks for colorectal cancer among the female Icelandic flight attendants, but described an elevated risk for tumors of the lymphatic system. Similar to breast cancer risks, findings based on the data from the Nurses’ Health Study raise the possibility that a longer duration of rotating night-shift work may increase the risk of colorectal cancer. In a large, prospective study of shift work and colorectal cancer, the risk of colorectal cancer was significantly elevated in women who had worked for more than 15 years on rotating night shifts, compared with those who never worked rotating night shifts.

LAN, hormone levels and shift work

As acute melatonin suppression by LAN has been implicated as an endocrine disruptor in shift workers, recent studies have compared melatonin levels among this group and those working day shifts. Grundy et al.56 examined light exposures and melatonin levels in 123 rotating shift nurses. Despite being exposed to significantly higher light levels during the working nights, peak melatonin levels and daily change in melatonin levels were similar across day shifts and night shifts in these rotating shift workers. Peplonska et al.57 examined 6-sulfatoxymelatonin (aMT6s), a measure of total nighttime melatonin secretion, in 354 nurses and midwives and found no significant differences in aMT6s concentrations between women working on rotating shifts and those working on day shifts. Of those working on rotating shifts, workers who reported having worked, on average, 8 or more night shifts per month had significantly lower aMT6s concentrations than those who worked fewer nights per month. In another study, Langley et al.58 found no significant association between levels of melatonin and sex hormones (oestradiol, oestrome, progesterone and prolactin) among rotating shift workers. These results were consistent with those from women in the Nurses’ Health Study cohort, whose melatonin levels were not associated with sex hormone levels.59 Dumont et al.60 measured ambulatory light exposure and 24-h melatonin production (aMT6s) in 13 full-time rotating shift workers working both night and day/evening shift periods. The authors found no difference in total 24-h aMT6s excretion between the two working periods. Night shifts were associated with a desynchronization between the melatonin and the sleep–wake cycles. Light exposures were not correlated with aMT6s levels excreted during the night of work, but were negatively correlated with total 24-h aMT6s excretion over the entire night-shift period. The authors suggest that circadian desynchrony may have induced the overall lower levels of melatonin excretion.60

Although more work still needs to be performed, these initial field measurement results do not rule out LAN as a potential risk factor for cancer in shift workers, but they cast some doubt on the role of melatonin as a mediator between LAN and serum estrogen levels.

Other health issues associated with shift work

Although causality has not been established, shift work has also been associated with increased risk of heart disease,61 ischemic stroke,62 depression,63 type 2 diabetes,64 obesity,65 gastrointestinal dysfunction66 and reproductive problems.67, 68

Implications for practice

In addition to the health risks discussed above, coping with night-shift work is harder as a result of the natural tendency to be asleep at night. Light can acutely impact alertness in rotating shift workers or it can phase shift the timing of their biological clocks, so that they are more entrained to their working shifts. Acute effects are much easier to achieve because their benefits are perceived shortly after the light exposures. Phase-shifting effects, on the other hand, allow shift workers to cope with being awake at night by providing entrainment to the night shift. Light exposure control throughout the 24 h is, however, needed to maintain entrainment to the night shift, making it harder for workers to comply with the new light regimen. The reversed schedule would only work for permanent shift workers, rather than rotating shift workers who work 2 to 4 nights per week.

Studies have shown that acute exposure to high levels of bright LAN (levels typically>2500 lux at the cornea) increases alertness, measured subjectively and objectively. Badia et al.69 showed that exposure to 90 min of 5000 to 10 000 lux of white light during the nighttime increased brain activities in the alerting range. Cajochen et al.70 also showed that exposure to 3190 lux at the eye of white light increased brain activities, and that much lower levels of short-wavelength (blue) light increased brain activities and reduced sleepiness at night.71 In a field study, it was shown that 15-min exposure to 2500 lux on the workplane (about 500 lux at the cornea) delivered via metal halide table lamps (white light) during break times improved subjective ratings and increased tympanic temperatures of nurses working in a Newborn Intensive Care Unit (NICU).72

Phase shifting the circadian system using light has been shown to be an effective way to increase adaptation to the night shift because the worker is no longer producing melatonin at night; rather, as a result of a 12-h phase shift, workers produce melatonin during the day, when they are supposed to be asleep. This is certainly the preferred lighting solution because it eliminates any adverse effects of being awake while the circadian clock is ready to go to sleep. However, lifestyle changes are required to accomplish and maintain the shift in the timing of the biological clock because light exposure needs to be controlled throughout the 24-h cycle. Improvement in certain types of performance tasks, greater subjective and objective alertness and wakefulness, better sleep quality during the day and possibly better health are some of the benefits associated with a circadian adaptation to night-shift work. Smith et al.73 proposed a compromise solution, where light is applied at the first half of the shift to delay the dim light melatonin onset (DLMO) in rotating shift workers. DLMO occurs when melatonin levels rise above a certain threshold, typically about 2 h before sleeping. Evening light exposures would delay the onset of melatonin, and thus, delay their sleep times, turning shift workers into extreme ‘night owls.’ Although this compromise solution was never tested in the field, it is hypothesized that this extreme ‘night owl’ behavior would help shift workers cope better with staying awake at night and still be awake during the daytime hours when they were off their shift.

As discussed above, in most studies to date, the alerting effects of light have been linked to its ability to suppress melatonin.74 In a recent study, however, Figueiro et al.75 demonstrated that exposures to both short-wavelength (blue) and long-wavelength (red) lights in the middle of the night increased beta power (more cognition) and reduced alpha power (less sleepiness) relative to preceding dark conditions, although only blue light significantly suppressed melatonin relative to darkness. Exposures to high (that is, 40 lux at the cornea), but not low (that is, 10 lux at the cornea), levels of red and of blue light significantly increased heart rate relative to darkness.75 Figueiro and Rea76 demonstrated that both 470-nm (blue) and 630-nm (red) lights can significantly increase nighttime cortisol levels, heart rate and performance (Figure 1). These findings suggest that melatonin suppression is not needed to modulate nighttime alertness. These results are consistent with studies showing alerting effects of light during the daytime, when melatonin levels are low.77, 78

Figure 1

Left: The matching to sample (MTS) throughput score (Tput) is based on an accuracy/speed ratio calculated by the performance vigilance test software. MTS Tput was greater after the red and blue light conditions, but not after the dark condition, when compared to initial measurements in darkness. Right: Same analysis for reaction time (RT) Tput; a higher Tput score signifies better performance. A color reproduction of this figure is available on the Journal of Perinatology online.

Therefore, the combination of red light with low ambient white light might be a good alternative to maintain melatonin levels high at night and still provide an alerting stimulus to those trying to stay awake while the body is telling them to sleep.

Implications for NICU design

As the time frame between planning the design for an NICU until it is replaced is often 20 to 30 years, it is important to consider whether the growing evidence of adverse health effects of night-shift work might have implications for the design process that is going on now. We propose that important considerations do exist in at least two categories: lighting for staff and enhanced design for safety.

It will be apparent that the visual and circadian needs of staff are likely to be quite different from those of patients. Whereas most babies can and should remain in a dim light environment at night, some staff members may have difficulty staying alert in that setting. Unit designs that provide no space for a nurse to perform his/her charting or collaborate with colleagues away from the bedside with lighting conditions most suitable for his/her needs may endanger both the health of the nurse and the safety of the baby. Alternatively, personal light treatment devices can be provided to each worker so that they can have individualized light treatments (for example, light goggles delivering red light) while still at bedside.

We do not currently know what is the safest and healthiest lighting environment for night-shift workers. It is unlikely that it will be the same for all staff regardless of age, visual acuity, ‘night owl’ characteristics and even genetic susceptibility to cancer. In this setting, NICU design should create adequate space for staff members to gather away from the infant care space, where lighting levels can be adjusted to meet the needs of staff members without impinging on the infant care space. Both work and lounge spaces should allow a worker to choose an area where the light level and spectrum are most suitable to his/her needs. Alternatively, the introduction of napping may help because it can dissipate some of the sleep pressure that is usually high in night-shift workers. A brief sleep period has been identified as a potential strategy to improve performance, reduce fatigue and increase vigilance for individuals working extended hours or during night shifts. Smith-Coggins et al.79 studied 49 emergency department nurses and physicians and showed that those in a nap group experienced less fatigue and fewer performance lapses on night shifts than subjects in a control group. For restorative napping to occur, it is important that managers and workers have a safe and comfortable resting place and that the sleep latency (3- to 10-min period after awakening) is considered when planning on allowing staff to take naps.80

Future research

Future research targeting the link between LAN and breast cancer risk should focus on ecological measurements of light/dark and activity/rest patterns. It is important to measure the 24-h light exposures that rotating shift workers are being exposed to in the field and how it may impact melatonin levels. Threshold for suppression of melatonin needs to be determined outside laboratory conditions. Moreover, it is important to measure circadian disruption in the field. Rea et al.81 and Miller et al.82 proposed a metric (phasor magnitude) to quantify circadian disruption using light/dark and activity/rest patterns collected using a novel personal light meter device.82 Phasor magnitude is the correlation between circadian light exposure and activity. A higher magnitude indicates the subject has a consistent, 24-h schedule with respect to activity and light. Lower magnitudes indicate a low correlation between daily cycles of light and activity irrespective of phase differences.

As shown in Figure 2, phasor magnitudes decrease as number of shift-work nights increases. Therefore, future work should use tools such as the circadian light meter83, 84 and phasor analyses to determine optimum shift-work schedules to minimize disruption.

Figure 2

Phasor magnitudes for day shift (0 nights worked) and rotating shift nurses plotted as a function of number of nights worked. The “all-at-once” phasor analyses technique computes the circular correlation function of the entire data set (e.g., seven days) in one operation. The relationship between two sets of time-series data (light/dark and activity/rest) can be quantified through phasor analysis, which incorporates a fast Fourier transform power and phase analysis of the circular correlation function computed from the two data sets. If the power in the longer, infradian, or shorter, ultradian, periods in the circular correlation is large, the magnitude of the 24-h phasor is reduced. Graph adapted with permission from Sage and from Miller et al.82

Until we have a better grasp of the light stimulus and how it may impact melatonin levels or promote circadian disruption in the field, it will be very hard to establish the link between LAN, melatonin suppression, circadian disruption and cancer risks in shift workers.


  1. 1

    Beers TM . Flexible schedules and shift work: replacing the '9-to-5' workday? Mthly Labor Rev (Bureau of Labor Statistics) 2000; 123: 6.

    Google Scholar 

  2. 2

    Moore RY . Circadian rhythms: basic neurobiology and clinical applications. Annu Rev Med 1997; 48: 253–266.

    Article  CAS  PubMed  Google Scholar 

  3. 3

    Rea M, Figueiro M, Bullough J . Circadian photobiology: an emerging framework for lighting practice and research. Light Res Technol 2002; 34: 177–190.

    Article  Google Scholar 

  4. 4

    Berson D, Dunn F, Takao M . Phototransduction by retinal ganglion cells that set the circadian clock. Science 2002; 295: 1070–1073.

    CAS  Article  Google Scholar 

  5. 5

    Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E et al. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci 2001; 21: 6405–6412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Thapan K, Arendt J, Skene DJ . An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol 2001; 535: 261–267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Rea MS, Figueiro MG, Bullough JD, Bierman A . A model of phototransduction by the human circadian system. Brain Res Rev 2005; 50: 213–228.

    Article  PubMed  Google Scholar 

  8. 8

    Jewett M, Rimmer D, Duffy J, Klerman E, Kronauer R, Czeisler C . Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients. Am J Physiol 1997; 273: R1800–R1809.

    CAS  PubMed  Google Scholar 

  9. 9

    Khalsa SB, Jewett ME, Cajochen C, Czeisler CA . A phase response curve to single bright light pulses in human subjects. J Physiol 2003; 549: 945–952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Glickman G, Hanifin J, Rollag M, Wang J, Cooper H, Brainard G . Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans. J Biol Rhythms 2003; 18: 71–79.

    Article  CAS  PubMed  Google Scholar 

  11. 11

    Hebert M, Martin SK, Lee C, Eastman CI . The effects of prior light history on the suppression of melatonin by light in humans. J Pineal Res 2002; 33: 198–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Chang AM, Scheer FA, Czeisler CA . The human circadian system adapts to prior photic history. J Physiol 2011; 589: 1095–1102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Straif K, Baan R, Grosse Y, Secretan B, Ghissassi FE, Bouvard V et al. Carcinogenicity of shift-work, painting, and fire-fighting (on behalf of the WHO International Agency for Research on Cancer Monograph Working Group). Lancet Oncol 2007; 8: 1065–1066.

    Article  PubMed  Google Scholar 

  14. 14

    Arendt J . Melatonin and the Mammalian Pineal Gland 1st edn Chapman & Hall: London, 1995.

    Google Scholar 

  15. 15

    Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ . A review of the multiple actions of melatonin on the immune system. Endocrine 2005; 27: 189–200.

    Article  CAS  PubMed  Google Scholar 

  16. 16

    Erren TC, Reiter RJ, Piekarski C . Light, timing of biological rhythms, and chronodisruption in man. Naturwissenschaften 2003; 90: 485–494.

    Article  CAS  PubMed  Google Scholar 

  17. 17

    Chen LJ, Gao YQ, Li XJ, Shen DH, Sun FY . Melatonin protects against MPTP/MPP+ -induced mitochondrial DNA oxidative damage in vivo and in vitro. J Pineal Res 2005; 39: 34–42.

    Article  CAS  PubMed  Google Scholar 

  18. 18

    Panzer A, Lottering ML, Bianchi P, Glencross DK, Stark JH, Seegers JC . Melatonin has no effect on the growth, morphology or cell cycle of human breast cancer (MCF-7), cervical cancer (HeLa), osteosarcoma (MG-63) or lymphoblastoid (TK6) cells. Cancer Lett 1998; 122: 17–23.

    Article  CAS  PubMed  Google Scholar 

  19. 19

    Hill SM, Blask DE . Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Res 1988; 48: 6121–6126.

    CAS  PubMed  Google Scholar 

  20. 20

    Cos S, Fernandez F, Sanchez-Barcelo EJ . Melatonin inhibits DNA synthesis in MCF-7 human breast cancer cells in vitro. Life Sci 1996; 58: 2447–2453.

    Article  CAS  PubMed  Google Scholar 

  21. 21

    Cos S, Fernandez R, Guezmes A, Sanchez-Barcelo EJ . Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res 1998; 58: 4383–4390.

    CAS  PubMed  Google Scholar 

  22. 22

    Mediavilla MD, Cos S, Sanchez-Barcelo EJ . Melatonin increases p53 and p21WAF1 expression in MCF-7 human breast cancer cells in vitro. Life Sci 1999; 65: 415–420.

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Cos S, Mediavilla MD, Fernandez R, Gonzalez-Lamuno D, Sanchez-Barcelo EJ . Does melatonin induce apoptosis in MCF-7 human breast cancer cells in vitro? J Pineal Res 2002; 32: 90–96.

    Article  CAS  PubMed  Google Scholar 

  24. 24

    Ying SW, Niles LP, Crocker C . Human malignant melanoma cells express high-affinity receptors for melatonin: antiproliferative effects of melatonin and 6-chloromelatonin. Eur J Pharmacol 1993; 246: 89–96.

    Article  CAS  PubMed  Google Scholar 

  25. 25

    Sze SF, Ng TB, Liu WK . Antiproliferative effect of pineal indoles on cultured tumor cell lines. J Pineal Res 1993; 14: 27–33.

    Article  CAS  PubMed  Google Scholar 

  26. 26

    Shiu SY, Li L, Xu JN, Pang CS, Wong JT, Pang SF . Melatonin-induced inhibition of proliferation and G1/S cell cycle transition delay of human choriocarcinoma JAr cells: possible involvement of MT2 (MEL1B) receptor. J Pineal Res 1999; 27: 183–192.

    Article  CAS  PubMed  Google Scholar 

  27. 27

    Petranka J, Baldwin W, Biermann J, Jayadev S, Barrett JC, Murphy E . The oncostatic action of melatonin in an ovarian carcinoma cell line. J Pineal Res 1999; 26: 129–136.

    Article  CAS  PubMed  Google Scholar 

  28. 28

    Kanishi Y, Kobayashi Y, Noda S, Ishizuka B, Saito K . Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines. J Pineal Res 2000; 28: 227–233.

    Article  CAS  PubMed  Google Scholar 

  29. 29

    Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK, Krause JA et al. Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Res 2005; 65: 11174–11184.

    Article  CAS  PubMed  Google Scholar 

  30. 30

    Reiter RJ . Mechanisms of cancer inhibition by melatonin. J Pineal Res 2004; 37: 213–214.

    Article  CAS  PubMed  Google Scholar 

  31. 31

    Haus E, Smolensky M . Biological clocks and shift work: circadian dysregulation and potential long-term effects. Cancer Causes Control 2006; 17: 489–500.

    Article  PubMed  Google Scholar 

  32. 32

    Haus E . Chronobiology of the mammalian response to ionizing radiation. Potential applications in oncology. Chronobiol Int 2002; 19: 77–100.

    Article  PubMed  Google Scholar 

  33. 33

    Filipski E, King VM, Li X, Granda TG, Mormont M-C, Liu X et al. Host circadian clock as a control point in tumor progression. J Natl Cancer Inst 2002; 94: 690–697.

    Article  PubMed  Google Scholar 

  34. 34

    Filipski E, King VM, Li X, Granda TG, Mormont M-C, Claustrat B et al. Disruption of circadian coordination accelerates malignant growth in mice. Pathol Biol 2003; 51: 216–219.

    Article  PubMed  Google Scholar 

  35. 35

    Schernhammer ES, Hankinson SE . Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst 2005; 97: 1084–1087.

    Article  CAS  PubMed  Google Scholar 

  36. 36

    Fu L, Lee CC . The circadian clock: pacemaker and tumour suppressor. Nat Rev Cancer 2003; 3: 350–361.

    Article  CAS  PubMed  Google Scholar 

  37. 37

    You S, Wood PA, Xiong Y, Kobayashi M, Du-Quiton J, Hrushesky WJM . Daily coordination of cancer growth and circadian clock gene expression. Breast Cancer Res Treat 2005; 91: 47–60.

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Metz RP, Qu X, Laffin B, Earnest D, Porter WW . Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary gland. Dev Dyn 2006; 235: 263–271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Pukkala E, Auvinen H, Wahlberg G . Incidence of cancer among Finnish airline cabin attendants. BMJ 1995; 311: 649–652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Rafnsson V, Tulinius H, Jonasson JG, Hrafnkelsson J . Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes Control 2001; 12: 95–101.

    Article  CAS  PubMed  Google Scholar 

  41. 41

    Tynes T, Hannevik M, Andersen A, Vistnes AI, Haldorsen T . Incidence of breast cancer in Norwegian female radio and telegraph operators. Cancer Causes Control 1996; 7: 197–204.

    Article  CAS  PubMed  Google Scholar 

  42. 42

    Hansen J . Increased breast cancer risk among women who work predominantly at night. Epidemiology 2001; 12: 74–77.

    Article  CAS  PubMed  Google Scholar 

  43. 43

    Davis S, Mirick DK, Stevens RG . Night shift work, light at night, and risk of breast cancer. J Natl Cancer Inst 2001; 93: 1557–1562.

    Article  CAS  PubMed  Google Scholar 

  44. 44

    Schernhammer ES, Laden F, Speizer FE, Willet WC, Hunter DJ, Kawahi I et al. Rotating night shifts and risk of breast cancer in women participating in the Nurses’ Health Study. J Natl Cancer Inst 2001; 93: 1563–1568.

    Article  CAS  PubMed  Google Scholar 

  45. 45

    Megdal SP, Kroenke CH, Laden F, Pukkala E, Schernhammer ES . Night work and breast cancer risk: a systematic review and meta-analysis. Eur J Cancer 2005; 41: 2023–2032.

    Article  PubMed  Google Scholar 

  46. 46

    Hansen J, Stevens RG . Night shiftwork and breast cancer risk: overall evidence. Occup Environ Med 2011; 68: 236.

    Article  PubMed  Google Scholar 

  47. 47

    Lie J-AS, Kjuus H, Zienolddiny S, Haugen A, Stevens RG, Kjærheim K . Night work and breast cancer risk among Norwegian nurses: assessment by different exposure metrics. Am J Epidemiol 2011; 173: 1272–1279.

    Article  PubMed  Google Scholar 

  48. 48

    Pesch B, Harth V, Rabstein S, Baisch C, Schiffermann M, Pallapies D et al. Night work and breast cancer—results from the German GENICA study. Scand J Work Environ Health 2010; 36: 134–141.

    Article  PubMed  Google Scholar 

  49. 49

    Pronk A, Ji B-T, Shu X-O, Xue S, Yang G, Li H-L et al. Night-shift work and breast cancer risk in a cohort of Chinese women. Am J Epidemiol 2010; 171: 953–959.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50

    Farriol M, Venereo Y, Orta X, Castellanos JM, Segovia-Silvestre T . In vitro effects of melatonin on cell proliferation in a colon adenocarcinoma line. J Appl Toxicol 2000; 20: 21–24.

    Article  CAS  PubMed  Google Scholar 

  51. 51

    Anisimov VN, Popovich IG, Zabezhinski MA . Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats. Carcinogenesis 1997; 18: 1549–1553.

    Article  CAS  PubMed  Google Scholar 

  52. 52

    Anisimov VN, Kvetnoy IM, Chumakova NK, Kvetnaya TV, Molotkov AO, Pogudina NA et al. Melatonin and colon carcinogenesis. Exp Toxicol Pathol 1999; 51: 47–52.

    Article  CAS  PubMed  Google Scholar 

  53. 53

    Anisimov VN, Kvetnoy IM, Chumakova NK, Kvetnaya TV, Molotkov AO, Pogudina NA et al. Melatonin and colon carcinogenesis. III. Effect of melatonin on proliferative activity and apoptosis in colon mucosa and colon tumors induced by 1,2-dimethylhydrazine in rats. Exp Toxic Pathol 2000; 52: 71–76.

    Article  CAS  Google Scholar 

  54. 54

    Rafnsson V, Gunnarsdottir H . Mortality study of fertiliser manufacturers in Iceland. Br J Ind Med 1990; 47: 721–725.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Taylor PJ, Pocock SJ . Mortality of shift and day workers 1956-68. Br J Ind Med 1972; 29: 201–207.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Grundy A, Tranmer J, Richardson H, Graham CH, Aronson KJ . The influence of light at night exposure on melatonin levels among Canadian rotating shift nurses. Cancer Epidemiol Biomarkers Prev 2011; 20: 2404–2412.

    Article  CAS  PubMed  Google Scholar 

  57. 57

    Peplonska B, Bukowska A, Gromadzinska J, Sobala W, Reszka E, Lie J-A et al. Night shift work characteristics and 6-sulfatoxymelatonin (MT6s) in rotating night shift nurses and midwives. Occup Environ Med 2012; 69: 339–346.

    Article  PubMed  Google Scholar 

  58. 58

    Langley AR, Graham CH, Grundy AL, Tranmer JE, Richardson H, Aronson KJ . A cross-sectional study of breast cancer biomarkers among shift working nurses. BMJ Open 2012; 2: e000532.

    Article  PubMed  PubMed Central  Google Scholar 

  59. 59

    Schernhammer ES, Kroenke CH, Laden F, Hankinson SE . Night work and risk of breast cancer. Epidemiology 2006; 17: 108–111.

    Article  PubMed  Google Scholar 

  60. 60

    Dumont M, Lanctôt V, Cadieux-Viau R, Paquet J . Melatonin production and light exposure of rotating night workers. Chronobiol Int 2012; 29: 203–210.

    Article  CAS  PubMed  Google Scholar 

  61. 61

    Viitasalo K, Lindström J, Hemiö K, Puttonen S, Koho A, Härmä M et al. Occupational health care identifies risk for type 2 diabetes and cardiovascular disease. Prim Care Diabetes 2012; 6: 95–102.

    Article  PubMed  Google Scholar 

  62. 62

    Brown DL, Feskanich D, Sánchez BN, Rexrode KM, Schernhammer ES, Lisabeth LD . Rotating night shift work and the risk of ischemic stroke. Am J Epidemiol 2009; 169: 1370–1377.

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63

    Drake CL, Roehrs T, Richardson G, Walsh JK, Roth T . Shift work sleep disorder: prevalence and consequences beyond that of symptomatic day workers. Sleep 2004; 27: 1453–1462.

    Article  PubMed  Google Scholar 

  64. 64

    Pan A, Schernhammer ES, Sun Q, Hu FB . Rotating night shift work and risk of type 2 diabetes: two prospective cohort studies in women. PLoS Med 2011; 8: e1001141.

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65

    Antunes LC, Levandovski R, Dantas G, Caumo W, Hidalgo MP . Obesity and shift work: chronobiological aspects. Nutr Res Rev 2010; 23: 155–168.

    Article  CAS  PubMed  Google Scholar 

  66. 66

    Knutsson A, Bøggild H . Gastrointestinal disorders among shift workers. Scand J Work Environ Health 2010; 36: 85–95.

    Article  PubMed  Google Scholar 

  67. 67

    Lawson CC, Rocheleau CM, Whelan EA, Lividoti Hibert EN, Grajewski B, Spiegelman D et al. Occupational exposures among nurses and risk of spontaneous abortion. Am J Obstet Gynecol 2012; 206: 327 e1–8.

    Article  PubMed  Google Scholar 

  68. 68

    Mahoney MM . Shift work, jet lag, and female reproduction. Int J Endocrinol 2010; 2010: 813764.

    Article  PubMed  PubMed Central  Google Scholar 

  69. 69

    Badia P, Myers B, Boeckner M, Culpepper J, Harsh JR . Bright light effects on body temperature, alertness, EEG and behavior. Physiol Behav 1991; 50: 583–588.

    Article  CAS  PubMed  Google Scholar 

  70. 70

    Cajochen C, Zeitzer JM, Czeisler CA, Dijk DJ . Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness. Behav Brain Res 2000; 115: 75–83.

    Article  CAS  PubMed  Google Scholar 

  71. 71

    Cajochen C, Munch M, Kobialka S, Krauchi K, Steiner R, Oelhafen P et al. High sensitivity of human melatonin, alertness, thermoregulation and heart rate to short wavelength light. J Clin Endocrinol Metab 2005; 90: 1311–1316.

    Article  CAS  PubMed  Google Scholar 

  72. 72

    Figueiro MG, Rea MS, Boyce P, White R, Kolberg K . The effects of bright light on day and night shift nurses’ performance and well-being in the NICU. Neonatal Intens Care 2001; 14: 29–32.

    Google Scholar 

  73. 73

    Smith MR, Fogg LF, Eastman CI . A compromise circadian phase position for permanent night work improves mood, fatigue, and performance. Sleep 2009; 32: 1481–1489.

    Article  PubMed  PubMed Central  Google Scholar 

  74. 74

    Figueiro MG, Bullough JD, Bierman A, Fay CR, Rea MS . On light as an alerting stimulus at night. Acta Neurobiol Exp (Wars) 2007; 67: 171–178.

    Google Scholar 

  75. 75

    Figueiro MG, Bierman A, Plitnick B, Rea MS . Preliminary evidence that both blue and red light can induce alertness at night. BMC Neurosci 2009; 10: 105.

    Article  PubMed  PubMed Central  Google Scholar 

  76. 76

    Figuero MG, Rea MS . The effects of red and blue lights on circadian variations in cortisol, alpha amylase and melatonin. Int J Endocrinol 2010; 2010: 829351.

    Google Scholar 

  77. 77

    Phipps-Nelson J, Redman JR, Bijk DJ, Rajaratnam SM . Daytime exposure to bright light, as compared to dim light, decreases sleepiness and improves psychomotor vigilance performance. Sleep 2003; 26: 695–700.

    Article  PubMed  Google Scholar 

  78. 78

    Vandewalle G, Balteau E, Phillips C, Degueldre C, Moreau V, Sterpenich V et al. Daytime light exposure dynamically enhances brain responses. Curr Biol 2006; 16: 1616–1621.

    Article  CAS  PubMed  Google Scholar 

  79. 79

    Smith-Coggins R, Howard SK, Mac DT, Wang C, Kwan S, Rosekind MR et al. Improving alertness and performance in emergency department physicians and nurses: the use of planned naps. Am Emerg Med 2006; 48: 596–604.

    Article  Google Scholar 

  80. 80

    Jewett ME, Wyatt JK, Ritz-De Cecco A, Khalsa SB, Dijk DJ, Czeisler CA . Time course of sleep inertia dissipation in human performance and alertness. J Sleep Res 1999; 8: 1–8.

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Rea MS, Bierman A, Figueiro MG, Bullough JD . A new approach to understanding the impact of circadian disruption on human health. J Circadian Rhythms 2008; 6: 7.

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82

    Miller D, Bierman A, Figueiro MG, Schernhammer E, Rea MS . Ecological measurements of light exposure, activity, and circadian disruption in real-world environments. Light Res Technol 2010; 42: 271–284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Bierman A, Klein TR, Rea MS . The Daysimeter: a device for measuring optical radiation as a stimulus for the human circadian system. Meas Sci Technol 2005; 16: 2292–2299.

    Article  CAS  Google Scholar 

  84. 84

    Figueiro MG, Hammer R, Bierman A, Rea MS . Comparisons of three practical field devices used to measure personal light exposures and activity levels. Light Res Technol 2012 in press.

Download references


We like to acknowledge Mark Rea, Rebekah Mullaney and Nicholas Hanford for their technical and editorial assistance. The Office of Naval Research (award no. N000141110572) funded some of the work presented in this manuscript. This publication has been sponsored by Lifespan Healthcare LLC, Philips Healthcare and Pediatrix Medical Group. The sponsoring entities for this publication had no involvement in the preparation or alteration of the manuscripts.

Author information



Corresponding author

Correspondence to M G Figueiro.

Ethics declarations

Competing interests

Rensselaer Polytechnic Institute received speaking fees from Acuity Lighting on behalf of MGF. RDW is employed by Pediatrix and owner of WhiteBriar Corporation.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Figueiro, M., White, R. Health consequences of shift work and implications for structural design. J Perinatol 33, S17–S23 (2013).

Download citation


  • shift work
  • circadian system
  • melatonin
  • circadian rhythms
  • cancer
  • newborn intensive care unit design

Further reading


Quick links