Shift Work

Clinically, it may be most useful to personalize the shift work assessment to the individual patient and their ad libitum schedule. Work and commute hours that would interfere with one person’s sleep-wake schedule may not interfere with those of a second patient. For instance, working at a restaurant until 11 pm may not cause any physiological effects for a teenager whose ad libitum sleep schedule is 1 am to 11 am. That same work schedule may cause negative effects though for a 50-year-old person whose ad libitum schedule is sleeping from 9 pm to 5 am. Women tend to have more difficulty adapting to night shift work, likely because of advanced core body temperature rhythms compared to men, along with an earlier peak in alertness.(7)

The Challenge of Shift Work

Advancing or “backward” rotating shifts are known to be the most difficult, as our intrinsic body clock “tau” is greater than 24 hours, making it easier to stay awake progressively later than go to sleep early. Most shift workers prefer to alternate their sleep hours from daytime as required while working nights, to nocturnal sleep during off days.t is difficult to sleep on this schedule because the body clock cannot shift this rapidly.(8)  Typically, it’s thought that the intrinsic body clock can shift at most 0.5 - 1 hour each day.(9)  Trying to sleep during the day on work days, and sleep during the night on free days, keeps the circadian rhythm set for a diurnal pattern. The symptoms and health consequences result from being awake at the time the body is programmed to sleep and sleeping at the time the body is programmed to be awake. For these reasons, it appears that only 3% of night shift workers fully adapt, and less than 25% have a substantial adjustment in their body clock.(10)

The circadian system has multiple levels, from the central pacemaker in the suprachiasmatic nucleus (SCN), to the peripheral clocks at the tissue and cellular level. (11) In shift work, misalignment between the levels of the circadian system is created as each responds to the misaligned light-dark cues by shifting a different amount.(12) For example, in 2017 Cuesta, et al.(13) found that the clock genes BMAL and PER3 shifted 2.5-3 hours later in response to a night shift schedule, while the centrally controlled melatonin and cortisol release patterns were not altered, and neither were other clock genes. One of the most consistent effects of shift work is that the amplitude of the circadian oscillation is dampened. This is seen in the cortisol, melatonin, core body temperature, PER3, and activity level rhythms.(12) However, although 11.8% of the transcriptome is rhythmic, even after four consecutive night shifts it will remain aligned with a day-orientation.(14)  

“Disruption of the circadian system caused by night-shift work results not only in a misalignment between

the circadian system and the external light-dark cycle, but also in a state of internal

desynchronization between various levels of the circadian system.” (12)

Physiologic changes are observed in multiple systems of shift workers. Of significant concern are pro-inflammatory changes in immune cells. The typical circadian pattern of total lymphocytes, interleukin-6, memory B-cells, T-helper cells, and cytotoxic T-cells is reversed from normal, with a low at 9 pm which increases over the night to peak at 7 am.(15)  This is important for the clinician both during the interpretation of lab work, and in the screening and prevention of the increased health risks experienced by shift workers.

Health Implications of Shift Work

Shift workers are at increased risk for a wide variety of conditions, in addition to the immediate sleep complaints of longer sleep latency, short sleep duration, sleep disruption, and daytime impairment.(16) Central among these are weight gain/obesity, metabolic syndrome, cardiovascular disease, autoimmune conditions, and cancer, particularly of the breast.(17) Additionally, between 48-82% of shift workers report digestive upset such as constipation or diarrhea and abdominal pain.(17)  

Obesity and metabolic syndrome are increasing worldwide. Working the night shift increases the odds of metabolic disease by 36% and increased waist circumference by 27%.(18) Another study found an even greater risk, at an odds ratio of 92% of developing metabolic syndrome for night shift workers.(16) The odds of developing gestational diabetes is increased by 75% among evening shift workers compared to day shift workers.(19) Previous research on the risk of obesity associated with shift work has been inconclusive. However, a meta-analysis in 2020 demonstrated an association, particularly in those working night shifts.(20)

Cardiovascular disease (CVD) risk is significantly increased by 17% above those who work days, with CVD mortality increased by 20%. After the first five years of shift work, the CVD risk increases 7.1% every five years, demonstrating a ‘dose response’.(21)

Social jet lag (an indicator of circadian misalignment) among night workers is a risk factor for CVD, with each hour of social jet lag above 1.5 hours increasing risk by >30%.(22) Within 90 days of beginning an early morning shift, 62% of new bus drivers developed a non-dipping nocturnal blood pressure pattern, an early risk factor for CVD.(23)

Shift work may have a role in autoimmune disease. Research in rheumatoid arthritis found an association with rotating shifts, though also a protective effect with permanent night shift.(24) The circadian pattern of IL-6 (an inflammatory cytokine) shifts after three consecutive night shifts, and this mis-timing may contribute to autoimmune disease.(25)  A meta-analysis of thyroid function found that shiftwork increases both TSH and FT4, but had no impact on thyroid autoantibodies.(26) However, older primary research found an increased risk of sub-clinical autoimmune thyroiditis among shift workers (7.7% versus 3.8% in day workers) due to significantly increased anti-thyroid peroxidase antibodies (TPO).(27) In the primary care setting, regular screening for thyroid disease would be indicated.

In 2020, the International Agency for Research on Cancer declared shift work as “probably carcinogenic to humans” (Group 2A).(28) Their assessment was based upon strong mechanistic evidence, sufficient evidence in animal models, and limited evidence in human research. They found associations between night shift and breast, colon, prostate, and rectal cancers. The primary increase is seen in breast cancer, with an increase after 20 years of shift work, or intensive periods of consecutive nights (Hansen). Other meta-analyses demonstrated an increased risk (1.13 odds) of breast cancer for people with short-duration shiftwork of less than 10 years, compared to longer shiftwork having an increased risk of 1.08.(29) Other research has investigated prostate cancer, finding no association with night shift work.(30)

How to Make Shift Work ‘Work’

With 15 million people suffering from shift work disorder in the USA alone(17), along with millions more worldwide, the need for effective treatment is great. There are a wide variety of treatment options, which must be personalized to the individual and their shift work schedule.

Dietary Considerations

Optimal timing of meals for shift workers, as it’s been established that meal timing is a zeitgeber. This is also an important area of intervention as shift workers are at increased risk of metabolic disease. Indeed, meals at 11:30 pm increase glucose and insulin more than at other times of day.(31) Research shows that keeping meals in the daytime (aligned with the circadian system instead of the nocturnal wake period) reduces glucose intolerance in a night shift model.(32) Consuming 300mg of caffeine at the beginning of the night shift, alone or in combination with a nap, has been demonstrated to improve alertness and performance during the night shift.(33)

Lifestyle Factors

Including shift work coping practices in nursing education and for other occupations where shift work is prevalent may be appropriate.

• A study of night shift working nurses in Ethiopia found an increased risk of shift work disorder with various behaviors which included more than eleven night shifts per month, sleeping less than seven hours, and substance use including alcohol and cigarettes. To decrease this risk, strategies, such as napping, decreasing substance use, and limiting night shifts to two nights in a row were recommended.(34)

• More engaged coping styles among nurses on a forward rotating shift is associated with better dietary intake in terms of fewer calories, fat, carbohydrate, and sugar intake.(35)

• Giving more days off between consecutive work shifts can also give the hypothalamic-pituitary axis more time to recover.(36)

• Increasing the free time between consecutive work shifts from 31 hours to 55 hours improved subjective ratings of fatigue and stress, though did not improve objective measures such as hair cortisol and salivary C-reactive protein.(37) The ideal amount of time between work stints is unknown at this time.

Research by Smith and Eastman demonstrated that for shift workers it is advantageous to design a schedule with 3-4 core hours of sleep that are always the same, regardless of whether it’s a work day or an off day.(8) This allows the circadian system to shift late enough that they are better able to sleep during the day, and maintain better alertness during night work. Other components of this protocol include low dose melatonin 5-7 hours before bed on the earlier nights, blue-blocking glasses during the morning commute home after work, alerting light pulses during the night shift, and a light “break” of 30 minutes after the main sleep period.

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Light Exposure

It’s important for shift workers to also control light exposure, by wearing blue-light blocking glasses from the time they leave work in the morning until they are in bed with the lights off. This daily practice will allow their natural melatonin to rise. (38) Wearing the blue-light blocking glasses on off days for two hours before bed would also be indicated. Re-entrainment from day-orientation to night shift will be quicker than re-entrainment from night shift to days, and the time necessary can be decreased by bright light exposure.(39) Moderate-intensity short light bursts during the night will decrease sleepiness. The duration of bright light needed to phase shift is still inconclusive. More research is needed.(40)

Other Lifestyle Considerations

Caffeine and naps both will increase alertness when used strategically.(33)  Although exercise in the hours before sleep typically does have a delaying effect, adding exercise to light therapy to delay the circadian rhythm for shift work did not have an additive effect.(41)

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A comprehensive plan to moderate the effects of shift work would include the following;

1. Patient education about best coping strategies, and avoidance of maladaptive coping

2. Targeted naps before work, and possibly during a work shift, to enhance alertness. Specifically, a nap for 1-2 hours total, starting three to four hours before the night shift.

3. Precisely timed light exposure with therapeutic intensity and wavelength

4. Strategic caffeine, with caffeine use limited to therapeutic goals

5. Precisely timed darkness with control of light and blue-light blocking glasses

6. Standardized meal times both to phase shift and to minimize digestive upset

7. Standardized exercise times to phase shift

Melatonin Supplementation

Studies using melatonin have explored how shift work, particularly night work, with its exposure to light at night, may increase the risk of cancer, aggravate both gastrointestinal and cardiovascular disease, complicate pregnancy, and interfere with drug therapy.(42)  Multiple studies, opinions, and guidelines have suggested melatonin as the primary therapy for improved health and sleep of shift workers.(43–45) 

In shift work, melatonin can be used in two ways- as a chronobiotic or hypnotic.

• Chronobiotic- On days off, melatonin can be used to shift sleep onset earlier, as per the phase response curve.(46)  The dose would be a low dose of 0.3-0.5 mg, five to seven hours before the desired bedtime.

• Hypnotic- On work days, melatonin can be used as a hypnotic, by taking a 3 mg dose when going to bed in the morning, after work.

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Melatonin supplementation of 3 mg taken after the night shift, reduced intra-rater experience of daytime sleepiness.(47) Three milligrams of melatonin have also been shown to effectively advance the circadian rhythm when taken 11 hours before the sleep-midpoint. However, this dose was associated with increased sleepiness after ingestion, so the authors concluded a lower dose would be indicated.(48) Research by Burgess, et al. indicates that a low dose of 0.5 mg taken at that time will also phase-advance.(46)