Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being

In the paper

“However, a number of studies have found no association between cancer and shift work [64,65,66,67].”

What the sources say

• Supported

  The Discussion reports that having ever done night shift work was not associated with increased breast cancer risk in the GENICA study. The introduction also notes two other studies reporting no increased breast cancer risk. These findings support the claim that some studies found no association, specifically for breast cancer and night shift work; the paper does not claim that all forms of cancer or shift work show no association. (LLM, conf=0.88)

  cites [64] 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(2):134–41. doi: 10.5271/sjweh.2890 . source
• Not checked yetcites [65] Kubo T, Oyama I, Nakamura T, Kunimoto M, Kadowaki K, Otomo H, et al. Industry-based retrospective cohort study of the risk of prostate cancer among rotating shift workers. Int J Urol. 2011;18:206–11. doi: 10.1111/j.1442-2042.2010.02714.x . source
• Supported

  The Discussion reports that this cohort study found no evidence of an association between night-shift work and breast cancer risk. As one of several citations attached to the sentence, it supports an example of a study finding no association, though its finding is specific to breast cancer and night-shift work. (LLM, conf=0.91)

  cites [66] Pronk A, Ji B, Shu X, Xue S, Yang G, Li H, et al. Night-shift work and breast cancer risk in a cohort of Chinese women. Am J Epidemiol. 2010;171(9):953–9. doi: 10.1093/aje/kwq029 . source
• Partly supported

  The Discussion reports no association between night shift work and breast cancer incidence in three UK studies and in the prospective evidence overall. The cited paper does not establish the broader claim for cancer generally or for all forms of shift work. (LLM, conf=0.86)

  cites [67] • Travis RC, Balkwill A, Fensom GK, Appleby PN, Reeves GK, Wang SX, et al. Night shift work and breast cancer incidence: three prospective studies and a meta-analysis of published studies. J Natl Cancer Inst. 2016;108(12):djw169. doi: 10.1093/jnci/djw169 . Review of reseearch on night shift work and breast cancer. sourceExperimental — accuracy not yet measured

In the paper

“Findings in animal models with environmentally disturbed circadian systems (simulated shift work) indicate that circadian disruption increases the progression of cancer, possibly through dysregulation of the cell cycle, accumulation of DNA damage, and reduced tumor suppression [49,50,51,52].”

What the sources say

• Not checked yetcites [49] Lee S, Donehower LA, Herron AJ, Moore DD, Fu L. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS One. 2010;5(6):e10995. doi: 10.1371/journal.pone.0010995 . source
• Not checked yetcites [50] • Kettner NM, Voicu H, Finegold MJ, Coarfa C, Sreekumar A, Putluri N, et al. Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis. Cancer Cell. 2016;30(6):909–24. doi: 10.1016/j.ccell.2016.10.007 . Study in mice linking circadian misalignment with altered gene expression, liver dysfunction, and carcinogenesis. source
• Not checked yetcites [51] • Papagiannakopoulos T, Bauer MR, Davidson SM, Heimann M, Subbaraj L, Bhutkar A, et al. Circadian rhythm disruption promotes lung tumorigenesis. Cell Metab. 2016;24(2):324–31. doi: 10.1016/j.cmet.2016.07.001 . Study in mice showing the effects of circadian disruption on cancer progression in lung tissue. source
• Not checked yetcites [52] • Van Dycke KC, Rodenburg W, van Oostrom CT, van Kerkhof LW, Pennings JL, Roenneberg T, et al. Chronically alternating light cycles increase breast cancer risk in mice. Curr Biol. 2015;25(14):1932–7. doi: 10.1016/j.cub.2015.06.012 . Study in mice linking altered light/dark cycles with breast cancer. source

In the paper

“Sleep displacement and altered meal timing due to shift work disturb hormonal balance—including key regulators of satiety and hunger, the hormones leptin and ghrelin, respectively [13].”

What the sources say

• Not checked yetcites [13] Nguyen J, Wright Jr KP. Influence of weeks of circadian misalignment on leptin levels. Nat Sci Sleep. 2009;2:9–18. doi: 10.2147/NSS.S7624 . source

In the paper

“the implications of circadian misalignment between the biological clock and the sleep/wake cycle are perhaps best illustrated by how such misalignment increases the risk of workplace accidents and injuries.”

In the paper

“Persistent stimulation of the HPA axis by external stressors in the face of circadian misalignment may lead to erosion of mental health in shift workers.”

In the paper

“These peripheral oscillators are normally in sync with the master clock in the SCN, but altered sleep/wake schedules associated with shift work may desynchronize them [46].”

What the sources say

• Not checked yetcites [46] •• Ackermann K, Plomp R, Lao O, Middleton B, Revell VL, Skene DJ, et al. Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans. Chronobiol Int. 2013;30(7):901–9. doi: 10.3109/07420528.2013.784773 . Demonstration of interaction between sleep loss and circadian misalignment at the level of gene expression. source

In the paper

“Disrupted rhythmicity in the gut microbiome may be involved in an immediate and frequently reported, yet hitherto poorly understood, effect of shift work, namely, gastrointestinal discomfort [42,43].”

What the sources say

• Not checked yetcites [42] Knutsson A. Health disorders of shift workers. Occup Med. 2003;53:103–8. doi: 10.1093/occmed/kqg048 . source
• Not checked yetcites [43] Nojkov B, Rubenstein JH, Chey WD, Hoogerwerf WA. The impact of rotating shift work on the prevalence of irritable bowel syndrome in nurses. Am J Gastroenterol. 2010;105:842–7. doi: 10.1038/ajg.2010.48 . source

In the paper

“In humans, presumably as a long-term consequence of altered glucose metabolism, shift work is associated with increased risk of type II diabetes [27,28].”

What the sources say

• Not checked yetcites [27] 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;3(12):e1001141. doi: 10.1371/journal.pmed.1001141 . source
• Not checked yetcites [28] • Knutsson A, Kempe A. Shift work and diabetes—a systematic review. Chronobiol Int. 2014;31(10):1146–51. doi: 10.3109/07420528.2014.957308 . Review of the evidence linking shift work with risk of diabetes. source

In the paper

“In fact, the impact of altered stressor responses on the quality of sleep may be a critical mediator of emotion regulation [97], resilience to stress [98], and ultimately tolerance for shift work [1].”

What the sources say

• Not checked yetcites [97] • Van Someren EJ, Cirelli C, Dijk DJ, Van Cauter E, Schwartz S, Chee MWL. Disrupted sleep: from molecules to cognition. J Neurosci. 2015;35(41):13889–95. doi: 10.1523/JNEUROSCI.2592-15.2015 . Discussion of the impact of sleep disturbance on cognitive functioning. source
• Not checked yetcites [98] •• Floam S, Simpson N, Nemeth E, Scott-Sutherland J, Gautam S, Haack M. Sleep characteristics as predictor variables of stress systems markers in insomnia disorder. J Sleep Res. 2015;24(3):296–304. doi: 10.1111/jsr.12259 . Study of the relationship between sleep and inflammatory and stress markers. source
• Not checked yetcites [1] Härmä M. Individual differences in tolerance to shiftwork: a review. Ergonomics. 1993;36(1–3):101–9. doi: 10.1080/00140139308967860 . source

In the paper

“Metabolic syndrome and diabetes risk may be further increased by the timing of eating and food digestion being out of sync with peripheral oscillators in the liver [34] and gut [35].”

What the sources say

• Not checked yetcites [34] • Zwighaft Z, Reinke H, Asher G. The liver in the eyes of a chronobiologist. J Biol Rhythm. 2016;31(2):115–24. doi: 10.1177/0748730416633552 . Overview of research on the liver as a model system for circadian rhythms in peripheral organs. source
• Not checked yetcites [35] Schieving LA. Biological clocks and the digestive system. Gastroenterology. 2000;119(2):536–49. doi: 10.1053/gast.2000.9305 . source

In the paper

“Circadian misalignment causes internal desynchronization of the HPA axis [70,71].”

• Also stated in: § Mental Health · plain

  “As described above, circadian misalignment disrupts the internal synchronization of the HPA axis.”

What the sources say

• Not checked yetcites [70] Kalsbeek A, van der Spek R, Lei J, Endert E, Buijs RM, Fliers E. Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis. Mol Cell Endocrinol. 2012;349(1):20–9. doi: 10.1016/j.mce.2011.06.042 . source
• Not checked yetcites [71] Gonnissen HK, Hulshof T, Westerterp-Plantenga MS. Chronobiology, endocrinology, and energy- and food-reward homeostasis. Obes Rev. 2013;14(5):405–16. doi: 10.1111/obr.12019 . source

In the paper

“However, in shift workers, meal times must be altered in accordance with the displaced sleep/wake schedule, which disrupts the coordination between leptin and ghrelin and dysregulates downstream biological systems related to diet, weight, and metabolism.”

In the paper

“However, adverse heart health outcomes seem to be tied not only to shift work and circadian misalignment, but also the presence of psychological and psychosocial stressors [80,81].”

What the sources say

• Not checked yetcites [80] Szosland D. Shift work and metabolic syndrome, diabetes mellitus and ischemic heart disease. Int J Occup Med Environ Health. 2010;23(3):287–91. doi: 10.2478/v10001-010-0032-5 . source
• Not checked yetcites [81] Thomas C, Power C. Shift work and risk factors for cardiovascular disease: a study at age 45 years in the 1958 British birth cohort. Eur J Epidemiol. 2010;156(Pt 6):1661–72. doi: 10.1099/mic.0.037804-0 . source

In the paper

“Sleep displacement and altered meal timing due to shift work also disturb glucose metabolism [25], through mechanisms that have yet to be elucidated.”

What the sources say

• Not checked yetcites [25] Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435–9. doi: 10.1016/S0140-6736(99)01376-8 . source

In the paper

“That said, many studies have reported an association between shift work exposure and increased risk of breast cancer [59,60].”

What the sources say

• Not checked yetcites [59] He C, Anand ST, Ebell MH, Vena JE, Robb SW. Circadian disrupting exposures and breast cancer risk: a meta-analysis. Int Arch Occup Environ Health. 2015;88(5):533–47. doi: 10.1007/s00420-014-0986-x . source
• Not checked yetcites [60] Lin X, Chen W, Wei F, Ying M, Wei W, Xie X. Night-shift work increases morbidity of breast cancer and all-cause mortality: a meta-analysis of 16 prospective cohort studies. Sleep Med. 2015;16(11):1381–7. doi: 10.1016/j.sleep.2015.02.543 . source

In the paper

“Despite the established link between circadian misalignment and hormone regulation related to heart health, the specific mechanisms connecting shift work and CVD remain elusive.”

In the paper

“It has long been recognized that shift work has a negative impact on health and well-being.”

What the sources say

• Not checked yetcites [1] Härmä M. Individual differences in tolerance to shiftwork: a review. Ergonomics. 1993;36(1–3):101–9. doi: 10.1080/00140139308967860 . source
• Not checked yetcites [2] Saksvik IB, Bjorvatn B, Hetland H, Sandal GM, Pallesen S. Individual differences in tolerance to shift work—a systematic review. Sleep Med Rev. 2011;15:221–35. doi: 10.1016/j.smrv.2010.07.002 . source

In the paper

“Shift work-related metabolic dysfunction and the various health consequences thereof, including obesity, metabolic syndrome, and type II diabetes (discussed above), also potentiate the development of CVD [88,89].”

What the sources say

• Not checked yetcites [88] Puttonen S, Härmä M, Hublin C. Shift work and cardiovascular disease-pathways from circadian stress to morbidity. Scand J Work Environ Health. 2010;36(2):96–108. doi: 10.5271/sjweh.2894 . source
• Not checked yetcites [89] Burgueno A, Genna C, Gianotti TF, Sookoian S, Pirola CJ. Increased levels of resistin in rotating shift workers: a potential mediator of cardiovascular risk associated with circadian misalignment. Atherosclerosis. 2010;210:625–9. doi: 10.1016/j.atherosclerosis.2009.12.032 . source

In the paper

“Night shift work has also been found to increase the risk of other cancers, including lung, colon, bladder, prostate, rectal, and pancreatic cancer as well as non-Hodgkin’s lymphoma [61,62,63].”

What the sources say

• Not checked yetcites [61] Erren TC, Pape HG, Reiter RJ, Piekarski C. Chronodisruption and cancer. Naturwissenschaften. 2008;95:367–82. doi: 10.1007/s00114-007-0335-y . source
• Not checked yetcites [62] Parent M, El-Zein M, Rousseau M, Pintos J, Siemiatycki J. Night work and risk of cancer among men. Am J of Epidemiol. 2012;176(9):751–9. doi: 10.1093/aje/kws318 . source
• Not checked yetcites [63] Rao D, Yu H, Bai Y, Zheng X, Xie L. Does night-shift work increase the risk of prostate cancer? A systematic review and meta-analysis. Onco Targets Ther. 2015;8:2817–26. doi: 10.2147/OTT.S89769 . source

In the paper

“Although moderators such as diet, exercise, and body weight are important, the evidence of a general connection between shift work and poor metabolic health is strong.”

In the paper

“Indeed, research findings regarding shift work and cancer have been mixed.”

In the paper

“If findings from laboratory sleep restriction studies generalize to shift work, then this may be expected to promote weight gain through enhanced appetite for calorie-dense foods with high carbohydrate content [20], consumption of food at night, and increased caloric intake overall [21].”

What the sources say

• Not checked yetcites [20] Spiegel K, Tasali E, Penev P, Van Cauter E. Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004;141:846–50. source
• Not checked yetcites [21] Spaeth AM, Dinges DF, Goel N. Effects of experimental sleep restriction on weight gain, caloric intake, and meal timing in healthy adults. Sleep. 2013;36(7):981–90. doi: 10.5665/sleep.2792 . source

In the paper

“Dysfunction of the gastrointestinal tract may also explain the significantly higher rate of ulcers in night workers compared to day workers [44], and may have impactful consequences for shift workers’ long-term health.”

What the sources say

• Not checked yetcites [44] Pietroiusti A, Forlini A, Magrini A, Galante A, Coppeta L, Gemma G, et al. Shift work increases the frequency of duodenal ulcer in H pylori infected workers. Occup Environ Med. 2006;63:773–5. doi: 10.1136/oem.2006.027367 . source

In the paper

“Thus, when melatonin is suppressed, naturally occurring DNA damage may accumulate faster than it can be repaired, which may contribute to the increased risk of cancer that has been observed among shift workers [57].”

What the sources say

• Not checked yetcites [57] •• Bhatti P, Mirick DK, Randolph TW, Gong J, Buchanan DT, Zhang JJ, et al. Oxidative DNA damage during sleep periods among nightshift workers. Occup Environ Med. 2016;73(8):537–44. doi: 10.1136/oemed-2016-103629 . Demonstration of the effect of displaced sleep on DNA damage and repair. source

In the paper

“Working at night has been estimated to increase the risk of developing MetS by more than 50% [37].”

What the sources say

• Not checked yetcites [37] Wang F, Zhang L, Zhang Y, Zhang B, He Y, Xie S, et al. Meta-analysis on night shift work and risk of metabolic syndrome. Obes Rev. 2014;15:709–20. doi: 10.1111/obr.12194 . source

In the paper

“However, the health consequences of shift work should first be understood in terms of a fundamental misalignment between the circadian (i.e., near-24-hour) rhythm of the endogenous biological clock and the timing of the sleep/wake cycle [3].”

What the sources say

• Not checked yetcites [3] Kogi K. International research needs for improving sleep and health of workers. Ind Health. 2005;43:71–9. doi: 10.2486/indhealth.43.71 . source

In the paper

“The increased diabetes risk may be further amplified by unhealthy changes in lifestyle associated with shift work (e.g., smoking, alcohol consumption, and lack of exercise) [33].”

What the sources say

• Not checked yetcites [33] Suwazono Y, Sakata K, Okubo Y, Harada H, Oishi M, Kobayasho E, et al. Long-tern longitudinal study on the relationship between alternating shift work and the onset of diabetes mellitus in male Japanese workers. J Occup Environ Med. 2006;48(5):455–62. doi: 10.1097/01.jom.0000214355.69182.fa . source

In the paper

“As many as 20% of shift workers ultimately opt out of shift work due to sleep disturbances and adverse stress reactions [82].”

What the sources say

• Not checked yetcites [82] Tenkanen L, Sjoblom KR, Kalimo R, Alikoski T, Härmä M. Shift work, occupation and coronary heart disease over 6 years of follow-up in the Helsinki Heart Study. Scand J Work Environ Health. 1997;23:257–65. source

In the paper

“This results in competition between the need for sleep and other demands, such as exercise, healthy eating, and personal care. These latter activities are then often done quickly or to a lesser standard (e.g., fast food), or foregone altogether, making it difficult for shift workers to maintain a healthy lifestyle [107].”

What the sources say

• Not checked yetcites [107] • Phiri LP, Draper CE, Lambert EV, Kolbe-Alexander TL. Nurses’ lifestyle behaviours, health priorities and barriers to living a healthy lifestyle: a qualitative descriptive study. BMC Nurs. 2014;13(38):1–11. doi: 10.1186/s12912-014-0038-6 . Study of shift work and other obstacles to a healthy lifestyle in nurses. source

In the paper

“The empirical evidence suggests that circadian misalignment is associated with a range of short- and long-term, negative health outcomes related to metabolic and gastrointestinal health, cancer, heart health, and mental health (see Figure 1).”

In the paper

“The potential for workers to self-select out of shift work causes a systematic confound in population health research known as the “healthy worker effect” [105].”

What the sources say

• Not checked yetcites [105] Knutsson A, Åkerstedt T. The healthy-worker effect: self-selection among Swedish shift workers. Work Stress. 1992;6:163–7. source

In the paper

“Shift work-induced circadian misalignment not only affects sleep and health, it also determines when people can exercise, eat, socialize, and have sex—all factors that support physical and mental health.”

In the paper

“The overarching implication is that the health consequences of shift work may be greater yet than what the available literature would already suggest at face value.”

In the paper

“HPA axis desynchrony due to circadian misalignment, increased exposure to stressors during night work, and reduced access to protective psychosocial factors lead to an increase in long-term adverse health outcomes.”