Sunday, April 19, 2015

Shift Work, an Overlooked Motor of the Diabesity Epidemic? Revisiting the Impact of Continuous and Sporadic Shift and Night Work on Belly Size, Trigs and Glucose Control

Stress at work only adds to the ill effects of shift work and night shifts will have on the health, body composition and life quality of  people who work when they're supposed to sleep.
You will probably remember the problems arising from shift work from the Circadian Rhythm Series. In said articles I did yet only scratch the surface of an underestimated problem that may ironically make (among others) those sick who are responsible for the well-being of us all: Nurses, doctors, flight controllers, etc.

The effects, this appears to be certain by now, can be triggered by both, irregular sleeping and eating patterns, and they relate to changes in melatonin, cortisol, ghrelin, and leptin. Changes with consequences that reach from the nasty but usually unproblematic ability to shed those last lbs of body fat covering your abs to cancer and death.
Even if you don't work shifts, melatonin may be a supplement to consider!

Melatonin as potent as Letrozole

Melatonin for Bone & Tooth Health

M. Sleep Aid W/ Anti-Alzheimer's Effect

Melatonin vs. Fructose Overloads

Melatonin as Anabolic On-Switch

M. Anti-Alzheimer + Anti-Body Fat Agent
You're asking yourself why this is a SuppVersity topic? Well with an estimated 20% of the economically active population in North America and Europe being engaged in some type of shifts involving night work (Harrington. 2001), it is very likely that a similar percentage of the visitors of this website are affected, too. And still, one thing that may distinguish the average SuppVersity reader on night shifts from the rest of the pack (hopefully) is that he or she does not share the same unhealthy lifestyle habits, such as smoking, poor diet, and sedentarism Costa et al. (2003) observed in their analysis of the lifestyle habits of in their 2003 study.

Overall, it is a complex mix of direct and indirect interrelationship of social problems and aspects related to misalignment of biological rhythms experienced by shift workers predisposes them to a number of deleterious health effects.
  • Figure 1: Especially older men & women and former smokers on shift work have a sign. increased abdominal obesity risk (Van Amelsvoort. 1999)
    Studies show that overweight and obesity are more prevalent in shift and night workers than day workers (Van Amelsvoort. 1999).
  • Shift and night work have been associated with increased risk of developing other metabolic disorders.
  • Shift and night workers are more likely to suffer from as insulin resistance, diabetes, dyslipidemias, and metabolic syndrome (Ulhôa. 2015).
  • And many shift and night workers suffer from an alteration in food intake (Esquirol. 2009; Crispim. 2012).
As Ulhôa et al. point out in a recently published review of the literature, a disruption of the circadian rhythm we've evolved as a means of adapting to environmental changes is an important motor of the endocrine abnormalities which are at the heart of many if not all of the previously listed health problems:
"The expression of biological rhythms takes place via interactions between central and peripheral endogenous molecular mechanisms, which enable the organism to adapt to changes in the external environment [24]. Circadian rhythms are aligned with periodic environmental events such as the light-dark cycle. In addition, circadian rhythms are interlinked; that is, there is a coupling of endogenous rhythms. These synchronized internal mechanisms ensure that all the physiological and behavioral rhythms occur in a coordinated fashion during the 24-hour cycle. This implies that the health of individuals whose timing between biological rhythms and environmental cycles is not kept in balance can be affected. Desynchronization is defined as a change in the relationship of phases between two or more rhythms, a situation that can have a number of deleterious effects on health" (Ulhôa. 2015).
As you will know, the main synchronizing agent of the central biological clocks in the control of circadian rhythms is the alternation between the light and dark cycle. Luminosity information is conveyed to the Central Nervous System (CNS) via the retinohypothalamic tract (Cipolla‐Neto. 2014), where melanopsin plays the role of key photoreceptor in this process.

Consequences of the absence or reduction in melatonin production. The consequences are of two types: those related to the metabolism leading to insulin resistance, glucose intolerance and dyslipidemia and those related to circadian synchronization of metabolic processes leading to chronodisruption (Cipolla‐Neto. 2014).
Driven by the light-dark cycle, the CNS orchestrates the circadian rhythms of many behaviors, tissues, hormones, and genes, as well as other physiological processes. In recent decades, studies have shown that molecular mechanisms occur in cells of peripheral tissues autonomously and that their circadian rhythms persist in vitro.

The synchronizers of peripheral clocks (located in organs, tissues, and cells) are neurohumoral factors such as glucocorticoids and melatonin, as well as social rhythms such as feeding and work times.

Biological rhythms modulate practically all physiological processes of mammals where circadian control over the endocrine system has been shown to be of vital importance. However, alterations in alignment of environmental cycles with rhythms of the organism may induce alterations in the complex mechanism of hormonal and metabolic timing.
This article may make shift work sound worse than it actually is, mostly because the data cited is based on "average Joes & Janes" who do not work out, make sure they get enough quality sleep, don't use blindfolds and ear-plugs to make the most of their daytime sleep, don't give a shit about what they eat and (ab)use cigarettes and snacks to keep awake during their shifts. Since I assume you are way above average, your personal risk is probably going to be much lower than that of the average shift worker.
Among permanent night workers, less than 3% exhibited complete circadian adjustment (Folkard. 2008), revealing that the majority of these workers experience misalignment of biological rhythms and its deleterious effects. While most of the abnormalities of the circadian rhythm are related to the circadian hormone melatonin, their real-world effects on our health are mediated by various hormones:

  • Cortisol - modulator #1 - It is well-accepted that there is a causal link between shift work and a messed up cortisol rhythm which should be characterized by a steep incline in cortisol in the AM and a progressive decline of the stress hormone from AM to PM (learn more).

    In a laboratory-based study showed that subjects whose usual 12-hour sleep pattern was inverted from night to day experienced misalignment and inversion of their circadian rhythm.
    "Circadian misalignment, when subjects ate and slept ≈12 h out of phase from their habitual times, systematically decreased leptin (−17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (−20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state" (Scheer. 2009).
    The authors implicated this effect as the cause for the glucose increase and cardiometabolic consequences that occur acutely in jetlag and chronically in shift work (Scheer. 2009). These circadian rhythms changes, including alterations in cortisol expression, have been associated with the development of cardiovascular diseases and cancer (Machi. 2012). A pertinent question raised by the academic community concerns the type of shift that would be less harmful to workers’ health.
    Figure 2: Continuous vs. rotating types of shift work affect the cortisol rhythm differently (Wong. 2012).
    While all four, regular and irregular night and rotating shifts change cortisol level as compared to a daytime work schedule, night shifts are generally more strongly associate with stressors at the work place with regular shift work having a more pronounced effect on the cortisol rhythm (e.g. full suppression of AM rise in cortisol | Ulhôa. 2011). In spite of that, the study by Wang et al. (2012 | cf. Figure 2) suggests that rotating shift works have a more pronounced ill effect on endothelial function than continuous shift work.

    It is yet not just the continuity that matters. Ulhôa et al. point out in their previously cited 2015 review of the literature, most individuals who work very early mornings (morning shift) have partial sleep deprivation, obesity, and low morning cortisol concentration compared to those who work the afternoon shift. They also highlight that "[c]ircadian rhythm misalignment, including alteration in cortisol expression, is further aggravated in the presence of job strain" (Ulhôa. 2015). In that, work stress and sleep loss synergize and maximize the alterations in cortisol rhythm, "[t]herefore, it can be asserted that endocrine alterations are influenced by shift work, sleep, or circadian system changes or by a combination of these factors" (Ulhôa. 2015).
  • Diet and triglyceride metabolism - modulator #2 - Besides the well-known risks, such as poor diet and sedentarism, shift and night work have been similarly associated with weight gain, one of the central features and driving motors of obesity. In their previously cited review Ulhôa et al. report that "[e]pidemiologic evidence shows that shift and night work are associated with elevated risk of metabolic disorders, perhaps as a result of poor physiological adaptation to sleep loss, leading to chronic sleepiness and feeding at unfavorable circadian times, which in turn contribute to chronic circadian misalignment" (Ulhôa. 2015). In that, not all the negative affects are triggered by circadian misalignment.
    Figure 3: Nigh time (squares) eating / snacking is associated with increased triacylglycerol levels (left) and worsened glucose clearance and insulin sensitivity (right | Al-Naimi. 2004)
    People who work on shifts or do night work have fewer opportunities to practice physical activity, they exhibit a reduced meal frequency and consume more snacks (according to Kroencke et al. the increased snack intake adds an average of 200-300kcal, mostly from "junk", to the shift workers diets | probably a result of messed up leptin and ghrelin levels specifically in those who switch back and forth between night and day shifts; cf. Fogteloo. 2003; Scheer. 2009; Marqueze. 2013). In addition, scientists have found that both, the quality and quantity of foods consumed, suffers and increases respectively.

    Next to these behavioural influence, the nocturnal decline in digestive efficacy (Al-Naimi. 2004), the already increased trigylceride levels (our biological rhythm dictates higher levels at night than during the day; this is because we'd need them during sleep to fuel our energetic demands | Al-Naimi. 2004; Holmbäck. 2003). Since high triglycerides inhibit the uptake of glucose and in view of the fact that night-time eating triggers a greater response of triacylglycerol compared to day-time eating, it is no wonder that night time workers exhibit a blunted insulin sensitivity. Due to the elevated insulin and triglyceride levels body fat storage kicks in and it is only a question of weeks or months before the effects will become visible on the scale and in the mirror. 
  • Insulin resistance and full-blown diabetes - modulator #3 - While I did already touch on the triglyceride driven reduction in insulin sensitivity with modulator #2, the "trigs" are not the only contributor to an increase in insulin resistance in shift workers.

    There is also a direct reduction in GLUT4 glucose transporter expression, which would normally be sustained by melatonin. The impact of reduced GLUT4 expression could also explain that laboratory-based experiments have shown that individuals who sleep outside normal times have reduced sensitivity to insulin, without a commensurate increase in insulin secretion (Leproult. 2014).  With often chronically elevated insulin levels, it's also no wonder that the risk of a high β-cell activity was increased almost threefold in shift workers who work at night and very early shift.
    Figure 4: Relative risk of developing type II diabetes in shift workers according to age (Ika. 2013).
    In conjunction with the severe circadian misalignment, the downstream effects of shift work are thus significant promoters of the development of diseases such as insulin resistance and diabetes, independently of factors such as job strain and physical activity. In fact, previous studies have suggested a twofold greater risk for developing type 2 diabetes mellitus (Figure 4 | Ika. 2013 | see Figure 4), as well as poor glycemic control among shift workers compared to nonshift workers. Interstingly, though, no clear association, however, was observed between seasonal shift work and diabetes mellitus. 
This is how your melatonin levels should look like (Altun. 2007). By supplementing you may partly restore the normal ups and downs even if you're working night shifts.
As you can see, the link between shift work, obesity and chronic disease is complex too complex to actually believe that the mere ingestion of a melatonin supplement 30min to 1h before you go to bed would counter all the negative effects of chronic and/or temporary shift work / night shifts. What you can expect from 3-5mg is yet an improvement in your ability to fall asleep (Sadeghniiat-Haghighi. 2008), improved daytime sleep and night alertness (in night workers | Jorgensen. 1998), and - assuming you don't take the unphysiological time-release preparations no hangovers (Sharkey. 2001)... ah, and yes, melatonin may also help with the increased cancer risk I discussed in previous articles about melatonin | Comment on Facebook!
  • Al-Naimi, S., et al. "Postprandial metabolic profiles following meals and snacks eaten during simulated night and day shift work." Chronobiology international 21.6 (2004): 937-947.
  • Altun, A., and B. Ugur‐Altun. "Melatonin: therapeutic and clinical utilization." International journal of clinical practice 61.5 (2007): 835-845.
  • Cipolla‐Neto, J., et al. "Melatonin, energy metabolism, and obesity: a review." Journal of pineal research 56.4 (2014): 371-381.
  • Costa, Giovanni, Claudia Roberta de Castro Moreno, and Lúcia Rotenberg. "Saúde e trabalho em turnos e noturno." Trabalho em turnos e noturno na sociedade 24 horas. Atheneu, 2003. 79-98.
  • Crispim, Cibele Aparecida, et al. "Adipokine levels are altered by shiftwork: a preliminary study." Chronobiology international 29.5 (2012): 587-594.
  • Esquirol, Yolande, et al. "Shift work and metabolic syndrome: respective impacts of job strain, physical activity, and dietary rhythms." Chronobiology international 26.3 (2009): 544-559.
  • Fogteloo, A. J., et al. "Impact of meal timing and frequency on the twenty-four-hour leptin rhythm." Hormone research 62.2 (2003): 71-78.
  • Folkard, Simon. "Do permanent night workers show circadian adjustment? A review based on the endogenous melatonin rhythm." Chronobiology international 25.2-3 (2008): 215-224.
  • Harrington, J. Malcolm. "Health effects of shift work and extended hours of work." Occupational and Environmental medicine 58.1 (2001): 68-72.
  • Holmbäck, Ulf, et al. "Endocrine responses to nocturnal eating–possible implications for night work." European journal of nutrition 42.2 (2003): 75-83.
  • Ika, K., et al. "Shift work and diabetes Mellitus among male workers in Japan: does the intensity of shift work matter?" Acta Medica Okayama 67 (2013):9-23.
  • Jorgensen, K. Michael, and Michael D. Witting. "Does exogenous melatonin improve day sleep or night alertness in emergency physicians working night shifts?." Annals of emergency medicine 31.6 (1998): 699-704.
  • Leproult, R., Holmbäck, H., Van Cauter E. "Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss." Diabetes (2014).
  • Machi, Mari S., et al. "The relationship between shift work, sleep, and cognition in career emergency physicians." Academic Emergency Medicine 19.1 (2012): 85-91.
  • Marqueze, Elaine Cristina, Melissa Araújo Ulhôa, and Claudia Roberta de Castro Moreno. "Effects of irregular-shift work and physical activity on cardiovascular risk factors in truck drivers." Revista de Saúde Pública 47.3 (2013): 497-505.
  • Sadeghniiat-Haghighi, Khosro, et al. "Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial." Journal of circadian rhythms 6.1 (2008): 10.
  • Scheer, Frank AJL, et al. "Adverse metabolic and cardiovascular consequences of circadian misalignment." Proceedings of the National Academy of Sciences 106.11 (2009): 4453-4458.
  • Sharkey, Katherine M., Louis F. Fogg, and Charmane I. Eastman. "Effects of melatonin administration on daytime sleep after simulated night shift work." Journal of sleep research 10.3 (2001): 181-192.
  • Ulhôa, Melissa Araújo, et al. "When does stress end? Evidence of a prolonged stress reaction in shiftworking truck drivers." Chronobiology international 28.9 (2011): 810-818.
  • Ulhôa, M. A., et al. "Shift Work and Endocrine Disorders." International Journal of Endocrinology 2015 (2015).
  • Van Amelsvoort, L. G., E. G. Schouten, and F. J. Kok. "Duration of shiftwork related to body mass index and waist to hip ratio." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 23.9 (1999): 973-978.
  • Wong, Imelda S., et al. "Job strain and shift work influences on biomarkers and subclinical heart disease indicators: a pilot study." Journal of occupational and environmental hygiene 9.8 (2012): 467-477.