Rachel R. Markwald

Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain

Insufficient sleep is associated with obesity, yet little is known about how repeated nights of insufficient sleep influence energy expenditure and balance. We studied 16 adults in a 14- to 15-d-long inpatient study and quantified effects of 5 d of insufficient sleep, equivalent to a work week, on energy expenditure and energy intake compared with adequate sleep. We found that insufficient sleep increased total daily energy expenditure by ∼5%; however, energy intake—especially at night after dinner—was in excess of energy needed to maintain energy balance. Insufficient sleep led to 0.82 ± 0.47 kg (±SD) weight gain despite changes in hunger and satiety hormones ghrelin and leptin, and peptide YY, which signaled excess energy stores. Insufficient sleep delayed circadian melatonin phase and also led to an earlier circadian phase of wake time. Sex differences showed women, not men, maintained weight during adequate sleep, whereas insufficient sleep reduced dietary restraint and led to weight gain in women. Our findings suggest that increased food intake during insufficient sleep is a physiological adaptation to provide energy needed to sustain additional wakefulness; yet when food is easily accessible, intake surpasses that needed. We also found that transitioning from an insufficient to adequate/recovery sleep schedule decreased energy intake, especially of fats and carbohydrates, and led to −0.03 ± 0.50 kg weight loss. These findings provide evidence that sleep plays a key role in energy metabolism. Importantly, they demonstrate physiological and behavioral mechanisms by which insufficient sleep may contribute to overweight and obesity.

Effects of caffeine on the human circadian clock in vivo and in vitro

Caffeine delays the human circadian clock and affects cellular timekeeping through an adenosine receptor–dependent mechanism. Your daily drug resets your clock Your morning cup of coffee may be shifting your circadian clock. Burke et al. show that caffeine—widely available, legal, and psychoactive—inserts a delay into the ~24-hour metabolic rhythm that keeps your body running in time with the world. In a sensitive, within-subject experimental design, five people were kept under highly controlled conditions for 49 days. Before bedtime, they were given various treatments: either a double-espresso caffeine dose, exposure to bright or dim light, or a placebo. The caffeine delayed their internal clock by 40 min, a shift about half as long as bright light, a stimulus known to robustly lengthen the circadian phase. The authors used cultured cells to determine that the drug acted directly on the adenosine receptor, which increases the intracellular messenger molecule cyclic AMP. The fact that cyclic AMP forms a key cog in the inner workings of the clock links caffeine’s biochemical effects to its delay of the circadian rhythm. Not only do these results reinforce the common advice to avoid caffeine in the evening, but they also raise the intriguing possibility that caffeine may be useful for resetting the circadian clock to treat jet lag induced by international time zone travel. Caffeine’s wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. We show that evening caffeine consumption delays the human circadian melatonin rhythm in vivo and that chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro, primarily with an adenosine receptor/cyclic adenosine monophosphate (AMP)–dependent mechanism. In a double-blind, placebo-controlled, ~49-day long, within-subject study, we found that consumption of a caffeine dose equivalent to that in a double espresso 3 hours before habitual bedtime induced a ~40-min phase delay of the circadian melatonin rhythm in humans. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3 hours of evening bright light (~3000 lux, ~7 W/m2) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of the circadian period by caffeine. By pharmacological dissection and small interfering RNA knockdown, we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, was sufficient to account for caffeine’s effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine influenced a core component of the cellular circadian clock. Together, our findings demonstrate that caffeine influences human circadian timing, showing one way that the world’s most widely consumed psychoactive drug affects human physiology.

Combination of light and melatonin time cues for phase advancing the human circadian clock.

STUDY OBJECTIVES Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. DESIGN Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. SETTING Sleep and chronobiology laboratory environment free of time cues. PARTICIPANTS Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). RESULTS Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. CONCLUSION Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity

Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration.

Circadian Misalignment and Sleep Disruption in Shift Work: Implications for Fatigue and Risk of Weight Gain and Obesity

The interplay of circadian timing and metabolic physiology represents a new frontier in biomedical research. Emerging evidence from animal models indicates that circadian physiology impacts weight gain, including the observation of obesity in clock gene mutants and most recently the finding that food intake restricted to the habitual sleep time of mice leads to weight gain as compared to the same amount of food intake during the normal wake episode. Eating at night is common in work schedules with long work hours and with work operations during the nighttime hours (e.g., health care, emergency response, security personnel) and in circadian sleep disorders including, but not limited to, shift work disorder. Shift work and shift work disorder are associated with circadian misalignment, sleep disruption, and fatigue, all of which may contribute to weight gain and obesity via the modification of feeding hormones and perhaps total daily energy expenditure. Future research is needed to explore the impact of circadian misalignment/sleep disruption and the resulting fatigue on metabolic physiology in shift workers, the mechanisms underlying this association and to develop effective countermeasures to promote shift worker health and well-being.

Performance of a Portable Sleep Monitoring Device in Individuals with High Versus Low Sleep Efficiency.

STUDY OBJECTIVES Portable and automated sleep monitoring technology is becoming widely available to consumers, and one wireless system (WS) has recently surfaced as a research tool for sleep and sleep staging assessment outside the hospital/laboratory; however, previous research findings indicate low sensitivity for wakefulness detection. Because difficulty discriminating between wake and sleep is likely to affect staging performance, we sought to further evaluate the WS by comparing it to the gold-standard polysomnography (PSG) and actigraphy (ACT) for overall sleep/wakefulness detection and sleep staging, within high and low sleep efficiency sleepers. METHODS Twenty-nine healthy adults (eight females) underwent concurrent WS, PSG, and ACT assessment in an overnight laboratory study. Epoch-by-epoch agreement was determined by comparing sleep/wakefulness decisions between the WS to both PSG and ACT, and for detection of light, deep, and rapid eye movement (REM) sleep stages between the WS and PSG. RESULTS Sensitivity for wakefulness was low (40%), and an overestimation of total sleep time and underestimation of wake after sleep onset was observed. Prevalence and bias adjusted kappa statistic indicated moderate-to-high agreement between the WS and PSG for sleep staging. However, upon further inspection, WS performance varied by sleep efficiency, with the best performance during high sleep efficiency. CONCLUSIONS The benefit of the WS as a sleep monitoring device over ACT is the ability to assess sleep stages, and our findings suggest this benefit is only realized within high sleep efficiency. Care should be taken to collect data under conditions where this is expected.

A Sleep Primer for Military Psychologists

This chapter was designed to familiarize psychologists and other mental health professionals working in military settings with key issues and lines of research regarding the role of sleep in the US armed forces. The first section of the chapter provides an overview of sleep regulating physiology and processes, which features the two-process model, and then includes a discussion of the stages and assessment of sleep. The second section of the chapter discusses the clinical impact of sleep on physiological and mental health. The third section reviews applied research investigating the role of sleep in the performance of military duties in operational/field settings such as aviation, ground, and maritime warfare environments. The chapter concludes with a discussion of sleep health across research, clinical, and operational milieu.