Influence of Caffeine Consumption on the Human Circadian System
Condition: Caffeine; Caffeine Withdrawal; Sleep; Circadian Rhythm
Study type: Interventional

Summary: 
      Surveys indicate that 85% of the adult population consume caffeine on a daily basis. Caffeine
      acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and
      how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly
      unexplored. This study quantifies the influence of regular caffeine intake and its cessation
      on circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being,
      neurobehavioral performance and associated cerebral mechanisms. The knowledge is expected to
      contribute important insights on recent societal changes in sleep-wake behavior (e.g.,
      shorter sleep duration and delayed sleep phase) and the related increase in people suffering
      from sleep problems.
    

Detailed description: 
      Surveys indicate that 85% of the adult population consume caffeine, often on a daily basis.
      Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine.
      Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness
      is fairly unexplored. The circadian timing system promotes wakefulness at the end of the
      biological day ("wake maintenance zone") and promotes sleep after the onset of the endogenous
      melatonin secretion ("opening of sleep gate"). There is mounting evidence that circadian and
      sleep homeostatic mechanisms continuously interact at the neurobehavioral, hormonal and
      cerebral level. Furthermore, earlier evidence has shown that the strength of circadian
      wake-promotion and the timing of circadian rhythmicity differs according to a genetic
      predisposition in the adenosinergic system. Thus, it was assumed that the daily consumption
      of caffeine may substantially impact on both circadian and homeostatic sleep-wake processes
      at different systemic levels.

      This study aimed at quantifying the influence of regular caffeine intake and its cessation on
      circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being,
      neurobehavioral performance and associated cerebral mechanisms. Specifically, the study
      investigated the effects of sleep-wake regulatory adaptations to regular caffeine consumption
      and acute caffeine cessation a) on night-time sleep structure and sleep intensity
      (electroencephalography, EEG), b) on circadian wake-promotion (nap sleep during the
      biological day) and circadian timing of hormonal rhythms, and c) on waking quality, as
      indexed by subjective ratings, objective measures of neurobehavioral performance, and
      cerebral mechanisms (EEG and functional magnetic resonance imaging [MRI]).

      Twenty young healthy regular caffeine consumers were examined in a double-blind,
      placebo-controlled within-subjects design with three conditions: Regular caffeine intake,
      regular placebo intake, and cessation of regular caffeine intake. In the laboratory,
      circadian sleep-wake promotion was assessed by combining EEG and multimodal MRI techniques.
      Circadian timing was assessed by salivary melatonin and cortisol rhythms. Sleep and waking
      quality were quantified by continuous polysomnography (during sleep at night and during a nap
      in the evening), waking EEG, subjective ratings (sleepiness, mood, craving, withdrawal
      symptoms) and cognitive performance (vigilance and working memory). Each of the three
      laboratory parts lasted more than 40 h under strictly controlled conditions (i.e., dim light,
      constant ambient temperature etc.). Subsequent to each laboratory condition, actimetry and
      sleep diaries served to assess sleep- and waking patterns in the field under caffeine vs.
      placebo conditions.

      The aim was to substantially advance the knowledge about the impact of the commonly
      encountered caffeine consumption on the sleep-wake regulatory system. Furthermore, the
      project was intended to substantially contribute to the understanding of complex interplay
      between sleep-wake regulatory mechanisms in response to acute or long-term changes in the
      adenosinergic system.
    

Intervention name(s): Caffeine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 150 mg caffeine, 3 times/day (wakeup + 45 min, +255 min, and +475 min); Mannitol, 3 times/day (wakeup + 45 min, +255 min, and +475 min)
Other intervention name(s): Mannitol
Intervention MeSH terms: Mannitol; Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The project adopted a double blind, placebo-controlled, randomized within-subjects design. Screenings took place at the Centre for Chronobiology at the Psychiatric University Hospital Basel (UPK, single center). Data collection took place at Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital of Basel. Each participant went through three study sessions, i.e. caffeine, placebo, withdrawal. Each of the session consisted of 9 days of pre-ambulatory part, 2 days of laboratory visit, and 7 days of post-ambulatory part.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Caffeine; Withdrawal; Sleep; Circadian rhythm