The influence of daily daytime caffeine intake on human sleep-wake regulation

Caffeine is the most widely consumed natural stimulant in history. While caffeine is commonly used to mitigate sleepiness and to boost performance, it is intentionally avoided to prevent adverse consequences on nocturnal sleep. The latter has been particularly investigated under conditions of acute evening intake. Sleep disrupting effects are mainly attributed to caffeine’s impact on the homeostatic component of sleep-wake regulation as caffeine antagonizes the sleep factor adenosine. This results in delayed sleep onset and superficial sleep. Furthermore, evidence accumulates that acute caffeine intake in the evening impacts also on the circadian axis of sleep-wake regulation by reducing and delaying melatonin secretion, which is the primary endogenous marker of the internal timekeeping system. The overarching aim of the present thesis was to investigate whether these caffeine-induced alterations in the homeostatic and circadian sleep-wake features can also be detected under chronic exposure to caffeine timed to morning and afternoon hours, which presents a common intake pattern in coffee drinkers.
Twenty male young habitual caffeine consumers participated in a double-blind, crossover study comprising a placebo (3 x placebo daily), a caffeine (3 x 150 mg caffeine daily), and a withdrawal (3 x 150 mg caffeine for eight days then change to placebo) condition, each lasting 11 days. After nine days of continuous treatment, volunteers were studied during a 43-h laboratory part under strictly controlled conditions. During scheduled wakefulness, we regularly assessed sleepiness, vigilance performance, and circadian hormonal markers (i.e., melatonin and cortisol) while polysomnography was recorded during scheduled sleep episodes at different times of the day to quantify sleep structure and intensity.
First, we were interested whether daily caffeine intake in the morning and afternoon hours disrupts nighttime sleep structure and intensity, indexed as reduced slow-wave sleep (SWS) duration and decreased slow-wave activity (SWA; 0.75-4.5 Hz). Surprisingly, neither daytime caffeine consumption nor its acute cessation strongly impaired nighttime sleep architecture or subjective sleep quality in comparison to placebo. Nevertheless, during both caffeine and withdrawal conditions spectral power density in the sigma frequencies (12-16 Hz) was reduced, starting 8 and 15 hours after the last caffeine intake in the caffeine and withdrawal condition, respectively. Opposite to the reported higher sigma power after acute caffeine intake in other studies, the observed reduction in the sigma frequencies might point to early signs of caffeine withdrawal which occur as soon as regular caffeine intake is stopped.
Second, we investigated whether daily daytime caffeine intake impacts on circadian hormonal rhythms and wake-promotion as well as waking performance. Interestingly, our results indicate that habitual caffeine consumption in the morning and afternoon hours does not strongly affect the diurnal secretion of melatonin and cortisol nor enhances circadian wake-promotion in the evening. Moreover, in contrast to the common perception of the stimulating properties of caffeine, such a common intake pattern did not go along with clear-cut benefits in sleepiness or vigilance performance when comparing it to the placebo condition. However, the abrupt cessation from caffeine was associated with increased subjective sleepiness, worse vigilance performance, and increased sleep pressure in the evening as indexed by shortened sleep latency, increased total sleep time, and longer SWS. Together, these findings suggest an adaptation after repeated intake, presumably in the homeostatic aspect of sleep-wake regulation, which manifests itself as soon as chronic caffeine intake is ceased. In contrast to previous studies, we did not find evidence for circadian phase shifts.
In a last step, we explored the impact of daily caffeine intake and its acute cessation on circadian-regulated rapid eye movement (REM) sleep promotion in a sleep episode timed to the morning hours. Similar to nighttime sleep, total sleep time, and sleep architecture at this time of day were not strongly affected by caffeine or its withdrawal. Nonetheless, after daily daytime caffeine intake it took volunteers longer to enter REM sleep, its accumulation was slower, and subjective quality of awakening was worse compared to continuous placebo intake. As the latter might be counteracted in turn by caffeine intake, it might encourage caffeine consumption particularly in people who shift their sleep to morning or daytime hours which often occurs in shift-workers.
Taken together, we have first evidence that repeated daytime caffeine intake in the morning and afternoon hours does not strongly disrupt nocturnal sleep nor hormonal markers of the circadian timing system such as the diurnal secretion of melatonin and cortisol. However, daily daytime caffeine intake might still weaken the circadian sleep signal under conditions of strong circadian REM sleep promotion. Moreover, the daily exposure to caffeine bears the risk of developing withdrawal symptoms as early as 8 hours after its last intake, such as increased sleepiness, worse performance, and subtle changes in nighttime sleep. Together these withdrawal-induced alterations point to changes primarily in the homeostatic component of sleep-wake regulation and might be attributed to differences in adenosine signaling. The circadian timekeeping system, however, stays rather stable under conditions of daily daytime caffeine intake. In summary, this thesis provides novel insights into the consequences of daily presence and nightly abstinence of the world’s most popular psychoactive substance on homeostatic and circadian measures of sleep-wake regulation.