PT  - JOURNAL ARTICLE
AU  - Janine Weibel
AU  - Yu-Shiuan Lin
AU  - Hans-Peter Landolt
AU  - Corrado Garbazza
AU  - Vitaliy Kolodyazhniy
AU  - Joshua Kistler
AU  - Sophia Rehm
AU  - Katharina Rentsch
AU  - Stefan Borgwardt
AU  - Christian Cajochen
AU  - Carolin Reichert
TI  - Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake
AID  - 10.1101/641480
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 641480
4099  - http://biorxiv.org/content/early/2019/05/19/641480.short
4100  - http://biorxiv.org/content/early/2019/05/19/641480.full
AB  - To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, it is unknown whether such a regular intake pattern affects timing and quality of wakefulness, as regulated by an interplay of circadian and sleep-homeostatic mechanisms. Thus, we investigated the effects of daily caffeine intake and its withdrawal on circadian rhythms and wake-promotion in 20 male young habitual caffeine consumers. We applied a double-blind, within-subject design with a caffeine (150 mg, 3 x daily), a placebo, and a withdrawal condition each lasting ten days. Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep, as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h under controlled laboratory conditions. Neither the time course of melatonin (i.e., onset, amplitude, or area under the curve) nor the time course of cortisol were significantly affected by caffeine intake or its withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses, as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both, placebo and caffeine conditions. Thus, the typical timing of habitual caffeine intake in humans may not necessarily shift circadian phase nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.