Effects of chronic caffeine consumption on sleep and the sleep electroencephalogram in mice

Panagiotou, Maria; Meijer, Michiel; Meijer, Johanna H.; Deboer, Tom

doi:10.1177/0269881118806300

“…There is evidence that consumers develop tolerance to the substance already after several days, such that effects of a particular dose of caffeine, for instance on sleep [17] or alertness [10] become weakened. However, in line with a recent study in animals [18], it has also been shown that continuous hourly caffeine intake over four weeks strengthens circadian wake-promotion, as indicated by a reduced ability to sleep prior to habitual bedtime [19]. Interestingly, timing of melatonin secretion was not shifted by the long-term treatment.…”

Section: Introductionsupporting

confidence: 81%

“…Importantly, based on the absence of a clear-cut shift in circadian timing in the withdrawal condition, it seems unlikely that the participants might have developed tolerance to the phase-shifting effects of the drug. Moreover, recent animal studies on repeated caffeine treatment indicate no [38,41] or only slight [18] caffeine-induced phase delays in locomotor activity under normal light-dark cycles. Taken together the available evidence indicates that the effects of repeated daytime caffeine intake on human circadian timing under entrained conditions seem to be small or absent.…”

Section: Discussionmentioning

confidence: 99%

Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake

Weibel

¹

,

Lin

²

,

Landolt

³

et al. 2019

Preprint

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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 sleepwake regulation.Caffeine, caffeine withdrawal, and sleep-wake regulation

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“…Thus, it seems at first glance in contrast to the reported increases in this frequency range 10 , 21 and the well-known alerting effects after acute caffeine intake 18 . However, during conditions of chronic caffeine intake, mice showed a deeper sleep compared to placebo 33 . Moreover, repeated caffeine intake enhances the sensitivity of adenosine binding 34 presumably due to upregulated adenosine receptors 26 – 28 or changes in the functions of adenosine receptor heteromers 35 .…”

Section: Discussionmentioning

confidence: 89%

The impact of daily caffeine intake on nighttime sleep in young adult men

Weibel

¹

,

Lin

²

,

Landolt

³

et al. 2021

Sci Rep

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Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12–16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.

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“…18 However, during conditions of chronic caffeine intake, mice showed a deeper sleep compared to placebo. 47 Moreover, repeated caffeine intake enhances the sensitivity of adenosine binding 48 presumably due to increased adenosine plasma levels, 38 upregulated adenosine receptors [39][40][41][42] or changes in the functions of adenosine receptor heteromers. 49 These neuronal alterations in the adenosinergic system might drive the commonly observed changes in the homeostatic sleep-wake regulation such as increased sleepiness when caffeine intake is suddenly ceased.…”

Section: Discussionmentioning

confidence: 99%

The impact of daily caffeine intake on nighttime sleep: signs of overnight withdrawal?

Weibel

¹

,

Lin

²

,

Landolt

³

et al. 2020

Preprint

View full text Add to dashboard Cite

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 x 150 mg caffeine daily), withdrawal (3 x 150 mg caffeine for eight days, then switch to placebo), and placebo (3 x placebo daily). After nine days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture, nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement (NREM) sleep was reduced in both caffeine and withdrawal conditions when compared to placebo.These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure or subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day. Statement of SignificanceCaffeine consumption is highly prevalent worldwide and has been repeatedly shown to acutely disrupt sleep, particularly when consumed after several days of abstinence or close to bedtime.However, commonly, caffeine is consumed daily and during daytime. Our well-controlled laboratory study revealed that this common pattern of intake affects nighttime sleep differently:While slow-wave sleep duration or slow-wave activity were rather similar compared to placebo, caffeine intake surprisingly reduced EEG power density in the sigma frequencies. In the light of earlier studies, this might present early signs of caffeine withdrawal which occurs due to overnight caffeine abstinence. The present findings provide novel insights into the impact of daily presence and nightly abstinence of caffeine on nighttime sleep in regular consumers.

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Effects of chronic caffeine consumption on sleep and the sleep electroencephalogram in mice

Cited by 25 publications

References 49 publications

Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake

Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake

The impact of daily caffeine intake on nighttime sleep in young adult men

The impact of daily caffeine intake on nighttime sleep: signs of overnight withdrawal?

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