Neurotransmisores

Abstract

Objectives:

To explore the relationship between plasma concentrations of caffeine and subjective and polysomnographic measures of sleep in both good sleeper controls (GSC) and individuals with primary insomnia (PI), following the consumption of low-moderate quantities of caffeine in the home environment.

Methods:

65 PI and 29 GSC, each consuming < 4 four coffee cup equivalents of caffeine daily, were recruited. Subjects completed a diary detailing sleep habits and caffeine consumption, one night of polysomnography, and a blood sample for measurement of plasma caffeine and its metabolites at bedtime. Plasma concentrations of caffeine, its primary metabolite, paraxanthine, and other metabolites were determined for each subject and correlated with self-report and polysomnographic measures.

Results:

No statistically significant differences were found between GSC and PI with respect to number of caffeinated beverages consumed (p = 0.91), estimated absolute caffeine ingestion (p = 0.48), time of caffeine consumption (p = 0.22), or plasma concentrations of caffeine (p = 0.92) or paraxanthine (p = 0.88). Significant correlations were found between plasma concentrations of caffeine/paraxanthine and endorsed caffeine intake (r = 0.58, p < 0.05) and estimated absolute caffeine ingestion (r = 0.57, p < 0.05). Plasma caffeine/paraxanthine was significantly correlated with percent stage 1 sleep (r = 0.32, p < 0.05). However, plasma concentrations of caffeine/paraxanthine were not significantly correlated with other subjective or polysomnographic measures of sleep disturbance in either GSC or PI.

Conclusions:

These data suggest that low-moderate amounts of caffeine consumed in the home environment, and mostly during morning hours, have little effect on subjective or polysomnographic measures of sleep in GSC or PI.

Citation:

Youngberg MR; Karpov IO; Begley A; Pollock BG; Buysse DJ. Clinical and physiological correlates of caffeine and caffeine metabolites in primary insomnia. J Clin Sleep Med 2011;7(2):196-203.

Keywords: Insomnia, caffeine, paraxanthine, xanthine, metabolite

Insomnia is one of the most commonly encountered complaints in medical practice. Insomnia is characterized by sleep disturbances such as long sleep onset latency, or frequent awakenings, and daytime consequences such as mood disturbance, cognitive impairment, fatigue, and an overall reduction in perceived quality of life.1,2 Epidemiological evidence indicates that 33% of the general population experience at least one symptom of insomnia, and about 6% have a specific insomnia diagnosis.3 Nearly 90% of the American population regularly consumes caffeine, a methylated xanthine which may both disrupt sleep and increase alertness in the setting of poor or insufficient sleep.4 Despite this, the degree to which regular daily doses of caffeine, individual differences in metabolism, and individual variations in pharmacodynamic sensitivity to the effects of caffeine on sleep in good sleepers or those with insomnia remains poorly defined.

Caffeine is one of the most widely used drugs in the world, found most commonly in coffee and tea, but also in hundreds of sodas, energy drinks, and snacks. The ability of caffeine to enhance mood, arousal, and improve attention is widely recognized.5 For example, a recent study demonstrated that caffeine improves simple reaction time, numeric working memory, and sentence verification accuracy. These improvements occur in both habitual caffeine users as well as abstainers, strengthening the hypothesis that the effects of caffeine occur independently of habitual use by the individual.6 Caffeine is frequently self-administered to attenuate the effects of mental fatigue and daytime sleepiness through interactions with physiological sleep regulatory processes. For example, caffeine's ability to suppress somnolence is directly related to the time of administration and the status of the subject's concomitant homeostatic sleep drive.7 Caffeine exerts a greater effect during periods of prolonged sleep deprivation than during a period of rested wakefulness.

BRIEF SUMMARY

Current Knowledge/Study Rationale: Caffeine disrupts objective measures of sleep in controlled laboratory studies of adults, but less is known about caffeine-sleep relationships with habitual use in the home environment. The aim of this study was to examine the relationships between plasma caffeine levels and objective sleep measures in adults with chronic insomnia or good sleep.

Study Impact: Caffeine and xanthine plasma levels in the evening were significantly related to reported caffeine intake, but were not related to sleep measures in insomnia or good sleeper groups. Low to moderate amounts of caffeine may not be a major source of sleep disruption among individuals with chronic insomnia.

The biochemical basis of caffeine's effects lies in its ability to antagonize adenosine A1 and A2A receptors in the cholinergic basal forebrain and ventrolateral pre-optic nucleus of the hypothalamus, respectively.8,9 In this manner, caffeine functions to block the brain's recognition of a key chemical indicator of prolonged wakefulness and mental fatigue, adenosine, in areas of the brain involved with sleep-wake regulation.

Caffeine administration also alters physiologic markers of sleep in a variety of experimental paradigms. Acute administration of caffeine mimics the symptoms and polysomnographic (PSG) correlates of insomnia, including increased sleep onset latency and reduced sleep efficiency.10–12 Caffeine administration attenuates the increase in delta density and decrease in spindle activity typically observed during recovery sleep following total sleep deprivation.13,14 These effects can be long lasting. Early morning caffeine intake in experimental studies is sufficient to induce these EEG changes during night sleep many hours later, even as plasma caffeine concentrations approach zero.15

Paradoxically, high levels of caffeine intake are also positively correlated with indicators of daytime sleepiness. Increased levels of caffeine intake have been associated with reduced time in bed,16 and high levels of daytime sleepiness are associated with high levels of caffeine intake.17 Other studies have found similar findings even among children.18,19 However, these cross-sectional data cannot determine whether caffeine is inducing sleep disturbance or whether subjects are self-administering caffeine to counteract daytime sleepiness due to other types of sleep disturbance.

Caffeine appears to have differential effects upon insomniacs and good sleepers. Individuals with situational insomnia and those with elevated scores on a test of predisposition to insomnia greater sleep disturbance from a caffeine challenge than good sleepers.20;21

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