Clinical and physiological correlates of caffeine and caffeine metabolites in primary insomnia

J Clin Sleep Med. 2011 Apr 15;7(2):196-203.


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.

Keywords: Insomnia; caffeine; metabolite; paraxanthine; xanthine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Caffeine / adverse effects*
  • Caffeine / blood
  • Caffeine / metabolism
  • Chromatography, High Pressure Liquid
  • Electroencephalography
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Polysomnography
  • Sleep / drug effects
  • Sleep / physiology
  • Sleep Initiation and Maintenance Disorders / chemically induced*
  • Sleep Initiation and Maintenance Disorders / physiopathology
  • Theophylline / adverse effects
  • Theophylline / blood


  • Caffeine
  • Theophylline
  • 1,7-dimethylxanthine