Concentration-effect relationships of plasma caffeine on EEG delta power and cardiac autonomic activity during human sleep

Acute caffeine intake affects brain and cardiovascular physiology, yet the concentration-effect relationships on the electroencephalogram (EEG) and cardiac autonomic activity during sleep are poorly understood. To tackle this question, we simultaneously quantified the plasma caffeine concentration with ultra-high-performance liquid chromatography, as well as the EEG, heart rate and high-frequency (0.15-0.4 Hz) spectral power in heart rate variability (HR-HRV), representing parasympathetic activity, with standard polysomnography during undisturbed human sleep. Twenty-one healthy young men ingested in randomized, double-blind, cross-over fashion, 160 mg caffeine or placebo in a delayed, pulsatile-release caffeine formula at their habitual bedtime, and initiated a four-hour sleep opportunity 4.5 hours later. The mean caffeine levels during sleep exhibited high individual variability between 0.2 and 18.4 µmol/l. Across the first two NREM-REM sleep cycles, EEG delta (0.75-2.5 Hz) activity and heart rate were reliably modulated by waking and sleep states. Caffeine dose-dependently reduced delta activity and heart rate, and increased HR-HRV in NREM sleep when compared to placebo. The average reduction in heart rate equaled 3.24 ± 0.77 beats per minute. Non-linear statistical models suggest that caffeine levels above ∼ 7.4 µmol/l decreased EEG delta activity, whereas concentrations above ∼ 4.3 µmol/l and ∼ 4.9 µmol/l, respectively, reduced heart rate and increased HR-HRV. The findings provide quantitative concentration-effect relationships of caffeine, EEG delta power and cardiac autonomic activity and suggest increased parasympathetic activity during sleep after intake of caffeine.