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Controlled Clinical Trial
. 2015 Jun;16(6):800-4.
doi: 10.1016/j.sleep.2015.01.018. Epub 2015 Feb 11.

Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms

Melissa A St Hilaire  1 , Steven W Lockley  2
Affiliations
Controlled Clinical Trial

Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms

Melissa A St Hilaire et al. Sleep Med. 2015 Jun.

Abstract

Objective/background: Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep-wake disorder.

Patients/methods: Three totally blind males (63.0 ± 7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48 h every 1-2 weeks. Participants completed daily sleep-wake logs, and rated their alertness and mood using nine-point scales every ~2-4 h while awake on urine sampling days. Caffeine capsules (150 mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period τ and compared to placebo (n = 2) or no treatment (n = 1) in a single-masked manner.

Results: Non-24-h aMT6s rhythms were confirmed in all three participants (τ range = 24.32-24.57 h). Daily administration of 150 mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p <0.0001) but did not decrease the occurrence of daytime naps compared with placebo.

Conclusions: Although caffeine was able to improve daytime alertness acutely and may therefore provide temporary symptomatic relief, the inability of caffeine to correct the underlying circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep-Wake Disorder in the blind appropriately.

Keywords: Alertness; Blindness; Caffeine; Circadian; Entrainment; Non-24-hour sleep–wake disorder.

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Figures

Fig. 1
Fig. 1
(A–C) Raster double plots of the self-reported sleep times (horizontal black bars), including naps, in totally blind participants S33 (A), S84 (B), and S85 (C). Sequential study days are shown on the ordinate and clock time is double-plotted on the abscissa. Circadian acrophases, which were estimated from cosinor fits to 48-h profiles of aMT6s rhythms, are superimposed (open circles) along with a best-fit regression line (dashed lines) to illustrate the intrinsic non-24-h period. The size of the circle is inversely proportional to the standard error of the circadian phase estimate; the best-fit regression was weighted based on these standard errors. Circadian period was estimated for each condition for each participant. S33: no treatment τ = 24.49 ± 0.21 h; placebo τ = 24.28 ± 0.27 h; caffeine τ = 24.46 ± 0.11 h. S84: no treatment τ = 24.25 ± 0.06 h; caffeine τ = 24.35 ± 0.02 h. S85: no treatment τ = 24.51 ± 0.10 h; placebo t = 24.59 ± 0.03 h; caffeine τ = 24.59 ± 0.03 h. (D–G) Nighttime sleep duration (D), sleep offset (E), and daytime nap duration (F) plotted as a function of beat cycle phase and alert–sleepy scales (G) plotted as a function of circadian phase during the placebo/no treatment (gray circles) and caffeine (black squares) arms of the study across all three participants. Each parameter was normalized in each participant as the deviation from the mean (y-axis; 45° bins), where 0° represents the time at which the midpoint of sleep (for D–F) or the rating assessment (G) coincided with the acrophase of the aMT6s rhythm (x-axis) as a function of the treatment condition (placebo/no treatment vs. caffeine). Significant circadian rhythms are indicated by filled symbols and nonsignificant rhythms by open symbols. Phase bins in which caffeine was significantly different from the placebo/no treatment condition are indicated (*).
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