A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening

Abstract Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake....

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Autores principales:	Dario A. Dornbierer, Firat Yerlikaya, Rafael Wespi, Martina I. Boxler, Clarissa D. Voegel, Laura Schnider, Aslihan Arslan, Diego M. Baur, Markus R. Baumgartner, Tina Maria Binz, Thomas Kraemer, Hans-Peter Landolt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d46e8cd1eeb4df3b4c16337b30ea4b2
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spelling	oai:doaj.org-article:5d46e8cd1eeb4df3b4c16337b30ea4b22021-12-02T17:13:17ZA novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening10.1038/s41598-021-98376-z2045-2322https://doaj.org/article/5d46e8cd1eeb4df3b4c16337b30ea4b22021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98376-zhttps://doaj.org/toc/2045-2322Abstract Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation’s ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach. Trials registration: NCT04975360.Dario A. DornbiererFirat YerlikayaRafael WespiMartina I. BoxlerClarissa D. VoegelLaura SchniderAslihan ArslanDiego M. BaurMarkus R. BaumgartnerTina Maria BinzThomas KraemerHans-Peter LandoltNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dario A. Dornbierer Firat Yerlikaya Rafael Wespi Martina I. Boxler Clarissa D. Voegel Laura Schnider Aslihan Arslan Diego M. Baur Markus R. Baumgartner Tina Maria Binz Thomas Kraemer Hans-Peter Landolt A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
description	Abstract Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation’s ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach. Trials registration: NCT04975360.
format	article
author	Dario A. Dornbierer Firat Yerlikaya Rafael Wespi Martina I. Boxler Clarissa D. Voegel Laura Schnider Aslihan Arslan Diego M. Baur Markus R. Baumgartner Tina Maria Binz Thomas Kraemer Hans-Peter Landolt
author_facet	Dario A. Dornbierer Firat Yerlikaya Rafael Wespi Martina I. Boxler Clarissa D. Voegel Laura Schnider Aslihan Arslan Diego M. Baur Markus R. Baumgartner Tina Maria Binz Thomas Kraemer Hans-Peter Landolt
author_sort	Dario A. Dornbierer
title	A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
title_short	A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
title_full	A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
title_fullStr	A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
title_full_unstemmed	A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
title_sort	novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5d46e8cd1eeb4df3b4c16337b30ea4b2
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A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening

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