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First published online on November 15, 2007.
Copyright © 2007 by The Physiological Society
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jphysiol.2007.143180v1
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Received August 16, 2007
Revised September 6, 2007
Accepted after revision November 9, 2007

A 3 pulse phase response curve to 3 mg melatonin in humans

Helen J Burgess1*, Victoria L Revell2, and Charmane I Eastman1

1 Rush University Medical Center
2 University of Surrey

* To whom correspondence should be addressed. E-mail: helen_j_burgess{at}rush.edu.

Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a 3 pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free-running subjects. Young healthy subjects (n=27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 minute saliva samples. In between were 3 days in an ultradian dim light (<150 lux)/dark cycle (LD 2.5:1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individual’s phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free-run). The resulting PRC has a phase advance portion peaking about 5 hours before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 hours after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 hours and 1.3 hours, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects.


Key words: Circadian rhythm • Melatonin • Phase • Ultradian




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Erratum
J. Physiol., March 15, 2008; 586(6): 1777 - 1777.
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