Abstract
Introduction
Melatonin is recommended for hastening adaptation to phase shift, but there is little information on appropriate formulations.
Materials and methods
We evaluated the efficacy of three melatonin formulations for circadian phase advance and delay: (a) 3 mg regular release (RR), (b) 3 mg sustained release (SR), and (c) 3 mg surge-sustained release (SSR; consisting of 1 mg RR and 2 mg SR). Circadian phase was assessed by salivary melatonin dim light melatonin onset (DLMO) or offset (MelOff) using thresholds of (1) 1.0 pg/ml and (2) mean baseline + 2 standard deviations (BL + 2SD). Subjects spent from Tuesday evenings until Thursday in the laboratory. Melatonin (or placebo) was administered at 1600 hours (phase advance) Wednesday, with DLMO assessment on Tuesday and Thursday and at 0600 hours (phase delay) Wednesday, with DLMO assessment Tuesday, Wednesday, and MelOff Thursday morning. Phase advances using the 1.0 pg/ml DLMO were as follows: placebo, 0.73 h; RR, 1.23 h (p < 0.003); SR, 1.44 h (p < 0.0002); SSR, 1.16 h (p < 0.012), with no difference between formulations.
Results and discussion
Similar but smaller phase advances were found with BL + 2SD. Using MelOff, posttreatment phase position for the RR formulation was delayed compared to placebo by 1.12 h (p < 0.012), 1.0 pg/ml, and 0.75 h (p < 0.036), BL+2SD. Phase shifts for the SR and SSR conditions could not be determined due to persistent high melatonin levels during sampling times. Similar phase advances were induced by all formulations, and slow clearance of slow release preparations impeded the determination of phase delays.
Conclusion
Appropriately timed 0.5 mg melatonin doses may avoid these problems.
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The views, opinions, and/or findings in this report are those of the authors and should not be construed as an official Defence Research & Development Canada (DRDC), Department of National Defence (DND) Canada, or US Department of Defense (DoD) position, policy or decisions, unless so designated by other official documentation. Citations of commercial organizations and trade names in this report do not constitute an official DRDC, DND Canada, or US DoD endorsement or approval of the products or services of these organizations. Funding for this research was provided by the Canadian Forces.
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Paul, M.A., Miller, J.C., Gray, G.W. et al. Melatonin treatment for eastward and westward travel preparation. Psychopharmacology 208, 377–386 (2010). https://doi.org/10.1007/s00213-009-1737-7
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DOI: https://doi.org/10.1007/s00213-009-1737-7