Melatonin treatment for eastward and westward travel preparation

Abstract

Melatonin is recommended for hastening adaptation to phase shift, but there is little information on appropriate formulations. 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. 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. Appropriately timed 0.5 mg melatonin doses may avoid these problems.