Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

Abstract

Objective: Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin.

Methods: Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance.

Results: Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light.

Conclusions: A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms.

Keywords: Bright light; Circadian misalignment; Circadian rhythms; DLMO; Jet lag; Melatonin.

Figure 1

Protocol Diagram. The 2-week protocol included Baseline Days (1–11) and Treatment Days (12–14). Days 12, 13, and 14 are also referred to as Treatment Days 1, 2, and 3 respectively in the text. The horizontal lines anchored with circles illustrate scheduled sleep times. A participant with a baseline bedtime of midnight (0) and baseline wake-up time of 08:00 is shown as an example. Baseline sleep schedules always allowed for 8 hours of time in bed, but bed and wake times varied among participants as they were based on self-reported sleep times before beginning the study. The sleep schedule was gradually advanced on days 12, 13 and 14. Participants ingested 0.5 mg melatonin (M) 5 hours before their baseline bedtime on the first treatment day and then 1 hour earlier on each subsequent treatment day. Bright light (~ 5000 lux) from a single light box was administered within 5 minutes of waking on each of the 3 treatment days. On Days 7 and 15, participants completed a circadian phase assessment to determine the dim light melatonin onset (DLMO).

Figure 2

Morning bright light patterns (~ 5000 lux) for each group. Dark bars indicate when lights were on relative to wake-up time. Between bright light pulses, participants remained in room light (~20 lux at the angle of gaze).

Figure 3

Phase shifts to intermittent morning bright light plus afternoon melatonin. (A) Black circles illustrate the phase advance shifts for each individual, and horizontal lines illustrate mean phase shifts for each bright light group. (B) Mean DLMO at baseline and final assessments for the 2 h group in comparison to the 1 h group, which differed in bright light exposure duration (30 minutes versus 15 minutes). (C) Mean DLMO at baseline and final assessments for the 2 h group in comparison to the 0.5 h group, which differed in light exposure number (four versus one 30-minute light exposure). The phase advance was significantly larger in the 2 h group.

Figure 4

Scatter plots showing the association between the time of the morning bright light (relative to the DLMO) and the magnitude of the phase advance. Light start time is the interval between the baseline DLMO and the start of morning light exposure on the first treatment morning. A linear regression line (solid line) was fit separately for each group.

Figure 5

Mean subjective ratings of jet lag at baseline (days 2–6) and Treatment Day 3 (from wake up on day 13 to bedtime on day 14) for the three bright light groups. The 2 h group is differentiated by an open symbol and dotted line to more easily compare it to the 1 h (closed circle) and 0.5 h (closed triangle) groups. There was a slight increase in subjective jet lag (the maximum score is 36), but there were no differences among the groups.