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Clinical Trial
. 2000 Aug 1;526 Pt 3(Pt 3):695-702.
doi: 10.1111/j.1469-7793.2000.00695.x.

Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

J M Zeitzer  1 , D J Dijk, R Kronauer, E Brown, C Czeisler
Collaborators, Affiliations
Clinical Trial

Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

J M Zeitzer et al. J Physiol. .

Abstract

Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

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Figures

Figure 1
Figure 1. Phase shift of the human circadian pacemaker and acute suppression of plasma melatonin
Melatonin profiles during days on which the first constant routine (CR) (1 and 2), the single experimental light exposure 6.5 h in duration (3), and the second CR (4) occurred are shown for three representative subjects (1799, 1855, 17A2). In the dimmest light condition, exposure to the dim light stimulus (∼3 lx) had little effect on either the phase of the melatonin rhythm (phase shift (ΔΦ) 0.07 h) or concentration of plasma melatonin (suppression 11 %). In the brightest light condition (∼9100 lx), light both shifted the rhythm (ΔΦ -3.2 h) and completely suppressed plasma melatonin (98 %). Exposure to dim room light (∼106 lx) evoked more than half of the shift observed in the brightest light condition (ΔΦ -1.8 h compared with -3.2 h) and a nearly equal amount of suppression (88 %). During the CRs and day of experimental light exposure, subjects were exposed to no more than 5 lx in the horizontal angle of gaze at any time except during the scheduled sleep episodes (hatched bars < 0.03 lx) and the experimental light exposure (labelled open boxes, see Fig. 2). Individual subject data were plotted on a time scale in which their habitual wake time was assigned a reference value of 08.00 h. Phase of the melatonin maximum (midpoint of the upward and downward mean crossings) during each CR is noted as the ▵. For graphical purposes, ordinate values were normalized to each subject's absolute peak plasma melatonin concentration.
Figure 2
Figure 2. Illuminance-response curve of the human circadian pacemaker
The shift in the phase of the melatonin rhythm (A), as assessed on the day following exposure to a 6.5 h experimental light stimulus, has been fitted with a four parameter logistic model (see Table 1) using a non-linear least squares analysis. Acute suppression of plasma melatonin (B) during the light exposure also has been fitted with a four parameter logistic model (see Table 2) using a non-linear least squares analysis. The logistic models predict an inflection point of the curve (i.e. the sensitivity of the system) at ∼120 lx. Saturation of the phase-shift response is predicted to occur with ∼550 lx and saturation of the melatonin-suppression response is predicted to occur with ∼200 lx. Individual subjects are represented by ▪, the model by the continuous line, and the 95 % confidence intervals by the dotted lines.
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