Melatonin suppression in human subjects by bright and dim light in Antarctica: time and season-dependent effects

Neuroscience Letters, 137 (1992) 181-184 © 1992 Elsevier Scientific Publishers Ireland Ltd. All rights reserved 0304-3940/92/$ 05.00

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Melatonin suppression in human subjects by bright and dim light in Antarctica: time and season-dependent effects J. Owen a and Josephine Arendt b aBritish Antarctic Survey Medical Unit, RGIT Survival Centre, Aberdeen (UK) and bSchool of Biological Sciences, University of Surrey, Guildford (UK) (Received 25 September 1991; Revised version received 18 December 1991; Accepted 23 December 199 l)

Key words: Melatonin; Light; Season Full-spectrum light, of sufficiently high intensity, will suppress the secretion of melatonin at night in humans. Individual sensitivity to such suppression is variable, and the factors determining such sensitivity are largely unknown. By analogy with animal work previous short or long-term exposure to different light intensities may be an important determinant. We exploited the Antarctic environment to investigate these possibilities. Groups of healthy men, living on the British Antarctic Survey Base at Halley (75 ° South) were exposed to dim (range 290-310 lux) and bright (range 2100-2300 lux) light either from 01.004)2.00 h or 05.004).600 h, both in winter and in summer. Plasma melatonin concentrations were determined by radioimmunoassay in serial blood samples taken before, during and after light treatment, and in control (darkness) conditions. Light suppression of melatonin was more effective in the latter part of the night in winter and this was particularly well-differentiated for dim light.

The role of light in human physiology is incompletely understood. In animals, light-dark cycles are of major importance in the timing of daily and seasonal rhythms acting, at least in part, through their effects on the pineal gland and secretion of the pineal hormone melatonin [15, 19]. Light of suitable intensity, duration, and timing is able to phase-shift human circadian rhythms [3, 4, 8, 14]. Furthermore, when exposed to controlled artificial photoperiod [22] or extreme natural photoperiod [1, 10] humans can manifest seasonal changes in the duration of melatonin. In 1980, Lewy et al. [9] demonstrated that full suppression of melatonin secretion at night in humans required bright (~ 2500 lux) light. Partial, but significant suppression has been shown with 300 lux [2]. Melatonin suppression in some animals appears to be dependent on the time of night and on previous light exposure [16, 17]. Whether this is true in the case of humans is a question of some importance since light sensitivity may determine the adaptability or otherwise of circadian rhythms to forced phase-shift (shift-work, jet-lag). One single report [21] addresses the seasonal variation, and one other [1 l] the circadian dependence of light sensitivity in humans. We have taken advantage of the unusually large variaCorrespondence: J. Arendt, School of Biological Sciences, University of Surrey, Guilford, UK.

tions in natural light in Antarctica to investigate this area further. Subjects were members of Base personnel staffing the British Antarctic Survey Base of Halley (75°S) during 1988-89. Base personnel remain on Halley for at least 12 months and are thus exposed long-term to the extreme ambient light conditions. For 3 months during the winter the sun does not rise and maximum light intensity ranges up to 500 lux. In summer for 3 months the sun does not set and exposure to light intensities of at least 100,000 lux is possible. Base personnel usually spend several hours each day outside in natural light in summer. Normal healthy men (n -- 9, age range 22-33, mean _+S.E.M. 26.6 _+ 1.2 years) volunteered to take part in the study after explanation of the procedures involved. They were free to withdraw from the project at any stage. Night shift work was avoided for at least 2 weeks before and during the study. Subjects were free of medication with the exception of minor analgesics. They were divided into two groups, designated to receive bright light treatment from 01.00-02.00 h (Group A, n--5) or 05.00-06.00 h (Group B, n=4). Between 1 and 2 weeks after the winter solstice control blood samples (10 ml) were taken at hourly intervals from 20.000 h to 09.00 h from all volunteers into lithiumheparin tubes via indwelling cannulae in an arm vein. Subjects maintained their normal bedtime (23.00-24.00

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Fig. 1. Plasma melatonin concentrations (pg/ml, x_+S.E.M.) in subsets of volunteers sampled in darkness (control: O), with dim light (mean: 300 lux, *) and with bright light (mean: 2200 lux, V) from either 01.0002.00 h or 05.00~06.00 h in winter or in summer. One-way ANOVA at 02.00 and 06.00 h indicated significant suppression by dim (P < 0.01) and bright (P < 0.001) light in winter at 06.00 h, and by bright light in summer at 02.00 h (P < 0.01) compared to control. Dim light achieved greater suppression at 06.00 h than 02.00 h in winter (difference from control, P < 0.05, unpaired t-test). N: number of subjects.

h) and rising (08.00 h) routine. Between these times they remained in darkness and blood samples were obtained with the aid of a dim red light (< 1 tux). One week after the control blood sampling, subjects were treated as follows: Group A were exposed to 300 (mean, range 290310) lux full spectrum light (Vitalite, Duro-test Corporation, NJ) from 01.00 to 02.00 h, and Group B received the same lux from 05.00 to 06.00 h. Before and after light treatment subjects adhered to the same routine as described for the control sampling. Blood samples (10 ml) were taken as follows: Group A, dark: 24.00 h, 01.00 h; during light exposure: 01.30 h, 02.00 h; dark: 02.30 h, 03.00 h, 04.00 h. Group B, dark: 04.00 h, 05.00 h; during light exposure: 05.30 h, 06.00 h; dark: 06.30 h, 07.00 h, 08.00 h. One week after dim light exposure subjects were treated with bright light (2200 mean, range 2100 - 2300 lux) at 01.00 02.00 h (Group A) and 05.00 - 06.00 h (Group B). The procedure and sampling were identical

to those described for dim light. The entire sequence (control profile, dim and bright light treatment) was repeated in summer beginning 1-2 weeks after the summer solstice. All blood samples were centrifuged and plasma was frozen at -20°C until assayed for melatonin. For assay samples were transported, frozen, to Guildford, UK. Plasma melatonin was measured by the method of Fraser et al. [5]. Inter-assay coefficients of variation were less than 7% at 25.4, 42.8, and 89.6 pg/ml (n-- 10). The results were expressed both as pg/ml and as a percentage of the pre-light treatment time point (01.00 h or 05.00 h). The effects of bright and dim light were compared to the control profile at 02.00 h, for early light treatment, and at 06.00 h for late light treatment, by one way ANOVA using both pg/ml and the transformed data (% of pre-light values). In addition, the effects of dim vs. bright light were compared at 02.00 and 06.00 h for early and late light treatment. In winter, one subject showed extreme delay in the onset of melatonin secretion, which occurred at 07.00 h, and was eliminated from the analysis. In summer, another subject was clearly differentiated from the group, with a very short duration of melatonin secretion. This one individual lived separately from the main base in a surface hut during the summer and was thus exposed to more natural light than the main base complement sleeping underground. This subject was also eliminated from the analysis. The loss of these two subjects left 4 individuals in the early light treatment group in winter and summer, 4 subjects in the late light treatment group in winter and, with another volunteer leaving for unrelated reasons, 3 subjects in the late light treatment group in summer. This low n accounts for low significance levels, although the data are clear and consistent. The onset of melatonin secretion (taken as the first time point more than 2 S.D.'s from mean baseline) was an hour earlier in summer than in winter. In no group were the pre-light treatment time points significantly different between control and treatment (unpaired t-test, P>0.05). The effects of light treatment compared to control values, expressed as pg/ml melatonin are shown in Fig. 1, and as % of pre-light values in Fig. 2. The two procedures yield slightly different results. Using untransformed values, the effects of both dim and bright light in winter were non-significant at 02.00 h (although inspection of the data clearly indicates suppression by bright light) but highly significant at 06.00 h compared with control. In summer there was significant suppression by bright but not dim light at 02.00 h with no significant effects at 06.00 b. When the data were expressed as a percentage ofpre-light values, both dim and bright light significantly suppressed melatonin in winter

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Fig. 2. Plasma melatonin concentrations expressed as % of values found at 01.00 h or 05.00 h (% pre-light, x _+ S.E.M.) in subsets of volunteers sampled in darkness (control: e), with dim light (mean: 300 lux, *) and with bright light (mean: 2200 lux, T) from either 01.00-02.00 h or 05.00 06.00 h in winter and in summer. One-way ANOVA at 02.00 h and 06.00 h indicated significant suppression by dim and bright light in winter at 02.00 h (dim, P < 0.01, bright P < 0.01) in winter at 06.00 h (dim, P < 0.05, bright P < 0.01) and by bright light in summer at 02.00 h (P < 0.01) compared to control. Dim light induced greater suppression at 06.00 h than 02.00 h in winter (% of pre-light values P < 0.05, unpaired t-test), N: number of subjects.

at 02.00 h and at 06.00 h compared to control, the suppression being greater at 06.00 h than 02.00 h for dim light (P<0.05, unpaired t-test). A similar trend was evident for bright light. In summer, as for the untransformed values, significant suppression was only found at 02.00 h with bright light. In all cases, following light suppression mean plasma melatonin concentrations increased again as previously noted by others in humans [8, 11, 12, 21] although animals may respond differently, depending on the time of night [6]. There was no evidence of a rebound to levels higher than control. Experiments performed on British Antarctic bases ine-

vitably involve small numbers of subjects. In this report, the late-treatment group in summer (n -- 3) is included for completeness but is too small to draw conclusions. When considering the most appropriate form of analysis for such small groups, subjects are best used as their own controls. Thus more weight is given in this discussion to the use of transformed data (% of pre-light values). This method of analysis has previously been used by Thompson et al. [21]. The early onset of melatonin secretion in summer has been previously reported [3, 7] and the steeper gradient of the melatonin rise in controls in winter is the major factor leading to significantly greater suppression in winter than summer at 02.00 h in transformed data. Thompson et al. [21] concluded that no seasonal variations in light suppression during the early part of the night are seen in normal subjects, however they did not relate their results to a comparable control night with no light treatment. It is possible that their conclusions would have been modified if profiles obtained during darkness had been used for comparison, as summer phase advances have been seen in temperate as well as polar latitudes [3, 7]. However their experimental conditions were very different from ours and no direct comparisons are justified. Probably the most interesting finding of this study is the substantially greater and more significant suppression of melatonin at 06.00 h compared to 02.00 h in winter, which is evident in both the transformed and untransformed data. Previous work by Mclntyre et al. [11] suggested that human light sensitivity as assessed by melatonin suppression may not increase in the course of the night, contrary to the original suggestion by Terman and Terman [20]. However Mclntyre et al. based their comments on extrapolated, not observed, control values. Their experiments were, moreover, performed in more temperate latitudes, and their lowest light intensity stimulus was 1000 lux. Our results are unique in that the human visual system in the Antarctic winter has the possibility of long-term adaptation to unusually low light intensity. This may be why our results agree with previous work in animals [16] and support Terman and Terman [20]. Such a variation in light sensitivity may be entirely mediated by the retina, where visual sensitivity peaks during the subjective night and drops during the day (see R6m6 et al. [18] for a recent review of rhythmic ocular processes). Thus, in order to interpret the magnitude of melatonin suppression or phase shifts induced by a light pulse, the light exposure of each individual, prior to the test, should be known. We have previously noted [13] that suitably timed treatment with bright light will hasten the rate of readaptation of the melatonin rhythm after night-shift work in

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Antarctica in winter. We may speculate that if such techniques are applied in a temperate industrial environment, less exposure to bright light may be necessary in winter to adapt by phase-advance (treatment in the subjective morning) than by phase delay (treatment in the subjective evening). Such considerations have financial implications to industrial concerns. This work was supported by the British Antarctic Survey and in part by the Wellcome Trust (J.A.). We would like to thank Professor A. Wirz-Justice for a critical reading of this manuscript and for constructive comments and suggestions.

1 Beck-Friis, J., Von Rosen, D., Kjellman, B.F., Ljungen, J.G. and

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