Effects of a chronic reduction of short-wavelength light input on melatonin and sleep patterns in humans: Evidence for adaptation

Abstract

Light is an important environmental stimulus for the entrainment of the circadian clock and for increasing alertness. The intrinsically photosensitive ganglion cells in the retina play an important role in transferring this light information to the circadian system and they are elicited in particular by short-wavelength light. Exposure to short wavelengths is reduced, for instance, in elderly people due to yellowing of the ocular lenses. This reduction may be involved in the disrupted circadian rhythms observed in aged subjects. Here, we tested the effects of reduced blue light exposure in young healthy subjects (n = 15) by using soft orange contact lenses (SOCL). We showed (as expected) that a reduction in the melatonin suppressing effect of light is observed when subjects wear the SOCL. However, after chronic exposure to reduced (short wavelength) light for two consecutive weeks we observed an increase in sensitivity of the melatonin suppression response. The response normalized as if it took place under a polychromatic light pulse. No differences were found in the dim light melatonin onset or in the amplitude of the melatonin rhythms after chronic reduced blue light exposure. The effects on sleep parameters were limited. Our results demonstrate that the non-visual light system of healthy young subjects is capable of adapting to changes in the spectral composition of environmental light exposure. The present results emphasize the importance of considering not only the short-term effects of changes in environmental light characteristics.

Full text

Chronobiology International, Early Online: 1–8, (2014)
!Informa Healthcare USA, Inc.
ISSN: 0742-0528 print / 1525-6073 online
DOI: 10.3109/07420528.2014.893242
ORIGINAL REPORT
Effects of a chronic reduction of short-wavelength light input on
melatonin and sleep patterns in humans: Evidence for adaptation
Marina C. Gime
´nez
1,2
, Domien G. M. Beersma
1
, Pauline Bollen
2
, Matthijs L. van der Linden
3
, and
Marijke C. M. Gordijn
1,2
1
Research Unit of Chronobiology, Center for Life Sciences, University of Groningen, Groningen, The Netherlands,
2
Chrono@Work B.V., Groningen, The Netherlands, and
3
Oculenti, University Medical Center Groningen, Groningen,
The Netherlands
Light is an important environmental stimulus for the entrainment of the circadian clock and for increasing alertness.
The intrinsically photosensitive ganglion cells in the retina play an important role in transferring this light information
to the circadian system and they are elicited in particular by short-wavelength light. Exposure to short wavelengths
is reduced, for instance, in elderly people due to yellowing of the ocular lenses. This reduction may be involved in
the disrupted circadian rhythms observed in aged subjects. Here, we tested the effects of reduced blue light exposure
in young healthy subjects (n¼15) by using soft orange contact lenses (SOCL). We showed (as expected) that
a reduction in the melatonin suppressing effect of light is observed when subjects wear the SOCL. However, after
chronic exposure to reduced (short wavelength) light for two consecutive weeks we observed an increase in
sensitivity of the melatonin suppression response. The response normalized as if it took place under a polychromatic
light pulse. No differences were found in the dim light melatonin onset or in the amplitude of the melatonin rhythms
after chronic reduced blue light exposure. The effects on sleep parameters were limited. Our results demonstrate that
the non-visual light system of healthy young subjects is capable of adapting to changes in the spectral composition of
environmental light exposure. The present results emphasize the importance of considering not only the short-term
effects of changes in environmental light characteristics.
Keywords: Adaptation, human, melatonin rhythms, short-wavelength light, sleep rhythms
INTRODUCTION
Light has a large impact on our everyday life. It does not
only allow for vision but also for non-image-forming
responses. Light is the environmental cue primarily
responsible for the entrainment of the biological clock,
i.e. the synchronization of our physiological and psy-
chological rhythms to the 24-h rhythm of the environ-
ment. Impaired entrainment can lead to discomfort
and higher risks for diseases (Pritchett et al., 2012;
Rajaratnam & Arendt, 2001; Ru
¨ger & Scheer, 2009).
Light also has activating effects (Cajochen, 2007; Ru
¨ger
et al., 2006) and can acutely suppress the production
of melatonin (Lewy et al., 1980).
In the late 1990s, a new photoreceptor with a key role
in transferring light information for non-image-forming
responses was discovered (Freedman et al., 1999; Lucas
et al., 1999). This is the intrinsically photosensitive
retinal ganglion cell (ipRGC) containing the photopig-
ment melanopsin with a sensitivity peak at around
480 nm (Berson et al., 2002; Hattar et al., 2002; Provencio
et al., 2000, 1998). A similar sensitivity peak for non-
visual responses was also observed in many human
studies (Brainard et al., 2001; Cajochen et al., 2005;
Lockley et al., 2003, 2006; Revell et al., 2005; Thapan
et al., 2001; Warman et al., 2003).
Aging is a natural process by which input of espe-
cially short wavelengths is reduced as a consequence of
a denser ocular lens (Gime
´nez et al., 2010; Van Norren &
Vos, 1974; Weale, 1988). Whether the weak and/or
disturbed circadian rhythms observed in the elderly
(e.g. fragmented sleep, early awakening and lower
melatonin levels) (Van Someren, 2000) can be explained
by this reduction in (short wavelength) light input needs
further research.
The present study investigates the effects of a reduc-
tion in short wavelengths light input at the level of the
ocular lens on melatonin and sleep rhythms and on
suppression of nocturnal melatonin in healthy human
Correspondence: Marina C. Gime
´nez, Research Unit of Chronobiology, Center for Life Sciences, University of Groningen,
The Netherlands, E-mail: marina.gimenez@gmail.com
Submitted November 2, 2013, Returned for revision February 5, 2014, Accepted February 6, 2014
1
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

subjects. By means of soft orange contact lenses (SOCL)
we mimicked, to a certain extent, the aging effects of the
lens in healthy young subjects. This allowed us to assess
the effects of exposure to short wavelengths in a realistic
natural scenario as well as to separate the effects of
altered lens transmittance from other aging effects.
We hypothesized that reduced (short wavelength) light
input would result in a less stable activity-rest cycle
(see review Dijk et al., 2000), in a reduction in the
nocturnal melatonin secretion (see review Skene &
Swaab, 2003) as well as in a reduction in the suppression
of nocturnal melatonin by light (Brainard et al., 1997;
Duffy et al., 2007; Herljevic et al., 2005). Knowledge
about the response to changes in environmental
light exposure will be relevant for understanding
rhythm disturbances in the elderly. It will also increase
our understanding of the impact of changing the
light environment in everyday life, a topic that is of
interest to an interdisciplinary audience of health
specialists, light industry and architects (Fournier &
Wirz-Justice, 2010).
MATERIALS AND METHODS
Subjects
Fifty subjects started the selection procedure for the
study. Only those between 18 and 30 years who were
healthy, non-smoker, non-color blind (Ishihara test) and
of an intermediate chronotype (midsleep on free days
between 3.7 and 6.3 a.m. according to the Munich
Chronotype Questionnaire, Roenneberg et al., 2003)
were selected to participate. Subjects who had worked
on night shifts or traveled across more than two time
zones during the two weeks prior to the study were
excluded.
The study required participants to wear in the
experimental condition the SOCL during 2 consecutive
weeks 24 h per day. To assess participants’ eyes health
condition a check-up by a contact lens specialist
(coauthor M.L. vd L.) was conducted at the University
Medical Center of Groningen (UMCG), the Netherlands.
After screening, 22 subjects were selected of whom 15
completed the study (7m: 8f, mean age ± sd: 23.5 ± 4.6
years). Most dropouts were due to irritations in one or
both eyes and some due to discomfort. Special care was
taken in order to exclude subjects who did not feel
comfortable after wearing the SOCL for 24–48 h.
The experimental protocol conformed to inter-
national ethical standards (Portaluppi et al., 2008) and
was approved by the Medical Ethics Committee of the
UMCG, the Netherlands, all subjects signed a written
informed consent form prior to their participation. All
subjects were financially compensated for their
participation.
Soft orange contact lenses
The SOCL (CE: 0120, with UV protection) were supplied
by Ultravision International Ltd., UK. These lenses are
normally used for medical purposes and are designed
so that they can be continuously worn (24 h/day) for
up to three consecutive months. The lenses reduce the
overall light intensity in particular of short wavelengths.
Light transmittance in the visible range of the spectrum
(from 420 to 700 nm) was reduced by 37%. In the
short wavelengths range (420–500 nm), the reduction
in transmittance was 53% and 57% when considering
the melanopsin sensitivity peak (480 nm). Figure 1
compares the relative light transmittance per wave-
length (400–700 nm) of an average 25-year healthy
subject without (van de Kraats & van Norren, 2007)
and with the SOCL, with the average transmission
of cataractous eyes of 14 elderly subjects whose ret-
inal light reflectance is severely reduced (data from
Gime
´nez et al., 2010).
Experimental design
In randomized sequence, a control condition (13 sub-
jects wore their own contact lenses and 2 subjects
no lenses) and an experimental condition (all subjects
wore the SOCL) were assigned to each of 15 subjects (8
subjects started with the control and 7 subjects started
with the SOCL condition). The SOCL were adjusted
according to the subjects’ needs for visual corrections.
Each condition lasted 16 days. They were timed at least
two weeks apart to avoid potential carry-over effects.
For each subject both conditions started on the same
day of the week (this differed between subjects) in order
to control for the possible pattern of behavior through-
out the week within each subject.
Subjects came to the lab for two consecutive nights
on days 15 and 16. Melatonin profiles were assessed
on night 15. Subjects arrived at the lab at 18:00 h.
Light levels were dimmed (55 lux). Saliva samples were
taken using cotton swabs (Sarstedt BV, Etten-Leur,
the Netherlands) every hour from 19:00 to 00:00 h,
then every half hour until 2:00 h and every 2 h from
FIGURE 1. Relative light transmittance. Spectral composition of
relative light transmittance through the ocular lens of an average
25-year-old subject without (continuous black line, from Van de
Kraats & Van Norren, 2007) and with the SOCL (dashed black line),
in comparison with an average cataractous eye (n¼14 patients)
(gray line from Gime
´nez et al., 2010).
2 M. C. Gime
´nez et al.
Chronobiology International
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

3:00 until 9:00 h. After the last sample collection subjects
were offered breakfast and left the lab. On night 16
the suppression of nocturnal melatonin by light was
assessed. For this purpose subjects returned to the lab at
18:00 h. Light levels were dimmed and saliva samples
were collected as in the previous night. After the 00:00 h
sample and until 2:00 a.m. subjects were asked to sit
in front of two polychromatic light boxes (600 lux
measured vertically at the eye level, 190.5 mW/cm
2
,
Pharos Max, Osram Dulux-L tubes, ßLumie, see
Figure 2 for spectral composition). During these two
hours subjects watched a movie on a TV monitor
situated in between both light boxes in order to keep
the direction of gaze constant. Illuminance at the
eye level was regularly checked during the 2 h and
adjusted if necessary. After the light pulse subjects were
allowed to sleep. The acute effect of the SOCL was
assessed on a separate night outside the 16 days of
each condition and not within 7 days if timed after
the experimental condition. For this purpose, the SOCL
were worn only 30 min before the light pulse started
and during the 2-h light pulse (in contrast with 16 days
of continuously wearing the SOCL). Subjects were
free to read or watch videos during the nights in the
lab. Subjects were carefully instructed about the collec-
tion of saliva samples for melatonin assessment.
Eating was restricted to the first 15 min after each
sample. Chocolate, bananas, coffee and tea were not
allowed during the whole sampling period. Ten minutes
prior to each sample subjects were asked to sit quietly to
avoid influence of posture (Deacon & Arendt, 1994).
Samples were centrifuged immediately after collection
and stored at 20 C until analysis.
Actigraphy data (1-min epochs) were collected con-
tinuously during the 16 days (ActiwatchÕ, Cambridge
Neurotechnologies, UK) together with sleep logs.
Subjects rated subjective sleep quality after waking
up by providing a score (1–10 scale, 1 ¼very bad,
10 ¼excellent). During the last five days sleepiness
ratings were assessed by means of the Karolinska
Sleepiness Scale (KSS) (A
˚kerstedt & Gillberg, 1990) at
five different time points: at waking up, at 12:00, at
16:00, at 20:00 and at bedtime.
Light exposure (lux) was collected by means of
Actiwatches-L on 1-min epoch basis. Careful instruc-
tions were given to the subjects not to cover the light
sensor by sleeves.
Data analysis
Salivary melatonin concentration was assessed by radio-
immunoassay (RK-DSM, Bu
¨hlmann laboratories AG,
Siemens Medical Solutions Diagnostics, Breda, the
Netherlands). All samples from an individual were
analyzed within the same series. The limit of detection
for the RIA was 0.3 pg/ml with an intra-assay variation of
6.7% at a low melatonin concentration (mean 1.5 pg/ml,
n¼30) and 6.5% at a high melatonin concentration
(mean ¼15 pg/ml, n¼30). Inter-assay variation was
12.2% at low melatonin concentration (mean ¼2.1 pg/
ml, n¼15) and 19.7% at high melatonin concentration
(mean ¼17.5 pg/ml, n¼16).
The full melatonin profiles of the control condition
were fitted to a bimodal skewed baseline cosine function
(Van Someren & Nagtegaal, 2007). All melatonin values
are expressed as a fraction of the maximal fitted value
on the control night for the individual subject. Dim light
melatonin onset (DLMO) was defined as the time
when the threshold at 25% of the maximum value of
the fitted curves was crossed. The suppressing effect of
light on melatonin concentration during the 2 h of light
exposure was estimated for each subject as the differ-
ence between the area under the control curve and the
curve during light exposure (AUC pg h/ml). The AUC
was calculated from time point 00:30 until time
point 2:00. The results are discussed as percentage of
suppression relative to the control curve.
Sleep analysis 5 software (Cambridge Neurotech Ltd,
Cambridge, UK) set at a medium sensitivity was
used together with sleep logs. The Actiwatch algorithm
looks at each data point from each epoch and those
surrounding it and makes a total score based on these
activity counts. The adjacent activity scores influence
the total score in the following way: within 1 min of the
scored epoch activity levels are reduced by a factor
of 5 in comparison to the epoch being scored and
this value is added to the scored value of the epoch
under consideration. When the total score is above the
sensitivity threshold the epoch is designated as wake
otherwise as sleep. For automatic determination of
Sleep Start the algorithm looks for a period of at least
10 min of consecutively recorded immobile data, with
no more than 1 epoch of movement within that
time, following the bed time (sleep logs). The start of
this defined period is classified as sleep start and the
difference in this and bedtime is used to determine sleep
latency. For sleep end the algorithm looks for a 10-min
consecutive period of activity around the get up time
(sleep logs) and then works back to find the last epoch
of immobility before the start of such a sequence and
FIGURE 2. Spectral composition. Spectral composition of the
Osram Dulux L 36 W/835 tubes of the Pharos Max light boxes.
Chronic reduction of short-wavelength light 3
!Informa Healthcare USA, Inc.
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

classifies that as sleep end. Sleep onset, midsleep
and sleep offset were used to describe sleep timing.
All timing variables are shown for work and days off.
We further investigated sleep efficiency (percentage
of time spent asleep while in bed), the average activity
of the least active 5 h, and the average activity of the
10 most active hours (Van Someren et al., 1999; Witting
et al., 1990). The analysis of the sleep parameters is
based on the first 14 days of each condition. The last
two nights spent in the lab were excluded since sleep
disturbances were introduced during the sampling of
melatonin.
Light analysis 5 software (Cambridge Neurotech
Ltd, Cambridge, UK) was used to calculate the average
light intensity (lux), the maximum intensity (lux) and
the time spent above 1000 lux.
The effects of the SOCL on the melatonin suppression
response, on DLMO and on the amplitude of the
melatonin profile were tested by means of paired
t-test. A two-way analysis of variance (ANOVA) was
used to test the effects of the SOCL on sleep for the
factors: condition (control vs. SOCL), day of the week
(work days vs. days off), and the interaction effect. For
the analysis on the effects of the SOCL on KSS a repeated
measures ANOVA was conducted for the factors: condi-
tion (control vs. SOCL), time (waking up 12, 16, 20 h and
bed time), and for the interaction effects. A paired t-test
was used to evaluate the differences in light exposure
during the two weeks control and the SOCL condition.
RESULTS
Melatonin suppression by light
The course of melatonin in the evening and the
percentage of melatonin suppression during the light
pulse relative to control melatonin profile can be seen
from Figure 3(A) and (B). The melatonin suppression
30 min after placing the SOCL (300-SOCL) was signifi-
cantly less (average ± SEM: 17% ± 9%) than the suppres-
sion in the control (SC) condition (average ± SEM:
30% ± 9%) (t¼2.65, p50.05). This result shows that
the SOCL indeed filtered the light reaching the retina
enough to reduce the suppression of melatonin.
After wearing the SOCL for 16 days (16 d-SOCL) no
differences were found in the suppression of melatonin
when compared with the SC condition (average ± SEM:
33% ± 6%, t¼0.15, p¼0.88). The suppression of mela-
tonin in the 300-SOCL condition was significantly less
than in the 16 d-SOCL condition (t¼2.37, p50.05).
Two out of the 15 subjects showed no suppression of the
nocturnal melatonin level to light at all in the control
condition.
Melatonin profile
No significant differences were found in the timing
of the DLMO between the control and the SOCL
condition after 16 days (average ± SD: control:
21:50 ± 1:03 h; SOCL: 21:37 ± 1:35 h, t¼0.831, p¼0.42).
No significant differences were observed in the ampli-
tude of the melatonin rhythm (average ± SD: control:
95.4% ± 3.7%; SOCL: 100.7% ± 23%, t¼0.852, p¼0.41).
Sleep characteristics
Sleep timing and sleep characteristics for work and
days off are summarized in Table 1. Wearing the SOCL
for 14 days had no significant effect neither in the timing
of sleep nor on its efficiency or subjective quality.
A main effect of day of the week was observed for all
timing variables (all p50.01) except for sleep onset
latency and for subjective sleep quality. No interaction
effect between condition and type of day of the week
was observed. A tendency of sleep onset latency being
slightly shortened in the SOCL as compared with the
control condition was observed. While no differences
were observed in the average activity during the least 5
active hours (L5) (average ± SD: control: 11.1 ± 3.2, SOCL:
11.8 ± 3.9, t¼0.84, p¼0.41) a small but significant
(t¼2.3, p50.05) reduction in the average activity of the
FIGURE 3. Melatonin. (A) Average melatonin curves. Dark (tri-
angles), medium (circles) and light grey (squares) represent the
melatonin profiles during the suppression protocol in the control
condition (SC), after 16 days of wearing the SOCL (16 d-SOCL), and
after 30 min of wearing the SOCL (300-SOCL), respectively. The
block represents the time at which the 600-lux white light pulse
was given. (B) Melatonin suppression (%) relative to the control
melatonin profile values during the 2 h of light exposure. Asterisks
denote significant differences.
4 M. C. Gime
´nez et al.
Chronobiology International
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

10 most active hours (M10) was shown in subjects
wearing the SOCL (average ± SD: 54.9 ± 3.2) in compari-
son to the control condition (average ± SD: 55.9 ± 2).
KSS scores were analyzed to test whether condition
had an effect in addition to the well-known effect of the
time of day (a U-shaped curve with higher, more sleepy,
values at waking up and before bedtime). No effect of
the SOCL was found on the KSS scores (average ± SD:
control: 4.7 ± 1.2; SOCL: 4.8 ± 1.1, F(1, 14) ¼0.01,
p¼0.94). Only time-of-day contributed significantly
to the explained variance (pattern over time: F¼21.138
(4, 11), p50.001, data not shown).
Light exposure
No differences in the average light exposure, neither
in the maximum nor on the average light exposure
duration above 1000 lux were observed between condi-
tions (Table 2).
DISCUSSION
The aim of the present study was to investigate the acute
but also the chronic effects of exposure to diminished
short-wavelength light throughout the day as it occurs,
for instance, in the elderly population, on the suppres-
sion of the nocturnal melatonin by light and on
melatonin and sleep–wake rhythms. The study yields
three primary conclusions. (1) We found that melatonin
suppression by light is sharply reduced when subjects
wear the SOCL during the test (+30 min before). (2) This
reduction disappears when subjects have worn the
SOCL continuously for 16 days. (3) After two weeks,
the use of the SOCL had no effect on circadian rhythms
of sleep and melatonin. In view of these conclusions,
the implications of reduced exposure to blue light in
the elderly population and in society in general are
discussed.
Melatonin suppression by light
Light of short wavelength has been shown to have a
larger suppressing effect on melatonin concentrations
when compared with longer wavelengths (Brainard
et al., 2001; Cajochen et al., 2005; Thapan et al., 2001).
Studies where short wavelengths were blocked by means
of goggles during a simulated night shift in bright light
conditions found nocturnal melatonin levels similar
to those observed under dim light conditions (i.e. no
significant suppression of the nocturnal melatonin)
(Kayumov, 2005; Sasseville et al., 2006). Our results are
consistent with these studies in showing that melatonin
concentrations in subjects wearing the SOCL during the
600-lux light pulse from midnight until 2 a.m. are not
significantly different from the dim light melatonin
values. A complete blockage of short wavelengths is
most likely not needed to achieve this result since our
lenses cut down the irradiance in the short wavelengths
range by about 50%.
In order to understand the effect of exposure to a
reduction in short wavelength light in a situation such
as in the elderly another approach is needed. Here,
this reduction due to yellowing of their lenses is
continuously present, 24 h a day, and the long-term
effects of this reduction need to be assessed. The results
of this manipulation are discussed in the following
sections.
TABLE 1. Sleep characteristics. Sleep timing, efficiency and subjective quality obtained by a combination of sleep
diaries and actiwatch data.
Work days Days off
Control 16-day OL Control 16-day OL
Bed time
a
00:25 ± 40 min 00: 05 ± 1 h 1 min 1:24 ± 11 min 1:46 ± 1 h 28 min
Sleep onset
a
00:39 ± 40 min 00:18 ± 47 min 1:43 ± 1 h 9 min 1:59 ± 1 h 30 min
Sleep offset
a
7:46 ± 54 min 7:39 ± 47 min 9:22 ± 55 min 9:25 ± 1 h 23 min
Sleep onset latency (min)
b
14.4 ± 9 12.1 ± 7.3 19.1 ± 18.4 12.6 ± 8.9
Midsleep
a
4:13 ± 39 min 3: 58 ± 42 min 5:32 ± 52 min 5:42 ± 1 h 19 min
Sleep efficiency (%)
a
81.1 ± 4.4 80.1 ± 5.5 80.1 ± 6.2 79.8 ± 4.5
Subjective sleep quality
a
6.4 ± 0.8 6.3 ± 0.9 7.2 ± 1 6.9 ± 0.8
Data are shown as average ± SD.
a
Significant main effect of day of the week (p50.01).
b
Main effect of condition p¼0.06.
No significant effect of interaction between condition and day of the week was observed (0.7 5p40.1).
TABLE 2. Light exposure characteristics. Average light intensity, average maximum intensity and average time spent
above 1000 lux as obtained from actiwatch data.
Control 16-day OL Tp
Average light intensity (lux) 552 ± 335 515 ± 340 0.41 0.69
Average max. light intensity (lux) 16945 ± 7860 15697 ± 7848 0.82 0.42
Average time spent above 1000 lux 2 h 19 min ± 1 h 19 min 2 h 1 min ± 1 h 17 min 1.04 0.31
Data are shown as average ± SD.
Chronic reduction of short-wavelength light 5
!Informa Healthcare USA, Inc.
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

Adaptation to reduced (short wavelength) light
exposure
After wearing the SOCL for 24 h a day for two
consecutive weeks, the suppression of the nocturnal
melatonin by light was as large as the suppression
observed in the control condition (without the SOCL).
Previous studies have shown that light history has a
large impact on non-image-forming responses. In time
frames ranging from hours up to a week exposures to
dimmer light conditions have lead to an increase in
sensitivity of the biological clock system as measured
by means of melatonin suppression (He
´bert et al.,
2002; Jasser et al., 2006; Owen & Arendt, 1992; Smith
et al., 2004). Our findings do not only imply an
increase in sensitivity but rather a restoration/normal-
ization of the response to the levels of the control
condition. We further found that after wearing the
SOCL for two weeks neither DLMO nor the amplitude
of the melatonin rhythm differed significantly from
the control condition. This also means that light
exposure for the assessment of the suppression
response occurred on average at the same circadian
phase. In conclusion, these findings suggest that
during these two weeks adaptation to the changes in
the spectral composition of light occurred. Adaptation
is the process that potentially compensates for light
intensity differences. One could argue that differential
exposure to light could have lead to the observed
results. Subjects would have had to naturally, but
systematically, expose themselves to just enough more
light in order to compensate for the difference
between the control and the SOCL condition to
restore melatonin suppression values to those
observed in the control condition. Our light exposure
data reveal no differences between both conditions,
allowing us to discard differential light exposure as a
key factor for our findings.
Neither the previous studies nor the present one
were designed to precisely assess the temporal charac-
teristics of adaptation. It would be valuable to develop
an adaptation curve to changes in the spectral compos-
ition during the day (i.e. after how many hours/days
of selective exposure to certain wavelengths during
daytime is the melatonin suppression response restored
to reach dim light melatonin levels again). Restoration
after exposure to darkness should be considered.
In mice circadian phase responses to light are reduced
rapidly by prior light exposure and fully restored by
prolonged (18 h) dark exposure (Comas et al., 2007).
If the lenses have caused ‘‘dark adaptation’’, this
would enhance sensitivity to entraining light stimuli
and thus compensate for the reduced penetration of
blue light to the ipRGCs. Alternatively, redistribution
of sensitivity across photoreceptors could explain
our observations. It is reasonable to surmise the occur-
rence of compensatory processes under the constant
presence of relatively small changes in light inten-
sity and spectral composition. Data collection at
intermediate time points would allow to quantify more
accurately the rate of adaptation. Such experiments
are critical to gain an insight in sensitization and
desensitization of the non-image forming system by
light and darkness.
Effects of SOCL on circadian rhythms of
melatonin and sleep
We observed no differences in the timing of sleep
or melatonin rhythms after wearing the SOCL for two
weeks in comparison to the control condition. Only
slight changes in sleep onset latency and in the activity
during the 10 most active hours were found. The slight
tendency to a shorter sleep onset latency and the
reduction in M10 shown in the SOCL condition could
indicate an increased tiredness and/or less alerting/
activating effects of light as expected after exposure to
less light (Cajochen, 2007; Ru
¨ger et al., 2006). Studies
in humans have shown that complete absence of
short-wavelength light before bedtime improves sleep
(Burkhart & Phelps, 2009; Santhi et al., 2012), while its
presence leads to the opposite effect (Mu
¨nch et al., 2006;
Santhi et al., 2012) in a blue-amount-dependent manner
(Santhi et al., 2012). The use of orange goggles during
the morning hours (from awakening until 15:00 h) lead
to a phase delay of the DLMO (Figueiro & Rea, 2010).
These studies tested the effect of (lack of) blue light
at specific times of the day. Our study shows that sleep
and melatonin rhythms after two weeks of continuous
partial absence of blue light are not different from
sleep and melatonin rhythms after two weeks of unfil-
tered light exposure.
It could be argued that the reduction of light expos-
ure due to the SOCL was not large enough to induce
sleep disturbances or a shift in phase in these
young people. However, the melatonin suppression
data indicate that there is a reduction in lens transmit-
tance that leads to a reduction in melatonin suppression
after wearing the lenses for 30 min. If changes in
melatonin suppression are achieved by means of the
SOCL it is expected that those changes in light input
are also capable of inducing a shift in phase (Zeitzer
et al., 2000). In this sense, adaptation to the new light
environmental conditions seems a plausible explanation
for the lack of effects observed after wearing the SOCL
for two consecutive weeks.
Thus, neither the melatonin profile nor the sleep
characteristics suggest that entrainment of the circadian
system is compromised by the relatively long-term
application of SOCL. The reduction we achieved by
means of the SOCL is relatively similar to that of a
cataractous eye at about 480 nm at which the sensitivity
of the ipRGCs peak (Panda et al., 2005; Provencio et al.,
2002). At shorter wavelengths the discrepancy becomes
larger. If, as in young subjects very short wavelengths
lead to increased alerting effects (Revell et al., 2006)
in the elderly, this could, in the long term, have
implications for the timing of sleep. The present study
6 M. C. Gime
´nez et al.
Chronobiology International
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

does not support the idea that the general circadian
characteristics of the elderly can be explained by the
age-related reduction in (short wavelength) light trans-
mittance only. The effects observed in the present study
were marginal and probably of a transitional nature,
whereas in the elderly the impaired circadian output
remains. In agreement with our observations, a recent
study shows that the increased lens filtering that occurs
with aging does not lead to a proportional change in the
response of the non-image forming system (Najjar et al.,
2014). Najjar et al. suggest that compensatory mechan-
isms might take place in healthy elderly. Their com-
parisons are of a between (young vs. elderly) and not
a within (elderly with and without blue input) nature.
Healthy young subjects might have a more plastic non-
visual system than elderly people. With pathological
aging the plasticity might become less and may lose
its capability to fully adapt to changing situations.
Still, exposure to bright light, exercise and melatonin
can promote restoration of diminished-non-visual
responses in elderly subjects (for review see (Van
Someren et al., 2002). These improvements are
mainly based on studies conducted in institutionalized
subjects where light conditions are far from being
optimal. Further studies are needed in order to gain an
insight in the mechanisms of adaptation/compensation
to reduced short-wavelength light input in the young
and elderly.
CONCLUSION
In this study, exposure to light was exclusively modified
by using contact lenses that absorb some of the, mainly,
short wavelengths. There were no behavioral restrictions
whatsoever. In this way, the study approaches the
effects of light history on sensitivity of the circadian
system in a rather realistic manner: the altered lens
transmittance is continuously present, as it is, for
instance, in elderly people. Our observation that the
system in healthy young people is able to adapt to
the spectral composition of the light is remarkable.
Apparently, the circadian system continues to function
as a time keeping mechanism: it regulates entrainment
and alertness as if nothing had changed. Such adapta-
tions are likely to serve important functions. They may
help healthy humans to adjust to different life styles,
such as living indoors or outdoors, and to seasonal and/
or latitudinal changes. Whether similar adaptations
still occur in healthy aged individuals and no longer in
subjects suffering from severe cataract remains to be
investigated.
ACKNOWLEDGEMENTS
The authors thank Prof Dr Serge Daan for his insightful
comments on the manuscript and Bu
¨hlmann labora-
tories A.G. for the direct saliva melatonin radioimmuno-
assay tests provided for this study.
DECLARATION OF INTEREST
Financial support was obtained from the 6th European
Framework project EUCLOCK (018741) and ßLumie
(Outside In, Cambridge, Limited). The authors report no
conflicts of interest. The authors alone are responsible
for the content and writing of the paper.
REFERENCES
A
˚kerstedt T, Gillberg M. (1990). Subjective and objective sleepiness
in the active individual. Int J Neurosci. 52:29–37.
Berson DM, Dunn FA, Takao M. (2002). Phototransduction by
retinal ganglion cells that set the circadian clock. Science. 295:
1070–3.
Brainard GC, Rollag MD, Hanifin JP. (1997). Photic regulation of
melatonin in humans: Ocular and neural signal transduction.
J Biol Rhythms. 12:537–46.
Brainard GC, Hanifin JP, Greeson JM, et al. (2001). Action spectrum
for melatonin regulation in humans: Evidence for a novel
circadian photoreceptor. J Neurosci. 21:6405–12.
Burkhart K, Phelps JR. (2009). Amber lenses to block blue light and
improve sleep: A randomized trial. Chronobiol Int. 26:1602–12.
Cajochen C. (2007). Alerting effects of light. Sleep Med Rev. 11:
453–64.
Cajochen C, Mu
¨nch M, Kobialka S, et al. (2005). High sensitivity of
human melatonin, alertness, thermoregulation, and heart rate
to short wavelength light. J Clin Endocrinol Metab. 90:1311–16.
Comas M, Beersma DGM, Spoelstra K, Daan S. (2007). Circadian
response reduction in light and response restoration in dark-
ness: A ‘‘skeleton’’ light pulse PRC study in mice (Mus
musculus). J Biol Rhythms. 22:432–44.
Deacon S, Arendt, J. (1994). Posture influences melatonin concen-
trations in plasma and saliva in humans. Neurosci Lett. 167:
191–4.
Dijk DJ, Duffy JF, Czeisler CA. (2000). Contribution of circadian
physiology and sleep homeostasis to age-related changes in
human sleep. Chronobiol Int. 17:285–311.
Duffy JF, Zeitzer JM, Czeisler CA. (2007). Decreased sensitivity
to phase-delaying effects of moderate intensity light in older
subjects. Neurobiol Aging. 28:799–807.
Figueiro MG, Rea MS. (2010). Lack of short-wavelength light
during the school day delays dim light melatonin onset
(DLMO) in middle school students. Neuro Endocrinol Lett.
31:92–6.
Fournier C, Wirz-Justice A. (2010). Light, Health and Wellbeing:
Implications from chronobiology for architectural design.
World Health Design: Architecture. 3:44–9.
Freedman MS, Lucas RJ, Soni B, et al. (1999). Regulation of
mammalian circadian behavior by non-rod, non-cone, ocular
photoreceptors. Science. 284:502–4.
Gime
´nez MC, Kanis MJ, Beersma DGM, et al. (2010). In vivo
quantification of the retinal reflectance spectral composition
in elderly subjects before and after cataract surgery:
Implications for the non-visual effects of light. J Biol
Rhythms. 25:123–31.
Hattar S, Liao HW, Takao M, et al. (2002). Melanopsin-containing
retinal ganglion cells: Architecture, projections, and intrinsic
photosensitivity. Science. 295:1065–70.
Herljevic M, Middleton B, Thapan K, Skene DJ. (2005).
Light-induced melatonin suppression: Age-related reduction
in response to short wavelength light. Exp Gerontol. 40:237–42.
He
´bert M, Martin SK, Lee C, Eastman CI. (2002). The effects of
prior light history on the suppression of melatonin by light in
humans. J Pineal Res. 33:198–203.
Jasser SA, Hanifin JP, Rollag MD, Brainard GC. (2006). Dim light
adaptation attenuates acute melatonin suppression in humans.
J Biol Rhythms. 21:394–404.
Chronic reduction of short-wavelength light 7
!Informa Healthcare USA, Inc.
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.

Kayumov L. (2005). Blocking low-wavelength light prevents noc-
turnal melatonin suppression with no adverse effect on
performance during simulated shift work. J Clin Endocrinol
Metab. 90:2755–61.
Lewy AJ, Wehr TA, Goodwin FK, et al. (1980). Light suppresses
melatonin secretion in humans. Science. 210:1267–9.
Lockley SW, Brainard GC, Czeisler CA. (2003). High sensitiv-
ity of the human circadian melatonin rhythm to resetting
by short wavelength light. J Clin Endocrinol Metab. 88:
4502–5.
Lockley SW, Evans EE, Scheer FAJL, et al. (2006). Short-wavelength
sensitivity for the direct effects of light on alertness, vigilance,
and the waking electroencephalogram in humans. Sleep. 29:
161–8.
Lucas RJ, Freedman MS, Mun
˜oz M, et al. (1999). Regulation
of the mammalian pineal by non-rod, non-cone, ocular photo-
receptors. Science. 284:505–7.
Mu
¨nch M, Kobialka S, Steiner R, et al. (2006). Wavelength-
dependent effects of evening light exposure on sleep architec-
ture and sleep EEG power density in men. Am J Physiol Regul
Integr Comp Physiol. 290:R1421–8.
Najjar RP, Chiquet C, Teikari P, et al. (2014). Aging of non-visual
spectral sensitivity to light in humans: Compensatory mechan-
isms? PloS One. 9:e85837.
Owen J, Arendt J. (1992). Melatonin suppression in human
subjects by bright and dim light in antarctica: Time and
season-dependent effects. Neurosci Lett. 137:181–4.
Panda S, Nayak SK, Campo B, et al. (2005). Illumination of the
melanopsin signaling pathway. Science. 307:600–4.
Portaluppi F, Touitou Y, Smolensky MH. (2008). Ethical and
methodological standards for laboratory and medical biological
rhythm research. Chronobiol Int. 25:999–1016.
Pritchett D, Wulff K, Oliver PL, et al. (2012). Evaluating the
links between schizophrenia and sleep and circadian rhythm
disruption. J Neural Transm. 119:1061–75.
Provencio I, Jiang G, De Grip WJ, et al. (1998). Melanopsin: An
opsin in melanophores, brain, and eye. Proc Natl Acad Sci USA.
95:340–5.
Provencio I, Rodriguez IR, Jiang G, et al. (2000). A novel human
opsin in the inner retina. J Neurosci. 20:600–5.
Provencio I, Rollag MD, Castrucci AM. (2002). Photoreceptive net
in the mammalian retina. This mesh of cells may explain how
some blind mice can still tell day from night. Nature. 415:493.
doi: 10.1038/415493a.
Rajaratnam SM, Arendt J. (2001). Health in a 24-h society. Lancet.
358:999–1005.
Revell VL, Arendt J, Fogg LF, Skene DJ. (2006). Alerting effects of
light are sensitive to very short wavelengths. Neurosci Lett. 399:
96–100.
Revell VL, Arendt J, Terman M, Skene DJ. (2005). Short-wavelength
sensitivity of the human circadian system to phase-advancing
light. J Biol Rhythms. 20:270–2.
Roenneberg T, Wirz-Justice A, Merrow M. (2003). Life between
clocks: Daily temporal patterns of human chronotypes. J Biol
Rhythms. 18:80–90.
Ru
¨ger M, Scheer FAJL. (2009). Effects of circadian disruption on the
cardiometabolic system. Rev Endocr Metab Disord. 10:245–60.
Ru
¨ger M, Gordijn MCM, Beersma DGM, et al. (2006). Time-of-day-
dependent effects of bright light exposure on human psycho-
physiology: Comparison of daytime and nighttime exposure.
Am J Physiol Regul Integr Comp Physiol. 290:R1413–20.
Santhi N, Thorne HC, van der Veen DR, et al. (2012). The spectral
composition of evening light and individual differences in the
suppression of melatonin and delay of sleep in humans. J Pineal
Res. 53:47–59.
Sasseville A, Paquet N, Se
´vigny J, He
´bert M. (2006). Blue blocker
glasses impede the capacity of bright light to suppress mela-
tonin production. J Pineal Res. 41:73–8.
Skene DJ, Swaab DF. (2003). Melatonin rhythmicity: Effect of age
and Alzheimer’s disease. Exp Gerontol. 38:199–206.
Smith KA, Schoen MW, Czeisler CA. (2004). Adaptation of human
pineal melatonin suppression by recent photic history. J Clin
Endocrinol Metab. 89:3610–14.
Thapan K, Arendt J, Skene DJ. (2001). An action spectrum for
melatonin suppression: Evidence for a novel non-rod, non-cone
photoreceptor system in humans. J Physiol (Lond). 535:261–7.
Van de Kraats J, van Norren D. (2007). Optical density of the aging
human ocular media in the visible and the UV. J Optic Soc Am A
Opt Image Sci Vision. 24:1842–57.
Van Norren D, Vos JJ. (1974). Spectral transmission of the human
ocular media. Vision Res. 14:1237–44.
Van Someren EJW. (2000). Circadian and sleep disturbances in the
elderly. Exp Gerontol. 35:1229–37.
Van Someren EJW, Nagtegaal E. (2007). Improving melatonin
circadian phase estimates. Sleep Med. 8:590–601.
Van Someren EJW, Riemersma RF, Swaab DF. (2002). Functional
plasticity of the circadian timing system in old age: Light
exposure. Prog Brain Res. 138:205–31.
Van Someren EJ, Swaab DF, Colenda CC, et al. (1999). Bright light
therapy: Improved sensitivity to its effects on rest-activity
rhythms in Alzheimer patients by application of nonparametric
methods. Chronobiol Int. 16:505–18.
Warman VL, Dijk DJ, Warman GR, et al. (2003). Phase advancing
human circadian rhythms with short wavelength light. Neurosci
Lett. 342:37–40.
Weale RA. (1988). Age and the transmittance of the human
crystalline lens. J Physiol. 395:577–87.
Witting W, Kwa IH, Eikelenboom P, et al. (1990). Alterations in the
circadian rest-activity rhythm in aging and Alzheimer’s disease.
Biol Psychiatry. 27:563–72.
Zeitzer JM, Dijk DJ, Kronauer R, et al. (2000). Sensitivity of the
human circadian pacemaker to nocturnal light: Melatonin
phase resetting and suppression. J Physiol (Lond) 526 Pt. 3:
695–702.
8 M. C. Gime
´nez et al.
Chronobiology International
Chronobiol Int Downloaded from informahealthcare.com by 46.182.221.229 on 03/06/14
For personal use only.