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Evening use of light-emitting eReaders negatively

affects sleep, circadian timing, and

next-morning alertness

Anne-Marie Chang

a,b,1,2

, Daniel Aeschbach

a,b,c

, Jeanne F. Duffy

a,b

, and Charles A. Czeisler

a,b

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women’s Hospital, Boston, MA 02115;

Division of Sleep

Medicine, Harvard Medical School, Boston, MA 02115; and

Institute of Aerospace Medicine, German Aerospace Center, 51147 Cologne, Germany

Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved November 26,

2014 (received for review September 24, 2014)

In the past 50 y, there has been a decline in average sleep duration

and quality, with adverse consequences on general health. A

representative survey of 1,508 American adults recently revealed

that 90% of Americans used some type of electronics at least

a few nights per week within 1 h before bedtime. Mounting

evidence from countries around the world shows the negative

impact of such technology use on sleep. This negative impact on

sleep may be due to the short-wavelength–enriched light emitted

by these electronic devices, given that artificial-light exposure has

been shown experimentally to produce alerting effects, suppress

melatonin, and phase-shift the biological clock. A few reports have

shown that these devices suppress melatonin levels, but little is

known about the effects on circadian phase or the following sleep

episode, exposing a substantial gap in our knowledge of how this

increasingly popular technology affects sleep. Here we compare

the biological effects of reading an electronic book on a light-emit-

ting device (LE-eBook) with reading a printed book in the hours

before bedtime. Participants reading an LE-eBook took longer to

fall asleep and had reduced evening sleepiness, reduced melatonin

secretion, later timing of their circadian clock, and reduced next-

morning alertness than when reading a printed book. These results

demonstrate that evening exposure to an LE-eBook phase-delays

the circadian clock, acutely suppresses melatonin, and has important

implications for understanding the impact of such technologies on

sleep, performance, health, and safety.

sleep

chronobiology

phase-shifting

digital media

electronics

The use of electronic devices for reading, communication, and

entertainment has greatly increased in recent years. Greater

portability, convenience, and ease of access to reading materials

in electronic form add to the popularity of these devices. The use

of light-emitting devices immediately before bedtime is a con-

cern because light is the most potent environmental signal that

impacts the human circadian clock and may therefore play a role

in perpetuating sleep deficiency (1). The circadian-timing system

synchronizes numerous internal physiological and biochemical

processes, including the daily rhythm of sleep propensity (2), to

external environmental time cues. For optimal sleep duration

and quality, the timing of the sleep episode must be appropri-

ately aligned with the timing of the circadian clock. In humans,

exposure to light in the evening and early part of the night, even

at low intensity, suppresses the release of the sleep-facilitating

hormone melatonin (3–5) and shifts the circadian clock to a later

time (3, 6), both of which make it more difficult to fall asleep at

night. Light exposure in the biological evening/night also acutely

increases alertness (7, 8), but not much is known about its impact

on alertness the following day. Here we present results from a

randomized study comparing the effects of reading before bed-

time using a light-emitting eReader (LE-eBook) with reading a

printed book by reflected light. We examined circadian timing and

suppression of melatonin, polysomnographic (PSG) recordings of

sleep, and subjective and objective measures of sleepiness both in

the evening while reading and the following morning.

Results

Twelve healthy young adults (mean ±SD: 24.92 ±2.87 y; six

women) completed a 14-d inpatient protocol. The randomized,

crossover design (shown in Fig. 1) consisted of two conditions:

(i) reading an LE-eBook in otherwise very dim room light for

∼4 h before bedtime for five consecutive evenings, and (ii)

reading a printed book in the same very dim room light for ∼4h

before bedtime for five consecutive evenings. All participants

completed both reading conditions but were randomized to the

order. Hourly blood samples were collected during portions of

Significance

The use of light-emitting electronic devices for reading, com-

munication, and entertainment has greatly increased recently.

We found that the use of these devices before bedtime pro-

longs the time it takes to fall asleep, delays the circadian clock,

suppresses levels of the sleep-promoting hormone melatonin,

reduces the amount and delays the timing of REM sleep, and

reduces alertness the following morning. Use of light-emitting

devices immediately before bedtime also increases alertness at

that time, which may lead users to delay bedtime at home. Overall,

we found that the use of portable light-emitting devices immedi-

ately before bedtime has biological effects that may perpetuate

sleep deficiency and disrupt circadian rhythms, both of which can

have adverse impacts on performance, health, and safety.

Author contributions: A.-M.C., J.F.D., and C.A.C. designed research; A.-M.C. performed

research; A.-M.C. and D.A. analyzed data; and A.-M.C. and C.A.C. wrote the paper.

Conflict of interest statement: Dr. Czeisler has received consulting fees from or served as

a paid member of scientific advisory boards for: Boston Celtics; Boston Red Sox; Citgo Inc.;

Cleveland Browns; Merck; Novartis; Purdue Pharma LP; Quest Diagnostics, Inc.; Teva

Pharmaceuticals Industries Ltd.; Valero Inc.; Vanda Pharmaceuticals, Inc. Dr. Czeisler

currently owns an equity interest in Lifetrac, Inc.; Somnus Therapeutics, Inc.; Vanda Phar-

maceuticals, Inc., and between October 2012 and October 2013, Apple, Inc. and Microsoft,

Inc. Dr. Czeisler received royalties from McGraw Hill, Penguin Press/Houghton Mifflin

Harcourt, and Philips Respironics, Inc. and has received grants and research support from

Cephalon Inc., National Football League Charities, Philips Respironics, ResMed Founda-

tion, San Francisco Bar Pilots and Sysco. Dr. Czeisler is the incumbent of an endowed

professorship provided to Harvard University by Cephalon, Inc. and holds a number of

process patents in the field of sleep/circadian rhythms (e.g., photic resetting of the human

circadian pacemaker). Since 1985, Dr. Czeisler has also served as an expert witness on

various legal cases related to sleep and/or circadian rhythms, including matters involving

Bombardier, Inc.; Delta Airlines; FedEx; Greyhound; Michael Jackson’s mother and chil-

dren; Purdue Pharma, L.P.; United Parcel Service and the United States of America.

This article is a PNAS Direct Submission.

Freely available online through the PNAS open access option.

See Commentary on page 946.

Present address: Department of Biobehavioral Health, Pennsylvania State University,

University Park, PA 16802.

To whom correspondence should be addressed. Email: amchang@psu.edu.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.

1073/pnas.1418490112/-/DCSupplemental.

1232–1237

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the study for assessment of plasma melatonin concentrations.

Sleep latency (i.e., interval between lights-out and the timing of

sleep onset) was assessed from PSG recordings on the fourth and

fifth nights of each condition. In addition, we assessed total sleep

time (TST), sleep efficiency (the percentage of time in bed spent

asleep), and the time spent in each sleep stage. Participants rated

their sleepiness using a computerized Karolinska Sleepiness Scale

(KSS) (9) every evening and morning, and waking electroen-

cephalogram (EEG) measures were recorded on two evenings and

two mornings of each reading condition. More detailed methods

are described in Materials and Methods.

LE-eBook Effects on Levels and Circadian Timing of Melatonin. The

LE-e-book condition suppressed evening levels of melatonin by

55.12 ±20.12%, whereas the print-book condition showed no

suppression (−18.77 ±39.57%) as measured during the fifth

night (P<0.001; Fig. 2 Aand B). Dim light melatonin onset

was >1.5 h later on the day following the LE-eBook condition

(22:31 ±0:42) than in the print-book condition (21:01 ±0:49;

P<0.001; Fig. 2 Cand D).

Impact of Reading Condition on Sleep. In the LE-eBook condition,

participants averaged nearly 10 minlongertofallasleepthaninthe

print-book condition (mean ±SD, 25.65 ±18.78 min vs. 15.75 ±

13.09 min; P=0.009; mixed model; Fig. 3A). Participants also had

significantly less rapid eye movement (REM) sleep following the

LE-eBook condition (109.04 ±26.25 min vs. 120.86 ±25.32 min in

the print-book condition; P=0.03; Fig. 3 Band C), reflecting

a lower average rate of accumulation of REM sleep during sleep

(Fig. 3B). There was no difference between conditions in TST, sleep

efficiency, or the duration of non-REM sleep (stages 1–3; Fig. 3C)

in the sleep episode, which were scheduled for eight hours each.

Effects on Acute Evening Alertness and Morning Sleepiness. Reading

the LE-eBook was associated with decreased sleepiness in the

evening. An hour before bedtime, study participants rated

themselves as less sleepy (P<0.01; Fig. 3D), and their EEG

showed less power within the delta/theta frequency range (1.0–

7.5 Hz; Fig. 3 Dand E) in the LE-eBook condition. The fol-

lowing morning, however, the results for self-reported sleepiness

were reversed, with participants feeling sleepier the morning

after reading an LE-eBook the prior evening (P<0.001; Fig.

3D). Furthermore, not only did they awaken feeling sleepier, it

took them hours longer to fully “wake up”and attain the same

level of alertness than in the printed book condition.

Many eReaders Emit Short-Wavelength Light. Full spectral profiles

for the LE-eBook used by the study participants in the current

study and for the incident reflected light in the print book con-

ditions are shown in Fig. 4. Table 1 displays the illuminance

measures (cyanopic, melanopic, rhodopic, chloropic, and eryth-

ropic lux in comparison with photopic lux) for both the LE-eBook

and the reflected light of the print book, using the recently pro-

posed light measurement strategy that takes into account non–

image-forming retinal responses to light (see Methods). Light

readings for the LE-eBook as well as from several light-emitting

and non–light-emitting eReaders and other electronic devices are

shown in Table S1. Light from the LE-eBook is short-wavelength–

enriched, with a peak at 452 nm in the blue light range, compared

with broad-spectrum light (white light), with a peak at 612 nm. As

shown in Table S1, measurements from several other light-

emitting devices are also enriched for short-wavelength light.

Discussion

We found that, compared with reading a printed book in reflected

light, reading a LE-eBook in the hours before bedtime decreased

subjective sleepiness, decreased EEG delta/theta activity, and

suppressed the late evening rise of pineal melatonin secretion

during the time that the book was being read. We also found that,

compared with reading a printed book, reading an LE-eBook in

the hours before bedtime lengthened sleep latency; delayed the

phase of the endogenous circadian pacemaker that drives the

timing of daily rhythms of melatonin secretion, sleep propensity,

and REM sleep propensity; and impaired morning alertness.

These results indicate that reading an LE-eBook in the hours

before bedtime likely has unintended biological consequences

that may adversely impact performance, health, and safety. The

results of this study are of particular concern, given recent evi-

dence linking chronic suppression of melatonin secretion by

nocturnal light exposure with the increased risk of breast, co-

lorectal, and advanced prostate cancer associated with night-shift

work (for review, see ref. 10), which has now been classified as

a probable carcinogen by the World Health Organization (11, 12).

Moreover, the observation that the endogenous circadian mela-

tonin phase was 1.5 h later when reading an LE-eBook compared

with reading from a printed book suggests that using a light-

emitting device in the hours before bedtime is likely to increase

the risk of delayed sleep-phase disorder and sleep onset insomnia

(13), especially among individuals living in society who self-select

their bedtimes and wake times. Induction of such misalignment of

circadian phase is likely to lead to chronic sleep deficiency (1).

The decreased sleepiness before bedtime and longer sleep

latency we observed in the LE-eBook condition is likely due to

both an acute alerting effect of light and a delay of the circadian

timing system. Suppression of melatonin by exposure to evening

light may be an underlying mechanism by which light acutely

increases alertness, as seen in the present study and in previous

reports (14–19). Other studies, however, have not found a re-

lationship between alertness and melatonin levels during light

exposure (20, 21) or have shown changes in alertness induced by

light exposure during the day, when melatonin levels are at low

Fig. 1. Representative raster plot of the 14-d study protocol. Black bars

indicate the 10:00 PM–6:00 AM sleep episode in darkness. Gray bars denote

dim room light (∼3 lx of white light in the angle of gaze; Materials and

Methods), and white bars denote typical indoor room light (∼90 lx in the

angle of gaze). Striped bars show the constant posture (CP) procedures.

Reading sessions are marked either by the LE-eBook or the print-book and

symbols. Participants were randomized to the order of reading condition.

Ambient room light level for all reading sessions was dim (∼3 lx).

Chang et al. PNAS

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PHYSIOLOGY SEE COMMENTARY

or undetectable levels (22–24). The circadian-phase delay, as

marked by the endogenous melatonin rhythm, probably also

contributed to the delay of sleep onset that occurred after study

participants were reading the LE-eBook. The significant differ-

ence in sleep latency occurred even though the scheduled bedtime

was fixed at 10:00 PM each night during the study protocol to

ensure an 8-h sleep opportunity in bed. Thus, these results likely

underestimate the impact that use of these devices in the hours

before bedtime has on self-selected sleep timing and duration.

The effects of the LE-eBook on sleepiness the following

morning, however, cannot be due to the acute effects of light

observed the previous evening. Individuals were sleepier the

morning after reading in the LE-eBook condition than after

reading a printed book the evening before; however, the light

levels in the morning were identical for both reading conditions.

Therefore, the difference in morning sleepiness between the

conditions is most likely due to differences in the prior sleep

episode and/or the circadian-phase delay. Indeed, it did take

longer for participants to fall asleep after the LE-eBook condi-

tion, but there was no difference in average sleep duration and

the magnitude of the difference in sleep latency is unlikely to

account for the effect on alertness observed 8 h later. The dif-

ference in REM sleep between the conditions may have con-

tributed to the difference in morning sleepiness ratings. Given

that the majority of REM sleep occurs in the latter portion of the

sleep episode (25) (i.e., closer to wake time), participants had

significantly less REM sleep in the LE-eBook condition. Because

most spontaneous awakenings occur out of REM sleep (26, 27),

this reduction in REM sleep in the LE-eBook condition may

have also impacted sleepiness upon awakening. The significant

phase delay after the LE-eBook condition suggests that the

evening light from the LE-eBook phase delayed the circadian

clock, delaying the nadir of the circadian rhythm of sleep pro-

pensity (2) and thereby resulting in a robust, albeit indirect, effect

on morning sleepiness. A phase delay of the circadian clock is

consistent with the slower rise in the rate of accumulation of REM

sleep. The change in the timing of REM sleep likely represents

a delay in the circadian rhythm of REM sleep propensity, which is

temporally coincident with the sleep propensity rhythm (25).

The spectral composition of the light emitted by the LE-eBook

may explain why the magnitude of the melatonin-suppressing

and phase-shifting response observed was greater than would be

predicted for this moderately low level of light (3). In humans,

exposure to short-wavelength monochromatic light in the even-

ing has been shown to induce greater circadian and alerting

responses than exposure to the same number of photons of

longer-wavelength monochromatic light (17–19, 28–34), even

though the shorter-wavelength light may have a much lower il-

luminance level when measured in photopic lux (35). For this

reason, it has recently been proposed that lux is an inappropriate

measure for estimation of the impact of light on melatonin

suppression, circadian-phase shifting, and other non–image-

forming effects of retinal light exposure (35).

This study had a number of limitations. First, melatonin sup-

pression was assessed on the fifth and final evening of each

reading condition. Although it is likely that the phase shift in the

LE-eBook condition had already occurred by this time, melato-

nin suppression was calculated by using the shifted area under

the curve (AUC) from the following evening and thus should

control for any phase shift. Therefore, the greater suppression

seen was not due to an effect of a delayed phase in the LE-eBook

condition. Second, the duration of the evening reading sessions

were 4 h long. However, given that the average teenager in the

United States spends 7.5 h per day engaged in recreational

media plus time spent on homework—which both occur in the

late afternoon/evening, including the hour before bedtime (36),

and which both involve exposure to light-emitting screens (e.g.,

LE eReaders, computers, televisions, tablets, smartphones, video

game consoles, etc.)—the 4-h exposure interval used in this study is

likely in the range of screen time exposure experienced by millions

of Americans each evening. Third, in the present study, the

LE-eBook was set to maximum brightness throughout the 4-h

Fig. 2. Melatonin suppression (Aand B) and phase shifting (Cand D) during and after the LE-eBook and print book reading conditions. (A) Average

waveforms of melatonin (±SEM) during the fifth night of each reading condition. The black bar denotes the scheduled sleep episode (22:00–06:00). (B)

Percent suppression for each condition for each participant (filled symbols) and group average (±SEM; open symbols). (C) Average waveforms of melatonin

(±SEM) on the evening/night after each reading condition. (D) Average phase shift of melatonin onset for each condition for each participant (filled symbols)

and group average (±SEM; open symbols). The main effect of Condition was significant (P<0.05, mixed model).

1234

www.pnas.org/cgi/doi/10.1073/pnas.1418490112 Chang et al.

reading session, whereas, by comparison, the print-book condi-

tion consisted of reflected exposure to very dim light. However,

a number of newer models of light-emitting devices are even

brighter than those used in this study. Moreover, in this study, the

LE-eBook reader was held at a fixed distance (30–45 cm) from the

eye, further from the eye than many people might have chosen

(therefore reducing retinal light exposure), particularly for users

of smaller devices who may hold the smaller screens closer to the

eyes. Lastly, although the short-wavelength light from the LE-

eBook may have been responsible for the effects reported here,

this study did not include a light-emitting device with longer

wavelength for comparison, so our findings may be due to the

difference in irradiance level rather than spectral composition.

This study demonstrates that use of a light-emitting electronic

device in the hours before bedtime can have significant impact

on sleep, alertness, and the circadian clock. The 10-min-shorter

sleep latency after the print-book condition compared with sleep

latency after the LE-eBook condition is similar to the effect size

of eszopiclone treatment on sleep latency in patients with pri-

mary insomnia (37). Our findings provide evidence that the

electric light to which we are exposed between dusk and bedtime

has profound biological effects. Because technology use in the

hours before bedtime is most prevalent in children and adoles-

cents (36), physiological studies on the impact of such light ex-

posure on both learning and development are needed. Further

investigation of the physiological and medical effects of elec-

tronic devices is warranted, because the acute responses to the

short-wavelength–enriched light emitted by them may have

longer-term health consequences than previously considered.

Materials and Methods

Informed written consent was obtained from study participants before enroll-

ment in the study. The protocol was approved by the Partners Human Research

Committee, and all procedures were conducted according to the Declaration of

Helsinki. Study participants were compensated for their participation.

Study Participants and Screening Procedures. Twelve young healthy adults

completed the 14-d in-patient study protocol (six females and six males; mean

age ±SD: 24.92 ±2.87). Potential participants were extensively screened for

physical and psychological health, which included questionnaires, laboratory

tests, physical examination, EKG, eye examination, and psychological in-

terview to determine suitability for participation in the study. Participants

with chronic medical or psychological conditions or sleep disorders and those

taking prescription medications were excluded from study. History of night

work or shift work in the prior 3 y and travel across more than one time zone

in the previous 3 mo was also exclusionary. The presence of any eye or vision

abnormality or the inability to read in dim light without the use of corrective

lenses was exclusionary. Participants were instructed to refrain from use of

medications, drugs, alcohol, nicotine, or caffeinated products for 3 wk be-

fore admission, which was verified by toxicological testing upon admission

to the laboratory. Participants were also required to maintain a fixed 8-h

sleep schedule (10:00 PM to 6:00 AM), to complete a daily sleep/wake log,

and to call in their bedtimes and wake times every day during this 3-wk

interval. This sleep schedule was verified by wrist actigraphy (Actiwatch-L;

Philips/Respironics) during the week before admission.

Study Protocol. Participants lived in a private room in the Intensive Physio-

logical Monitoring Unit of the Center for Clinical Investigation of Brigham

and Women’s Hospital during the 14-d protocol. They were scheduled to

sleep on the identical fixed 8-h sleep schedule (10:00 PM to 6:00 AM) they

maintained for 3 wk before admission. The randomized, crossover protocol

design consisted of two conditions: (i) reading an LE-eBook (iPad; Apple Inc.,

Cupertino, CA) in otherwise very dim room light for ∼4 h before bedtime for

five consecutive evenings, and (ii) reading printed books in the same very

dim room light for ∼4 h before bedtime for five consecutive evenings

(Fig. 1). Primary outcome measures included sleep latency, timing and

amount of melatonin secretion, and self-reported ratings and EEG measures

of sleepiness/alertness. On three occasions (days 1, 7, and 13) participants

completed constant posture (CP) procedures for 4 h before and 4 h after the

8-h sleep episode.

Fig. 3. Sleep and sleepiness/alertness measures during and after the print-

book and LE-eBook reading conditions. (A) Mean (±SEM) sleep latency to

stage N2 in minutes for each reading condition. *P=0.009, mixed model. (B)

Mean (±SEM) accumulation of REM across 8-h sleep episode for each con-

dition. *P=0.029. (C) Mean duration (in minutes) of sleep stages N1 (white),

N2 (light gray), N3 (dark gray), and REM (patterned), and total sleep time

(TST; numbers at top of bar) for each reading condition. *P=0.029. (D)

Mean (±SEM) alertness ratings (circles) during and on the morning after each

reading condition with respect to clock hour. Mean delta/theta activity in

the waking EEG, power density in the 1.0–7.5 Hz range (squares), that was

derived from C3/M2 during the fourth and fifth reading sessions of each

condition is also shown. (E) Power density in the waking EEG during the

LE-eBook condition (open circles) expressed as a percentage of the printed-

book condition (100%; dashed line). Two-way mixed-model ANOVA on

log-transformed absolute power densities per 0.5-Hz was significant for

condition (P<0.04). Filled triangles at the bottom indicate EEG frequency

bins for which the difference between conditions was significant (P<0.05,

post hoc paired ttests).

Fig. 4. Spectral radiometric profile of the LE-eBook device (gray) and in-

cident light reflected by the printed book (black). The peak irradiance for

the LE-eBook eReader is ∼450 nm and for the reflected light is 612 nm.

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Reading Sessions and Lighting Conditions. A total of 10 reading sessions—5in

the LE-eBook condition and 5 in the printed book condition—were sched-

uled during the 14-d study. Participants were randomized to the order of

reading condition. Reading sessions began at 6:00 PM and ended at 10:00

PM just before bedtime, with a 15-min “break”scheduled at 8:45–9:00 PM.

For the first ∼3 h portion of the reading session (6:00–8:45 PM) participants

read while seated in a fixed location in the room. During the break, they

were allowed to stop reading and do other activities (walk around the room,

prepare for bed, etc.) until 9:00 PM, when they resumed the reading session.

For this last hour, participants read while seated in bed. During LE-eBook

reading sessions, the light-emitting device was set to maximum brightness

and placed in a stand that held it at a fixed angle. This stand was placed on

a table directly in front of the individual at a 30- to 45-cm distance from their

eyes. Participants were allowed to turn pages on the LE-eBook, but were

asked not to hold it while reading or make any adjustments to the settings.

During the printed book reading sessions, participants were allowed to hold

the book at any desired distance from their eyes. Participants selected their

own reading materials and supplied their own printed books. There were

two requirements regarding reading material in either electronic or printed

form: (i) it had to consist of printed text on the page (no pictures, illus-

trations, graphic novels, magazines, puzzles, etc.); and (ii) it had to be con-

sidered “pleasure”or “leisure”reading (no textbooks, reference books, or

coursework). A technician was present for all reading sessions to coordinate

and administer the reading session, ensure compliance of the participants,

and collect and record the light measurements.

Light readings were recorded during all reading sessions at multiple times:

at the beginning, at the end, and at 1 h intervals during the reading sessions.

Illuminance was measured by using an IL1400 radiometer/powermeter with

a SEL-033/Y/W detector (International Light, Inc., Peabody, MA) with the

sensor placed next to the participant’s eye and pointed at the LE-eBook or

printed book. For the LE-eBook reading condition, the distance between the

participant and the LE-eBook in the stand was adjusted (e.g., moved closer

or farther) if the light reading measured outside of the range of 30–50

photopic lux in the angle of gaze so that the light measurement was

maintained within range.

Ambient room lighting during the study was from ceiling-mounted 4100K

fluorescent lamps (Philips Lighting, Eindhoven, The Netherlands). During

reading sessions, CP, and upon waking, the room light was ∼0.0048 W/m

137 cm from the floor in the vertical plane with a maximum <0.025 W/m

187 cm from the floor in the horizontal plane anywhere in the room. During

the rest of the waking episodes, participants were in typical indoor room

lighting of ∼0.23 W/m

at 137 cm from the floor in the vertical plane, with

a maximum of 0.48 W/m

at 187 cm from the floor in the horizontal plane

anywhere in the room. During all scheduled sleep episodes, participants

were in darkness.

Radiometric light measurements of electronic devices were conducted in

the same light conditions and at the same distance (30–45 cm) as during the

reading sessions (described above). The irradiance output in the range of

380–780 nm at 4-nm intervals was converted to 1-nm intervals for calculation

of the human retinal photopigment illuminance measures (cyanopic, mela-

nopic, rhodopic, chloropic, and erythropic lux) (35).

CP Procedures. CP procedures occurred on day 1 (baseline) and on days 7 and

13, after the five consecutive nights of each reading condition for the as-

sessment of circadian phase of the melatonin rhythm. Participants remained

in bed in a semirecumbent posture with minimal activity for 4 h before and

4 h after the 8-h sleep episode. Room temperature and dim light conditions

remained constant during the CP; participants were in darkness fully

recumbent during the sleep episode.

Plasma Melatonin. Hourly blood samples were collected via an indwelling

forearm IV catheter during portions of the protocol for measurement of

melatonin levels. Samples were collected and then frozen (−80 °C) for

subsequent assay. Plasma melatonin samples were assayed (SolidPhase Inc.,

Portland, ME) using the BÜHLMANN Melatonin Radio-immunoassay (ALPCO

Diagnostics, Salem, NH), which has a functional sensitivity of 0.9 pg/mL and an

analytical sensitivity of 0.3 pg/mL, an intraassay precision of 7.9–8.2%, and

interassay precision of 11.7%.

Melatonin suppression was determined by using the AUC (by trapezoidal

method) during the 4-h reading session on the fifth night of each reading

condition and comparing it to the AUC during the corresponding 4-h time

window during the CP 24 h following the reading session. Circadian phase of

the dim light melatonin onset (DLMO) was calculated as the time at which levels

of melatonin rose above 25% of the peak-to-trough amplitude of a three-

harmonic waveform fitted to the 24-h melatonin data from the CP (38, 39).

Phase shifts were calculated as the difference between the DLMO from the

CP after the five-night reading condition and the DLMO from the CP before

the reading condition (i.e., shift =DLMO from day 13 –DLMO from day 7).

Because of missing blood samples during the fifth night of one reading

session, one study participant was excluded from analysis of melatonin

suppression. Another participant was excluded from analysis of DLMO timing

due to missing blood samples during one of the CPs. Therefore, melatonin

suppression and phase were each determined in 11 participants.

Sleep and Wake Recordings. PSG was recorded during the final two sleep epi-

sodes and for several hours before and after the sleep episode of each reading

condition for a total of four PSG recordings per study participant. Surface

electrodes were applied to specific locations on the face and scalp to record the

EEG (F3/M2, F4/M1, C3/M2, C4/M1, O1/M2, O2/M1), and the left and right

electrooculogram, and the submental electromyogram. The data were collected

by using the Vitaport-3 system (TEMEC Instruments B.V., Kerkrade, The Neth-

erlands). Signals were sampled at 256 Hz, low-pass filtered, and stored at 128 Hz.

For sleep recordings, data were scored in 30-s epochs according to standard

criteria (40). Sleep measures included latency to sleep onset (time from lights

off until the first occurrence of stage N2), TST, sleep efficiency (ratio of TST/

the time spent in bed), wake after sleep onset, and time spent in each stage

of sleep (N1, N2, N3, and REM). Wake recordings were scored in 30-s epochs

to verify wakefulness and identify any unintentional episodes of sleep.

Waking EEG recordings collected during the 3-min KDT were also quantified

by spectral analysis. They were first inspected visually to identify and remove

2-s epochs contaminated by artifacts such as eye blinks and eye or body

movements. The data were then subjected to a Fast Fourier Transform

procedure, and power spectra were calculated for 2-s epochs over the fre-

quency range of 0.5–20.0 Hz in 0.5-Hz bins.

Subjective and Objective Measures of Sleepiness/Alertness. Subjective sleepi-

ness was measured with a computer-administered KSS. The KSS is a 9-point

Likert scale with all numbers having valid point values, but only the odd numbers

have descriptions: 1 representing “extremely alert,”3representing“alert,”

5representing“neither alert nor sleepy,”and 9 representing “extremely

sleepy”(9, 41). Study participants completed the KSS each evening ∼1hbefore

bedtime and several times each morning: within 1–5 min after scheduled wake

time and then every 4–10 min for 1 h after wake time. Participants typically

completed the KSS in <30 s, and the computer screen was set to a dim light

level of <8lx(0.025W/m

) from the participants’eye in the angle of gaze.

Participants also completed the Karolinska Drowsiness Test (KDT; ref. 9)

(3 min eyes open) during which they were instructed to relax, keep eyes open,

and maintain a fixed gaze on a black dot in front of them while avoiding any

movements or frequent blinking. The KDT allowed for waking EEG recording

under standardized and reproducible conditions where artifacts from move-

ment were minimized.

Table 1. Photopic illuminance and human retinal photopigment-weighted illuminance

measures from the LE-eBook device and light reflected by the printed book

Device Photopic lux Cyanopic lux Melanopic lux Rhodopic lux Chloropic lux Erythropic lux

Print book* 0.91 0.45 0.65 0.68 0.81 0.92

LE-eBook 31.73 31.64 31.03 31.68 31.84 30.69

Radiometric light readings were taken in the same dim background room light conditions and from the same

distance (38–40 cm). The LE-eBook was set to the maximum brightness setting.

*Illuminance in the printed book condition was measured from the ambient room light emitted by the ceiling

fixtures and reflected by the book, using the recently proposed light measurement strategy that takes into

account non–image-forming retinal responses to light (see Methods).

1236

www.pnas.org/cgi/doi/10.1073/pnas.1418490112 Chang et al.

Statistical Analysis. Statistical analyses were performed by using SAS (Version

9.2; SAS Institute, Cary, NC). We compared sleep and circadian measures

between reading conditions using a mixed model analysis with factors Con-

dition (LE-eBook or printed book), Order, and their Interaction (Condition X

Order). Mixed model was also used for comparing KSS score and EEG power

with factors Condition,Order,Time (repeated measures in the first hour after

awakening), and the Interaction (Condition XTime). Post hoc paired Student

ttests were used for comparisons between conditions for subjective and

objective measures of sleepiness. Pvalues <0.05 were considered significant.

ACKNOWLEDGMENTS. We thank the study participants, the staff of the

Brigham and Women’s Hospital Center for Clinical Investigation [part of the

Harvard Catalyst Clinical and Translational Science Center (CTSC)], the staffs

of the Division of Sleep Medicine Sleep and EEG Core and Chronobiology

Core, Dayna Bradstreet for significant contributions to recruitment and con-

duct of the study, and Michael Herf and Robert Lucas, Ph.D. for assistance

with the spectral light analysis. We also thank Wei Wang, Ph.D. for assis-

tance with statistical analysis supported by the Harvard Catalyst CTSC

[National Center for Research Resources (NCRR) and the National Center

for Advancing Translational Sciences, National Institutes of Health (NIH)

Award UL1 RR025758 and financial contributions from the Brigham and

Women’s Hospital (BWH), Harvard University, and its other affiliated aca-

demic health care centers]. This work was supported by NIH Grant

R01HL077453. The inpatient studies were conducted in the Harvard CTSC,

supported by NCRR Grant UL1 RR025758. A-M.C. was supported in part by

NIH Grant K01HL115458. D.A. was supported in part by the German Aero-

space Center. J.F.D. was supported in part by NIH Grant R01HL094654. C.A.C.

was supported in part by NASA NNX10AF47G and the National Space Bio-

medical Research Institute through NASA NCC 9-58.

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