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The effect of caffeine on subsequent sleep: A systematic review and
meta-analysis
Carissa Gardiner
a
,
b
, Jonathon Weakley
a
,
b
,
c
,
*
, Louise M. Burke
d
, Gregory D. Roach
e
,
Charli Sargent
e
, Nirav Maniar
b
,
f
, Andrew Townshend
a
,
b
, Shona L. Halson
a
,
b
a
School of Behavioural and Health Sciences, Australian Catholic University, Brisbane, Australia
b
Sports Performance, Recovery, Injury and New Technologies (SPRINT) Research Centre, Australian Catholic University, Brisbane, Australia
c
Carnegie Applied Rugby Research (CARR) Centre, Institute of Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UK
d
Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
e
Appleton Institute for Behavioural Science, Central Queensland University, Wayville, Australia
f
School of Behavioural and Health Sciences, Australian Catholic University, Melbourne, Australia
article info
Article history:
Received 16 August 2022
Received in revised form
22 January 2023
Accepted 26 January 2023
Available online 6 February 2023
Keywords:
Stimulant
Adenosine
Sleepiness
Sleep disruption
Sleep behaviours
Sleep recommendations
abstract
The consumption of caffeine in response to insufficient sleep may impair the onset and maintenance of
subsequent sleep. This systematic review and meta-analysis investigated the effect of caffeine on the
characteristics of night-time sleep, with the intent to identify the time after which caffeine should not be
consumed prior to bedtime. A systematic search of the literature was undertaken with 24 studies
included in the analysis. Caffeine consumption reduced total sleep time by 45 min and sleep efficiency by
7%, with an increase in sleep onset latency of 9 min and wake after sleep onset of 12 min. Duration
(þ6.1 min) and proportion (þ1.7%) of light sleep (N1) increased with caffeine intake and the duration
(11.4 min) and proportion (1.4%) of deep sleep (N3 and N4) decreased with caffeine intake. To avoid
reductions in total sleep time, coffee (107 mg per 250 mL) should be consumed at least 8.8 h prior to
bedtime and a standard serve of pre-workout supplement (217.5 mg) should be consumed at least 13.2 h
prior to bedtime. The results of the present study provide evidence-based guidance for the appropriate
consumption of caffeine to mitigate the deleterious effects on sleep.
©2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
1. Introduction
Sleep is an essential component of physical and emotional
wellbeing [1]. Current recommendations outline the need for
healthy adults to achieve seven to nine h of sleep per night [2].
Despite the innate requirement to attain healthy sleep, insufficient
sleep is a growing public health challenge. It is estimated that
20e45% of the population around the world are sleep deprived
[3e6]. Short and fragmented sleep bouts may result in impaired
cognitive functioning, diminished mood, and increased risk of ac-
cident or injury [1]. When sustained chronically, insufficient sleep
contributes to the risk of health epidemics with a heightened
probability of cardiometabolic disease and mental health disorders
[7,8]. Negative outcomes of this nature carry a significant cost to the
individual and society, through compromised health and reduced
productivity [9]. As such, recommendations for positive sleep be-
haviours have been developed to provide individuals with strate-
gies to optimise their sleep quantity and quality [10 ].
A common behavioural recommendation to optimise sleep is to
avoid caffeine in close proximity to bedtime [10]. Caffeine is a
widely accessible psychostimulant found in foods, supplements,
and medications [11]. With its status as a socially acceptable drug,
caffeine is consumed by approximately 80% of the world's popu-
lation [12]. Caffeine is an adenosine antagonist suggested to acutely
reduce sleep pressure through action on the homeostatic compo-
nent of sleep-wake regulation [13]. This action stimulates the
central nervous system with a resulting decrease in the perception
of fatigue and sleepiness [14]. For this reason, caffeine is commonly
consumed throughout the day in response to insufficient sleep to
promote a state of wakefulness [15]. However, the use of caffeine to
stimulate wakefulness may result in impaired onset and mainte-
nance of subsequent sleep [16], potentially creating a cycle of
diminished sleep and subsequent caffeine reliance [17].
*Corresponding author. School of Behavioural and Health Sciences, Australian
Catholic University, Brisbane, Australia.
E-mail address: Jonathon.Weakley@acu.edu.au (J. Weakley).
Contents lists available at ScienceDirect
Sleep Medicine Reviews
journal homepage: www.elsevier.com/locate/smrv
https://doi.org/10.1016/j.smrv.2023.101764
1087-0792/©2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sleep Medicine Reviews 69 (2023) 101764
The half-life of caffeine displays large variation across healthy
adults (two to 10 h) [18], making it difficult to identify the appro-
priate time of day to discontinue caffeine intake to minimise dis-
ruptions to sleep. Currently, recommendations for positive sleep
behaviours display a lack of precision in terminology. For example,
the American Academy of Sleep Medicine warns that caffeine may
cause sleep disruption if taken “too close to bedtime”[19], while
the Sleep Health Foundation suggests consumers should “avoid
caffeine close to bedtime”[20]. The lack of precision in these rec-
ommendations may limit the ability of consumers to make
evidence-based decisions regarding the timing of their caffeine
intake. A previous systematic review by Clark and Landolt [21]
confirmed the negative association between caffeine and subse-
quent sleep. However, this review did not include a quantitative
synthesis of the findings. In particular, the impact of the dose and
timing of caffeine intake on subsequent sleep has yet to be quan-
tified systematically. The aims of this systematic review and meta-
analysis are to: 1) establish the level of evidence for the effect of
caffeine intake on the characteristics of subsequent sleep (i.e., total
sleep time, sleep onset latency, rapid eye movement (REM) onset
latency, wake after sleep onset, sleep efficiency, sleep architecture,
and subjective sleep quality; 2) quantify the effect of caffeine intake
on the characteristics of subsequent sleep; and 3) quantify the in-
fluence of the dose and timing of caffeine intake on the charac-
teristics of subsequent sleep. The review will provide evidence-
based guidance to support recommendations regarding caffeine
consumption to minimise decrements in subsequent sleep.
2. Methods
This systematic review and meta-analysis was conducted in
accordance with the Preferred Reporting Items for Systematic Re-
views and Meta Analyses (PRISMA) 2020 guidelines [22]. The
protocol was registered with the International Prospective Register
of Systematic Reviews (PROSPERO ID: CRD42021267812).
2.1. Databases and search strategy
Four electronic databases were systematically searched from
their inception until June 2021. These databases were CINAHL,
MEDLINE, SPORTDiscus, and Web of Science. The search strategy
was developed using the PICO (Population, Intervention, Compar-
ison, and Outcome) framework [22] and the search terms are
detailed in Table 1. The terms employed within each component
were searched using the Boolean operator “OR”and each compo-
nent was linked together through the Boolean operator “AND”to
run the search. Results were limited to peer-reviewed journal ar-
ticles published in the English language that examined humans
only. All search records were exported to the Endnote reference
managing software (V20, Thomson Reuters, Philadelphia, USA).
2.2. Study screening and selection
Duplicate results were removed, and the remaining articles
were screened by two independent reviewers (CG and JW) using
the Covidence systematic review software (Veritas Health Innova-
tion, Melbourne, Australia). Discrepancies in decisions were
resolved by a third reviewer (SH) when necessary. Title and abstract
screening were initially completed to remove articles outside the
scope of the review. For all remaining articles, full-text versions
were located for screening. Studies were included if they: 1)
employed a healthy adult population aged 18e65 years; 2) used a
controlled experimental design; 3) administered a measured
caffeine dose; and 4) implemented a protocol involving a measured
sleep episode initiated in the subsequent evening with a morning
waking. In instances where additional interventions were exam-
ined, such as exercise, studies were included if the effect of caffeine
could be isolated. Studies were excluded if: 1) the duration of
measured sleep was <90 min (defined as a napping protocol); 2)
the caffeine dose was administered >18 h prior to the scheduled
sleep episode; 3) the caffeine dose was administered after the onset
of the scheduled sleep episode; or 4) measures of sleep were not
reported.
2.3. Assessment of reporting quality
The methodological reporting quality of included studies was
assessed using the Cochrane Risk of Bias (RoB 2) tool for crossover
trials [23]. The tool specifies six domains to assess potential sources
of bias including that arising from the randomisation process,
period and carryover effects, deviations from the intended inter-
vention, missing outcome data, measurement of the outcome, and
selection of the reported result. Each domain is comprised of sig-
nalling questions that can be answered as “yes”,“probably yes”,
“no”,“probably no”,or“no information”. A risk of bias judgement is
generated for each domain by a pre-determined algorithm with
classifications of “low risk”,“some concern”,or“high risk”. Judge-
ments across domains are used to classify the overall risk of bias. A
study was deemed to be “low risk”only if this was true for all
domains. If not, a study was assessed for overall risk in accordance
with the highest risk of bias recorded across each domain.
2.4. Data extraction and synthesis
For each study, data were extracted into a pre-defined Microsoft
Excel (V2201, Microsoft, Washington, USA) template under the
categories of study details, characteristics of the participants, study
protocol, objective measurement tools, subjective measurement
tools, and sleep outcome measures. For the purpose of this review,
time in bed was defined as the period between lights off and lights
on with total sleep time defined as the time spent asleep during this
period. Sleep efficiency was calculated as the percentage of time in
bed spent asleep. Sleep onset latency was accepted as the time from
lights out to the first epoch of sleep, except where the author
defined this to occur beyond non-rapid eye movement (NREM)
stage one (N1) [24e30]. Where activity monitoring was employed
[31e33], sleep onset latency was accepted as the period between
bedtime and the start of sleep. REM onset latency was accepted as
the time from sleep onset to the first occurrence of REM, except in
one study where it was defined as the first occurrence of REM from
the first occurrence of NREM stage two (N2) [30]. Wake after sleep
onset was defined as the duration of time spent awake after the
onset of sleep and before the final awakening. Outcome data
Abbreviations
CI confidence interval
EEG electroencephalogram
PRISMA Preferred Reporting Items for Systematic Reviews
and Meta-Analyses
N1 non-rapid eye movement stage one
N2 non-rapid eye movement stage two
N3 non-rapid eye movement stage three
N4 non-rapid eye movement stage four
NREM non-rapid eye movement
REM rapid eye movement
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
2
reported as NREM stage three (N3) and NREM stage four (N4)
[28e30,34e36] or slow wave sleep [25,27,37e41] were classified as
N3 sleep in line with the current American Academy of Sleep
Medicine guidelines [42], except for two studies [24,43] where N3
and N4 were reported independently. Outcome data reported as a
combination of distinctly different sleep stages [27,36]were
excluded from the meta-analysis. All data were extracted as the
mean and standard deviation for each study condition. Where
mean data were reported with the standard error of the mean
[24,30,31,34,37,40,44e46], confidence interval (CI) [25], or coeffi-
cient of variability [35], calculations were performed to transform
these measures into standard deviations. One study [26] did not
report a measure of variance and was not included in the quanti-
tative synthesis of the review. Where necessary, corresponding
authors were contacted for further information.
2.5. Meta-analysis and meta-regression
Meta-analysis was performed using the “metafor”[47] and
“clubSandwich”[48] packages in the R programming language (R
Core Team, 2021). For each outcome variable, the mean difference
effect size and sampling variance for each study were calculated.
Since all included studies utilised a cross-over design, dependency
was accounted for when computing sampling variance using pre-
viously described methods [49]. However, none of the included
studies reported the required correlation between outcomes in the
two conditions (control and caffeine). Through author contact,
correlation data were obtained for four studies [41,45,46,50], which
were included in the computations. For the remaining studies, the
pooled correlation value was used from the four studies where
correlation data were obtained. Due to the uncertainty from
deriving the correlation from a subset of studies, a sensitivity
analysis was conducted to ensure the results were robust. Further
details of handling of correlation data and the sensitivity analysis
can be found in Supplementary Fig. S1.
Effect sizes were then pooled across studies using a random
effects model, with a restricted maximum likelihood method used
to estimate between-study variance. It was noted that some studies
included more than one caffeine condition, and therefore provided
multiple effect sizes estimates, where both the effect sizes and
standard errors were correlated. To account for these de-
pendencies, a nested random effects structure was used and a
covariance matrix was imputed. Since there is uncertainty around
the correlation value used for imputation, robust inference
methods with an adjustment for small samples was used, so that
the interpretation of fixed effects were unbiased [51]. Where
additional data were available related to the dose of caffeine and
the timing of intake, moderator (meta-regression) analysis was
performed to assess the influence of these potential effect modi-
fiers on sleep outcomes. Where a significant effect for timing of
intake was found, the meta-regression model was used to estimate
the cut-off time (i.e., the latest time at which caffeine can be
consumed without having a statistically significant effect on the
sleep outcome of interest). Since the meta-regression model esti-
mates the effect size and 95% CI for any given dose and timing of
caffeine, the cut-off time was determined as the first timepoint at
which the 95% CI of the effect size did not cross the null effect for a
given dose. Dosages were selected to reflect commonly consumed
caffeine products ea cup of black tea (typical caffeine content:
47 mg per 250 mL [55]), a cup of coffee (typical caffeine content:
107 mg per 250 mL [56]), and a standard serve of pre-workout
supplement (typical caffeine content: 217.5 mg [57]). Additionally,
the number of effect sizes (k) and participants (n) included in each
meta-analytic model are reported. A full summary of all meta-
analytical models is provided in Supplementary Tables S1eS4.
3. Results
3.1. Study selection and characteristics
The screening process identified 24 studies for inclusion in the
review as outlined in the PRISMA flow diagram (Fig. 1). All included
studies employed a controlled crossover design with the inter-
vention administered as an acute daily dose on the day of the
measured sleep bout, except for five studies where the daily dose
was administered for consecutive days including four [32,40], six
[52], nine [37], and 14 [46] days. The key characteristics of each
included study are presented in Table 2.
3.2. Assessment of reporting quality
Five studies were deemed to be at a high risk of bias. Two of
these studies [35,36] presented sleep staging data for the first
portion of the sleep bout (i.e., six and three h, respectively) without
providing context for this decision in the introduction or method,
and three of these studies [26,43,53] did not implement a washout
period with conditions administered across consecutive nights.
Without a wash-out period, the results may be confounded by
carryover effects from exposure to the prior condition. Three
additional studies [30,34,40] were deemed to be of some concern
with the absence of appropriate randomisation of interventions
with all participants exposed to the control condition followed by
the caffeine condition. The remaining 16 studies were deemed to be
of low risk of bias. A summary of the risk of bias assessment is
displayed in Table 3.
3.3. Objective sleep outcomes
3.3.1. Total sleep time
Twenty studies [24e27,29e37,40,41,43e46,50] reported mea-
sures of objective total sleep time. Caffeine consumption was
associated with 45.3 min less total sleep time compared to the
Table 1
Search strategy.
Population or Problem Intervention Comparison Outcome
Keywords “sleep”NOT “deprivation”NOT “dementia”NOT
“Parkinson*”NOT “sclerosis”NOT “cancer”NOT “infant”
NOT “neonate”NOT “child*”NOT “mice”NOT “mouse”NOT
“rat”NOT “rats”NOT “macaque*”
“caffeine”OR
“caffeinated”OR “1,3,7-
trimethylxanthine”OR
“coffee”
N/A “sleep quality”OR “quality of sleep”OR “sleep quantity”OR
“sleep duration”OR “sleep time”OR “time in bed”OR
“sleep efficiency”OR “sleep latency”OR “sleep onset”OR
“sleep stage”OR “sleep architecture”OR “slow wave”OR
“non rapid eye movement”OR “NREM”OR “rapid eye
movement”OR “REM”OR “sleep-wake”OR “sleep
maintenance”OR “sleep satisfaction”OR “wake after sleep”
OR “sleep arousal”OR “sleep disturbance”OR “awakening
from sleep”OR “EEG”OR “electroencephalogram”
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
3
control condition (Fig. 2a; 95%CI ¼29.0 to 61.5 min, k ¼37, n ¼340,
p<0.001). Meta-regression analysis (k ¼30, n ¼262) revealed a
significant influence of timing of intake (p ¼0.032) and the final
dose of caffeine (p ¼0.037) on total sleep time. The mean difference
in total sleep time between the control condition and a given dose
of caffeine decreased by 2.8 min (95%CI ¼0.4 to 5.2 min) for every
additional hour that caffeine was consumed prior to bedtime. In
addition, the mean difference in total sleep time between groups
increased by 0.2 min (95%CI ¼0.01 to 0.31 min) for every 1-mg
increase in caffeine dose.
3.3.2. Sleep onset latency
Nineteen studies [24e30,33e37,40,41,43e46,50] reported
measures of objective sleep onset latency. Sleep onset latency was
9.1 min longer in the caffeine condition compared to the control
condition (Fig. 2a; 95%CI ¼3.8 to 14.4 min, k ¼32, n ¼280,
p¼0.002). This effect was not moderated by the timing of intake
(p ¼0.071) or the final dose of caffeine (p ¼0.960) (k ¼26,
n¼232).
3.3.3. REM onset latency
Ten studies [24,29,30,34,35,37,40,44,46,50] reported measures
of objective REM onset latency. No significant differences in REM
onset latency were observed between the caffeine condition and
the control condition (Fig. 2a; mean difference ¼1.5 min, 95%CI ¼
8.1 to 5.2 min, k ¼14, n ¼114, p ¼0.581). This effect was not
moderated by the timing of intake (p ¼0.364) or the final dose of
caffeine (p ¼0.279) (k ¼13, n ¼108).
3.3.4. Wake after sleep onset
Thirteen studies [24,25,27,29,30,34,35,37,40,43,44,46,50] re-
ported measures of objective wake after sleep onset. The duration
of wake after sleep onset was 11.8 min longer in the caffeine con-
dition compared to the control condition (Fig. 2a; 95%CI ¼2.5 to
21.0 min, k ¼17, n ¼148, p ¼0.019). This effect was not moderated
by the timing of intake (p ¼0.205) or the final dose of caffeine
(p ¼0.419) (k ¼13, n ¼121).
3.3.5. Sleep efficiency
Eighteen studies [24e30,33e35,37,40,41,43e46,50] reported
measures of objective sleep efficiency. Sleep efficiency was reduced
by 7.0% in the caffeine condition compared to the control condition
Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) flow diagram outlining the process for selection of studies.
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
4
Table 2
Summary characteristics of the included studies.
Study Sample
(n)
Age (years) Habitual caffeine intake
(per day)
Caffeine dose
(mg)
Proximity to
bedtime
(min)
Method of
sleep
measurement
Reported sleep outcomes of
interest
Significant findings
(compared to
control)
Alford et al.,
1996 [24]
3 M; 3 F 23.8
b
Undisclosed Abstain across
study
4&8kg
1
~20 PSG
LSEQ
TST, SE, WASO, SOL, sleep stages
GTS, QOS, AFS
[SOL, WASO
YTST, SE, N3
[GTS
YQOS
Ali et al., 2015
[53]
10 F 23.6 ±4.2 <300 mg Abstain within
48 h prior to intervention
6kg
1
Undisclosed LSEQ GTS, QOS, AFS [GTS
YQOS
Bonnet &
Arand, 2003
[41]
35 M &
F
18 to 39
a
<250 mg Abstain across
study
400 30 PSG TST, SE, WASO, SOL, sleep stages [WASO, N1
YTST, SE, N2, N3, N4,
REM
Brezinova,
1974 [42]
2M;4F 56
b
150e440 mg No abstinence
period
300 15 PSG
VAS
TST, SOL, awake &sleep stages
d
Subjective quality
[SOL, awake &N1,
N2
YTST, N3, REM
YQuality
Carrier et al.,
2007 [43]
7M;
10 F
37.2 ±14.4 1 to 3 beverages Abstain on
day of intervention
200 As 2 equal
doses
60 &180 PSG TST, SE, WASO, SOL, ROL, sleep
stages
[SOL, N1
YSE, N2, N3
Drake et al.,
2013 [26]
6 M; 6 F 29.3 ±7.6 <5 beverages Abstain on day
of intervention
400 0, 180, &360 In-home PSG
Sleep diary
TST, SE, WASO, SOL, sleep stages
Subjective TST, WASO, SOL,
quality
[SOL, WASO
YTST, SE, N1 &N2,
N3
[SOL
YTST
Drake et al.,
2006 [27]
6 M; 4 F 32.6 ±15.5 <3 beverages Abstain on day
of intervention
3kg
1
60 PSG SE, SOL, sleep stages [SOL
4 M; 6 F 34.2 ±13.7 YSE
Drapeau et al.,
2006 [44]
6 M; 6 F 23.8 ±2.3 1 to 3 beverages 200 As 2 equal
doses
60 &180 PSG TST, SE, SOL, sleep stages, qEEG [SOL, sigma
frequency
5 M; 7 F 50.3 ±5.6 Abstain on day of
intervention
YTST, SE, N2, delta
frequency
Hindmarch
et al., 2000
[30]
15 M;
15 F
27.3 ±1.64 160 mge710 mg Abstain
within 48 h prior to
intervention
150, 300 &600
As 4 equal doses
120, 360,
600, &840
Activity
monitoring
LSEQ
TST GTS, QOS YTST
[GTS
YQOS
James, 1998
[51]
18 M;
18 F
23
b
3 to 5 beverages 5.2 kg
1
Undisclosed Sleep diary &
VAS
Subjective TST, quality No significant
changeAbstain across study As 3 equal doses
Júdice et al.,
2013 [31]
30 M 24.5 ±4.8 <100 mg 5 kg
1
Undisclosed Activity
monitoring
TST YTST
Abstain within 48 h prior to
intervention
As 2 equal doses
Karacan et al.,
1976 [25]
18 M 20 to 30
a
1 to 4 beverages 1.1, 2.,3 &
4.6 kg
1
30 PSG TST, SE, SOL, sleep stages [SOL, N1, REM
YTST, SE, N3
[SOL
YTST, quality
Abstain on day of
intervention
Sleep diary Subjective TST, SOL, quality
Landolt et al.,
1995 [29]
9 M 22.4 ±1.2 1 to 2 beverages 200 950 PSG TST, SE WASO, SOL, ROL, sleep
stages, qEEG
[SOL, sigma
frequency
Abstain across study YTST, SE, delta
frequency
Landolt et al.,
1995 [33]
8 M 23.3 ±0.9 1 to 3 beverages 100 0 PSG TST, SE, WASO, SOL, ROL, sleep
stages, qEEG
[SOL, sigma
frequency
Abstain on day of
intervention
YTST, SE, delta
frequency
Lloret-Linares
et al., 2012
[52]
26 M;
37 F
30.5 ±12 <3 beverages 4.5 &90 ~122 Sleep diary &
VAS
Subjective SOL, quality [SOL
No abstinence period YQuality
Miller et al.,
2014 [49]
6 M 27.5 ±6.9 <300 mg 6 kg
1
Undisclosed PSG TST, SE, WASO, SOL, ROL, sleep
stages
[SOL, WASO
Abstain within 48 h prior to
intervention
As 2 equal doses YTST, SE, REM
Nicholson &
Stone, 1980
[34]
6M
6M
26
b
24
b
Undisclosed
Abstain across study
100, 200, &300 0 PSG
VAS
TST, SE, SOL, ROL, WASO, sleep
stages
e
Subjective SOL, quality
[WASO, N1
YTST, SE, N3
YQuality
Okuma et al.,
1982 [28]
8 M 21.1
b
1 to 2 beverages 150 30 PSG TST, SE, WASO, SOL, ROL, sleep
stages
[SOL, WASO
Abstain within 48 h prior to
intervention
YTST, SE, N2
Paterson et al.,
2009 [23]
12 M 24.9
b
<600 mg 150 60 In-home PSG TST, SE, SOL, ROL, WASO, sleep
stages, qEEG
[SOL
Abstain on day of
intervention
YTST, SE, N2
Ramos-Campos
et al., 2019
[32]
15 M 23.7 ±8.2 250e572 mg 6 kg
1
Undisclosed Activity
monitoring
KSD
TST, SE, SOL YSE
Abstain within 48 h prior to
intervention
Quality, EOFA YQuality, EOFA
Robillard et al.,
2015 [39]
10 M;
12 F
23.5 ±1.9 1 to 3 beverages 200 &400 60 &180 PSG TST, SE, SOL, sleep stages, qEEG [SOL, N1, sigma
frequency
12 M;
13 F
51.7 ±11.5 Abstain on day of
intervention
As 2 equal doses YTST, SE, N2, N3,
REM, delta
frequency
Weibel et al.,
2021 [35]
20 M 26.4 ±4 300e600 mg 150 &450 480, 700, &
910
PSG TST, SE, WASO, SOL, ROL, sleep
stages, qEEG
YSigma frequency
(continued on next page)
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
5
(Fig. 2b; 95%CI ¼4.0 to 10.0%, k ¼31, n ¼274, p <0.001). This effect
was not moderated by the timing of intake (p ¼0.058) or the final
dose of caffeine (p ¼0.193) (k ¼25, n ¼226).
3.3.6. Sleep architecture
Eighteen studies [24e30,34e37,40,41,43e46,50] reported
measures of objective sleep architecture. Compared to the control
condition, caffeine consumption increased (þ6.1 min) the duration
of sleep in N1 (Fig. 2c; 95%CI ¼2.3 to 9.9 min, p ¼0.012), had no
effect on the duration of sleep in N2 (Fig. 2c; mean
difference ¼23.3 min, 95%CI ¼56.1 to 9.6 min, p ¼0.120),
reduced (11.4 min) the duration of sleep in the combined stages
N3 and N4 (Fig. 2c; 95%CI ¼4.3 to 18.5 min, p ¼0.012) (k ¼35,
n¼127), and had no effect on the duration of REM sleep (Fig. 2c;
mean difference ¼4.4 min, 95%CI ¼10.5 to 1.6 min, k ¼17,
n¼163, p ¼0.127). Compared to the control condition, caffeine
consumption increased (þ1.7%) the proportion of sleep in N1
(Fig. 2b; 95%CI ¼0.2 to 3.1%, p ¼0.033), had no effect on the pro-
portion of sleep in N2 (Fig. 2b; mean difference ¼2.8%, 95%
CI ¼6.4 to 0.4%, p ¼0.080), reduced (1.4%) the proportion of
sleep in the combined stages N3 and N4 (Fig. 2b; 95%CI ¼0.2 to
2.6%, p ¼0.028) (k ¼48, n ¼172), and had no effect on the pro-
portion of REM sleep (Fig. 2b; mean difference ¼0.02%, 95%
CI ¼1.67 to 1.6%, k ¼19, n ¼172, p ¼0.980).
3.3.7. Quantitative electroencephalogram (EEG)
Six studies [24,30,34,37,41,45] reported measures of EEG spec-
tral power during NREM sleep. A meta-analysis was not conducted
for EEG spectral power given the limited number of studies
reporting this outcome. Four studies [30,34,41,45] reported a sig-
nificant reduction in spectral power within the delta frequency
range (~0.5e4 Hz) in the caffeine condition compared to the control
condition and two studies [24,37] reported no significant change
compared to the control condition. Four studies [30,34,41,45]re-
ported a significant increase in spectral power within the sigma
frequency range (~12e16 Hz) in the caffeine condition compared to
the control condition, one study [37] reported a significant decrease
within the sigma frequency range compared to the control condi-
tion, and one study [24] reported no significant change compared
to the control condition.
3.3.8. Subjective sleep outcomes
Twelve studies [25e27,31,33,35e37,40,52e54] reported mea-
sures of subjective sleep through varying self-report tools detailed
in Table 2. A meta-analysis was not conducted for subjective sleep
due to a lack of homogeneity in the measured outcomes. Three
studies reported measures of subjective total sleep time with two
[26,27] identifying a significant reduction in the perceived duration
of sleep in the caffeine condition compared to the control condition
and one [52] reporting no significant change in comparison to the
control condition. Ten studies reported measures of subjective
sleep onset latency with seven [25e27,31,33,53,54] identifying a
significant increase in the perceived time to fall asleep in the
caffeine condition and three [35,37,40] reporting no significant
change in comparison to the control condition. Five studies
[25,27,37,40,54] reported no difference in perceived wake duration
after sleep onset between the caffeine condition and the control
condition. Twelve studies reported measures of subjective sleep
quality, with eight [25,26,31,33,35,36,53,54] identifying a signifi-
cant reduction in perceived sleep quality in the caffeine condition
compared to the control condition and four [27,37,40,52] reporting
no difference in perceived sleep quality between conditions.
3.3.9. Caffeine cut-off times for avoiding reductions in total sleep
time
The meta-regression analysis revealed a significant influence of
the timing of intake and the final dose of caffeine on total sleep
time. The model identified a cut-off time of 13.2 h prior to bedtime
for a standard serve of pre-workout supplement, a cut-off time of
8.8 h prior to bedtime for a cup of coffee, and no cut-off time for a
cup of black tea. Using a 10 p.m. bedtime as an example, the model
indicates that a cup of black tea can be consumed at any time prior
to bedtime without significantly reducing total sleep time, a cup of
coffee must be consumed before 1:12 p.m. to avoid a significant
reduction in total sleep time, and a pre-workout supplement must
be consumed before 8:50 a.m. to avoid a significant reduction in
total sleep time (Fig. 3). The model predicts that a significant
reduction in total sleep time will occur if caffeine is consumed after
these cut-off times in a time-dependent manner ei.e., the closer
consumption occurs to bedtime, the greater reduction in total sleep
time.
4. Discussion
This meta-analysis summarised and quantified the adverse ef-
fects of caffeine intake on the characteristics of subsequent night-
time sleep. Specifically, caffeine consumption reduced total sleep
time by 45 min, increased sleep onset latency by 9 min, and
Table 2 (continued )
Study Sample
(n)
Age (years) Habitual caffeine intake
(per day)
Caffeine dose
(mg)
Proximity to
bedtime
(min)
Method of
sleep
measurement
Reported sleep outcomes of
interest
Significant findings
(compared to
control)
Abstain across study As 3 equal
doses
c
LSEQ GTS, QOS, AFS No significant
change
Youngstedt
et al., 2000
[38]
8 M 24.5 ±4.3 100e400 mg 1200 120, ~465, &
~960
PSG TST, SE, WASO, SOL, ROL, sleep
stages
[SOL
YTST, N3
No significant
change
Abstain across study As 3 equal doses Sleep diary Subjective WASO, SOL, quality
Zhang et al.,
2020 [45]
12 M 37.1 ±14.9 <300 mg 103.6 660 &900 PSG TST, SE, WASO, SOL, ROL, sleep
stages
No significant
changeAbstain across study As 2 equal doses
Abbreviations: AFS- awake following sleep; EOFA-ease of falling asleep; GTS- getting to sleep; KSD- Karolinska sleep diary; LSEQ- Leeds sleep evaluation questionnaire; PSG-
polysomnography; N1- non-rapid eye movement (NREM) stage 1 sleep; N2- NREM stage 2 sleep; N3-: NREM stage 3 sleep; N4- NREM stage 4 sleep; qEEG-quantitative
electroencephalogram; QOS- quality of sleep; REM-rapid-eye movement (REM) sleep; ROL- REM onset latency; SE-sleep efficiency; SOL-sleep onset latency; TST-total
sleep time; VAS- visual analogue scale; WASO- wake after sleep onset.
~Approximate timing reported.
a
Mean not reported.
b
Standard deviation not reported.
c
150 mg as one dose with remaining two doses containing placebo.
d
First 3 h of sleep recording only.
e
First 6 h of sleep recording only.
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
6
increased wake after sleep onset by 12 min. These changes were
accompanied by a 7% reduction in sleep efficiency. Alterations in
sleep architecture were also identified; the duration (þ6.1 min) and
relative proportion (þ1.7%) of light sleep (i.e., N1) increased with
caffeine intake and the duration (11.4 min) and relative propor-
tion (1.4%) of deep sleep (i.e., N3 and N4) decreased with caffeine
intake. The impact of dose and timing of caffeine intake on subse-
quent sleep was also examined. The amount and timing of the final
caffeine dose reduced total sleep time. Specifically, the closer to
bedtime that high doses of caffeine were consumed, the greater
reduction in total sleep time. However, this relationship was not
identified for any other sleep outcomes. Importantly, by quanti-
fying the influence of the dose and timing of caffeine intake on
subsequent sleep, cut-off times for caffeine intake prior to bedtime
can be established. For example, one cup of black tea (typical
caffeine content: 47 mg per 250 mL [55]) can be consumed up until
bedtime without a significant effect on total sleep time. To avoid
reductions in total sleep time, a cup of coffee (typical caffeine
content: 107 mg per 250 mL [56]) must be consumed at least 8.8 h
prior to bedtime and a standard serve of pre-workout supplement
(typical caffeine content: 217.5 mg [57]) must be consumed at least
13.2 h prior to bedtime. Consuming a cup of coffee or a standard
Table 3
Results of the Cochrane Risk of Bias (RoB 2) tool.
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
7
serve of pre-workout supplement within this proximity to bedtime
is estimated to reduce total sleep time, with greater reductions the
closer consumption occurs to bedtime.
4.1. Objective sleep outcomes
4.1.1. Total sleep time
Across the 20 studies investigating the effect of caffeine on total
sleep time, 16 [24e27,29e32,34e36,40,41,43,45,50] demonstrated
a significant reduction. Of the four studies [33,37,44,46] that did not
report a significant effect (final caffeine intake ranging from 60 to
660 min prior to bedtime), two administered caffeine for nine [37]
and 14 [46] days consecutively prior to the measured sleep bout.
This sustained administration across numerous days may have
promoted tolerance to the acute effect of caffeine through an
upregulation of cerebral adenosine receptors. However, evidence of
this is currently limited to animal studies [58e61], with greater
uncertainty underpinning caffeine tolerance in humans [62].
Additionally, six studies [25,26,31,35,37,41] investigated a potential
dose-response relationship between caffeine intake and subse-
quent sleep, with five studies [25,26,31,35,41] demonstrating sub-
stantially less sleep (ranging from 24 to 114 min) when larger doses
of caffeine were consumed. The remaining study [37] that did not
report a dose-response effect administered 150 mg or 450 mg of
caffeine on the day of the measured sleep bout, with the lower dose
intended as a withdrawal from the prior eight days of caffeine
administration. Regardless, no effect was found for either condition
[37]. Finally, one study [27] investigated the timing relationship
with a fixed dose of caffeine (400 mg). When consumed zero, three,
or six h prior to bedtime, caffeine reduced total sleep time by ~1.2 h,
irrespective of the timing of intake. As such, there was no clear
relationship between the timing of caffeine consumption and total
sleep time.
The consumption of caffeine is associated with a 45-min
reduction in total sleep time over the subsequent evening.
Furthermore, the extent of this sleep loss is dependent on the final
amount of caffeine consumed and the proximity of this consump-
tion to bedtime. Specifically, larger doses of caffeine and con-
sumption closer to bedtime resulted in greater reductions in total
sleep time. Currently, sleep behaviour recommendations do not
account for the important influence of the dose and timing of
caffeine intake [19,20]. For example, when applying the findings of
this study to commonly consumed beverages, drinking a cup of
coffee (typical caffeine content: 107 mg per 250 mL [56]) would
likely equate to a 9-min greater reduction in total sleep time than a
cup of black tea (typical caffeine content: 47 mg per 250 mL [55]).
Alternatively, assuming a 10 p.m. bedtime, consumption of a fixed
dose of caffeine at 3 p.m. would equate to a 16-min reduction in
sleep than intake of the dose at 9 a.m. Given time in bed was
comparable between conditions in all but four studies
Fig. 2. Forest plot a) displays the sleep characteristics of total sleep time, sleep onset latency, rapid eye movement (REM) onset latency, and wake after sleep onset as absolute
measures (min). Forest plot b) displays sleep architecture outcomes of sleep efficiency, non-rapid eye movement (NREM) stage one, NREM stage two, NREM stage three, and REM as
relative measures (%). Forest plot c) displays sleep architecture outcomes of NREM stage one, NREM stage two, NREM stage three, and REM as absolute measures (min). Each circle
represents the mean difference between the control and caffeine condition, with the size of the circle representing the statistical weight of the effect size.
Fig. 3. Meta-analytic model accounting for both the timing and the amount of the final caffeine dose. With this, estimated caffeine cut off times for a) a cup of black tea (typical
caffeine content: 47 mg per 250 mL [55]), b) a cup of coffee (typical caffeine content: 107 mg per 250 mL [56]), and c) a standard serve of pre-workout supplement (typical caffeine
content: 217.5 mg [57]) are modelled for a 10 p.m. bedtime (x-axis). Each circle represents the mean difference (y-axis) between the control and caffeine condition, with the size of
the circle proportional to the statistical weight of the effect size. When looking at the zero reference line, any value above this indicates the caffeine group exhibited less total sleep
time compared to the control. The 95% confidence intervals are represented by the shaded band, and the estimated cut-off time occurs where this crosses the zero reference line. As
such, no clear cut off is identified for black tea (a). However, the cut off for coffee (b) occurs at 1:12 p.m. and for pre-workout supplement (c) at 8:50 a.m. Consumption of caffeine
anytime beyond these cut-offs is estimated to reduce total sleep time, with this reduction greater as consumption occurs closer to bedtime. Model parameters (estimate [95%CI]):
intercept, 21.02 [-8.53 to 50.57]; coefficient for time, 0.05 [-0.09 to 0.01]; coefficient for dose, 0.16 [0.01 to 0.31].
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
8
[24,32,33,50], the observed reduction in total sleep time cannot be
attributed to a reduced sleep opportunity but more likely disrup-
tion to the sleep bout. As homeostatic sleep pressure is suggestedto
increase with rising cerebral adenosine concentrations [14,63], the
action of caffeine in blocking A1 and A2a receptors may reduce the
propensity for sleep [64,65]. With a difference in total sleep time of
20 min identified as the threshold for clinically meaningful change
[66], these findings suggest the intake of caffeine may substantially
reduce the subsequent sleep duration of consumers.
4.1.2. Sleep onset latency
The effect of caffeine on sleep onset latency was investigated in
19 studies [24e30,33e37,40,41,43e46,50], with 14
[24e30,34,36,40,41,44,45,50] reporting a significant increase
following caffeine consumption. Of interest, one study [35]re-
ported no effect when caffeine was administered at bedtime,
despite the consumption of moderate to high doses (100, 200, &
300 mg). Similarly, one study [43] found no effect when a high dose
of caffeine (400 mg) was administered 30 min prior to bedtime. As
plasma caffeine concentration typically peaks between 30 and
120 min post consumption [67e69], it is feasible that consumption
in these studies was too close to bedtime to influence sleep onset.
Of the included studies, five [25,26,35,37,41] investigated the dose-
response relationship, with three [25,26,41] demonstrating sub-
stantially longer latencies (ranging from 13 to 62 min) with larger
doses of caffeine. Lastly, one study [27] investigated the relation-
ship between timing of consumption and sleep onset latency. In
comparison to the control condition (20.6 ±9.8 min), a significant
increase of 17.2 min was observed when 400 mg of caffeine was
consumed three hours (37.8 ±29.9 min) prior to bedtime. Although
similar mean increases were observed when caffeine was admin-
istered zero (43.0 ±38.9 min) and six (44.7 ±54.6 min) hours prior
to bedtime, there was no significant effect of these timings on sleep
onset latency, with greater variation in individual response.
Therefore, it appears there is a peak effect of caffeine on sleep onset
latency occurring approximately three hours post consumption.
Caffeine consumption increased sleep onset latency by 9.1 min.
Unexpectedly, this increase was not moderated by the amount or
the timing of the final caffeine dose. Given seven of the included
studies administered the caffeine as a split dose across two
[41,44e46,50] or three [37,40] time points, the moderating influ-
ence of each may be understated as the meta-regression modelling
accounted for the amount and timing of the final dose only. Even
though the influence of dose and timing could not be determined,
the adverse effect of caffeine on sleep onset latency was evident.
Given the action of caffeine on the central nervous system [64,70], a
heightened state of arousal may pose a substantial challenge to the
initiation of sleep. Thus, the findings emphasise the consumption of
caffeine prolongs the onset of subsequent sleep, with these delays
approaching the 10-min threshold of clinically meaningful change
[66]. It remains unclear whether this increase in sleep onset latency
is affected by the amount or timing of the final caffeine dose.
4.1.3. REM onset latency
Ten studies [24,29,30,34,35,37,40,44,46,50] investigated the ef-
fects of caffeine on REM onset latency, however none demonstrated
significant effects. Of the included studies, two [35,37] examined
the dose-response relationship with various doses of caffeine.
There was no meaningful change in REM onset latency when larger
doses of caffeine were consumed. It should be noted that no study
has systematically varied the timing of consumption using a fixed
caffeine dose. Therefore, no data were available on the relationship
between caffeine timing and REM onset latency.
The results of the current analysis showed a non-significant
effect of caffeine on REM onset latency (1.5 min). Furthermore,
the amount and timing of the final caffeine dose were not shown to
be moderating factors. As REM onset latency is measured from
sleep onset and not lights out, it remained largely unaffected by the
delayed initiation of sleep following caffeine consumption. Conse-
quently, the consumption of caffeine likely has no meaningful effect
on REM onset latency. It appears this lack of effect is not influenced
by the amount or timing of the final caffeine dose.
4.1.4. Wake after sleep onset
Wake after sleep onset was investigated in 13 studies
[24,25,27,29,30,34,35,37,40,43,44,46,50], with six
[25,27,29,35,43,50] demonstrating a significant increase when
caffeine was consumed. In one study [24], there was a non-
significant increase in wake after sleep onset when caffeine was
consumed (49.0 ±8.7 min v 43.0 ±6.4 min). Alternatively, another
study [30] showed no effect following the administration of a 200-
mg dose of caffeine in the morning. This may have been due to the
~16-h time frame between caffeine consumption and bedtime [30].
Of the included studies, three [25,35,37] investigated the dose-
response relationship, with one [25] demonstrating considerably
greater wake after sleep onset when larger doses of caffeine were
consumed. In this instance, increasing the dose from 4 mg kg
1
to
8mgkg
1
resulted in a 29.6-min mean increase in wake after sleep
onset [25]. Finally, one study [27] investigated the relationship
between timing of caffeine consumption and wake after sleep
onset. In comparison to the control condition (9.6 ±14.7 min),
caffeine (400 mg) caused a significant increase when consumed
three (37.2 ±43.0 min) and six (17.6 ±22.3 min) hours prior to
bedtime. Although demonstrating a similar mean increase in wake
after sleep onset, no significant effect was found when caffeine was
consumed at bedtime (27.0 ±40.1 min). As such, no clear timing
relationship was identified for the effect of caffeine on wake after
sleep onset.
The findings from the current analysis demonstrate an 11.8-min
increase in wake after sleep onset following the consumption of
caffeine. It was not apparent whether this increase was moderated
by the amount or the timing of the final caffeine dose. The observed
increase in wake after sleep onset indicates that the consumption of
caffeine disrupts sleep maintenance. Caffeine may cause brief epi-
sodes of wake across the sleep bout by reducing homeostatic sleep
propensity and heightening arousal state [64,65]. Consequently,
sleep appears to be fragmented by recurrent awakenings following
caffeine. These findings demonstrate that caffeine consumption
increases periods of wakefulness during sleep. However, the
observed increase in wake after sleep onset following caffeine
consumption fails to meet the 20-min threshold of clinically
meaningful change [66]. It could not be determined if the increase
in wake after sleep onset was influenced by the amount or the
timing of the final caffeine dose.
4.1.5. Sleep efficiency
Across the 18 studies assessing sleep efficiency, 15
[24e30,33e35,41,43e45,50] reported a significant reduction in
sleep efficiency following caffeine consumption. Of the three
studies [37,40,46] reporting no significant effect, two [37,46]
administered the caffeine dose over numerous days. Additionally,
one study [40] showed no effect following 1200 mg of caffeine
administered in three equal doses across the morning, afternoon,
and evening. In this instance, the authors attributed these findings
to a lack of statistical power [40]. Of the included studies, five
[25,26,35,37,41] investigated the dose-relationship with three
[25,26,41] demonstrating greater reductions (ranging from 5 to
23%) in sleep efficiency when larger doses were consumed. Finally,
one study investigated the timing relationship with significant re-
ductions in sleep efficiency when 400 mg of caffeine was
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
9
administered zero, three, and six hours prior to bedtime [27]. In
comparison to the control condition, reductions were similar across
all time points (~8%) with no clear timing relationship identified.
The current analysis demonstrates a 7% reduction in sleep effi-
ciency following the consumption of caffeine. However, this
reduction was not moderated by the amount or the timing of the
final caffeine dose. Although it may seem counterintuitive, not all
time in bed is spent asleep. This discrepancy between total sleep
time and time in bed is accounted for by the duration of wake
between lights off and lights on [71]. When large periods of time in
bed are spent awake, the duration of total sleep time is reduced
with a subsequent reduction in sleep efficiency. As previously
outlined, time in bed was comparable in all but four studies
[24,32,33,50]. Therefore, it appears the consumption of caffeine
reduces sleep efficiency through a reduction in total sleep time [72].
With the stimulating effect of caffeine, it is likely this reduction
occurs largely through the impaired onset and maintenance of
sleep [64]. The reduction in sleep efficiency following caffeine
consumption exceeds the 5% threshold of clinically meaningful
change [66], suggesting caffeine consumption causes considerable
detriment to subsequent sleep efficiency. It is not clear if this
reduction is influenced by the amount or the timing of the final
caffeine dose.
4.1.6. Sleep architecture
The effect of caffeine on absolute (min) sleep architecture was
investigated in 12 studies [24,27,30,34e36,40,41,44e46,50]. Of
these, two [35,41] reported an increase in N1 sleep, one [36]re-
ported an increase in N2 sleep, four [24,41,44,45] reported a
decrease in N2 sleep, six [27,35,36,40,41,44] reported a decrease in
N3 sleep, and three [36,41,50] reported a decrease in REM sleep. Of
the included studies, two [35,41] investigated the dose-relationship
between caffeine intake and absolute sleep architecture. Dose-
dependent reductions in the duration of N3 sleep [35,41] and
REM sleep [41] were identified, with greater reductions occurring
at larger doses. Additionally, one study [27] investigated the timing
relationship between caffeine intake and absolute sleep architec-
ture with the administration of caffeine zero, three, and six hours
prior to bedtime. Reductions in duration of the combined stages N1
and N2 sleep were comparable across time points of caffeine con-
sumption (~40 min) when compared to the control condition.
Similarly, the duration of N3 sleep was reduced in comparison to
the control (71.5 ±26.5 min) when caffeine was consumed zero
(56.7 ±21.5 min), three (57.0 ±16.8 min), and six (48.9 ±15.8 min)
hours prior to bedtime, although the reduction observed with
consumption 3 h prior to bedtime was not statistically significant.
These findings suggest there is no relationship between the timing
of caffeine intake and alterations in the duration of sleep stages.
The effect of caffeine on relative (%) sleep architecture was
investigated in 11 studies [25e29,35,37,41,43,44,50]. Of these, five
[26,35,41,43,44] reported an increase in N1 sleep, two [29,43]re-
ported a decrease in N2 sleep, and five [25,26,35,41,43] reported a
decrease in N3 sleep. There was no clear effect on the proportion of
REM sleep with one study [26] reporting an increase and one study
[43] reporting a decrease. Five studies [25,26,35,37,41] investigated
the dose-relationship between caffeine intake and relative sleep
architecture. Of these studies, three [26,35,41] reported a greater
increase in the proportion of N1 sleep, while four [25,26,35,41]
reported a greater reduction in the proportion of N3 sleep when
larger caffeine doses were consumed. Lastly, one study [27] inves-
tigated the timing relationship between caffeine intake and relative
sleep architecture with the administration of 400 mg of caffeine.
Relative sleep architecture was not significantly altered when
caffeine was consumed zero, three, or six h prior to bedtime. As
such, there was no evidence of a time-dependent effect of caffeine
on relative sleep architecture.
From the results of the current analysis, caffeine consumption
increased the duration (þ6.1 min) and proportion (þ1.7%) of N1
sleep and decreased the duration (11.1 min) and proportion
(1.4%) of N3 (and N4) sleep. No significant effect of caffeine was
shown on the duration or proportion of N2 or REM sleep. The
increased occurrence of N1 sleep and the decreased occurrence of
N3 sleep is indicative of a reduction in sleep depth. Through action
as an adenosine receptor antagonist, caffeine may diminish ho-
meostatic sleep pressure with a subsequent reduction in N3 sleep
[73]. In addition, caffeine increased the duration of wake across the
sleep bout. With increased awakenings, shifts between sleep stages
occur with a tendency for N1 sleep to re-emerge at the expense of
deeper stages of sleep [21]. Coupled together, these findings
demonstrate the consumption of caffeine alters sleep architecture
in a manner that increases light sleep (i.e., N1) and reduces deep
sleep (i.e., N3 and N4). With deep sleep suggested to be essential to
physiological restoration and memory processing [74,75], re-
ductions in N3 sleep may have neurobehavioral and health impli-
cations. However, the changes observed in this analysis are unlikely
to be sufficient to elicit clinically meaningful change in an in-
dividual's sleep architecture [72].
4.1.7. Quantitative EEG
The effect of caffeine on EEG spectral power was investigated in
six studies [24,30,34,37,41,45] with four [30,34,41,45] reporting a
significant reduction in spectral power within the delta frequency
range (~0.5e4 Hz) and a significant increase in spectral power
within the sigma frequency range (~12e16 Hz) during NREM sleep.
Slow wave activity within the delta frequency range is a commonly
reported marker of sleep intensity [14], and an increase in the
expression of slow waves during NREM sleep is suggested to reflect
an increase in homeostatic sleep pressure [76,77]. Findings from
the included studies indicate that caffeine consumption may
reduce subsequent sleep depth through attenuation of homeostatic
sleep pressure. However, it has recently been highlighted that the
kinetics of adenosine formation and breakdown appear to occur at
a faster rate than diurnal changes in NREM sleep EEG slow wave
activity [62]. Therefore, it remains unclear whether the observed
reduction in sleep depth following the consumption of caffeine is
due to the attenuation of homeostatic sleep pressure.
4.1.8. Subjective sleep outcomes
Twelve studies [25e27,31,33,35e37,40,52e54] investigated the
effect of caffeine on the perceptions of sleep. Collectively, caffeine
had an adverse effect on perceived total sleep time, sleep onset
latency, sleep efficiency, and sleep quality. There was no effect of
caffeine on perceived wake after sleep onset, even though con-
current increases in objective wake after sleep onset were reported
[25,27]. These findings suggest transient periods of wake may go
largely unnoticed. Of the five studies [25,26,31,35,37] investigating
the dose-response relationship, four [25,26,31,35] reported
heightened perceptions of sleep disruption with larger caffeine
doses. Additionally, perceptions of sleep disturbance were reported
when caffeine (400 mg) was administered zero and three h prior to
bedtime [27]. However, no perceived effect was reported when this
dose was consumed six h prior to bedtime, despite a significant
effect on objective sleep parameters [27]. Such findings suggest the
negative influence of caffeine on subsequent sleep is under-
estimated the further away from bedtime consumption occurs. In
fact, the relationship between objective and subjective sleep
quality is not well defined [78]. Regardless, perceptions of sleep
capture individual outcomes, which have a strong influence in
driving behavioural decision making [79]. Therefore, subjective
C. Gardiner, J. Weakley, L.M. Burke et al. Sleep Medicine Reviews 69 (2023) 101764
10
sleep outcomes are an important metric when evaluating the effect
of caffeine on subsequent sleep and should be incorporated
alongside objective measures.
4.1.9. Practical significance
Substantial changes in sleep quantity and quality were observed
following the consumption of caffeine. Specifically, there was a 45-
min reduction in total sleep time, a 9-min increase in sleep onset
latency, a 12-min increase in wake after sleep onset, and a reduc-
tion of 7% in sleep efficiency. With the exception of wake after sleep
onset, these changes are considered to be clinically significant
suggesting caffeine consumption will substantially impair subse-
quent sleep [66]. Current sleep recommendations outline the need
for healthy adults to achieve seven to nine h of sleep per night [2].
In addition, satisfactory sleep quality is indexed by a sleep onset
latency less than 30 min, wake after sleep onset of less than 20 min,
and a sleep efficiency of 85% or above [72]. With the extent of
change observed in these outcomes in the present analysis, it is
likely that the consumption of caffeine will increase the risk of
insufficient sleep. It has been shown that mild sleep restriction
(~1 h) can disrupt emotional regulation [80] and impair cognitive
and behavioural function [81,82]. When mild sleep restriction is
sustained over 14 days, the decrements in behavioural alertness
and working memory are similar to those experienced after one
night of sleep deprivation [82]. Given that decrements in perfor-
mance associated with sleep restriction can accrue in a cumulative
manner, the decrease in sleep quantity and quality resulting from
the consumption of caffeine may impair cognitive and behavioural
function over time. The consumption of caffeine increased the
proportion of N1 sleep by 1.7% and decreased the proportion of N3
(and N4) sleep by 1.4%. Healthy sleep architecture is comprised of
less than 5% of N1 sleep and 16e20% of N3 sleep [72]. Therefore, it
appears the consumption of caffeine may result in considerable
increases in the occurrence of N1 sleep relative to normative values.
However, it is unlikelythat the decrease in N3 (and N4) sleep would
be of sufficient magnitude to alter normal sleep architecture [72].
The deleterious effect of caffeine on subsequent sleep may be
lessened in habitual consumers due to a potential tolerance to the
substance [62]. A pattern of regular caffeine intake exposes the
central nervous system to the continuous presence of caffeine.
Although evidence is scarce in humans [62], repeated caffeine
exposure in rodents indicates an adaptive response in the adeno-
sinergic system characterised by an increase in cerebral adenosine
concentrations [83] and an upregulation in cerebral adenosine re-
ceptors [58e61]. Of the studies included in the present analysis,
two involved the administration of caffeine for more than one
week. The administration of 450 mg of caffeine for nine days [37]
and 100 mg of caffeine for 14 days [46] resulted in no significant
impairment to sleep. Rather, a reduction in spectral power within
the sigma frequency range was reported [37], with reductions in
this frequency band observed under conditions of increased sleep
pressure [84,85]. Collectively, these findings suggest chronic
caffeine exposure may elicit adaptation in the adenosinergic system
that normalises function in response to the continual presence of
caffeine and its metabolites. Even though tolerance has not been
clearly established in humans [62], it is important to consider that
the impairments to sleep reported in this analysis may be reduced
with repeated caffeine consumption.
4.1.10. Practical recommendations
One of the aims of the present study was to quantify the influ-
ence of caffeine dose and timing on subsequent total sleep time.
From the analysis, cut-off times of consumption (Fig. 3) to minimise
the negative effect of caffeine were established for common
caffeine products. Assuming a 10 p.m. bedtime, there is no clear cut
off time for consumption of black tea (typical caffeine content:
47 mg per 250 mL [55]). This suggests a single cup of black tea may
be consumed at any time prior to bedtime without a significant
reduction in total sleep time. However, there is an estimated
reduction in total sleep time if a cup of coffee (typical caffeine
content: 107 mg per 250 mL [56]) is consumed after approximately
1 p.m. The reduction in total sleep time is greater as caffeine is
consumed closer to bedtime (Fig. 3). Similarly, the consumption of a
standard serve of a pre-workout supplement (typical caffeine
content: 217.5 mg [57]) is predicted to reduce total sleep time if
consumed at any point after 8:50 a.m. These findings suggest the
cut-off time for doses of caffeine contained in a standard cup of
coffee or a standard serve of pre-workout supplement occur sub-
stantially earlier than anecdotally expected, and well before tim-
ings based on the typical half-life of three to six h [18