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The Impact of Omega-3 on Improving Sleep Quality: A Systematic Review of Current Clinical Research

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Abstract and Figures

Introduction: Omega-3 fatty acids are known to improve cardiovascular and metabolic outcomes. While studies have suggested that omega-3 may also enhance sleep quality and regulate melatonin, the data on its efficacy for individuals with poor sleep quality or related disorders must be more consistent. We aim to pave the way for future investigations, ultimately contributing to the clinical management of sleep health. Methods: 87 articles were retrieved from MEDLINE and Cochrane databases through a systematic search strategy, and 19 articles from 2002 to 2022 were included. Inclusion criteria encompassed randomized controlled trials (RCTs) and observational studies focused on the impact omega-3 on outcomes related to sleep clinical parameters. Exclusion criteria included preclinical studies and literature reviews. Results: The review identified 19 eligible studies, consisting of 9 RCTs and ten observational studies. The results displayed a complex relationship between omega-3 supplementation and sleep quality, with some studies suggesting positive effects, particularly in specific subpopulations. In contrast, others showed no significant impact or even negative effects on sleep. Among the RCTs, 7 showed positive and promising results in favor of omega-3 supplementation for sleep quality, while 1 RCT indicated the need for further studies, and 1 RCT suggested no benefit of omega-3 on sleep quality. Among observational studies, 7 reported positive and promising outcomes with omega-3 supplementation, 2 indicated no benefit in improving sleep quality, and 1 suggested further studies. Conclusion: Based on the available data, our systematic review found that omega-3 improved sleep quality in 74% of the included clinical research; however, such evidence still needs to be conclusive due to high heterogeneity among study designs. Therefore, well-designed clinical studies are required to confirm this conclusion.
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The Impact of Omega-3 on Improving Sleep
Quality: A Systematic Review of
Current Clinical Research
Camila Bernardes1,2,#*
, Igor Malheiros Assad2,3,#, Vitor Yukio Yonekura2,#,
Marilia Ribeiro de Azevedo Aguiar2,4, Stalin Canizares2, Luis Rivera-Quinto2,5,
María Lucía Sequeira2, Lukas Rudzevicius2,6, Aline Aparecida Lacerda Gruber2,
Agustin Perez-Londono2,7, Ahmad G. A. Khater2,8, Dongwoo Nam2,9,
Franja Dugar2,10, Maria Isabel Bojorquez Ortiz2,11, Vanesa Scholl2,12, Yinxue Linsey Zhao2,13
1
D’Or Institute for Research and Education (IDOR), Botafogo, Rio de Janeiro, Brazil;
2
Principles and Practice of Clinical Research (PPCR)
Course, Executive and Continuing Professional Education, Harvard T.H. Chan School of Public Health, Boston, USA; 3Department of
Medicine, Universidade Federal de São Paulo, São Paulo, Brazil; 4Department of Internal Medicine, Faculdade de Medicina da
Universidade de São Paulo, São Paulo, Brazil;
5
Johns Hopkins Bloomberg School of Public Health;
6
Klinikum Chemnitz gGmbH, Klinik
für Neurochirurgie, Chemnitz; 7Division of Urologic Surgery, Beth Israel Deaconess Medical Center; 8Faculty of Oral and Dental
Medicine, Egyptian Russian University, Cairo, Egypt;
9
Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung
Hee University, Seoul, Korea; 10 University Hospital Basel, Switzerland; 11Universidad Francisco Marroquín, Guatemala; 12Molecular
Biology Laboratory, Conciencia Clinic, Neuquen, Argentina; 13 University of Pennsylvania, United States.
Abstract
Introduction: Omega-3 fatty acids are known to improve cardiovascular and metabolic outcomes. While studies have
suggested that omega-3 may also enhance sleep quality and regulate melatonin, the data on its efficacy for individuals with
poor sleep quality or related disorders must be more consistent. We aim to pave the way for future investigations, ultimately
contributing to the clinical management of sleep health.
Methods: 87 articles were retrieved from MEDLINE and Cochrane databases through a systematic search strategy, and
19 articles from 2002 to 2022 were included. Inclusion criteria encompassed randomized controlled trials (RCTs) and
observational studies focused on the impact omega-3 on outcomes related to sleep clinical parameters. Exclusion criteria
included preclinical studies and literature reviews.
Results: The review identified 19 eligible studies, consisting of 9 RCTs and ten observational studies. The results displayed
a complex relationship between omega-3 supplementation and sleep quality, with some studies suggesting positive effects,
particularly in specific subpopulations. In contrast, others showed no significant impact or even negative effects on sleep.
Among the RCTs, 7 showed positive and promising results in favor of omega-3 supplementation for sleep quality, while
1 RCT indicated the need for further studies, and 1 RCT suggested no benefit of omega-3 on sleep quality. Among
observational studies, 7 reported positive and promising outcomes with omega-3 supplementation, 2 indicated no benefit in
improving sleep quality, and 1 suggested further studies.
Conclusion: Based on the available data, our systematic review found that omega-3 improved sleep quality in 74% of the
included clinical research; however, such evidence still needs to be conclusive due to high heterogeneity among study designs.
Therefore, well-designed clinical studies are required to confirm this conclusion.
*Corresponding author: camila.faria-2023@ppcr.org
# Camila Bernardes, Igor Malheiros Assad and Vitor Yukio
Yonekura have contributed equally to this work.
Received: September 4, 2023 Accepted: December 15, 2023
Published: February 16, 2024
Editor: Felipe Fregni
Reviewers: Karla Loss, Jorge Sakon, Juan Whaley,
Carlos Lehuedé Expósito, Clara Maria Raggio
Keywords: omega-3, sleep, sleep quality
DOI: http://dx.doi.org/10.21801/ppcrj.2023.94.5
Introduction
Due to their clinical benefits, Long-chain polyun-
saturated fatty acids (LC-PUFA), namely omega-3,
constitute a field of scientific interest. A potential
application of omega-3 is in the realm of sleep con-
ditions. Improving sleep patterns minimizes the risk
of cardiovascular disease (Bertisch et al., 2018) and
dysglycemia (Kay et al., 2016) and improves cogni-
Review
tive function, alertness, and attention (Lee et al., 2015;
Louca et al., 2014). Studies have also highlighted
that LC-PUFA enhances melatonin regulation and
helps sustain the structure of the neuronal membrane
(Catalá, 2010; Zhang et al., 1998). Thus, investiga-
tors have analyzed the potential benefits of omega-3
supplementation on sleep clinical parameters.
Nonetheless, there is conflicting data on how
omega-3 can benefit populations suffering from poor
sleep quality or correlated disorders. Daily physio-
logical cycles, which are fundamental for the body’s
normal function, are regulated by sleep and circadian
rhythm. (Vasey et al., 2021). Sleep can be divided
into NREM and REM sleep, and NREM can be fur-
ther divided into three stages - N1, N2, and N3. The
cues the body follows to synchronize its rhythm are
called zeitgeber, and there are two types: photic and
nonphotic. Omega-3 is believed to act as a nonphotic
zeitgeber by raising melatonin levels, a known en-
dogenous synchronizer (Checa-Ros & D’Marco, 2022).
Moreover, omega-3 has been shown to protect the
glymphatic system, which is essential to clean the
brain from neurotoxins (Ren et al., 2017).
In this mini-review, our objective is to comprehend
the current evidence in the literature regarding the
impact of omega-3 on sleep. Furthermore, we aim to
pave the way for future investigations, ultimately con-
tributing to the clinical management of sleep health.
Materials and Methods
This study follows the PRISMA guidelines for
reporting systematic reviews (Liberati et al., 2009).
Eligibility Criteria
The inclusion criteria were: (1) RCT or observational
studies (cohort, cross-sectional studies, surveys,
and unspecified studies); (2) oral ingestion of
omega-3 through regular diet or supplementation or
assessment of LC-PUFA plasma levels; and (3) sleep
quality or clinical parameters primary outcomes.
The exclusion criteria were (1) literature reviews,
(2) preclinical studies, and (3) gray literature. Our
population included patients regardless of baseline
covariates.
Information Sources and Selection process
This mini-review examined studies published from
the date of incorporation on databases up to Septem-
ber 1st, 2023, within the publication interval of 2002
to 2022. The search strategy is specified in Table 1.
Four reviewers independently screened the titles
and abstracts of papers obtained after running
the search strategy on MEDLINE (PubMed) and
Cochrane Library. Publications that fulfilled the
inclusion criteria were included for screening.
Articles selected after two rounds of screening were
included for data extraction and quality assessment.
Data Collection and Items
A standardized data extraction process was designed
to retrieve information from each article, including
authorship, country, year of publication, study
design, number of participants and baseline char-
acteristics, measurement tools of the intervention
and control, primary and secondary outcomes, and
corresponding results. For randomized clinical
trials (RCT), parameters such as sampling method,
randomization strategy, blinding procedure, and
sample size calculation were also evaluated. The
extracted information was transcribed into an Excel
spreadsheet and verified by four additional authors.
The final version deleted duplicates, and a PRISMA
flow diagram was performed in Figure 1.
Risk of Bias Assessment
Paired reviewers assessed the risk of bias of included
RCTs using the revised version of the Cochrane Risk
of Bias (RoB 2.0) Tool (Higgins et al., 2016) and
the observational studies using the Risk Of Bias In
Non-randomized Studies - of Exposure (ROBINS-E)
tool (Higgins et al., 2023).
Results
Study Selection
Our study identified 87 articles (66 from MEDLINE
and 21 from Cochrane). All RCTs retrieved from
Cochrane were duplicates. Out of the 66 records
screened, 27 were found to be eligible for more de-
tailed review. Of the 27 studies, three were excluded
due to wrong exposure/intervention, four due to
wrong outcome, and one due to wrong design. Only
19 studies were included in the final review. Study
characteristics
Nine RCTs were included (Table 2). We had no
restrictions on participants’ characteristics, resulting
in a varied population, including neonates, children,
young adults, and pregnant women. All studies used
convenience sampling methods. Interventions in-
cluded omega-3 as external dietary supplements con-
taining either DHA or EPA - the two most important
forms of omega-3 fatty acids - except one in which
authors decided to administer omega-3 through fish
intake. Matched placebo compounds were used to
allow proper blinding in some of the studies with
Principles and Practice of Clinical Research (2023) 9; 4 35
Review
Figure 1: PRISMA flow diagram.
Table 1: Search strategies.
36 Principles and Practice of Clinical Research (2023) 9; 4
Review
inactive compounds, except one that assessed the
supplement’s effect on sleep and pruritus and admin-
istered an active standard treatment. The remaining
placebo elements included corn oil or refined olive
oil. The duration of the RCTs varied from 12 weeks
to 12 months, and the frequency of administration
varied among them. Five studies used objective sleep
measures, such as actigraphy, pressure-sensitive mat-
tresses, and Sleep State Test. Four used question-
naires, such as the Child Sleep Habits Questionnaire,
Brief Infant Sleep Questionnaire, and sleep diaries,
to gather subjective data on sleep patterns. One of
the studies assessed infant sleep patterns after the
mother consumed a DHA-containing diet all the
other studies measured sleep patterns from the sup-
plemented participants.
The studies which corresponded to observational
designs (Table 3) included cohort studies (n = 2),
cross-sectional studies (n = 4), surveys (n = 1) and
unspecified studies (n = 3). They mainly assessed the
dietary patterns using subjective sleep quality scales,
including self-reported questionnaires, previously
diagnosed sleep disorders, and other objective scales,
including the apnea-hypopnea index or objective
evaluations, such as those provided by actigraphy.
All participants in these studies were over 18 years
old except for two studies in which pregnant women
were the subjects of the intervention, and the out-
come was evaluated in the neonate, demonstrating
an adverse effect of the supplement on their future
sleep pattern (Sugimori et al., 2022, Cheruku et
al., 2022). Many studies proved no retrospective
significance between the intervention and improving
sleep quality (Zhang et al., 2022; Titus et al., 2017).
One of them even found omega three’s statistically
significant negative effect on sleep disorders (Lui et
al., 2021). The remaining studies showed an overall
positive association between omega-3 and sleep
behavior (Jansen et al., 2020; Murphy et al., 2021;
Christian et al., 2016; Jackson et al., 2020; Liu et al.,
2022).
Risk of Bias in Studies
According to Cochrane’s RoB 2.0, five clinical trials
have a low risk of bias, one has some concerns about
the risk of bias, and three have a high risk of bias.
Studies by (Judge et al., 2012), (Hansen et al., 2014),
and (Montgomery et al., 2014) raised some bias con-
cerns as no information about allocation concealment
was reported. Also, the studies by (Judge et al., 2012,
Hansen et al., 2014 and Pantan et al., 2021) were as-
sessed as having some bias concerns since we could
not find any protocols to compare them with the re-
ported results. Furthermore, the studies by (Hansen
et al., 2014) and (Montgomery et al., 2014) did not
report any information about the blinding process,
raising some concerns of bias in the second domain
(Bias due to deviations from the intended interven-
tions); additionally, not all participants completed
the study of (Hansen et al., 2014) and handled such
attrition using an "As treated analysis," which raised
further concerns in the third domain (Bias due to
missing outcome data).
According to the ROBINS-E, two observational
studies have a low risk of bias, six studies have some
concerns about discrimination, and two studies have
a high risk of bias. All studies, except for (Christian
et al., 2016) and (Jansen et al., 2020), have some
bias ranging from some concerns (six studies) to
very high (one study) in the fifth domain due to
inappropriate handling of missing data. The studies
by (Christian et al., 2016), (Luo et al., 2021), (Murphy
et al., 2021), (Sugimori et al., 2022), and (Zhang et
al., 2022) were assessed as some concerns of bias in
the third domain due to inappropriate selection of
participants into research. The studies by (Luo et
al., 2021), (Cheruku et al., 2022), (Liu et al., 2022),
and (Zhang et al., 2022) assessed some concerns of
bias and (Murphy et al., 2021) as a high-risk in the
sixth domain due to discrimination arising from the
outcome measurement. Figures 2 and 3 summarize
the risk of bias assessment.
Results of Individual Studies and Syntheses
A positive association between omega three and
most sleep parameters analyzed was observed
in most studies, as shown in Tables 2 and Table
3. However, we observed a negative relationship
between the supplement and total sleep disturbance
score in the pediatric population. When analyzing
neonates, differences between the supplements
and placebo were insignificant except in specific
subgroups, including males. The remaining adult
population shows overall homogeneous results.
Judge et al. showed significant differences in sleep
quality, including arousals, compared to placebo (on
D1 (P=0.006) and D2 (P=0.011). Other studies in
similar populations showed similar results regarding
sleep quality in subjective (Heydarbaki et al., 2021;
Yokoi et al., 2022) and objective study parameters
(Patan et al., 2021). Nevertheless, other authors
have observed discrepancies among the objective
parameters, like actigraphy, used to assess sleep
patterns after similar interventions (Hansen et al.,
2014), as seen in Table 2.
Principles and Practice of Clinical Research (2023) 9; 4 37
Review
Figure 2: Risk of bias assessment for randomized controlled trials
Figure 3: Risk of bias assessment for observational studies.
Table 2: Main characteristics of included clinical trials.
38 Principles and Practice of Clinical Research (2023) 9; 4
Review
Table 3: Main characteristics of included observational studies.
Principles and Practice of Clinical Research (2023) 9; 4 39
Review
Discussion
This review investigated the effect of omega-3 sup-
plementation on sleep by summarizing the results
in the literature. Nineteen studies, among RCT and
observational studies, were analyzed with diverse
outcomes. Thirteen studies demonstrated positive
results for Omega-3 on sleep, 8 RCTs, and five obser-
vational studies. The other six studies indicate no or
even a negative effect.
In RCT studies, five used objective and subjective
sleep measures to gather information on sleep pat-
terns. Five studies employed a placebo-controlled
and blinded design, which could have helped reduce
the placebo effect and ensure more objective results,
even more so considering some of the measures were
self-reported.
Studies involved participants of different ages, in-
cluding one that evaluated infants in the first 48
postnatal hours, two that included children, three
that included adults, and one that considered older
adults. Further studies are necessary to corroborate
specific subpopulations with appropriate omega-3
targets.
Regarding interventions, five studies administered
DHA, while one combined DHA and EPA supple-
mentation. A different research administered a com-
bination of DHA and arachidonic acid (AA), an
omega-6 fatty acid. A contrasting approach was used
in one of the studies since investigators studied the
effects of consuming fatty fish, a natural source of
omega-3.
(Judge et al., 2012) suggests DHA intake during
pregnancy might benefit infant sleep patterns. (Mont-
gomery et al., 2014) in children aged 7-9 years, DHA
supplementation did not significantly affect subjec-
tive sleep measures but showed a positive effect on
objective criteria in a small subgroup. (Boone et al.,
2019) also showed positive results while analyzing
since they concluded toddlers born preterm did not
show significant differences in sleep patterns over-
all with DHA and AA supplementation, but there
were improvements in specific subgroups. These sub-
groups involved male children and children of care-
givers with depressive symptoms in the intervention
group. In (Heydarbaki et al., 2021), omega-3 supple-
mentation improved sleep quality in hemodialysis
patients. In the study by (Patan et al., 2021), DHA-
rich oil improved sleep efficiency and reduced sleep
latency in healthy adults (although participants re-
ported feeling less energetic). (Yokoi-Shimizu et al.,
2022) Also, positive results were found in older adults
since DHA and EPA supplementation improved sleep
quality in these individuals. This improvement might
be explained again by the effect omega-3 in increas-
ing the melatonin level in those patients and be par-
ticularly important in the elderly since melatonin
levels decrease with age (Godfrey et al., 2022). In
(Hansen et al.’s 2014) study which did not use sup-
plementation - fish consumption positively impacted
sleep and daily functioning in male forensic patients.
The study designs took into account confounders
such as age. (Kay et al., 2016) carried out the tri-
als with matching age, sex, and race. The statistical
analyses adjusted for age differences using linear
regression (Ebbesson S.O. et al., 2005) or propen-
sity scores (Bertisch et al., 2018). Normality was at-
tested using Kolmogorov Smirnov or Shapiro Wilks
test if parametric methods were used. Other studies
used non-parametric methods to compare baseline
characteristics, including age, sex, and race. How-
ever, the statistical power should have been reported.
Differences in baseline characteristics explain mixed
results. However, positive effects of omega-3 sup-
plementation on sleep quality, especially in specific
subgroups, were found. The significant heterogene-
ity of response to supplementation, especially in the
pediatric population, could be explained by the dif-
ference in outcome measurements, as the answer was
assessed using self-reported outcomes via question-
naires, diaries, or objective measures that could limit
the results’ pooling and generalizability.
Limitations we found in our mini-review include
the heterogeneous population and outcomes mea-
surements, jeopardizing statistical analysis of the re-
sults. Future research could benefit from focusing
on omega-3 regimens and specific population strata
that could take more advantage of supplementation,
such as those with a low omega-3 index. Future re-
search on omega-3 impact on sleep quality should
be designed as RCTs focused on determining effica-
cious regimens and exploring population groups that
possibly benefited from the intervention.
Conclusion
This literature review corroborates that the impact
of omega-3 on sleep still needs to be conclusive de-
spite several findings pointing towards the clinical
benefits of optimized ingestion of this compound.
Therefore, additional studies are warranted to inves-
tigate benefits further, clarify beneficiary populations,
and recommend regimens for potential clinical appli-
cation.
Funding
This research received no external funding.
Conflicts of Interest
The authors declare no conflict of interest.
40 Principles and Practice of Clinical Research (2023) 9; 4
Review
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Context Omega-3, a long-chain polyunsaturated fatty acid (LC-PUFA), may help promote healthy sleep outcomes. However, evidence from randomized controlled trials are inconclusive. Objective The objective of this systematic review and meta-analysis was to explore the impact of omega-3 LC-PUFA supplementation and related dietary intervention in clinical trials as well as omega-3 LC-PUFA exposure in longitudinal studies on human’s sleep-related outcome. Data Sources The PubMed, EMBASE, Cochrane Library, CINAHL, and AMED databases were searched from inception to November 2019. Randomized controlled trials, clinical trials that included a control group, and longitudinal studies that reported the intake of omega-3 LC-PUFA and sleep-related outcomes were included. Study Selection A total of 20 studies with 12 clinical trials and 8 longitudinal studies were identified for inclusion. Data Extraction Participant characteristics, study location, intervention information, and sleep-related outcome measurements were reported. Included studies were appraised with Cochrane risk-of-bias tools and the Newcastle-Ottawa Scale. Weighted mean differences (WMDs) and 95%CIs were pooled with fixed or random effect models. Results Omega-3 LC-PUFA may improve infants' sleep organization and maturity. It reduced the percentage of infants' active sleep (WMD = –8.40%; 95%CI, –14.50 to –2.29), sleep-wake transition (WMD = –1.15%; 95%CI, –2.09 to –0.20), and enhanced the percentage of wakefulness (WMD = 9.06%; 95%CI, 1.53–16.59) but had no effect on quiet sleep. Omega-3 reduced children’s total sleep disturbance score for those with clinical-level sleep problems (WMD = –1.81; 95%CI, –3.38 to –0.23) but had no effect on healthy children’s total sleep duration, sleep latency, or sleep efficiency. No effectiveness was found in adults’ total sleep duration, sleep latency, sleep efficiency, sleep quality, or insomnia severity. Conclusion Omega-3 LC-PUFA may improve certain aspects of sleep health throughout childhood. Additional robust studies are warranted to confirm the relationship between omega-3 LC-PUFA and sleep.
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Objectives Information on sleep quality and its effective factors in the patients undergoing hemodialysis are important factors in future planning for improving sleep quality and ultimately the quality of life in these patients. The present study investigated the effect of omega-3 on the sleep quality of hemodialysis patients. Methods The 52 hemodialysis patients were randomized into two groups and underwent two different treatment modes (A and B). The first group was given omega-3 and cetirizine and the second group only received cetirizine for six weeks. After one week wash out, the study was followed by crossover treatment in both groups for six weeks. Sleep quality and pruritus severity were evaluated in patients before the intervention and at the end of each treatment period using the Pittsburgh Sleep Quality Index and the Yosipovitch Itch Questionnaire. The collected data was analyzed using repeated measures ANOVA and the Pearson correlation coefficient. Results The results of the study showed that majority of the patients (94.2%) had poor sleep quality (sleep score > 5 based on the questionnaire) and 5.8% of the patients had favorable sleep quality (sleep score < 5). Repeated measures ANOVA showed that sleep quality scores were different in two groups in phases 0, I and II (p <0.001). Conclusions Sleep quality improved in both modes but more improvement was observed in mode A. Therefore, omega-3 fatty acids can be used as a suitable method for improving sleep quality in hemodialysis patients.