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Plant Extracts for Sleep Disturbances: A Systematic Review.

1. Introduction

Insomnia is defined as dissatisfaction with sleep quality or quantity in addition to at least one other symptom among difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep [1]. Occasional insomnia is a very common disturb that has been reported to be experienced by about 30% of the U.S. general population [1-3]. Sleep disorders have an important societal and economic impact, with a consequent reduction in labour productivity or increased risk of accidents [4-6]. Chronic insomnia is also a risk factor for a variety of significant health problems, such as cardiovascular disease [7,8], diabetes [9], and obesity [10], as well as bad mood and cognitive dysfunction [11-13]. Almost half of the individuals with sleep problems had never taken any steps to resolve them, and the majority of respondents had not spoken with a physician about their problems. Of those individuals who had consulted a physician, drug prescriptions had been given to approximately 50% in Western Europe and the USA [14]. The commonly used sleep aids based on benzodiazepine and non-benzodiazepine hypnotic drugs are often related to negative side effects such as daytime drowsiness, dependency, depression, hypnotic-withdrawal insomnia, and even excess mortality [15]. Moreover, there are limited data on long-term efficacy of hypnotic drugs [16]. Given these concerns and an increasing patient preference for nonpharmacological treatments [17], it is important to offer patients with insomnia evidence-based nonpharmacologic alternatives that may improve their sleep.

As defined in the Dietary Supplement Health and Education Act of 1994 (DSHEA), a dietary supplement is "a product (other than tobacco) intended to supplement the diet that bears or contains one or more dietary ingredients, including a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by humans to supplement the diet by increasing the total dietary intake of any of the aforementioned ingredients [18]." A growing body of evidence has shown promising results for these compounds in supporting health and body functions [19]. In particular, several dietary supplements are popularly used for sleep disorders [20], also in addition to other remedies (e.g., sleep hygiene and mind-body therapies) [21]. Moreover, no golden standard therapy is recommended to treat mild sleep disorders related to specific sleep stages (starting, maintaining, and ending sleep) [22, 23].

Our aim in this study was to systematically review recent literature on plant extracts and nutraceuticals administered orally and acting on sleep-related disorders. In particular, we differentiated the interventions and the outcomes of the studies based on the different sleep disorders (difficulty in initiating or maintaining sleep, quality and quantity of sleep, and waking up too early) and reviewed the available clinical data of the 7 most studied natural products: valerian, lavender, chamomile, hop, St. John's wort, hawthorn, and rosemary.

2. Materials and Methods

A literature search was performed using a primary medical search engine the PubMed database considering all articles published up to 05/03/2020; the registered review protocol can be found at: https://www.crd.york.ac.uk/PROSPEROFILES/126991_PROTOCOL_20190301.pdf. The review was registered on PROSPERO (international prospective register of systematic reviews in https://www.crd.york.ac.uk/prospero/), registration number CRD42019126991. The inclusion criteria were randomized, double-blind, placebo-controlled trials, noncontrolled trials, and cohort studies. We used the following search terms to search the PubMed register: (Oral food supplement) OR (Oral nutraceutical) OR (Oral natural products) AND (Sleep disorders) OR (Insomnia) AND "humans" [Filter] AND "English"[Filter]. The most studied compounds were singled out and further analyzed with a second search using the terms: (name of the compound) AND (Sleep disorders) OR (Insomnia) AND "humans"[Filter] AND "English"[Filter]. Only articles written in English and only studies conducted on humans were selected for this review. Additionally, the same research criteria were applied also for the Spanish language but no additional references were found. We contacted the study authors to retrieve the full article where only the abstract was available. We selected 7 emerging compounds and 35 relevant reports, excluding duplicates, nonrelevant articles, reviews, and works with no full article available (Figure 1). Information was extracted from each included trial in view of: (1) type of food supplement for sleep disorders (herbal component, dose, length of the treatment, and additional substances) and (2) clinical endpoints considering the different stages of sleep and sleep problems: sleep latency, sleep maintenance, quality of sleep, and quantity of sleep. Finally, the risk of bias of individual studies was considered both at study or outcome level, and the Jadad scale [24] for quality rating was used to assess the quality of works. Parameters considered were randomization, blinding, withdrawals, sample size, quality of data reported, and statistical analysis. Publication bias and selective reporting within studies are likely to be affecting the selected literature for this review.

3. Results

3.1. Valerian (Valeriana officinalis). Valerian is the most studied plant for sleep disorders. We selected 17 articles on this subject to be included in the present review. The results of clinical trials performed to test valerian as a sleep aid are controversial and conflicting. Several studies showed an improvement in sleep quality [25-32] after administration of valerian at doses ranging from 160 to 600 mg a day. Differently, other studies reported no improvement in sleep quality (measured with Pittsburgh sleep quality index, PSQI, or perceived) [33-35]. Additionally, valerian was shown to reduce wake time after sleep onset [25, 27], to improve sleep latency and duration [36, 37], and to ameliorate insomnia severity score [38]. Conversely, a study from Jacobs and collaborators showed no changes in the insomnia severity score (ISI) compared to placebo [39]. Diaper and collaborators in a small study observed no changes in polysomnographic parameters or psychometric measures after one dose of 300 mg or 600 mg of valerian [40], and Coxeter reported no changes in total sleep time or number of nocturnal awakenings in the participants' responses in a n-of-1 analysis of 24 subjects [41].

Some trials investigated the possible mechanism of action of the effect of valerian as sleep aid. The study from Mineo and collaborators showed that a single oral dose of Valeriana officinalis extract caused a significant reduction in intracortical facilitation, a change associated with reduced anxiety [42].

3.2. Lavender (Lavandula). In 2010, Woelk and collaborators showed in a double-blind, randomised study with 77 subjects that silexan, an oral lavender oil capsule preparation, is as effective as lorazepam in adults with generalised anxiety disorder (GAD). Hamilton Anxiety Rating Scale (HAM-A) scores for anxiety and sleep diary scores demonstrated comparable positive effects [43]. Two studies from Kasper et al. in 2010 [44] and 2015 [45] with a dose of 80 mg of silexan showed significant improvement in sleep quality (PSQI) and anxiety (HAM-A) compared to placebo. Finally, an open-label trial with silexan and 47 participants indicated a reduction of nocturnal awakening frequency and duration after 6 weeks of assumption of the food supplement [46].

3.3. Hop. A double-blind, randomized placebo-controlled trial on 171 volunteers with sleep difficulties reported no significant changes in sleep quality (PSQI) after assumption of the LZComplex3 (hops 500 mg) for 2 weeks [47]. Another study with 101 volunteers with chronic primary insomnia assuming two gelatine capsules of Cyclamax[R] (50 mg hop) per day for a month, showed no effects on sleep quality Leeds sleep evaluation questionnaire (LSEQ), melatonin metabolism, and sleep-wake cycle [48].

3.4. Chamomile. A study on sixty elderly people who assumed chamomile extract capsules (200 mg) twice a day for 28 consecutive days reported improvements in general sleep quality and sleep latency (PSQI) [49].

Chang and colleagues conducted a study on the effects of drinking chamomile tea on sleep quality in sleep disturbed postnatal women and found a modest improvement in the PSQS (postpartum sleep quality scale) subscale "physical symptoms-related sleep inefficiency" at 2 weeks but not at 4 weeks [50]. Finally, Zick and colleagues performed a pilot trial with 34 subjects with DSM-IV primary insomnia and found no significant improvements in ISI and PSQI [51].

3.5. Hawthorn (Crataegus oxyacantha). A double-blind, randomized, placebo-controlled study with 264 subjects showed a reduction in total and somatic Hamilton scale scores for anxiety (p = 0.005) [52].

No trial investigated directly the effects of hawthorn in sleep disorders.

3.6. St. John's Wort (Hypericum perforatum). Many clinical trials tested the herb St. John's wort for mild to moderate depression. Al-Akoum et al. reported that 900 mg of St. John's wort decreased scores of the sleep problem scale compared with placebo in perimenopausal women after 12 weeks of oral administration [53].

No trial investigated directly the effects of St. John's wort in sleep disorders.

3.7. Rosemary (Rosmarinus officinalis L.). A randomized clinical trial from Nematolahi and collaborators on subjects who received 500 mg of rosemary showed a significant improvement in sleep quality using the PSQI after one month, but not on sleep latency and sleep duration [54].

3.8. Valerian and Hops. Some clinical trials investigated the combined effect of different plant extracts on sleep related problems; the most studied combination of ingredients is valerian and hop.

Dimpfel and Suter reported that a single dose administration of a valerian and hop fluid extract improved total sleep time and quality of sleep in poor sleepers [55]. Maroo et al. tested a mixture of valerian, passion flower, and hop extract and found significant improvements in sleep time, sleep latency, number of nightly awakenings, and insomnia severity index after a 2 week treatment [56]. Koetter et al. showed a reduction of sleep latency after a treatment period which lasted for 4 weeks with a fixed extract combination of valerian and hop [57].

Conversely, Morin et al. found very modest effects of a valerian and hop combination and only in quality of life scores [58]. Finally, a study from Sun investigated the effects of a mixture of herbal extracts (kava, hop, valerian, and many others) on sleep disturbance in menopausal women. The authors reported that the formula significantly reduced global PSQI score and scores in five components (sleep quality, sleep latency, sleep duration, sleep disturbance, and daytime dysfunction) [59].

Table 1 shows the 35 studies included in this review.

Table 2 summarizes the effects of the different compounds on sleep parameters.

4. Discussion

Sleep disturbances are widespread and affect a high percentage of the general population [1-3].

Food supplements use for sleep complaints is extensively adopted. In a survey in the province of Quebec on almost 1000 subjects, 18.5% participants reported having used natural products as sleep aids [60].

The most commonly used plant extracts for insomnia are valerian, chamomile, and lavender. In general, the selected studies showed a good quality with an average of 3, 4 points in the Jadad scale (0-5) [24] for quality rating, only 6 studies were evaluated with a score <3 and 10 studies with a score of

5. Many studies, however, are limited by small numbers of participants and, in some instances, inadequate design and sparse use of objective measurements. As mentioned by Fernandez-San-Martin et al. in a metanalysis on lavender use for sleep disturbances [61], a wide range of dosages and types of preparations are often used and most measurement methods are open for interpretation. When the analysis is performed with quantifiable variables (latency time in minutes and sleep quality measured with VAS), no significant improvement is frequently found.

There is preliminary but conflicting evidence suggesting valerian and lavender as possible sleep aids for mild problems of quality of sleep, sleep latency, total sleep time, and waking up after sleep onset. Notably, the studies contrasted the efficacy of valerian rated with a high Jadad score (5 studies with score of 5, Table 1). On the other hand, a recent meta-analysis of randomized, placebo-controlled trials showed a significant effect of lavender oil (Silexan) in reducing the HAMA total score for psychic and somatic anxiety and for observer-assessed and self-assessed anxiety [62].

Valerian activity on sleep disturbances has been attributed to the presence of isovaleric acids and valepotriates with reported calming action [63] and GABA reuptake inhibition with sedative effects [64]. Considering the data presented in the literature, valerian seems more effective for chronic insomnia than acute episodes.

The main components of the lavender preparations are linalyl acetate and linalool [65]. In mice, these components led to anticonvulsant effects [66], depression of motor activity, and calming effects [65].

Sparse or no scientific data were found to support the efficacy of most products as hypnotics, including chamomile, hop (alone), hawthorn, St. John's wort, and rosemary. Notably, one recently published systematic review and a meta-analysis indicated chamomile as efficacious and safe for improving sleep quality and generalized anxiety disorders but highlighted scarce effect for insomnia [67, 68].

Other plant extracts have been proposed and tested in clinical trials. Kava kava has been well studied and has showed good results in reducing anxiety and hypnotic effects [69], but because of its hepatotoxic effects, the prescription has been forbidden [64]. In addition, extracts from poppy, passionflower, and lemon balm (Melissa) to mention the most popular ones have been investigated in sleep disturbances, but so far, the amount of data is not sufficient to evaluate their effect on these disorders.

Unfortunately, not many trials tested the efficacy of a combined nonpharmacological intervention based on the administration of plant extracts and standardized sleep hygiene in subjects with mild to moderate insomnia. This combination could improve the efficacy in many trials where a single herbal extract was tested. In support of this hypothesis, a study by Maroo et al. [56] showed that a composition of valerian, passionflower, and hop improved total sleep time, sleep latency, number of nightly awakenings, and insomnia severity index. Moreover, a pilot study testing a combination of melatonin, vitamin B6, and various plant extract showed a positive result in sleep quality, sleep onset latency, and total sleep duration [70].

The management of sleep complaints relies on both pharmacological and nonpharmacological approaches. The last years evidenced a decrease in using sedative and hypnotic drugs to treat these conditions. On the other hand, the population and the medical community are considering food supplements and other nonpharmacological approaches in the management of mild and recent insomnia [71]. To date, however, as pointed out in various recent systematic reviews [21, 72], more high-quality research is needed to confirm the effectiveness of plant extracts in sleep disorders, in particular for chronic conditions and in association with complementary and alternative medicine, such as sleep hygiene and mind-body therapies.

https://doi.org/10.1155/2020/3792390

Disclosure

An abstract and preliminary data relevant to this review were presented at the conference Vitafoods 2019 in Geneva in a poster titled as "Food supplements for sleep disorders: a systematic review."

Conflicts of Interest

SG, DFB and SR are employed at Opera CRO, the Contract Research Organization.

Authors' Contributions

SG, DFB, and SR conceived the work.

Acknowledgments

This work was entirely funded by Opera CRO S.r.l., Timisoara (Romania).

Supplementary Materials

PRISMA 2009 Checklist. (Supplementary Materials)

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[73] D. Moher, A. Liberati, J. Tetzlaff, D. G. Altman, and The PRISMA Group, "Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement," PLoS Medicine, vol. 6, no. 7, Article ID e1000097, 2009.

S. Guadagna [ID], (1) D. F. Barattini, (1) S. Rosu, (2) and L. Ferini-Strambi (3)

(1) Opera Contract Research Organization Srl, A TIGERMED Company, Timisoara, Romania

(2) University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania

(3) IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Centre,Milan, Italy

Correspondence should be addressed to S. Guadagna; guadagna@operacro.com

Received 19 December 2019; Revised 6 March 2020; Accepted 31 March 2020; Published 21 April 2020

Academic Editor: Ciara Hughes

Caption: Figure 1: Flow diagram of information according to PRISMA 2009 [73].
Table 1: List of studies with selected compounds.

Compound             First authors
                         (year               Design
                      published)

Valerian             Taavoni 2013        Triple-blind,
                         [30]         Randomized placebo-
                                        controlled trial

                     Taavoni 2011        Triple-blind,
                         [29]         Randomized placebo-
                                        controlled trial

                      Barton 2011         Double-blind
                         [35]         Randomized placebo-
                                        controlled trial

                     Cuellar 2009        Triple-blind,
                         [34]         Randomized placebo-
                                        controlled trial

                    Waldschutz 2008       Open-label,
                         [37]          prospective cohort
                                             study

                    Oxman 2007 [33]   Web-based randomized
                                       placebo-controlled
                                             trial

                      Muller 2006      Open, multicentre
                         [31]                study

                      Jacobs 2005        Internet-based
                         [39]         randomized, placebo-
                                        controlled trial

                      Diaper 2004      Placebo-controlled
                         [40]         three way crossover

                     Coxeter 2003      Randomized n-of-1
                         [41]                trials

                     Ziegler 2002     Randomized, double-
                         [28]          blind, comparative
                                             trial

                     Poyares 2002        Double-blind,
                         [27]         Randomized placebo-
                                        controlled trial

                       Herrera-       Double-blind, cross-
                     Arellano 2001       over, placebo-
                         [26]           controlled study

                     Wheatley 2001      Cross-over study
                         [38]           compared to kava

                      Donath 2000     Double-blind, cross-
                         [36]            over, placebo-
                                        controlled study

                     Lindahl 1988        Double-blind,
                         [32]         Randomized placebo-
                                        controlled trial

                    Leathwood 1982       Double-blind,
                         [25]         Randomized placebo-
                                        controlled trial

Lavender              Kasper 2015        Double-blind,
                         [45]         Randomized placebo-
                                        controlled trial

                     Uehleke 2012         Open-label,
                         [46]          exploratory trial

                      Kasper 2010        Double-blind,
                         [44]         Randomized placebo-
                                        controlled trial

                    Woelk 2010 [43]      Double-blind,
                                           Randomized
                                           lorazepam-
                                        controlled trial

Hop                  Scholey 2017        Double-blind,
                         [47]         Randomized placebo-
                                        controlled trial

                    Cornu 2010 [48]      Double-blind,
                                      Randomized placebo-
                                        controlled trial

Chamomile                Adib-            Single-blind
                    Hajbaghery 2017        randomized
                         [49]           controlled trial

                    Chang 2016 [50]    A single-blinded,
                                           randomized
                                           controlled

                    Zick 2011 [51]       Double-blind,
                                      randomized, placebo-
                                        controlled pilot
                                             trial

Hawthorn            Hanus 2003 [52]      Double-blind,
                                      randomized, placebo-
                                        controlled trial

St. John's wort      Al-Akoum 2009     Pilot doubleblind,
                         [53]              randomized

Rosemary            Nematolahi 2018      Double-blinded
                         [54]         randomized placebo-
                                        controlled trial

                    Maroo 2013 [56]      Double-blinded
                                      randomized Zolpidem-
                                        controlled trial

                     Dimpfel 2008        Double-blinded
                         [55]         randomized placebo-
                                        controlled trial

Valerian + hop       Koetter 2007        Double-blinded
                         [57]         randomized placebo-
                                        controlled trial

                    Morin 2005 [58]      Double-blinded
                                      randomized placebo-
                                        controlled trial

                     Sun 2003 [59]    Open, noncomparative
                                             trial

Compound             First authors
                         (year        Total patients
                      published)

Valerian             Taavoni 2013           100
                         [30]

                     Taavoni 2011           100
                         [29]

                      Barton 2011           119
                         [35]

                     Cuellar 2009           37
                         [34]

                    Waldschutz 2008         409
                         [37]

                    Oxman 2007 [33]         405

                      Muller 2006           918
                         [31]

                      Jacobs 2005           391
                         [39]

                      Diaper 2004           16
                         [40]

                     Coxeter 2003           24
                         [41]

                     Ziegler 2002           202
                         [28]

                     Poyares 2002           37
                         [27]

                       Herrera-             20
                     Arellano 2001
                         [26]

                     Wheatley 2001          19
                         [38]

                      Donath 2000           16
                         [36]

                     Lindahl 1988           27
                         [32]

                    Leathwood 1982          128
                         [25]

Lavender              Kasper 2015           170
                         [45]

                     Uehleke 2012           47
                         [46]

                      Kasper 2010           221
                         [44]

                    Woelk 2010 [43]         77

Hop                  Scholey 2017           171
                         [47]

                    Cornu 2010 [48]         101

Chamomile                Adib-              60
                    Hajbaghery 2017
                         [49]

                    Chang 2016 [50]         80

                    Zick 2011 [51]          34

Hawthorn            Hanus 2003 [52]         264

St. John's wort      Al-Akoum 2009          47
                         [53]

Rosemary            Nematolahi 2018         68
                         [54]

                    Maroo 2013 [56]         78

                     Dimpfel 2008           42
                         [55]

Valerian + hop       Koetter 2007           27
                         [57]

                    Morin 2005 [58]         184

                     Sun 2003 [59]          72

Compound             First authors
                         (year            Intervention
                      published)

Valerian             Taavoni 2013     160 mg of essence of
                         [30]          valerian and lemon
                                              balm

                     Taavoni 2011       530 mg valerian
                         [29]               extract

                      Barton 2011      450 mg ofvalerian
                         [35]

                     Cuellar 2009      800 mg ofvalerian
                         [34]

                    Waldschutz 2008      Doses were at
                         [37]             physicians'
                                           judgments

                    Oxman 2007 [33]    200 mg extract per
                                        tablet (valerina
                                            forte).

                      Muller 2006     Euvegals forte (160
                         [31]          mg valerian root)

                      Jacobs 2005      2 valerian softgel
                         [39]         capsules (3.2 mg of
                                        valerenic acids)

                      Diaper 2004      Acute valerian 300
                         [40]          mg or valerian 600
                                          mg 225 mg V.
                                      officinalis root and
                                        rhizome extract

                     Coxeter 2003
                         [41]

                     Ziegler 2002     600 mg/die valerian
                         [28]               extract

                     Poyares 2002       100 mg valerian
                         [27]              (valmane)

                       Herrera-        450 mg of valerian
                     Arellano 2001
                         [26]

                     Wheatley 2001     600 mg of valerian
                         [38]

                      Donath 2000      300 mg dry extract
                         [36]         valerian (sedonium)

                     Lindahl 1988          400 mg of
                         [32]            valepotriates

                    Leathwood 1982    400 mg valerian for
                         [25]                3 days

Lavender              Kasper 2015       80 mg of silexan
                         [45]          daily for 10 weeks

                     Uehleke 2012        1 X 80 mg/day
                         [46]         silexan over 6 weeks

                      Kasper 2010       80 mg of silexan
                         [44]          daily for 10 weeks

                    Woelk 2010 [43]      1 X 80 mg/day
                                      silexan over 6 weeks

Hop                  Scholey 2017     LZComplex3 (lactium,
                         [47]          Zizyphus, Humulus
                                      lupulus, magnesium,
                                      and vitamin B6) hop
                                       500 mg for 2 weeks

                    Cornu 2010 [48]       Two gelatine
                                          capsules of
                                       Cyclamax[R] (50 mg
                                        hop, 260 mg soya
                                      oil, 173 mg Cannabis
                                      sativa) per day for
                                            a month

Chamomile                Adib-         200 mg twice a day
                    Hajbaghery 2017       for 28 days
                         [49]

                    Chang 2016 [50]   one cup of chamomile
                                       tea per day for 2
                                             weeks

                    Zick 2011 [51]    270 mg of chamomile
                                       twice daily for 28
                                              days

Hawthorn            Hanus 2003 [52]    150 mg twice daily
                                          for 3 months

St. John's wort      Al-Akoum 2009     900 mg three times
                         [53]                daily

Rosemary            Nematolahi 2018     500 mg rosemary
                         [54]

                    Maroo 2013 [56]   300 mg valerian, 80
                                       mg passion flower,
                                         and 30 mg hop

                     Dimpfel 2008      460 mg of valerian
                         [55]          and 460 mg of hop
                                          single dose

Valerian + hop       Koetter 2007      500 mg of valerian
                         [57]          and 120 mg of hop
                                          for 4 weeks

                    Morin 2005 [58]   2 tablets of 187 mg
                                      of valerian and 41.9
                                        mg of hop for 28
                                              days

                     Sun 2003 [59]    200 mg valerian, 100
                                        mg hop, kava and
                                        other components

Compound             First authors          Reported
                         (year             outcomes/
                      published)            results

Valerian             Taavoni 2013     Improvement in sleep
                         [30]            quality (PSQI)

                     Taavoni 2011     Improvement in sleep
                         [29]            quality (PSQI)

                      Barton 2011      No improvement in
                         [35]         sleep quality (PSQI)

                     Cuellar 2009      No improvement in
                         [34]         sleep quality (PSQI)


                    Waldschutz 2008      Improved sleep
                         [37]         latency and duration

                    Oxman 2007 [33]    No improvement in
                                         sleep quality
                                           perceived

                      Muller 2006      Reduced dyssomnia
                         [31]

                      Jacobs 2005      No changes in ISI
                         [39]

                      Diaper 2004      No changes in EEG
                         [40]            parameters or
                                          psychometric
                                            measures

                     Coxeter 2003     No changes in total
                         [41]         sleep time or number
                                      of night awakenings

                     Ziegler 2002     Improvement in sleep
                         [28]               quality

                     Poyares 2002     Improvement in sleep
                         [27]           quality and wake
                                        time after sleep
                                             onset

                       Herrera-       Improvement in sleep
                     Arellano 2001    quality and morning
                         [26]              sleepiness

                     Wheatley 2001       Improvement in
                         [38]          insomnia severity
                                             scores

                      Donath 2000        Improvement in
                         [36]           slow-wave sleep
                                            latency

                     Lindahl 1988     Improvement in sleep
                         [32]               quality

                    Leathwood 1982    Improvement in sleep
                         [25]           quality and wake
                                        time after sleep
                                             onset

Lavender              Kasper 2015     Improvement in sleep
                         [45]          quality (PSQI) and
                                         anxiety (HAMA)

                     Uehleke 2012      Reduced waking-up
                         [46]            frequency and
                                            duration

                      Kasper 2010     Improvement in sleep
                         [44]          quality (PSQI) and
                                         anxiety (HAMA)

                    Woelk 2010 [43]      Improvement in
                                       anxiety (HAMA) and
                                      sleep quality (sleep
                                             diary)

Hop                  Scholey 2017     No changes in sleep
                         [47]            quality (PSQI)

                    Cornu 2010 [48]   No effects on sleep
                                        quality (LSEQ),
                                           melatonin
                                        metabolism, and
                                        sleep-wake cycle

Chamomile                Adib-           Improvement in
                    Hajbaghery 2017      general sleep
                         [49]          quality and sleep
                                         latency (PSQI)

                    Chang 2016 [50]   Improvement in PSQS

                    Zick 2011 [51]       No significant
                                       improvement in ISI
                                            and PSQI

Hawthorn            Hanus 2003 [52]       Reduction in
                                        Hamilton Anxiety
                                             Scale

St. John's wort      Al-Akoum 2009       Improvement in
                         [53]            general sleep
                                         quality (SPS)

Rosemary            Nematolahi 2018   Improvement in sleep
                         [54]            quality (PSQI)

                    Maroo 2013 [56]   Improvement in total
                                       sleep time, sleep
                                       latency, number of
                                      nightly awakenings,
                                            and ISI

                     Dimpfel 2008     Improvement in sleep
                         [55]         quality (deep sleep)
                                       and sleep quantity

Valerian + hop       Koetter 2007     Improvement in sleep
                         [57]               latency

                    Morin 2005 [58]      Improvement in
                                        quality of life
                                      (physical component)

                     Sun 2003 [59]    Improvement in sleep
                                         quality, sleep
                                         latency, sleep
                                        duration, sleep
                                       disturbance (PSQI)

Compound             First authors                               Jadad
                         (year                Journal            scale
                      published)

Valerian             Taavoni 2013          Complementary           3
                         [30]               Therapies in
                                         Clinical Practice

                     Taavoni 2011            Menopause             3
                         [29]

                      Barton 2011          The Journal of          3
                         [35]           Supportive Oncology

                     Cuellar 2009           Alternative            5
                         [34]           Therapies in Health
                                            and Medicine

                    Waldschutz 2008     The Scientific World       1
                         [37]                 Journal

                    Oxman 2007 [33]           PLoS One             5

                      Muller 2006          Phytomedicine           1
                         [31]

                      Jacobs 2005             Medicine             5
                         [39]

                      Diaper 2004           Phytotherapy           5
                         [40]                 Research

                     Coxeter 2003          Complementary           5
                         [41]               Therapies in
                                              Medicine

                     Ziegler 2002       European Journal of        NA
                         [28]             Medical Research

                     Poyares 2002           Progress in            3
                         [27]         Neuropsychopharmacology
                                           and Biological
                                             Psychiatry

                       Herrera-            Planta Medica           3
                     Arellano 2001
                         [26]

                     Wheatley 2001          Phytotherapy           1
                         [38]                 Research

                      Donath 2000        Pharmacopsychiatry        4
                         [36]

                     Lindahl 1988           Pharmacology           4
                         [32]             Biochemistry and
                                              Behavior

                    Leathwood 1982          Pharmacology           4
                         [25]             Biochemistry and
                                              Behavior

Lavender              Kasper 2015             European             4
                         [45]         Neuropsychopharmacology

                     Uehleke 2012          Phytomedicine           1
                         [46]

                      Kasper 2010          International           5
                         [44]                 Clinical
                                         Psychopharmacology

                    Woelk 2010 [43]        Phytomedicine           4

Hop                  Scholey 2017            Nutrients             5
                         [47]

                    Cornu 2010 [48]      BMC Complementary         3
                                          and Alternative
                                              Medicine

Chamomile                Adib-             Complementary           3
                    Hajbaghery 2017         Therapies in
                         [49]                 Medicine

                    Chang 2016 [50]     Journal of Advanced        3
                                              Nursing

                    Zick 2011 [51]       BMC Complementary         5
                                          and Alternative
                                              Medicine

Hawthorn            Hanus 2003 [52]       Current Medical          4
                                        Research and Opinion

St. John's wort      Al-Akoum 2009           Menopause             5
                         [53]

Rosemary            Nematolahi 2018        Complementary           3
                         [54]               Therapies in
                                         Clinical Practice

                    Maroo 2013 [56]      Indian Journal of         5
                                            Pharmacology

                     Dimpfel 2008       European Journal of        3
                         [55]             Medical Research

Valerian + hop       Koetter 2007           Phytotherapy           2
                         [57]                 Research

                    Morin 2005 [58]            Sleep               3

                     Sun 2003 [59]         The Journal of          0
                                          Alternative and
                                           Complementary
                                              Medicine

SPS = sleep problem scale, PSQI = Pittsburg sleep quality inventory,
PSQS = postpartum sleep quality scale, LSEQ = Leeds sleep evaluation
questionnaire, and ISI = insomnia severity index.

Table 2: Sleep outcomes.

Compounds                      SL        WASO       tst        QOS

Valerian                     check]     check]     check]     check]
Lavender                     check]     check]     check]     check]
Hop Chamomile                check]                           check]
Hawthorn St. John's wort                                      check]
Rosemary                                                      check]

SL = sleep latency, WASO = wake after sleep onset, TST = total sleep
time, and QOS = quality of sleep.
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Author:Guadagna, S.; Barattini, D.F.; Rosu, S.; Ferini-Strambi, L.
Publication:Evidence - Based Complementary and Alternative Medicine
Article Type:Clinical report
Date:May 31, 2020
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