Background. Sleep complaints are common health issues in the general population. These conditions are associated with poorer physical and psychological activity, and they may have important social, economic, and personal consequences. In the last years, several food supplements with different plant extracts have been developed and are currently taken for improving sleep. Study Objectives. The aim of this study is to systematically review recent literature on oral plant extracts acting on sleep disorders distinguishing their action on the different symptoms of sleep complaints: difficulty in initiating or maintaining sleep, waking up too early, and quality of sleep. Methods. We searched the PubMed database up to 05/03/2020 based on data from randomized, double-blind, placebo-controlled trials, noncontrolled trials, and cohort studies conducted in children and adult subjects. The search words used contained the following terms: oral food supplement and sleep disorders and the like. The most studied compounds were further analyzed with a second search using the following terms: name of the compound and sleep disorders. We selected 7 emerging compounds and 38 relevant reports. Results. Although nutraceutical natural products have been used for sleep empirically, there is a scarcity of evidence on the efficacy of each product in clinical studies. Valerian and lavender were the most frequently studied plant extracts, and their use has been associated (with conflicting results) with anxiolytic effects and improvements in quality and duration of sleep. Conclusions. Sleep aids based on plant extracts are generally safe and well tolerated by the population. More high-quality research is needed to confirm the effectiveness of food supplements containing plant extracts in sleep complaints; in particular, it would be interesting to evaluate the association between plant extracts and sleep hygiene guidelines and to identify the optimal products to be used in a specific symptom of sleep complaint, giving more appropriate tools to the medical doctor.
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 . 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 , and obesity , 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 . 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 . Moreover, there are limited data on long-term efficacy of hypnotic drugs . Given these concerns and an increasing patient preference for nonpharmacological treatments , 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 .” A growing body of evidence has shown promising results for these compounds in supporting health and body functions . In particular, several dietary supplements are popularly used for sleep disorders , also in addition to other remedies (e.g., sleep hygiene and mind-body therapies) . 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  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.