Systematic Review of Single Plant Herbal Sleep Aids

More than 30% of US residents report not getting enough sleep. Another 25% experience occasional sleeplessness (insomnia) and low sleep quality. About 37% of respondents in a US survey had fallen asleep at least once during the day in the preceding month due to insufficient sleep; 4.7% of them, while driving or working. Influenced by a variety of genetic and environmental factors, the etiology of insomnia is not fully understood. Insomnia is treated conventionally with several medicines including benzodiazepines and antihistamines. These may cause adverse events (AEs) including daytime drowsiness, dependency, depression, and suicidal ideation. Plant-derived sleep aids from traditional and/or complementary and alternative medicine (CAM) has been increasingly investigated as alternatives to conventional drugs. The authors systematically reviewed original reports of the effects of single-plant-derived extracts, administered orally, on sleep-related outcomes in humans. Their literature search strategies, participant characteristics of included studies, and other data are presented in supplemental material online.

In the studies included in the review, four well-known herbs predominated. Valerian (Valeriana officinalis, Caprifoliaceae) root has been the most-studied as a sleep aid by far, with 17 human trials included; 14 were randomized clinical trials (RCTs). Bioactive compounds in this perennial herb include valerenic acid, iridoids, isovaleric acid, isovaleramide, alkaloids, γ-aminobutyric acids (GABA), flavanones, and 6-methylapigenin. Although valerian’s mechanism of action is unknown, valerenic acid and valepotriates have been proposed to be related to the herb’s sleep-inducing effects. While it has been reported that valerian increased GABA concentrations in the synaptic cleft, it is unclear whether the GABA in valerian can cross the blood-brain barrier or if the herb promotes GABA production in the brain. Trials included in this review used several different measures of sleep quantity and quality as outcomes and reported conflicting results. Dosages of the various extracts used ranged from 225-1060 mg daily, usually taken once before bedtime. Extracts used, and their compounds, are not discussed or presented in summary tables. Of five RCTs that received the highest Jadad scale scores (5), four had small sample sizes (<50); only one, with a study group of 405, was specific to insomnia patients. It found only minimal differences between controls and those taking 600 mg daily of valerian for 14 days, except for significant improvement in subjective sleep quality in the valerian group. In RCTs with relatively large study groups, valerian (1060 mg daily for four weeks) improved subjective sleep quality compared to controls (30% vs. 4%) in 100 postmenopausal women; in 119 cancer patients, 450 mg daily was not effective for improving sleep or fatigue. In a six-week comparison of 600 mg daily of valerian and 10 mg daily of oxazepam, a benzodiazepine, in 202 patients with nonorganic insomnia, sleep quality improved comparably in both groups; however, no objective measures of sleep duration or quality were reported. An earlier systematic review of valerian reached the same conclusion as these authors: “it is safe but has insufficient evidence on its efficacy.”

Kava (Piper methysticum, Piperaceae) root extracts were used in three studies included in the review; in two, combined or in parallel with valerian. Results of the valerian arms of these trials are not included in the valerian summary. In vivo studies indicate that kava’s active compounds may modulate GABA. Results of studies included indicate some efficacy for kava in sleeplessness. The small number of trials may be related to earlier reports of kava’s potential liver-related AEs and remaining uncertainties as to its safety.

In three lavender (Lavandula spp., Lamiaceae) studies included, one RCT used an infusion of 2 grams of dried lavender flowers in 300 mg water and two RCTs used Silexan (Dr. Willmar Schwabe GmbH & Co KG; Karlsruhe, Germany), a capsule containing essential oil (EO) made with common lavender (L. angustifolia) flowers by steam distillation and approved in Germany as an anxiolytic. Although the latter two were performed by the same investigators with patients who had anxiety disorders and sleep disturbances, they reached conflicting results. A fourth study, an open-label exploratory trial, used lavender oil capsules identified as Silexan in the text but not the accompanying table. The table indicates in a subheading that all four studies used common lavender, but this is unclear from the text. The authors note that lavender EOs are also used in aromatherapy but included only trials of oral products. While lavender’s linalyl acetate and linalool are major constituents that may cause its sleep-enhancing activity by modulating glutamate and GABA, individual compounds did not exert their effects in vivo. As with valerian, lavender trial results were conflicting in these studies.

St. John’s wort (Hypericum perforatum, Hypericaceae) contains hyperforin and adhyperforin, compounds thought to increase monoamine neurotransmitter concentrations, despite some evidence to the contrary. In three small RCTs in diverse populations, it showed sleep-improving effects. However, St. John’s wort should be considered in light of a notice from the National Center for Complementary and Integrative Health (NCCIH) of its potential for causing serotonin syndrome.

Fourteen other herbs were studied in reports summarized in a table but not otherwise discussed; there were just one or two studies included for each of these, and the results varied considerably.

The poverty of evidence of plant-derived products’ overall efficacy in sleep hinders expensive studies to fully characterizing products used and their most effective compounds and dosage regimens.

The authors declare no conflicts of interest.

Resource:

Kim H, Lee SL, Kang I, et al. Natural products from single plants as sleep aids: a systematic review. J Med Food. May 2018;21(5):433-444. doi:10.1089/jmf.2017.4064.

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