Evaluation of capsules containing Valeriana fauriei root extract for sleep improvement: A randomized, double‐blind, placebo‐controlled, cross‐over comparative trial

Abstract

AimThis clinical trial aimed to clarify the sleep‐ameliorating effects of capsules containing Valeriana fauriei root (VF) extract and their adverse effects.MethodsThe trial was a randomized, double‐blind, placebo‐controlled, cross‐over comparative clinical trial involving participants with an Athens Insomnia Scale (AIS) of 6 or higher, selected by prescreening questionnaires. After randomization, the participants took VF (2 g as VF/day) or placebo capsules for two weeks and were asked to complete the Obstructive Sleep Apnea (OSA) sleep questionnaire daily to assess their sleep status and any changes in their physical condition. On the last day of each term, the participants reported their sleep improvement experience.ResultsNo significant differences were found between the VF and placebo groups on the OSA sleep questionnaire. Significantly, more participants in the VF‐treated group experienced improvements in sleep onset and quality than those in the placebo group. The sleep onset improved particularly in those with early awakening, whereas the sleep quality particularly improved in those with midnight awakening. Although a few participants experienced physical, gastrointestinal and psychological changes when taking VF capsules, there was no significant difference from the placebo group, and no serious adverse events occurred.ConclusionWe clinically determined that VF, a folk medicine, improves sleep onset and sleep quality in people with suspected insomnia without serious adverse events at the dosage of 2 g VF/day.

Safety evaluation of continuous administration of a high dose of Valeriana fauriei root extract in mice and in humans through an open‐label study

“…This may be because high doses of VF were administered in mice compared with humans, which may have caused changes in these values. However, these changes are slight; intake of a lower dose, 2 g/day, which had a sleep improvement effect [8], should not be a problem, but caution should be exercised with long-term administration of high doses.…”

“…A VF sample cultivated in Mie Prefecture, Japan, obtained from Kuki Sangyo Co., Ltd. (Yokkaichi, Japan), in 2018 (voucher no. A2018031901) was used, as in previous studies [6][7][8]. The sample was identified using anatomical studies with reference [6].…”

“…Participants kept daily diaries of their living conditions (food intake, exercise), sleep status, and physical changes. Regarding changes in physical condition, participants were asked to respond to the questions about experiencing mild gastrointestinal symptoms (dry mouth, upset stomach, diarrhea, and constipation) and psychiatric symptoms (sleepiness, headache, dizziness, and fatigue), as in the previous clinical trial [8]. Two weeks and four weeks after the start of treatment, the participants were examined at Nagoya City University Hospital, like at the preliminary examination.…”

“…For preparing soft capsules, the VF extract, dextrin, cyclodextrin, and silica were mixed at a ratio (w/w) of 300:291:3:6. Sankyo Co., Ltd. (Fuji, Japan) prepared soft capsules by adding glycerin fatty acid ester, beeswax, and rice oil as substrates and coating them with caramelcolored fish gelatin (1 g of VF per capsule), as in the previous clinical trial [8]. An amount of 102 ± 6 (n = 5) mg kessyl glycol diacetate (KGD), used as a quality criterion for VF, was contained per 10 capsules [8].…”

“…Valeriana fauriei root contains a lot of essential oil [5] and has competitive activity on the flunitrazepam-bindingsite of the GABA A receptor in vitro [6], and significantly shortens sleep latency and prolongs pentobarbitalinduced sleep in mice with caffeine-induced insomnia, partially mediated via the GABAergic nervous system [7]. In a previous report, we clinically elucidated that soft capsules containing ethanol extract of VF improve sleep onset and quality in people suspected of insomnia without serious adverse events at 2 g VF/day [8].…”