Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake

Abstract

Hericium erinaceus, a well known edible mushroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, “insentive” and “palpitation”, each of the mean score of the HE group was significantly lower than the placebo group. “Concentration”, “irritating” and “anxious” tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.

Introduction

H. erinaceus (Lion's mane mushroom), a well-known edible mushroom, has been used as traditional medicine in several Asian countries to treat various human diseases. The compounds isolated from its fruiting bodies contain numerous biological activities, such as anti-tumor, hypolipidemic, hemagglutinating, cytotoxic, anti-microbial, endoplasmic reticulum (ER) stress-suppressive, and antioxidant activities.

Especially, it has been reported that hericenones and erinacines stimulate nerve growth factor (NGF) synthesis in cultured astrocytes. Erinacines were isolated from the cultured mycelia of H. erinaceus and identified as diterpenoids; hericenones were isolated from the fruiting bodies. In addition, studies of the whole brain and cell cultures have shown that NGF affects the viability of cholinergic neurons and the level of activity of choline-acetyltransferase and acetylcholinesterase in the central nervous system. A clinical study has reported that H. erinaceus improved mild cognitive impairment in which the decrease of cholinergic neurons is involved. However, despite the clinical importance of H. erinaceus, there have been few studies elucidating its other effects on brain functions and the autonomic nervous system.

Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using a variety of questionnaires: the Kupperman Menopausal Index (KMI) for menopause, the CES-D scale for depression, the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, and the Indefinite Complaints Index (ICI) for indefinite complaints.

Materials and methods

The trial was randomized, double-blind, placebo-controlled and was conducted over 4 consecutive weeks. Thirty females aged 41.3 ± 5.6 years with a variety of indefinite complaints and no specified diseases participated. Exclusion criteria: less than 75% intake of test samples (n = 2), epimenorrhea (n = 1), no report (n = 1). All participants were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. An HE cookie contained 0.5 g of powdered fruiting body of H. erinaceus; a placebo cookie contained no powder. Each participant ate 4 cookies at any time of day. Both HE and placebo cookies were supplied by Aso Biotech Inc (Kumamoto, Japan). Each participant completed daily report forms (intake per day, physical condition, menorrhea) and was given questionnaires for psychometric measures before and after the trial.

Psychometric measures. Four outcome measures were used: 1) the Japanese 17-item version (0–3 scale) of KMI, to quantify perimenopausal somatic symptoms; 2) the Japanese 20-item version (0–3) of CES-D, to quantify depression; 3) the Japanese 19-item version (0–3) of PSQI, to quantify sleep quality and disturbances; and 4) the 40-item version (0–5) of ICI, using accumulated scores to quantify indefinite complaints. KMI is one of the most utilized assessments in menopause studies (depressive moods, vertigo, headache, palpitation, hot flashes, joint pain, loss of concentration, nervousness/irritability, profuse perspiration, sleep disturbances). CES-D is a short self-report scale for depressive symptomatology in the general population. PSQI is a self-rated questionnaire assessing sleep quality/disturbance over 1 month (19 items → 7 component scores). ICI is based on the 40-item Keio Indefinite Complaints Index (KICI) and validated to evaluate clinical treatment effects.

Statistics. Data were analysed with SPSS. t-test and chi-squared test determined significance of sample characteristics (age, BMI, KMI, CES-D, PSQI, ICI, alcohol, smoking, stressful events, menorrhea). The Wilcoxon signed rank test determined significance of KMI, CES-D, PSQI and ICI before vs after. Analysis of covariance (ANCOVA) was used for between-group comparisons, adjusting for pre-trial means. Statistical significance was set at P = 0.05.

Results

Sample characteristics. Of 30 participants, 2 took cookies less than 75%, 1 reported epimenorrhea (18 days menorrhea/month), and 1 sent no report. After exclusions, data on 26 participants (12 HE, 14 placebo) were analyzed. There were no significant differences between groups in physical (age, BMI), psychometric (KMI, CES-D, PSQI, ICI) or lifestyle characteristics (alcohol, smoking, stressful events, menorrhea) (Table 1).

Effect on menopause index (KMI). The mean KMI score after the trial was significantly lower than before in the HE group (P = 0.090; Table 2). No significant between-group difference in the pre–post change (Fig. 1a).

Effect on depression scale (CES-D). The mean CES-D score after the trial was significantly lower than before in the HE group (P = 0.033; Table 2). No significant between-group difference in change (Fig. 1b).

Effect on sleep quality index (PSQI). No significant difference between groups before and after the trial (Fig. 1c).

Effect on indefinite complaints index (ICI). The mean ICI score after the trial was significantly lower than before in the HE group (P = 0.004; Fig. 1d, e). Significance of each subscale was then determined. In two terms – “palpitation” (P = 0.032; Fig. 2c) and “insentive” (P = 0.047; Fig. 2d) – the HE group mean was significantly lower than placebo. In three terms – “irritating” (P = 0.076; Fig. 2a), “anxious” (P = 0.067; Fig. 2b) and “concentration” (P = 0.090; Fig. 2e) – the HE group mean tended to be lower than placebo.

Discussion

The present study investigated the clinical effects of 4 weeks of H. erinaceus intake on menopause, depression, sleep quality and indefinite complaints. For several indefinite complaints, ICI scores in the HE group were significantly lower than placebo. CES-D and ICI scores were lower after HE intake. The ICI terms “insentive” and “concentration” are relevant to depression, and “anxious” to anxiety. These results suggest that H. erinaceus may reduce depression and anxiety.

Hericenones and erinacines stimulate NGF synthesis in cultured astrocytes. Prior studies reported that NGF enhanced neurochemical differentiation following intraventricular injection, and such neurogenesis-inducing effects led to antidepressant and anti-anxiety activity. These reports support our suggestion that the NGF-enhancing action of H. erinaceus reduces depression and anxiety. Hericenones and erinacines are potential substances involved, but further clinical research is needed to identify them. It is also unknown whether hericenones and erinacines can pass the blood–brain barrier to promote NGF synthesis in vivo; further studies are needed to determine the active ingredients and mechanism.

As above, our results show that H. erinaceus intake may reduce depression and anxiety. It is also relevant to “frustration/irritability” and “palpitation”, since HE intake lowered these scores. These results suggest a mechanism different from the NGF-enhancing action. Additional research with other physiological markers (autonomic nerve activity, hormones) is needed to understand the mechanism. This research also demonstrates the effectiveness of H. erinaceus via questionnaire investigation and detects a between-group difference, showing this can be a valid, objective evaluating method for the effect of food on indefinite complaints.

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