ArticlePDF Available

The effects of Hericium erinaceus (Amyloban® 3399) on sleep quality and subjective well-being among female undergraduate students: A pilot study

Short communication
The effects of Hericium erinaceus (Amyloban
3399) on sleep quality
and subjective well-being among female undergraduate students: A
pilot study
Hisayoshi Okamura, Ph.D.
, Nobuko Anno, Ph.D.
, Akira Tsuda, Ph.D.
Takahiro Inokuchi, Ph.D.
, Naohisa Uchimura, M.D., Ph.D
Kazutoyo Inanaga, M.D., Ph.D.
Cognitive and Molecular Research Institute of Brain Diseases, Kurume University, Kurume, Fukuoka, Japan
Department of Food and Nutrition, Kyushu Nutrition Welfare University, Kitakyushu, Fukuoka, Japan
Department of Psychology, Kurume University, Kurume, Fukuoka, Japan
Research Institute of Medical Mass Spectrometry, Kurume University School of Medicine, Kurume, Fukuoka, Japan
Department of Psychiatry, Kurume University School of Medicine, Kurume, Fukuoka, Japan
Chikusuikai Institute for Neuroinformation, Chikusuikai Hospital, Yame, Fukuoka, Japan
article info
Article history:
Received 27 January 2015
Received in revised form
30 March 2015
Accepted 3 April 2015
Hericium erinaceus
Sleep quality
Salivary free-MHPG
1. Introduction
Currently in Japan, one out of every four to ve people suffers
from sleep disorders [1,2]. A very high percentage of undergraduate
students, who are at the last stage of adolescence, suffer from sleep
problems because of staying up late at night and sleeping until late
in the morning or maintaining irregular sleep patterns. These be-
haviors lead to disruption of circadian rhythms and deterioration of
quality of life, involving a decline in productivity due to daytime
sleepiness [3].
Compared with students who get adequate sleep (6e8 h per
night), students who habitually sleep in excess (more than 9 h per
night) or inadequately (less than 5 h per night) have a strong self-
awareness of emotional and physical distress as measured by
General Health Questionnaire (GHQ-28). In particular, the levels of
salivary free 3-methoxy-4-hydroxyphenylglycol (free-MHPG) (a
metabolite of central noradrenaline [NA]), and immunoglobulin A
(s-IgA) antibodies (which play a role in the immune system), are
substantially lower among students with excessive sleep. Our
previous study indicated that disturbance of sleep habits is closely
related to decline in subjective well-being, as well as a weakening
of immune functions and NA systems [4].
Hericium erinaceus (Lion's Mane mushroom) has long been used
for culinary and medicinal purposes. Its cognitive benets have
recently drawn more attention, and studies have investigated the
therapeutic use of this mushroom in patients with mild dementia
[5e7]. In addition, Nagano et al. [8] reported that after 4 weeks of H.
erinaceus administration, participants' feelings of depression, irri-
tability, and fatigue signicantly declined compared with those
before administration, suggesting its efcacy in improving mood.
These ndings suggest that H. erinaceus may be benecial for
people who suffer from circadian rhythm disorders and help alle-
viate sleep problems, while improving the quality of life for people
who lead an unhealthy or non-productive lifestyle by habitually
staying up late and sleeping in.
This pilot study evaluated the effects of a 4-week administration
of H. erinaceus (Amyloban
3399) on female undergraduate stu-
dents who were likely to have a high incidence of sleep problems.
We assessed changes in sleep quality and subjective well-being
with the GHQ-28 and PSQI (Pittsburg Sleep Quality Index).
Furthermore, we examined the level of salivary free-MHPG after
awakening, which is generally regarded as an accurate index of
chronic stress and depressive symptoms and reects sympathetic
nervous system activity [9]. Thus, we were able to conduct a
comprehensive analysis of the effects of Amyloban
3399 on sleep
quality and subjective well-being of female students.
*Corresponding author. Cognitive and Molecular Institute of Brain Diseases,
Kurume University, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. Tel.: þ81
942 31 7581; fax: þ81 942 31 7911.
E-mail address: (H. Okamura).
Contents lists available at ScienceDirect
Personalized Medicine Universe
journal homepage:
2186-4950/Copyright ©2015, International Society of Personalized Medicine. Published by Elsevier B.V. All rights reserved.
Personalized Medicine Universe 4 (2015) 76e78
2. Material and methods
2.1. Participants
The participants were eight female undergraduate students
(mean age: 21.7 ±0.4 years), all of whom had a National Dietitian
Exam scheduled within 1 month. None of the participants had a
history of serious illnesses or prescription medicine use.
2.2. Procedure
The participants were asked to visit the lab and were given a
brief description of the experimental procedures and saliva
collection method. A questionnaire sheet consisting of GHQ-28 and
PSQI questions was distributed. In addition to completing the
questionnaires, the participants were asked to ll out their grade
level, gender and age.
2.3. Measurements
2.3.1. Questionnaires
GHQ-28 [10]: This questionnaire assessed the participants'
mental health over the past week. This self-administered ques-
tionnaire consisted of 28 items, divided into four subscales: so-
matic symptoms,”“anxiety and insomnia,”“social dysfunction,
and depression.Participants responded to the questions using a
four-point scoring system. Each subscale had a seven-point
maximum. Cut-off points were the following: 2e3 points is a
mild, and 4 points and higher is considered a moderate for somatic
symptomsand anxiety and insomnia,,1e2 point score is mild,
and 3 points and higher is considered moderate symptom for
social dysfunctionand depression.
PSQI [11]: This questionnaire was used to assess sleep habits and
sleep quality over the 1-month period. There were 18 items con-
taining seven components (quality of sleep, sleep duration, sleep
latency, sleep efciency, sleep disturbance, use of sleep medication,
and excessive daytime sleepiness). Higher scores suggested poor
sleep quality, with a score of 5.5 being the cut-off point.
2.3.2. Saliva collection and free-MHPG measurement
Each participant was asked to collect saliva samples immedi-
ately upon waking. A Spitz device (Sarisoft) was used to collect
the samples, which were immediately stored in a 80
C freezer. All
samples were collected at the end of the study. The free-MHPG
level was measured using gas chromatography mass spectrom-
etry (Hitachi-M80B, Hitachi, Japan), as described by Yajima et al.
2.4. Administration of H. erinaceus
Participants in this study self-administered six tablets per day of
3399 (Mushroom Wisdom, Inc., East Rutherford, NJ
USA), divided into 2 or 3 doses. The supplement was taken with
food for a period of 4 weeks. Participants were not explained
anything about Amyloban
3399 during registration; they were
just told that This is a kind of supplement.
2.5. Ethical considerations
The ethics committee of the university approved this study.
Participants' safety was the priority and the research data were
used for the purposes of this study only. Participants' information
was kept condential. They were given written and oral explana-
tions before providing their consent.
2.6. Statistical analysis
Data analysis was performed with a Windows version of SPSS
(Statistical Package for the Social Sciences). A t-test was used to
evaluate the mean difference between GHQ-28 subscale scores,
PSQI scores, and average level of salivary free-MHPG before and
after administration of Amyloban
3399. In each statistical analysis,
ap-value less than 0.05 was considered statistically signicant, and
ap-value less than 0.10 was considered a marginally signicant
3. Results
The average PSQI score before administration of Amyloban
3399 was 7.3. Six of the participants scored higher than the cut-off
point (5.5) and two scored below. The scores (mean ±standard
deviation) for the GHQ-28 subscales were as follows: somatic
symptoms,3.8 ±2.7 (mild), anxiety and insomnia,5±1.9
(moderate), social dysfunction,1.9 ±2.1 (mild), and depression,
1.8 ±1.3 (mild).
On the anxiety and insomniasubscale of the GHQ-28, there
was a declining trend after 4 weeks of supplement administration
(t¼1.86, df ¼14, p<0.10). No signicant differences were observed
on the other subscales after the 4-week administration of Amylo-
3399. There were no statistically signicant differences in
PSQI scores associated with Amyloban
3399 use. However, after
the 4-week administration, the average score showed a decline
(pre-administration: 7.25, post-administration: 5.75), and the
number of participants who scored above the 5.5 cut off point
declined from six to four. After 4 weeks of Amyloban
administration, levels of salivary free-MHPG signicantly increased
compared with those during pre-administration (t¼2.25, df ¼14,
p<0.05; Table 1).
4. Discussion
This study comprehensively evaluated subjective ratings on the
GHQ-28 and PSQI questionnaires, as well as the objective assess-
ment of salivary free-MHPG levels, taken from 8 female under-
graduate students to assess the effects of 4 weeks of administration
of Amyloban
3399 on sleep quality and subjective well-being. The
average PSQI score from the eight participants before adminis-
trating Amyloban
3399 was 7.3 and was higher than the cut-off
point (5.5). In addition, the average score on the anxiety and
insomniasubscale of the GHQ-28 questionnaire before the
administration was 5 points, and the percentage of those exhibiting
moderate symptoms was high as well. These results reect a
disturbance in sleep habits, and an increase in negative mood and
anxiety levels associated with preparations for the national exam
that all the participants were scheduled to take in about a month.
Table 1
Comparison of before and after Hericium erinaceum intake.
Before Hericium
After Hericium
Somatic symptoms 3.8 ±2.7 3.4 ±1.7 p¼0.745
Anxiety and insomnia 5 ±1.9 3.3 ±1.8 p¼0.084
Social dysfunction 1.9 ±2.1 1.9 ±1.5 p¼1.000
Depression 1.8 ±1.3 1.0 ±1.6 p¼0.319
PSQI 7.3 ±2.6 5.8 ±2.9 p¼0.292
Salivary free-MHPG 5.6 ±1.9 9.5 ±4.0 p¼0.029
Values are represented as mean ±standard error.
The pvalues indicate the difference between before and after Hericium erinaceum
H. Okamura et al. / Personalized Medicine Universe 4 (2015) 76e78 77
After 4 weeks of Amyloban
3399 use, the anxiety and
insomniascore decreased. PSQI scores also decreased, although
this difference was not statistically signicant. Inanaga [13] has
reported that intake of Amyloban
3399 improves negative mood
such as irritability and anxiety, and raises incentive associated with
improved concentration and motivation. In addition, he also re-
ported that Amyloban
3399 was effective in improving symptoms
of sleep apnea [13]. These ndings suggest that taking H. erinaceus
3399) could improve negative mood and sleep disor-
der symptoms. However, 2 out of 8 participants in this study did not
have sleep problems as assessed by PSQI. Therefore, this study may
have lacked the statistical power necessary to examine the effects
of Amyloban
3399 on sleep disturbances. Further studies will be
required to investigate the effects of Amyloban
3399 on circadian
rhythm sleep disorders and/or sleep disturbance using a larger
number of participants.
In this study, the level of salivary free-MHPG before adminis-
tration of Amyloban
3399 was 5.6 ±1.9 ng/ml. This was low in
comparison with the levels from healthy participants in our pre-
vious studies (9.3 ±1.8 ng/ml) [4]. However, after 4 weeks of
3399 use, these levels increased to levels comparable
with those in healthy participants. It is suggested that the levels of
salivary free-MHPG in people with unidentied complaints are low
immediately after awakening. The possible correlation between
changes in salivary levels of free-MHPG after awakening and sub-
jective stress reaction needs to be investigated in further detail.
Shimbo et al. [14] reported that Erinacine A, which is isolated from
Hericium erinaceum, enhanced the synthesis of nerve growth factor
(NGF) by increasing the secretion of NA and catecholamines. Our
study was consistent with these ndings with regard to the in-
crease in salivary free-MHPG. Furthermore, an increase in salivary
free-MHPG levels coincided with a trend towards improvement in
anxiety levels and sleep quality. These results indicated that one of
the possible effects of Amyloban
3399 could be an ability to bal-
ance out the mind and body. Thus, the administration of H. erina-
ceus (Amyloban
3399) could improve mood and circadian rhythm
sleep disorder symptoms, as well as the quality of life, in unhealthy
people (semi-healthypeople at early stages of illness) who led an
unproductive lifestyle. However, salivary free-MHPG level is known
to be related to depressive mood and anxiety. Increased levels of
free-MHPG in conjunction with increased psychological stress have
also been reported [15,16]. Therefore, further studies would be
required to elucidate the impact of Amyloban
3399 on salivary
free-MHPG levels.
5. Conclusion
This pilot study assessed the effects of 4 weeks of administration
of Amyloban
3399 on subjective well-being and sleep quality in
female undergraduate students. The results revealed an increase in
salivary free-MHPG, which corresponded to an improvement in
anxiety and quality of sleep. Thus, we conclude that one of the
possible effects of Amyloban
3399 is to balance out the mind and
body. In the future, we will need to study the effects of Amyloban
3399 on sleep quality and everyday work, using a larger number of
student participants.
3399 made based on a proprietary extract called
Amycenonewas used for this study. It contains standardized
amounts of the following compounds:
1. Hericenone (0.5%) eHericenone stimulates synthesis of nerve
growth factor, which promotes nerve protection [17,18].
2. Amyloban (6%) eFat soluble compound, which reduces the
endoplasmic reticulum stress caused by amyloid beta and helps
increase the survival of nerve cells [7].
This work was supported by a Grant-in-Aid for Young Scientists
B: 24730613 from Japanese Society for the Promotion of Science to
Hisayoshi Okamura.
The author wishes to thank Masaki Shirota, CEO of Mushroom
Wisdom, Inc., E. Rutherford, NJ, USA that developed Amylo-
3399 as a dietary supplement, and Tomoko Nakamura, Vice
President of Sun Medica Co., Ltd., Tokyo Japan, who provided
3399 for use in this study.
[1] Shirakawa S, Ishigouoka J, Ishizuka Y, et al. Epidemiology of sleep disorders
and sleep habits of outpatients in general hospital of Japan. Study on the
diagnosis, treatment and epidemiology of sleep disorders. Annual Report of
the National Project Team, Tokyo. 1996. p. 7e23 [in Japanese].
[2] Kim K, Uchiyama M, Okawa M, et al. An epidemiological study of insomnia
among the Japanese general population. Sleep 2000;23:41e7.
[3] Reiko S. Sleep tendency of university studentsda survey among the rst year
students, vol. 4. Bulletin of Faculty of Human and Social Services, Yamanashi
Prefectural University; 2009. p. 51e8 [in Japanese].
[4] Okamura H, Tsuda A, Yajima J, et al. Sleeping time relates to perceived health
and psychoneuroimmunological responses. Jpn J Behav Med 2009;15:33e40
[in Japanese].
[5] Kawagishi H, Zhuang C, Shnidman E. The anti-dementia effect of Lion's Mane
mushroom (Hericium erinaceum) and its clinical application. Townsend Lett Dr
Patients April 2004:54e6.
[6] Kawagishi H, Zhuang C. Compounds for dementia from Hericium erinaceum.
Drugs Future 2008;33:149e55.
[7] Nagai K, Chiba A, Nishino T, et al. Dilinoleoyl-phosphatidylethanolamine from
Hericium erinaceum protects against ER stress-dependent Neuro2a cell death
via protein kinase C pathway. J Nutr Biochem 2006;17:525e30.
[8] Nagano M, Shimizu K, Kondo R, et al. Reduction of depression and anxiety by 4
weeks Hericium erinaceus intake. Biomed Res 2010;31:231e7.
[9] Sugaya N, Izawa S, Yamamo R, et al. 3-methoxy-4-hydroxyphenylglycol in-
creases after awakening in healthy young adults. Psychophysiology 2014;52:
[10] Nakagawa Y, Daibo I. Japanese version of the general health questionnaire.
Tokyo: Nihon Bunka Kagakusha; 1985 [in Japanese].
[11] Doi Y, Minowa M, Uchiyama M, et al. Development of the Japanese version of
the Pittsburgh sleep quality index. Jpn J Psychiat Treat 1998;13:755e63 [in
[12] Yajima J, Tsuda A, Yamada S, et al. Determination of saliva free-3-methoxy-4-
hydroxyphenylglycol in normal volunteers using gas chromatography mass
spectrometry. Biog Amines 2001;16:173e83.
[13] Inanaga K. Amycenone, a nootropic found in Hericium erinaceum. Per Med
Universe 2012;1:13e7.
[14] Shimbo M, Kawagishi H, Yokogoshi H. Erinacine A increases catecholamine
and nerve growth factor content in the central nervous system of rats. Nutr
Res 2005:617e23.
[15] Egami M, Imamura Y, Nabeta H, et al. Saliva levels of 3-methoxy-4-
hydroxyphenylglycol and clinical efcacy of mirtazapine or selective seroto-
nin reuptake inhibitors in patients with major depression. Hum Psycho-
pharmacol 2013;28:7e14.
[16] Yamada S, Yamauchi K, Yajima J, et al. Saliva level of free 3-methoxy-4-
hydroxyphenylglycol (MHPG) as a biological index of anxiety disorders. Psy-
chiatry Res 2000;10:217e23.
[17] Kawagishi H, Ando M, Sakamoto H, et al. Hericenones C, D and E, stimulators of
nerve growth factor (NGF)-synthesis, from the mushroom Hericium erinaceum
growth factor (NGF). Tetrahedron Lett 1991;32:4561e4.
[18] Furukawa S, Kawagishi H. Kagaku to Seibutu, vol. 29; 1991. p. 640e6 [in
H. Okamura et al. / Personalized Medicine Universe 4 (2015) 76e7878
... Commonly found in edible mushrooms. To date, three preclinical [77][78][79] and three clinical [80][81][82] studies have investigated the potential influence of H. erinaceus on affective functions. In a 2010 study on a small sample of 12 women undergoing menopause, Nagano et al. observed that 4-week supplementation with 2 g/day of powdered fruiting bodies of H. erinaceus caused a significant reduction in self-reported depression symptoms and indefinite complaints to levels that were-however-indistinguishable from the placebo group (n = 14), in which the reduction was also present, but statistically nonsignificant [81]. ...
... This effect could not be driven by erinacines (for chemical structure, see Table 2), the only compounds proven to date with the ability to cross the blood-brain barrier [83,84], as they are found only in the mycelium and not in the fruiting bodies of H. erinaceus [85]. Interestingly, Okamura et al. (2015) observed higher norepinephrine turnover (measured by free 3-Methoxy-4-hydroxyphenylglycol, i.e., MHPG levels in saliva), without any effect on self-reported somatic, anxiety, or depres-sion symptoms in eight women (no placebo group was included in the study) after 4 weeks of supplementation with 585 mg/day of hericenone [82]. Finally, in a subgroup of 15 obese individuals with high self-reported depression and anxiety symptoms, Vigna et al. (2019) found that administration of 1.5 g/day of H. erinaceus (1.2 g mycelium, 0.3 fruiting body) for 8 weeks caused a reduction in both anxiety and depression symptoms [80]. ...
... This effect could not be driven by erinacines (for chemical structure, see Table 2), the only compounds proven to date with the ability to cross the blood-brain barrier [83,84], as they are found only in the mycelium and not in the fruiting bodies of H. erinaceus [85]. Interestingly, Okamura et al. (2015) observed higher norepinephrine turnover (measured by free 3-Methoxy-4-hydroxyphenylglycol, i.e., MHPG levels in saliva), without any effect on self-reported somatic, anxiety, or depres-sion symptoms in eight women (no placebo group was included in the study) after 4 weeks of supplementation with 585 mg/day of hericenone [82]. Finally, in a subgroup of 15 obese individuals with high self-reported depression and anxiety symptoms, Vigna et al. (2019) found that administration of 1.5 g/day of H. erinaceus (1.2 g mycelium, 0.3 fruiting body) for 8 weeks caused a reduction in both anxiety and depression symptoms [80]. ...
Full-text available
Dietary interventions for people suffering from major depressive disorder (MDD) are an ongoing field of research. In this article, we present a comprehensive background for understanding the possibility of using edible medicinal mushrooms as an adjunctive treatment for MDD. We start with a brief history of MDD, its diagnosis, epidemiology and treatment, and the effects of diet on depression symptoms, followed by a review of neurobiological, behavioral, and clinical studies of medicinal mushrooms. We specifically highlight the results of preclinical and clinical studies on dietary supplementation with three selected mushroom species: Lion’s mane (Hericium erinaceus), Caterpillar mushroom (Cordyceps militaris), and Lingzhi/Reishi (Ganoderma lucidum). Preliminary small-sample clinical studies suggest that Lion’s mane can influence well-being of humans. In the case of Reishi, the results of clinical studies are equivocal, while in the case of Caterpillar Mushroom, such studies are underway. Edible mushrooms contain 5-hydroxy-L-tryptophan (5-HTP), which is a direct precursor of serotonin—a neurotransmitter targeted in pharmacotherapy of MDD. Therefore, in light of the well-recognized role of stress as a pathogenic factor of MDD, we also describe the neurobiological mechanisms of the interaction between stress and serotonergic neurotransmission; and summarize the current state of knowledge on dietary supplementation with 5-HTP in MDD.
... HE has been shown to possess pharmacological activity that can improve neurological conditions, including cognitive impairment [18], Alzheimer's disease [19], and Parkinson's disease [20]. Recently, HE was shown to ameliorate depressive-like symptoms in both preclinical [21][22][23] and clinical studies [24][25][26][27][28]. Several pathways have been reported to be involved in the antidepressant effects of HE, including anti-inflammatory pathways [21], neurogenic and neurotrophic modulation [22,23], and monoamine modulation [23]. ...
... The antidepressant effects of HE can be attributed to various bioactive compounds that can have diverse beneficial functions. Several bioactive compounds extracted from HE have been shown to stimulate the synthesis of nerve growth factor (NGF) and promote neurite outgrowth, which have a role in alleviating depressive-like symptoms [26,[29][30][31][32][33][34][35]. Furthermore, an in vivo study reported that HE enriched with erinacine A could modulate BDNF signalling, and enhance serotonin, dopamine, and noradrenaline expression levels [23]. ...
... Based on the hypothesis that HE can modulate the protein expression levels of pro-BDNF and mature BDNF in different tissues, consideration should be given to the brain region or treatment length in future studies, as these proteins are well known to be associated with antidepressant-like effects. Additionally, many studies have identified the bioactive compounds of HE that stimulate NGF expression [26,[29][30][31][32][33][34][35], however, the bioactive compounds that contribute to increased BDNF expression have yet to be identified. ...
Full-text available
Background: Depression is a severe neuropsychiatric disorder that affects more than 264 million people worldwide. The efficacy of conventional antidepressants are barely adequate and many have side effects. Hericium erinaceus (HE) is a medicinal mushroom that has been reported to have therapeutic potential for treating depression. Methods: Animals subjected to chronic restraint stress were given 4 weeks HE treatment. Animals were then screened for anxiety and depressive-like behaviours. Gene and protein assays, as well as histological analysis were performed to probe the role of neurogenesis in mediating the therapeutic effect of HE. Temozolomide was administered to validate the neurogenesis-dependent mechanism of HE. Results: The results showed that 4 weeks of HE treatment ameliorated depressive-like behaviours in mice subjected to 14 days of restraint stress. Further molecular assays demonstrated the 4-week HE treatment elevated the expression of several neurogenesis-related genes and proteins, including doublecortin, nestin, synaptophysin, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated extracellular signal-regulated kinase, and phosphorylated cAMP response element-binding protein (pCREB). Increased bromodeoxyuridine-positive cells were also observed in the dentate gyrus of the hippocampus, indicating enhanced neurogenesis. Neurogenesis blocker temozolomide completely abolished the antidepressant-like effects of HE, confirming a neurogenesis-dependent mechanism. Moreover, HE induced anti-neuroinflammatory effects through reducing astrocyte activation in the hippocampus, which was also abolished with temozolomide administration. Conclusion: HE exerts antidepressant effects by promoting neurogenesis and reducing neuroinflammation through enhancing the BDNF-TrkB-CREB signalling pathway.
... Additionally, a pilot study on eight female undergraduate students with sleep disorder demonstrated that a 4-week administration of Amyloban ® 3399 was associated with an improvement in anxiety and sleep quality, measured by the increase in the salivary level of free 3-methoxy-4-hydroxyphenylglycol, a biological index of anxiety disorders [124]. ...
... Timeline of the published papers relating the effects of H. erinaceus in clinical studies[72][73][74]85,86,124,127]. ...
Full-text available
A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer’s disease, depression, Parkinson’s disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies.
... It has also been reported to improve mental health and general well-being. Overall, consumption of Lion's Man can help improve mood and sleep (Okamura et al., 2015;Vigna et al., 2019), fight fatigue (He et al., 2017;Liu et al., 2015), reduce appetite (Khursheed et al., 2020), return circadian rhythms to normal (Furuta et al., 2016) and treat depression, anxiety and menopause (Chong et al., 2019;Nagano et al., 2010;Yao et al., 2015). ...
... The clinical testing protocols are still rather unstructured, having dominant shortcomings and gaps. No standard procedure for the evaluation of results is available, and the value of such studies is undermined in several respects [108,109]. Moreover, not all trials were randomized or had a placebo control [110,111] nor were double-blinded where safety and side effects are neglected. ...
Full-text available
Of the biologically active components, polysaccharides play a crucial role of high medical and pharmaceutical significance. Mushrooms have existed for a long time, dating back to the time of the Ancient Egypt and continue to be well explored globally and experimented with in research as well as in national and international cuisines. Mushroom polysaccharides have slowly become valuable sources of nutraceuticals which have been able to treat various diseases and disorders in humans. The application of mushroom polysaccharides for anticancer mycotherapy is what is being reviewed herein. The widespread health benefits of mushroom polysaccharides have been highlighted and the significant inputs of mushroom-based polysaccharides in anticancer clinical trials have been presented. The challenges and limitation of mushroom polysaccharides into this application and the gaps in the current application areas that could be the future direction have been discussed.
... A commercial product, Amyloban ® 3399, based on H. erinaceus, was tested in a pilot study among eight postgraduate female students in Japan. The product has been administered for four weeks and the researchers reported an increase in salivary-MHPG, corresponding to an improvement in anxiety and quality of sleep (Okamura et al., 2015). Although the results from these studies are promising, there is a lack of evidence-based clinical studies and pilot studies involving a larger number of participants. ...
Higher fungi (Basidiomycetes) are heavily researched in the last two decades which makes the beginning of the 21st century known as the age of fungiceuticals. The wide pool of in vitro and in vivo data, as well as clinical studies, promise us miraculous natural agents. However, the industry has its stance on the case of mushroom nutraceuticals. This chapter provides an overview of different aspects of medicinal mushroom commercialization: from the explanation of this new segment of products, proper fungal material identification, choosing the raw material, dosing, bioavailability, and drug delivery systems, safety and quality, organic certification, strategies in formulating them, to emerging fields of potential use, including antiviral products. Each of these aspects is discussed from both positive and negative sides present in today’s industry and market.
... Многие исследователи показали и другие полезные для здоровья эффекты гриба H. erinaceum. Студентки, принимавшие препараты с его экстрактами, заявили об улучшении качества сна [45]. Депрессия или тревога встречались гораздо реже и были менее интенсивными у женщин в менопаузе, которым давали порошкообразные плодовые тела гриба H. erinaceum, по сравнению с группой, получавшей плацебо [46]. ...
Full-text available
Medicinal mushrooms have become an attractive topic due to their bioactive compounds potentially useful for therapeutic use. Among the growing popularity of medicinal mushrooms is Hericium erinaceus. Hericium erinaceus is a medicinal edible mushroom with a long history of use in traditional Chinese medicine as well as in other countries of the East. Along with this, several of its biologically active compounds served as the basis for the creation of nutritional supplements. Its fruiting bodies and mycelium are rich in active substances that promote health. Tests of substances extracted from this fungus in animals and in vitro have given good results. They are beginning to be used in the treatment of cancer, liver diseases, Alzheimer’s and Parkinson’s diseases, and wound healing. They improve cognitive abilities, support the nervous and immune systems.
... As there is no standard for the procedure and evaluation of re-sults, the value of such studies is undermined in several respects. First of all, the basic experimental design, which often examines a sample that is too small and therefore not sufficiently representative, and can lead to false positive results [103,118]. Moreover, not all trials are randomized or have a placebo control [104,105], nor are double-blinded, and there is generally a lack of uniqueness of purpose, so only some parameters are taken into account and others are neglected, such as safety and side effects. ...
Full-text available
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
Full-text available
Major Depression Disease is a common mental illness that affects more than 322 million people worldwide and it is one of the leading causes of mental and physical disability. The etiology of depression is a complex interplay of psychological, social, and biological factors. Currently, psychopharmacotherapy is based mainly on the monoamine theory, which states that depression is caused by an insufficient level of monoamines such as serotonin, norepinephrine, and/or dopamine. Due to the relatively low efficacy of the typical antidepressant and the high prevalence of treatment-resistant depression (~30%), seeking new ways of prophylaxis, adjuvant therapy, or novel compounds with antidepressant activity, is a priority. According to studies that analyzed mushroom consumption patterns and depression prevalence, it was concluded that mushroom ingestion lowers the odds of depression. Medicinal mushrooms are considered functional foods because of their ability to synthesize and accumulate different types of metabolites, which enhance their health-promoting properties. The review aims to explain the antidepressant activity of edible/medicinal mushrooms by elucidating the mechanism from different perspectives: edible mushrooms as a source of serotonin precursors and psilocybin as a rapid-acting antidepressant. These compounds exhibit anti-neuroinflammatory and antioxidant activities that impact neurotrophin expression, the neurogenesis process, and influence on the gut–brain axis.
Background Mushrooms contain numerous bioactive compounds that may be associated with reduced anxiety including vitamin B12, nerve growth factor, antioxidants, and anti-inflammatory agents. We hypothesized that mushroom consumption is associated with a lower risk of depression in American adults. Methods Data from the National Health and Nutrition Examination Survey 2005–2016 was used. Up to two days of 24 h dietary recall were analyzed to assess mushroom intake frequency. Depression was measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). We used multivariable logistic regression models, adjusting for potential confounding factors. Results Among 24,699 participants (mean (SE) age: 45.5 (0.3) years), the weighted prevalence of depression was 5.9%. Mushrooms were consumed by 5.2% of participants. Compared with the lowest tertile of mushroom intake, participants in the middle tertile (median intake = 4.9 g/d, number of cases = 16) had lower odds of depression (adjusted OR = 0.31; 95% confidence interval [CI] 0.16, 0.60) while those in the highest tertile did not differ (median intake = 19.6 g/d, adjusted OR = 0.91; 95% CI: 0.47, 1.78, number of cases = 22) (P-trend = 0.42). Limitations Cross-sectional data and lack of information on specific types of mushrooms consumed. Conclusion Mushroom consumers had a lower odd of depression. However, we did not observe a dose-response relationship.
The saliva level of 3-methoxy-4-hydroxyphenylglycol (MHPG) was determined using gas chromatography-mass spectrometry, and comparing with the plasma level of MHPG in humans to assess the saliva level of MHPG as a biological index for detecting changes in the central and peripheral noradrenergic neuronal activity. Selected ion monitoring chromatogram of the saliva MHPG revealed high sensitivity, reproducibility and specificity. The saliva and the plasma level of free-MHPG were 10.3±3.2 ng/ml (mean±SD) and 5.3±0.8 ng/ml, respectively. There was a significant correlation between the saliva and plasma free-MHPG (r=0.942, p<0.001, n=15). Neither a diurnal variation nor gender difference were found in the saliva level of free-MHPG. Sulfatase treatment caused no increase in the saliva levels of free-MHPG, thus indicating that MHPG in the saliva was mostly the free type. These findings indicated that the measurement of saliva MHPG would be a less invasive method for sampling and be a useful marker to assess noradrenergic tone in human subjects instead of the measurement plasma MHPG.
Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) may reflect central noradrenergic activity. In this study, we investigated salivary MHPG changes after awakening, and explored their relationships with cortisol and peripheral autonomic activity. The participants were 25 college students. Saliva samples were collected on awakening and 30 min after awakening to determine MHPG and cortisol. Ambulatory electrocardiograms were obtained to assess heart rate, cardiac sympathetic index (CSI), and cardiac vagal index (CVI) before and after awakening. MHPG levels increased significantly during the first 30 min after awakening. Similarly, cortisol, heart rate, and CSI increased during the 30 min after awakening, but changes in MHPG did not correlate with changes in cortisol, heart rate, CSI, and CVI during that period. This study demonstrated that salivary MHPG levels increase after awakening, in common with cortisol, heart rate, and cardiac sympathetic activity.
The current paper describes the physiological and nootropic actions of Amycenone, which is an activator of brain function that is obtained from extracts of the Yamabushitake (Hericium erinaceum).Kawagishi and his group have studied compounds that are derived from medicinal mushrooms and their use in the treatment of dementia since 1991. They have found that H. erinaceum exerts important bioactivities, including the induction of nerve growth factor (NGF) synthesis, the inhibition of the cytotoxicity of beta-amyloid peptide, and the protection against neuronal cell death caused by oxidative or endoplasmic reticulum stress.Since NGF was first discovered in the 1940s, it has garnered attention as a substance in the brain that curbs the degeneration and loss of neurons and that promotes the repair and regeneration of nerve function. However, NGF cannot pass through the blood–brain barrier.Amysenone (Amyloban®3399, which contains a standardized extract of H. erinaceum) has been found to pass through the blood–brain barrier, and its safety as a health food is currently being ascertained.On the basis of the author's first-hand experiences, Amyloban®3399 was found to clearly increase alertness. The actions of Amyloban®3399 in treating sleep-related breathing disorders were examined. Amyloban®3399 was effective in improving sleep apnea and hypopnea syndrome.The use of Amyloban®3399 has been noted to result in the obvious restoration of cognitive function in mild cognitive disorder.
Novel compounds, hericenones C (3), D (4) and (5) were isolated from the mushroom Hericium erinaceum. These structures were determined by interpretation of the spectral data, and chemical and enzymatic reactions. These compounds have stimulating activity of the synthesis of nerve growth factor (NGF).
Our group has been conducting a search for compounds for dementia derived from medicinal mushrooms since 1991. A series of benzyl alcohol derivatives (named hericenones C to H), as well as a series of diterpenoid derivatives (named erinacines A to I) were isolated from the mushroom Hericium erinaceum. These compounds significantly induced the synthesis of nerve growth factor (NGF) in vitro and in vivo. In a recent study, dilinoleoyl-phosphatidylethanolamine (DLPE) was isolated from the mushroom and was found to protect against neuronal cell death caused by β-amyloid peptide (Aβ) toxicity, endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, the results of preliminary clinical trials showed that the mushroom was effective in patients with dementia in improving the Functional Independence Measure (FIM) score or retarding disease progression. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.
Nerve growth factor (NGF) is an essential protein for supporting growth and maintenance of peripheral sympathetic neurons. A novel diterpenoid erinacine, isolated from the cultured mycelia of Hericium erinacium, is known to have a potent stimulating effect on NGF synthesis. The effects of erinacine and related compounds in the brain in vivo are not known. In this study, we examined the effects of erinacine A on the production of NGF and catecholamines which stimulate NGF synthesis in the brain of rats. Rats were treated with erinacine A by intubation for the first 3 weeks from birth to weaning and intragastrically from weeks 4 to 5. Rats treated with this compound had increased levels of both noradrenaline and homovanillic acid in the locus coeruleus (LC) at 4 weeks of age and increased levels of NGF in both LC and hippocampus at 5 weeks of age. The effects of erinacine A were confirmed in the central nervous system in rats.
Objective: This study compared saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) in patients with major depressive disorder (MDD) to levels in healthy controls and explored whether sMHPG levels in patients with MDD were a predictive marker for antidepressant efficacy. Methods: sMHPG levels were compared in 53 patients with MDD and 275 age-matched healthy controls. Patients' depressive symptoms were assessed by the 17-item Hamilton Rating Scale for Depression at baseline and 4 weeks after treatment with selective serotonin reuptake inhibitors (SSRIs, n = 23) or mirtazapine (n = 30), followed by saliva sampling. The mirtazapine group included nine patients who had been treated with an SSRI for more than 4 weeks without any improvement. sMHPG levels were measured by gas chromatography-mass spectrometry. Results: sMHPG levels in MDD patients were significantly higher than in controls. The responder rate to drug treatment at 4 weeks was 62% for mirtazapine (13/21), 57% for SSRIs (13/23), and 89% (8/9) for SSRI plus mirtazapine. sMHPG at baseline in 13 responders treated with SSRIs, but not mirtazapine, was significantly higher than that in non-responder group and showed consequent reduction 4 weeks after treatment. The area under the receiver operating characteristic (ROC) curves of sMHPG for discrimination of SSRI responders and non-responders was 0.86 ± 0.10 (95% confidence interval: 0.64-1.0, p = 0.005). In contrast, the ROC curve of sMHPG levels for discrimination of mirtazapine responders and non-responders was not significant. Adjunctive treatment with mirtazapine to SSRI non-responders was effective, regardless of baseline sMHPG levels. Conclusion: sMHPG in patients with MDD was higher than in healthy controls. High baseline sMHPG levels in patients with MDD maybe a predictive marker for SSRI response.
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 "palpitatio", 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.