Ganoderma in Nerve Disorders

A MULTI-CENTRE, RANDOMISED, AND DOUBLE-BLIND STUDY OF GANODERMA LUCIDUM IN NEURASTHENIA

Guoliang Chen1, Jinxian Ye2, Yihuai Gao3, Shufeng Zhou4, Xihu Dai5

1Hospital of FujianUniversity of Traditional Chinese Medicine, Fuzhou, China.

2ShanghaiAcademy of Agricultural Sciences, Shanghai, China

3Landcare Research, Private Bag 92170, Auckland, New Zealand

4Division of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand

5Fuzhou General Hospital of Nanjing Military Region of the Peoples’ Liberation Army, Fuzhou, China

Abstract Ganoderma lucidum has been shown to reduce spontaneous motor activity in mice, prolong barbital sleeping time, prevent nicotine-induced convulsions, and inhibit pilocarpine-induced salivary secretion. G. lucidum has been used to treat various diseases including cancer, diabetes and neurasthenia in folk medicine of Asian countries. This randomised, double-blind, parallel-controlled study aimed to investigate the efficacy and safety of an extract of G. lucidum (GanopolyTM) in Chinese patients. A conventional herbal medication, Yang Xue An Shen Pian, with confirmed efficacy for the treatment of neurasthenia in China, was used as control. One hundred and eleven patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), were included from 3 centres in China from February 1996 through January 1997. Patients had at least 2 symptoms out of the following symptoms: muscular aches and pains, dizziness, tension headaches, sleep disturbance, inability to relax, irritability, and dyspepsia. They were required to be hospitalised for at least the first 7 days of the study and to remain in regular contact with the hospital throughout the remainder of the study. Those patients with mood disorders, panic disorders, and generalized anxiety disorder were excluded. Written consents were obtained from the patients. Ethical approval was from the Institutional Research Ethics Committee, and the study conducted in accordance with Good Clinical Practice guidelines. Exclusion criteria were as follows: (1) <18 years, (2) organic concurrent conditions, such as stroke and brain injury, (3) pregnant or lactating women, (4) patients who had taken or were taking Ganoderma preparations, (5) alcohol or drug addiction, (6) agitation due to organic, toxic or iatrogenic causes. Patients (n = 136) were randomized to receive GanopolyTM or Yang Xue An Shen Pian orally at 1800 mg three times a day for 8 weeks. Efficacy assessments comprised the Brief Psychiatric Rating Scale (BPRS) total and factor scores, and the Clinical Global Impression (CGI) severity of illness and global clinical improvement scores. A total of 136 patients were randomised and exposed to treatment. There were no significant differences between the groups in terms of demographic or baseline characteristics. Eleven and 13 patients in the Ganopoly and Yang Xue An Shen Pian group respectively withdrew from the study prematurely, mainly due to poor compliance and lost to follow-up. In 56 assessable patients in each treatment group, GanopolyTM resulted in a similar or greater percentage response compared to Yang Xue An Shen Pian in the Clinical Global Impression (CGI) improvement of illness scale. GanopolyTM significantly reduced physical and mental fatigue of patients, and increased their sense of well-being. Both medications were well tolerated and toxicities were mild.

Key words: Neurasthenia, Ganoderma lucidum, insomnia.

INTRODUCTION

Neurasthenia is a neurotic, stress-related, and somatoform disorder, with at least 2 symptoms out of the following symptoms: muscular aches and pains, dizziness, tension headaches, sleep disturbance, inability to relax, irritability, and dyspepsia, according to the definition of the 10th Revision of the International Classification of Disease (ICD-10) (World Health Organization, 1992). The definition of neurasthenia in China (Shen Jing Shuai Ruo in Chinese) is a variant of ICD-10 definition. In the Chinese Classification of Mental Disorders, 2nd Edition (CCMD-2), neurasthenia can be diagnosed in the presence (for at least 3 months) of a minimum of any 3 symptoms out of the following five groups of symptoms: weakness (mental fatigue, lack of energy, slow thinking, problems with memory and difficulty in concentration), emotional (dysphoria, worry, and irritability), excitement (easy excitability, e.g., uncontrollable and unpleasant increase in recollections and thought associations, though without an increased psychomotor activity), nervous pain (tension headache and myalgia), and various sleep disturbances (Chinese Medical Association, 1990). Studies in China, Switzerland, and Yugoslavia indicate that there are wide ranges of frequencies of the symptoms of neurasthenia (Starcevic, 1999). For example, irritability was reported in 75-100% of patients, inability to relax in 60-91%, headache in 50-90%, sleep disturbance in 39-78%, and muscular aches and pains in 25-53% (Kleinman, 1982). This range of frequencies was even wider for dizziness which was one of the very common (73%) symptoms of neurasthenia in China (Kleinman, 1982; Rin and Huang, 1989; Merikangas and Angst, 1994; Starcevic et al., 1996; Starcevic, 1999), but was symptomatic of 5% of Swiss patients with neurasthenia (Merikangas and Angst, 1994).

Tricyclic and benzodiazepine sedatives have been used for the treatment of neurasthenia in many countries (Marie-Cardine et al., 1985). However, these drugs have been associated with significant side effects. These, in turn, lead to problems with compliance and hence an increased risk of relapse. Approaches of Complementary Medicine, including acupuncture and herbal medicines have been shown to be beneficial on neurasthenia (Zhou, 1986). Ganoderma lucidum has been shown to reduce spontaneous motor activity in mice, prolong barbital-induced sleeping time, prevent nicotine-induced convulsions, and inhibit pilocarpine-induced salivary secretion (Jong and Birmingham, 1992). Adenosine isolated from the fruiting body of G. lucidum inhibited central inhibitory-reduced spontaneous motor activity, elevated pain threshold, prolonged the death time of mice induced by caffeine and relaxed skeletal muscle in mice (Kasahara and Hikino, 1987). A randomized, multi-centre, double-blind, parallel-controlled clinical study aimed to investigate the efficacy and safety of a G. lucidum extract, GanopolyTM, in the treatment of neurasthenia, and to compare results of GanopolyTM with those of another traditional medicine, Yang Xue An Shen Pian, which has been shown to be effective against neurasthenia.

Table 1. Demographic and baseline characteristics (exposed population, N*=*136).

Character

Ganopoly group

(N = 65)

Yang Xue An Shen Pian group (N = 71)

Total (N = 136)

Gender (N) (%)

Male

Female

36 (55%)

29 (45%)

37 (52%)

34 (48%)

73 (54%)

63 (46%)

Age (years)

32.5 * 9.5

29.7 * 8.2

31.1 * 8.9

Weight (kg)

61.8 * 14.8

56.7 * 11.7

59.3 * 12.8

Duration of current episode (days)

122.4 * 35.3

132.4 * 36.2

128.4 * 35.7

Previous psychotropic medication (%)

34 (61%)

37 (66%)

71 (63%)

 

Data were mean * SD.

MATERIALS AND METHODS

Patient selection

This double-blind, randomised, parallel-group study was conducted in 3 centres in China from February 1996 through January 1997. Patients of either gender (aged 18-65 years) with neurasthenia were included in the study. Patients were interviewed and assessed separately by two trained psychiatrists and the diagnosis of neurasthenia was confirmed by the criteria of ICD-10. Patients had at least 2 symptoms out of the following symptoms: muscular aches and pains, dizziness, tension headaches, sleep disturbance, inability to relax, irritability, and dyspepsia. They were required to be hospitalised for at least the first 7 days of the study and to remain in regular contact with the hospital throughout the remainder of the study. Those patients with mood disorders, panic disorders, and generalized anxiety disorder were excluded. Written consents were obtained from the patients. Ethical approval was from the Institutional Research Ethics Committee, and the study conducted in accordance with Good Clinical Practice guidelines and the declaration of Helsinki. Exclusion criteria were as follow: (1) <18 years, (2) organic concurrent conditions, such as stroke and brain injury, (3) pregnant or lactating women, (4) patients who had taken or were taking Ganoderma preparations, (5) alcohol or drug addiction, (6) agitation due to organic, toxic or iatrogenic causes.

Treatment

Patients were randomised to receive GanopolyTM or Yang Xue An Shen Pian orally at 1800 mg, three times daily before meals for 8 weeks. At each visit, investigators checked compliance with the study medication using a thorough pill-count. GanopolyTM or Yang Xue An Shen Pian was the only agent administered during the study period. GanopolyTM used in the study was generously provided to study patients by Encore International Co., Auckland, New Zealand. Yang Xue An Shen Pian was provided by Shanghai 2nd Traditional Medical Pharmacuetical Co., China. Both medications were prepared as capsules with the same shape and size.

Clinical evaluation

Efficacy assessments comprised the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962) total and factor scores, and the Clinical Global Impression (CGI) severity of illness and global clinical improvement scores before treatment and after 8 week’s treatment (Guy, 1976). The severity of individual symptom was scored to severe (+++, lack of work ability, severe insomnia), mild (++, partial work ability, superficial sleeping), and minor (+, some difficulty in sleeping). The severity of disease was classified into severe (* 7 symptoms, +++ or higher, with insomnia), mild (* 7 symptoms, ++ or higher, with insomnia), and minor (* 5 symptoms, ++ or higher, with insomnia). The primary criterion was the change in BPRS and CGI from day 0 to the end of the study (after 8 week’s treatment). Symptom improvement was defined as reduction of one score of severity (e.g. from +++ to ++) and significant improvement as reduction of two or more scores of severity. Safety was assessed by spontaneous reporting of complaints by the patient, physical examination, and CGI (side effects).

Statistical analysis

All criteria were analysed using two-sided tests of difference with an a risk of 0.05, continuous variables were analysed using one-way analysis of variance, binary or non-ordered variables were analysed using the C2 or Fisher’s exact test, and ordered or categorical variables were analysed using the Cochran-Mantel-Haenszel test.

RESULTS

Patient characteristics

A total of 136 patients were randomised and exposed to treatment. There were no significant differences between the groups in terms of demographic or baseline characteristics (Table 1). Eleven and 13 patients in the GanopolyTM and Yang Xue An Shen Pian group respectively withdrew from the study prematurely, mainly due to poor compliance and lost to follow-up.

Effects of GanopolyTM on neurasthenia

In 56 assessable patients in each treatment group GanopolyTM generally resulted in a similar or rarely significantly greater percentage improvement (general improvement or significant improvement on the CGI global improvement scale) compared with those patients receiving Yang Xue An Shen Pian.

Table 2. The effects of Ganopoly on neurasthenia.

Symptoms Ganopoly group Yang Xue An Shen Pian group
N of Patients Improvement (%) Significant Improvement (%) N of Patients Improvement (%) Significant Improvement (%)
Insomnia 56 34 (61) 18 (32) * 55 32 (63) 10 (13)
Dreaming excessively much 54 31 (54) 14 (26) 55 27 (49) 11 (20)
Early awaking 51 30 (58) 11 (22) 50 27 (54) 9 (18)
Dyspepsia 49 20 (41) 26 (53) 47 13 (27) 22 (47)
Nausea 38 4 (13) 28 (74) * 29 5 (17) 14 (48)
Vomiting 18 2 (17) 6 (50) 13 2 (16) 5 (38)
Weakness 52 21 (40) 18 (35) 49 17 (35) 17 (35)
Poor memory 38 12 (31) 9 (24) 38 8 (21) 8 (21)
Irritability 32 11 (34) 5 (16) 34 8 (23) 5 (15)
Anxiety 32 13 (40) 5 (16) 29 8 (33) 4 (14)
Headache 29 12 (41) 9 (31) * 31 12 (38) 7 (23)
Dizziness 32 11 (34) 11 (34) * 33 8 (31) 9 (21)
Tinnitus 18 3 (24) 10 (56) 19 4 (20) 8 (43)
Blurred eye 16 3 (15) 5 (35) 15 2 (13) 4 (27)
Light phobia 12 3 (25) 5 (42) * 10 2 (20) 3 (30)
Chest unwell 32 8 (25) 14 (44) 29 4 (14) 11 (38)
Myalgia 34 6 (18) 14 (41) 31 2 (7) 12 (38)
Arthritis 8 1 (13) 6 (75) 7 1 (14) 5 (71)
Excitability 12 2 (17) 6 (50) 11 7 (64) 4 (36)
Palpitation 21 9 (42) 10 (48) 17 5 (30) 7 (41)
Mental fatigue 10 1 (10) 7 (64) 17 1 (6) 9 (53)

* P < 0.05.

Safety

Both GanopolyTM and Yang Xue An Shen Pian were well tolerated. Two and three events of adverse effects were reported for the GanopolyTM and Yang Xue An Shen Pian groups respectively. These were mainly gastrological events.

DISCUSSION

In modern society, neurasthenia is common due to social stress derived from work and lifestyle. In a survey in the Australasian area, a total of 17.7% of people investigated had neurasthenia (Henderson et al., 2000). It is estimated that the incidence may be similar or higher in China. The diagnosis of neurasthenia usually uses the criteria of ICD-10. There is no consistency in the choice of treatment for neurasthenia.

Tricyclic and benzodiapenes have been widely used to treat this disease. However, side effects have been observed with these drugs. Herbal medicines are widely used in Asian countries, particularly in China and Japan. G. lucidum as a highly ranked herbal medicine has been used to treat a number of diseases including cancer, heart disease and infectious diseases (Gao, 2000). Pre-clinical studies have indicated that active components, particularly adenosine from G. lucidum have beneficial effects on the symptoms of central nervous system diseases in animal models (Kasahara and Hikino, 1987). This multi-centre, double-blind and parallel-controlled study indicates that GanopolyTM resulted in a similar or greater percentage response compared with Yang Xue An Shen Pian in the CGI improvement of illness scale. GanopolyTM was more effective in the reduction of the physical and mental fatigue of patients, and increased their sense of well-being. Both medications were well tolerated and toxicities were mild.

REFERENCES

Chinese Medical Association (1990) Chinese Classification of Mental Disorders. Hunan Medical University, Changsha, China.

Gao YH (2000) The miracle herb, scientific reports of Ganoderma. Yuanqizai Publisher, Taipei (in Chinese).

Guy W (1976) ECDEU assessment manual for psychopharmacology. US Department of Health, Education and Welfare, Rockville, MD.

Henderson S, Andrews G and Hall W (2000) Australia’s mental health: an overview of the general population survey. Austr NZ J Psychiat 34: 197-205.

Jong SC and Birmingham JM (1992) Medicinal benefits of the mushroom Ganoderma. Adv Appl Microbiol 37: 101-134.

Kasahara Y and Hikino H (1987) Validation of the oriental medicines. Part 122. Central actions of adenosine, a nucleotide of Ganoderma lucidum. Phytother Res 1: 173-176.

Kleinman A (1982) Neurasthenia and depression: a study of somatization and culture in China. Cult Med Psychiatry 6: 117-190.

Marie-Cardine M, Becache A, Chatelain R, Desmettre G, Gibour C, Houser M, Moene Y, Reyss-Brion MP, Saliba S and Sauret A (1985) Value of amineptin in the treatment of different depressive states. Apropos of 112 cases treated as part of a national multi-centric study. Encephale 11: 175-177.

Merikangas K and Angst J (1994) Neurasthenia in a longitudinal cohort study of young adults. Psychol Med 24: 1013-1024.

Overall JF and Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 280: 799-812.

Rin H and Huang MG (1989) Neurasthenia as nosological dilemma. Cult Med Psychiatry 13: 215-226.

Starcevic V (1999) Neurasthenia: cross-cultural and conceptual issues in relation to chronic fatigue syndrome. General Hosp Psychiatry 21: 249-255.

Starcevic V, Kelin K and Munjiza M (1996) Characteristics of neurasthenia: examination and cross-cultural applicability of ICD-10 Diagnostic Criteria for Research. Eur Psychiatry 11: 289-297.

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines, World Health Organization, Genera.

Zhou K (1986) Treatment of neurasthenia with combined western and traditional Chinese medicine by basing therapy on type differentiation of the disease. Chung-Hua Shen Ching Ching Shen Ko Tsa Chih – Chin J Neurol Psychiatry 19: 306-308.

 

3 thoughts on “Ganoderma in Nerve Disorders

  1. Dr Parwana
    I congratulate you on taking initiative on GANODERMA information for the public . I would suggest you may add the dose schedule and reflection of ailment observation. I would also like that you may now be more specific and base your observation more on scientifically proven facts. Let us shun generalization without science based proofs.
    Once again
    Thank you and best wishes
    Regards
    Prof. P D Juyal Ph D
    Registrar
    Guru Angad Dev Veterinary and animal sciences University
    Ludhiana

  2. Very shortly this web site will be famous among all blogging and site-building
    people, due to it’s fastidious posts

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