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IMPROVEMENT IN IMMUNE FUNCTION BY SUPPLEMENTCONTAINED β-GLUCANS― A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY ―Masatomo NAJIMA1), Mitsuhiko MUNEKATA2) and Hiroyuki SASAKI3)
1) JACTA (Japan Clinical Trial Association)
2) OZ Clinic3) LINKS Inc.

Abstract
Objectives: The objective of this research was to investigate the effectiveness of daily
ingestion of Reishi tablet, which contains β -glucans, on the immunological vigor of human.
Methods: In this randomized, placebo-controlled, double-blind trial, 27 people were
subjected. The SIV score (combination of the number of T cells, naive T cells, CD8+CD28+ T
cells, B cells and NK cells, and ratios of CD4/CD8 T cell and naive/memory T cell) and bloodpressure were measured as its primary outcomes.
Results: 6 subjects were withdrawn due to personal reasons and the remaining 21 subjects
completed the study. Signiﬁcant diﬀerences of T lymphocyte, T cells, CD8+CD28+ T cells
and the systolic blood pressure were observed between test and placebo samples after 12
weeks of ingestion.
Conclusion: We found out that the ingestion of the processed food of Reishi (Ganoderma
lucidum ) containing β-glucans for 12 weeks contributed to improving the immunologicalvigor of human and the systolic blood pressure. In addition, no safety-related matteroccurred during the 12-week test period.
Key words: Reishi, Ganoderma lucidum , β -glucan, immunological vigor, immune, SBP

1. INTRODUCTION
Modern Japanese society has been generally called asuper-aging society , after a ratio of the number of
elderly people aged 65 years older compared to the total
population, became 23% in 2010 1). Coupled with that, themedical spending of all the public is growing steadily, andSelf-medication is now receiving plenty of attention as
one of the measures to cope with this problem. According
to WHO, self-medication is deﬁned as the selection anduse of medicines by individuals to treat self-recognizedillnesses or symptoms 2). A typical example of thisdefinition includes utilizing OTC (over-the-counter)medicine with the correct knowledge. In addition to this,another type of self-medication may include reviewing
their dietary life. Immunity is an important function forthe human body to defend it from disease. Therefore it ishighly desirable to keep it at a high level to lead healthy
everyday lives 3). However, human face the decline ofimmunity since its peak at the age of 20, and this decline
is caused by various factors such as advancing age, stressor inadequate lifestyle, which are all unavoidable mattersin daily lives. The decline of immunity not only increases
the risks of disease or infection, but also diminishes thecountervailing power against stress and leads to thedecline of QOL (Quality of Life). Therefore, in order tolive a healthy life, it is important to maintain immunity athigh level.
Jo-yaku is one of the categories in traditional Chinese
medicine, which is not curative medicine but
characterized as a medication made for everyday
consumption in order to prevent illness and stayhealthy 5), and Reishi has been categorized as Jo-yaku
since ancient times. Reishi is the Japanese name for the
fruiting body of Ganoderma lucidum , a genus of fungi
belonging to the family Polyporaceae , and is one of themost well-known herbal remedies in traditional Chinese
medicine. This species of the Polyporaceae family offungus is also commonly referred to as Ling zhi , or God
s Herb .
It is believed that Ganoderma lucidum has six color
types (red, black, blue, white, yellow, and purple), andthe contained ingredients are different depending onthese types 6). There is a report that Ganoderma lucidum
has a function of controlling immunity; it boosts immunity
when it is weakening, and alleviates when excessing 7).
Also, in addition to this function it reportedly owns a wide
variety of other functions such as the controll of blood
glucose levels 8), lowering-blood-pressure 9), anti-allergy 10),and improving conditions of hyperlipidemia11) or type B
hepatitis 12). As for Ganoderma lucidum , there have been
many clinical studies carried out for examining its

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eﬀectiveness of controlling immunity function, but mostof the study s goal were to review the alleviation ofsymptoms such as cancer and therefore there are few
published reports that discuss whether it is effective incontrolling immunity in healthy humans.
Therefore in this study, we examined how Ganoderma
lucidum affects immunological vigor of healthy humans.
We used the processed food of Reishi (Ganoderma
lucidum ) containing β -glucans as the test product, andapplied a randomized, placebo-controlled, double-blind
study as the test method.

第 11 号（2016 年 11 月）

Table 1 Nutritional content of the test samples per 100 g
Item
Moisture
Protein
Lipid
Ash
Available carbohydrate
Dietary ﬁber
EnergySalt equivalent

ReishiPlacebo

2.5 g

4.0 g

4.4 g
3.3 g
3.5 g
43.2 g43.1 g306 kcal
0.023 gless than 0.1 g
2.2 g
1.9 g
91.9 g−387 kcal
1.64 g

2. METHODS
2.1. Trial design
A randomized, placebo-controlled, double-blind study was
conducted with the aid of a fund from LINKS Inc. (Tokyo)
at two centers (OZ clinic, Tokyo, and JACTA, Tokyo).
The study period was 12 weeks, from January 22 th toApril 15 th, 2016.
This study was conducted in accordance with the
ethical principles of the declaration of Helsinki. The study
protocol was approved by the Institutional Review Boardof Pharmaceutical Law Wisdoms (Tokyo). Written
informed consent was obtained from all subjects.
The allocation of the test product to the subjects was
carried out by the person in charge of allocation. The
allocation list was sealed and strictly controlled in a safe
deposit box of JACTA until the end of the study.
2.2. Subject
Healthy subjects participated in the present study. All of
the subjects in this study were public volunteers who had
enrolled in the monitor bank of CROee Inc. (Tokyo),recruited from December, 2015 through January, 2016.
2.2.1. Inclusion criteria(1) Healthy Japanese males and females aged between 30
and 59 years with daily tiredness and fatigue;(2) With relatively low self-examination of immunologicalvigor (SEIV) * 侒 90.
*: SEIV is a self-examination of immunological vigor with
Likert scales. (Appendix 1)
2.2.2. Exclusion criteria(1) Previously suffered with malignant tumors, heatfailure, or cardiac infarction;(2) Under the care of a doctor for the treatment ofchronic diseases such as atrial fibrillation, unevenheartbeat, rheumatism, diabetes, high blood pressure,and diseases of the liver, kidney, cerebral system,
circulatory system, and lipid metabolism;(3) Taking medicines, including herbal medicines;(4) Pregnant, nursing, or were likely to become pregnant
during the trial;(5) Judged to be unsuitable to participate in the trial by
the principle investigator.
2.3. Randomization
From all of 81 applicants, 54 were eliminated according to
SEIV or age. The inclusion criteria was judged by theprinciple investigator. All subjects were sequentiallyallocated to Group A (n ＝ 13, M; 6, F; 7) and Group B (n＝ 14, M; 8, F; 6) based on a random number table. In theprocess of subject assignment, background factors suchas gender, age, and SEIV were taken into consideration
to avoid biased distribution. Subjects in Group A ingested
the placebo and subjects in Group B ingested the test
sample for 12 weeks.
2.4. Description of test foods and blinding
The test product Genkatsu-Reishi ( Reishi ) was
prepared by LINKS Inc., and is a tablet containing β glucan. The amount of a daily intake is 12 tablets (1 tablet
weighs 320 mg, therefore 12 tablets weigh 3.84 g). The
Placebo does not contain β -glucan.
Table 1 shows the nutritional content of the sample.
Both tablets were indistinguishable in shape, color or
taste. Tablets were managed by the identiﬁcation symbol.
All involved were blinded.
2.5. Experimental procedures
2.5.1. Experimental protocol
Subjects consumed 12 tablets of the supplement with hotor cold water every day for 12 weeks. Subjects were
instructed as follows: to take the assigned foods as
indicated; to maintain their usual lifestyles and habits; toavoid excessive amounts of food, drink, or alcohol; tomaintain a daily record of lifestyle factors such as what
they ate and pedometer measurement during the test
period; and to send the diary to the study coordinator.
2.5.2. Outcome
According to the schedule shown in Table 2, we
measured parameters on eﬃcacy and safety.
2.5.2.1 SIV
The objective of this study is to verify immunologicalvigor of ingesting food of Reishi(Ganoderma lucidum )containing β -glucans. Immunological vigor was set as
the primary outcome. SIV was used to evaluate that. SIV
is the scoring system that can combine seven
immunological parameters, the number of T cells, naive
T cells, CD8+CD28+ T cells, B cells, and NK cells, andratios of CD4/CD8 T cell and naive/memory T cell, andexpress the immune status of individuals as a simple
numeral. This system also shows T lymphocyte age. Dueto this, we can compare the real age with the age

診療と新薬・第 53 巻

Table 2Term
Item

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Schedule for the study.
Screening

Pretrial test

●

●
●
●

SEIV
Informed consent
Selection and/or allocation
Immunological parameters
Blood pressure
Blood biochemical and urine analysis
Ingestion of test foods
Log

Test period (12 w)

●
●
●

●
●
●

● : Implementation↔ : Daily practice during the test period

Scoring of
immunological vigor

1) T cells ( /μl)2) CD8+CD28+ T cells ( /μl)3) CD4/CD8 T cell ratio4) naive T cells ( /μl)5) naive/memory T cell ratio6) NK cells ( /μl)7) B cells ( /μl)

Scoring

T lymphocyte age

Fig. 1 SIV

evaluated from immunological vigor s point of view (Fig.
1). The SIV scoring system is an index system, which
utilizes the database of test results for every particular
item, which are accumulated by Hirokawa andUtsuyama 13), and by using the database, its index is
calculated from several subsets. Therefore it enabled us
to evaluate the condition of a variety of immune cells in acomprehensive and multilateral manner, and it has
already been introduced in past research as the new
testing method of immune strength 14).
2.5.2.2. Blood pressure
As the primary outcome, blood pressure was tested.
Blood pressure was measured using an automatedsphygmomanometer UDEX-i (Elquest Corporation,
Japan). Measurements were performed three times
successively. The medium values were used as an
estimate of blood pressure.
2.5.2.3. Safety
As a secondary endpoint, blood biochemical and urine
analysis, and inquiries were made to assess safety.
Adverse events were collected by means of a written
questionnaire during the study.
2.6. Data analysis
A full analysis set was adopted in the present study andno sample size was used. All statistics were expressed asmean ± standard deviation (SD). For SIV, immunologicalparameters of blood, T lymphocyte age, blood pressure,
blood biochemical and urine, changes from the baseline in
the same group were assessed using the paired t-test.
Student s-t test was used for intergroup comparisons ofchanges from the baseline. Student s-t test was used tocompare subject s backgrounds between groups.
Multiplicity according to the occasions was not
adjusted. Any subjects with missing values were
eliminated from the analysis. Statistical analyses were
performed using Statcel 3 (Yanai, 2011). The results
were considered significant at a < 5% level in the twosided test.

3. RESULTS
3.1. Participant demographics
The 27 subjects were randomly assigned to intervention
groups and made a start with ingestion. 6 werewithdrawn due to being unwell or unexpected business,and the remaining 21 subjects completed the study. Thus,
data obtained with 21 subjects (Reishi; 13 < M; 7, F; 6 > ,Placebo; 8 < M; 3, F; 5 > ) was used for the analysis ofeﬃcacy (Fig. 2). There were no signiﬁcant diﬀerences in
the mean age, gender ratio or SEIV between groups(Table 3).

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Assessed for eligibility (n ＝ 81)〔M: 36, F: 45〕

Enrollment

Excluded (n ＝ 54)〔M: 22, F: 32〕¨Did not meet inclusion criteria (n ＝ 54)¨¨SEIV < 90 (n ＝ 51)〔M: 21, F: 30〕¨¨Age < 35 (n ＝ 3)〔M: 1, F: 2〕

Randomized (n ＝ 27)〔M: 14, F: 13〕

Group AGroup B

Allocation
Allocated to Placebo (n ＝ 13)〔M: 6, F: 7〕¨Received allocated intervention (n ＝ 13)¨Did not receive allocated intervention (n ＝ 0)

Allocated to Reishi (n ＝ 14)〔M: 8, F: 6〕¨Received allocated intervention (n ＝ 14)¨Did not receive allocated intervention (n ＝ 0)

Follow-Up
Lost to follow-up (n ＝ 0)

Lost to follow-up (n ＝ 0)
Discontinued intervention (n ＝ 1)

Discontinued intervention (n ＝ 5)
¨Unwell (n ＝ 2)〔M: 0, F: 2〕¨Unexpected business (n ＝ 3)〔M: 3, F: 0〕¨Unexpected business (n ＝ 1)〔M: 1, F: 0〕

AnalysisAnalysed (n ＝ 8)〔M: 3, F: 5〕¨Excluded from analysis (n ＝ 0)

Analysed (n ＝ 13)〔M: 7, F: 6〕¨Excluded from analysis (n ＝ 0)

Fig. 2 Flow diagram of subject disposition

3.2. SIVThe results of the statistical analysis of SIV, otherimmunological parameters and T lymphocyte age areshown in Table 4. Significant differences of T cells,
CD8 + CD28 + T cells, and T lymphocyte age wereobserved between two groups after 12 weeks ofingestion.
3.3. Blood pressure
Table 5 shows changes in blood pressure. ⊿ 0‑12 w of
SBP between two groups illustrated a significant
diﬀerence.
3.4. Blood and urine test
Table 6 and 7 shows blood biochemical and urine
parameters. With respect to the blood test, a signiﬁcantdiﬀerence was observed in Sodium and Potassium levels
in Reishi after 12 weeks of ingestion. The same diﬀerence
was found in Uric acid levels in Reishi (female) after 12
weeks of ingestion. In either case, since the difference

Table 3 Subject demographics
Item

Unit

ReishiPlacebo

Subjects
Male: female *Age *SEIV *

numbers
numbers
years
score

13
7:6
48.5 ± 7.4
115.5 ± 16.3

8
3:5
49.4 ± 5.2
106.9 ± 9.6

mean ± SD＊

No signiﬁcant diﬀerence

was minor one, the investigator judged it as the range ofphysiological variation (or clinically safe).
3.5. Safety
No adverse eﬀects associated with the test product wereobserved in the course of the reporting.

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Table 4 SIV, other immunological parameters and T lymphocyte age
Item

Unit

Time points

score

Scores/ Values

P-value 2)

Reishi (n ＝ 13) 1)

Placebo (n ＝ 8) 1)

12‑week⊿ 0‑12 w

16.6 ± 2.0
16.2 ± 3.0− 0.5 ± 1.9

17.1 ± 1.4
16.6 ± 1.2− 0.5 ± 1.6

0.963

numbers/μl

Baseline
12‑week⊿ 0‑12 w

1339.3 ± 336.6
1364.0 ± 397.8
24.7 ± 141.3

1554.4 ± 522.6
1291.0 ± 371.6− 263.4 ± 462.4

0.047 #

numbers/μl

Baseline
12‑week⊿ 0‑12 w

384.9 ± 146.8
363.4 ± 150.3− 21.5 ± 87.2

365.8 ± 133.3
305.5 ± 114.9 *− 60.3 ± 72.1

0.306

numbers/μl

Baseline
12‑week⊿ 0‑12 w

196.1 ± 108.6
218.5 ± 119.4
22.4 ± 52.7

274.5 ± 153.4
221.6 ± 77.1
− 52.9 ± 96.2

0.031 #

numbers/μl

Baseline
12‑week⊿ 0‑12 w

328.5 ± 159.3
338.6 ± 169.0
10.2 ± 89.0

279.0 ± 131.2
253.3 ± 117.2− 25.8 ± 79.6

0.363

numbers/μl

Baseline
12‑week⊿ 0‑12 w

282.2 ± 133.3
317.6 ± 179.0
35.5 ± 127.4

238.8 ± 84.7
217.6 ± 102.5− 21.1 ± 159.6

0.380

CD4/CD8 T cell
ratio

ratio

Baseline
12‑week⊿ 0‑12 w

3.76 ± 2.35
3.22 ± 1.30
− 0.54 ± 1.64

2.87 ± 1.69
2.73 ± 1.65 †− 0.13 ± 0.19

0.499

Naive/memory T
cell ratio

ratio

Baseline
12‑week⊿ 0‑12 w

0.87 ± 0.57
0.75 ± 0.40
− 0.12 ± 0.25

0.77 ± 0.46
0.75 ± 0.45
− 0.03 ± 0.19

0.383

T lymphocyte age

year

Baseline
12‑week⊿ 0‑12 w

54.4 ± 11.0
52.8 ± 10.8 †− 1.6 ± 3.2

50.1 ± 12.4
53.5 ± 7.5
3.4 ± 6.7

0.031 #

Baseline
SIV

T cells

Naive T cells

CD8+CD28+ T cells

B cells

NK cells

Scores and Values are expressed as the mean ± SD.
1) † p < 0.1, * p < 0.05, ** p < 0.01 against baseline.
2) # p < 0.05 between-group diﬀerences in change from baseline.

4. DISCUSSION
We conducted a randomized, placebo-controlled, doubleblind study to verify how the ingestion of the processedfood Reishi (Ganoderma lucidum ) containing β -glucans
affects immunological vigor of human. As the primary
outcome, the study showed significant differences inseveral items of SIV and other immunologicalparameters. The blood pressure also showed a signiﬁcant
improvement in SBP (systolic blood pressure). In
addition, as the secondary outcome, it proved that noabnormal change was triggered by the ingestion of thetest product.
Main Findings
This study examined how the ingestion of the test
product affects the immunity system of humans. In thisstudy, we used SIV (scoring of immunological vigor) byHirokawa, et al. as a comprehensive assessment methodof immunological vigor. Among seven parameters deﬁned
by this assessment method, the study result showed thesignificant improvement in T lymphocyte age , T
cells , and CD8+CD28+ T cell after the ingestion of thetest product for 12 weeks. CD8+CD28+ T cell is a cell
population which differentiate into the killer T cell thattargets a virus and a cancer cell. The number of CD28+ T
cells decrease with age, and as a result the score of
CD8 +CD28 + T cell is lowered. Along with this, theT-lymphocyte age calculated from its numerical value
also rose 15). Since this study used healthy Japanese males
and females aged between 35 and 59 years with daily
tiredness and fatigue as the test subject, it is possible for
immunity to decline during the 12-week test period74 （1042）

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Table 5Item

Unit

Time points

mmHg

SBP
<systolic bloodpressure>
DBP<diastolic bloodpressure>

Blood pressure
ValuesP-value 2)

Reishi (n ＝ 13) 1)

Placebo (n ＝ 8) 1)

12‑week⊿ 0‑12 w

119.3 ± 12.1
113.2 ± 11.2 **− 6.1 ± 5.3

109.1 ± 7.8
115.6 ± 8.8 **6.5 ± 4.4

< 0.001 ##Baseline
12‑week⊿ 0‑12 w

74.5 ± 13.4
73.3 ± 12.2
− 1.2 ± 7.8

72.4 ± 13.4
70.4 ± 9.8− 2.0 ± 9.4

0.826

Baseline

mmHg

第 11 号（2016 年 11 月）

Values are expressed as the mean ± SD1) ** p < 0.01 against baseline.
2) ## p < 0.01 between-group diﬀerences in change from baseline.

without any action. According to the evidence, the dataof the test group showed an improvement tendency by
the signiﬁcant decrease in the T-lymphocyte age, while
the placebo group showed a tendency of rising in age. On
the other hand, we could not find such tendency in thescores of B cells or NK cells. We also could not observe
the changes in SIV which is regarded as the total score of
immunity. Based upon these results, it is inferred thatthe ingestion of the test product was effective for the
maintenance of immunity; in particular the antiinﬂammatory power related to the T-cell system such as
CD28 + T cells. However, it is also inferred that theingestion did not show any inﬂuence in B cells or NK cells
and, as a result, the 12-week test period could not raise
the score of SIV.
We measured the blood pressure which can assess body
condition and is reported to have relationship withimmunity 16), and observed a significant improvement insystolic blood pressure. There is also a report that theingestion of Ganoderma lucidum by hypertensive rat
resulted in the decline of blood pressure 17). Although it isgenerally said that the systolic blood pressure rises withadvancing age 18), the result of this study illustrated thatthe ingestion of the test product (Reishi) contributes tocurbing the rise of systolic blood pressure.
T h e t es t p rod u c t m a i n l y c o ns i s t s o f R eis hi(Ganoderma lucidum ), a type of fungus which has been
regarded as the most valuable Chinese herb since ancient
times. Ganoderma lucidum consists of amino acids, β D-glucan and plenty of minerals such as calcium,
phosphorus, magnesium, potassium, sodium, iron,copper, zinc, and manganese 19). β-D-glucan is a type ofpolysaccharides and has many variations. Some variationsof β -D-glucan are considered to be effective against
cancer and are currently being used medically in the formof medicines such as Krestin or Lentinan 20)21). Althoughthe β -glucan contained in Ganoderma lucidum is now
under research and the detail remains unclear, it isbelieved that it has β -1,3-D-glucan as its main chain and
β -1, 6-D-glucan as a side chain 22)23), β -1,3/1,6-D-glucan

is an ingredient which is plentifully contained in fungus,
and the researchers have been continuously studying its
function of improving immunity and the protective /remedial effect against cancer, since its discovery.
Focusing on its functional mechanism, it is said that thesurface of immune cells called macrophages orlymphocyte has the receptor molecules β -1,3/1,6D-glucans link together with, and this linkage activatesthese immune cells24).
The β -glucans used in the medical settings areadministered into the body by injection. The orallyingested β -glucans, on the other hand, are not digestedby the digestive organs due to their long side chains, andarrive in the intestines in an unchanged form. There are
intraepithlial lymphocytes (IEL) between the epithelial
cells in the mucosa of intestines. These lymphocytes form
many lymphocyte-mechanisms in the intestinal system,
and because of this fact it is said that the gut immunity is
the largest immune tissue in the human body. There is areport that β -glucan is ingested by the macrophage
existing inside the intestinal canal as an activity of the gut
immunity25). This ingestion is thought to stimulate theactivity of T cells, NK cells and B cells of macrophage
white blood cells in the gut immunity, and stimulate thegeneration of interleukin26). Based on the above functional
mechanism, it is thought that the immunity scores mainly
about T cells in the result of SIV parameter have
improved. In addition, since β -glucan has a characteristicof not being digested, it has a function of trapping
cholesterol and carrying it out of the body. As a result, it
lowers the blood-cholesterol levels and contributes to theprevention of arterial sclerosis 27). Thanks to this function,
it can be expected to lower the systolic blood pressure 9).
Secondary Findings
In this study we examined the safety of the test productby blood and urine tests. Although both groups showedsigniﬁcant diﬀerences in the levels of sodium, potassium
or uric acid after ingestion, the differences were minor
and the investigator judged them as the range ofphysiological variation (or clinically safe).

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Table 6biochemical blood test

75（1043）

ValuesItem

Unit

Std. Value

GenderTime points

Reishi (n ＝ 13)〔M:7, F:6〕

Placebo (n ＝ 8)
〔M:3, F:5〕

Total Bilirubin

mg/dL

0.2‑1.2

M/F

Baseline
12‑week⊿ 0‑12 w

0.63 ± 0.28
0.60 ± 0.24
− 0.03 ± 0.13

0.53 ± 0.12
0.51 ± 0.14
− 0.01 ± 0.12

Total Protein

g/dL

6.3‑8.3

M/F

Baseline
12‑week⊿ 0‑12 w

7.4 ± 0.3
7.5 ± 0.3
0.1 ± 0.3

7.6 ± 0.6
7.7 ± 0.7
0.1 ± 0.2

Albumeng/dL

3.8‑5.3

M/F

Baseline
12‑week⊿ 0‑12 w

4.5 ± 0.3
4.5 ± 0.3
0.0 ± 0.1

4.4 ± 0.4
4.4 ± 0.5
0.0 ± 0.2

AST (GOT)

U/L

8‑38

M/F

Baseline
12‑week⊿ 0‑12 w

20.2 ± 6.2
17.1 ± 2.4 †− 3.2 ± 5.2

21.5 ± 5.6
20.5 ± 5.5− 1.0 ± 5.7

ALT (GPT)

U/L

4‑43

M/F

Baseline
12‑week⊿ 0‑12 w

21.3 ± 12.4
16.0 ± 5.1 †− 5.3 ± 9.9

17.6 ± 6.0
15.6 ± 3.6− 2.0 ± 4.5

ALP

U/L

110‑354

M/F

Baseline
12‑week⊿ 0‑12 w

238.2 ± 83.1
245.5 ± 96.7
7.3 ± 35.5

220.5 ± 110.7
213.6 ± 83.2
− 6.9 ± 32.7

LD (LDH)U/L

121‑245

M/F

Baseline
12‑week⊿ 0‑12 w

173.6 ± 39.4
172.5 ± 32.3
− 1.2 ± 14.7

170.3 ± 31.3
169.5 ± 31.3
− 0.8 ± 18.1

86 andunder

M

Baseline
12‑week⊿ 0‑12 w

40.0 ± 32.7
30.1 ± 14.0
− 9.9 ± 20.1

42.3 ± 20.6
34.3 ± 14.2
− 8.0 ± 8.7

48 andunder

F

Baseline
12‑week⊿ 0‑12 w

16.2 ± 4.9
17.2 ± 4.3
1.0 ± 2.6

38‑196

M

Baseline
12‑week⊿ 0‑12 w

170.1 ± 156.4
121.7 ± 60.1
− 48.4 ± 120.9

210.7 ± 114.0
143.0 ± 103.4− 67.7 ± 95.6

30‑172F

Baseline
12‑week⊿ 0‑12 w

83.8 ± 26.4
93.3 ± 33.3
9.5 ± 25.1

71.8 ± 22.4
137.8 ± 162.0
66.0 ± 141.6

γ-GT (γGTP)CK (CPK)

U/L

mg/dL

Total Cholesterolmg/dL

130‑219

M/F

Baseline
12‑week⊿ 0‑12 w

201.7 ± 33.4
207.3 ± 24.2
5.6 ± 23.3

222.3 ± 81.9
220.3 ± 105.2− 2.0 ± 28.7

Neutral Fat (TG)mg/dL

30‑149M/F

Baseline
12‑week⊿ 0‑12 w

166.7 ± 95.3
158.7 ± 122.4− 8.0 ± 84.0

89.3 ± 53.2
108.5 ± 74.6
19.3 ± 33.6

SodiummEq/L

135‑150

M/F

Baseline
12‑week⊿ 0‑12 w

144.6 ± 2.1
142.5 ± 1.8 **− 2.2 ± 1.9

144.3 ± 1.3
141.3 ± 1.8 **− 3.0 ± 1.5

Chloride

mEq/L

98‑110

M/F

Baseline
12‑week⊿ 0‑12 w

105.0 ± 1.7
104.8 ± 2.2− 0.2 ± 2.3

105.3 ± 1.7
104.1 ± 2.3 †− 1.1 ± 1.6

Potassium

mEq/L

3.5‑5.3

M/F

Baseline
12‑week⊿ 0‑12 w

4.5 ± 0.5
4.0 ± 0.4 **− 0.5 ± 0.3

4.7 ± 0.5
4.3 ± 0.5 *− 0.3 ± 0.3

Calcium

mg/dL

8.4‑10.2

M/F

Baseline
12‑week⊿ 0‑12 w

9.8 ± 0.3
9.6 ± 0.4
− 0.2 ± 0.4

9.7 ± 0.2
9.5 ± 0.3 *− 0.2 ± 0.2

Inorganic Phosphorus

mg/dL

2.5‑4.5

M/F

Baseline
12‑week⊿ 0‑12 w

3.6 ± 0.7
3.3 ± 0.6 †− 0.2 ± 0.4

3.5 ± 0.4
3.7 ± 0.5
0.3 ± 0.6 #Urea Nitrogen

mg/dL

8.0‑20.0

M/F

Baseline
12‑week⊿ 0‑12 w

15.9 ± 4.6
15.0 ± 2.4− 0.9 ± 4.1

13.5 ± 4.0
13.4 ± 3.5− 0.1 ± 2.9

0.61‑1.04

M

Baseline
12‑week⊿ 0‑12 w

0.90 ± 0.12
0.83 ± 0.17
− 0.06 ± 0.11

0.87 ± 0.05
0.84 ± 0.12
− 0.03 ± 0.08

0.47‑0.79

F

Baseline
12‑week⊿ 0‑12 w

0.62 ± 0.12
0.62 ± 0.05
0.01 ± 0.11

0.63 ± 0.04
0.61 ± 0.06
− 0.02 ± 0.03

60‑109M/F

Baseline
12‑week⊿ 0‑12 w

74.0 ± 18.8
69.4 ± 14.9
− 4.6 ± 11.4

75.6 ± 16.5
77.9 ± 25.7
2.3 ± 15.3

Creatinine

Blood Sugar (Serum)

mg/dL

mg/dL

Values are expressed as the mean ± SD.
p < 0.1, ** p < 0.01 against baseline.
p < 0.05 between-group diﬀerences in change from baseline.

†#

20.8 ± 10.5
24.4 ± 12.9 *3.6 ± 2.6

76 （1044）

診療と新薬・第 53 巻

第 11 号（2016 年 11 月）

Table 7 Transition of Urinalysis
ValuesItem

Uric acid

Unit

Std. Value

GenderTime points

Reishi (n ＝ 13)

Placebo (n ＝ 8)

〔M:7, F:6〕

〔M:3, F:5〕

6.4 ± 1.5
6.4 ± 1.2
0.1 ± 0.6

5.6 ± 1.1
5.2 ± 0.1
− 0.4 ± 1.1
4.6 ± 0.6
4.2 ± 0.4
− 0.3 ± 0.4 ##3.6‑7.0

M

Baseline
12‑week⊿ 0‑12 w

2.3‑7.0

F

Baseline
12‑week⊿ 0‑12 w

5.1 ± 1.0
5.4 ± 0.9 *0.3 ± 0.2

mg/dL

Speciﬁc Gravity−

1.010‑1.025

M/F

Baseline
12‑week⊿ 0‑12 w

1.022 ± 0.007
1.020 ± 0.007− 0.002 ± 0.008

1.020 ± 0.007
1.013 ± 0.007 †− 0.007 ± 0.010

pH−

4.5‑8.0

M/F

Baseline
12‑week⊿ 0‑12 w

6.3 ± 0.9
5.9 ± 0.7
− 0.4 ± 0.9

6.1 ± 0.9
5.9 ± 0.4
− 0.2 ± 0.8

Values are expressed as the mean ± SD.
†< 0.1, * p < 0.05 against baseline.

##p < 0.01 between-group diﬀerences in change from baseline.

During the test period six (6) test subjects discontinued
the test. The reasons for discontinuance were personal
ones such as illness (catching a cold) or business-related
matter, and had nothing to do with the ingestion of thetest product. Therefore, based upon the blood/urine test
and the medical interview, we observed no harmful
influence against biochemical and/or physiologicalmatters of the subjects, and this result indicated thesafety of the ingestion of the test product for 12 weeks oftest period.
General Information
It is generally said that immunity weakens with advancing
age. Up until now, the functionality of β -glucan had beenstudied in order to clarify its eﬀects for cancer patients or
hypertension patients. On the other hand, this study
indicated that the supplement containing β -glucan is also
effective for the immunity of healthy people.
Contemporary Japan is often described as a stressful
society , and this describes the irregular working hours
and other problems that lead to regular fatigue. The
supplement possibly helps these people to live healthierlife by normalizing their immunological response. The
everyday ingestion of tablet-type foods as a part of selfmedication may lower the risk of illness such as cold, andeventually contribute to the increase in healthy
population, the improvement of QOL and/or the reductionof medical expenditure.
Limitations
In this study we used the processed food Ganoderma
lucidum containing β -glucan, as its test product.
Although β -glucan has been under investigations andresearch mainly in the medical ﬁeld, the research is stillongoing as there are a wide variety of its original species.
Also, as for Ganoderma lucidum itself, since it has a large
variety such as red, black, blue, white, yellow andpurple, therefore its contents and functionality inside theliving organism is a matter of speculation.
In addition, while there are reports that the fungusderived β-glucan increases the activity of NK cells or B
cells, this study did not show an improvement of thesecells. This result may have been produced because thechange of immunity among healthy people tends to be
seen gradually over a long period of time and therefore a
12-week test period was too short to obtain any tangible
results. Or, it is also possible that the test product used
for this study is speciﬁc only to T cells and not eﬀective
for NK cells or B cells. In any case, there are still
uncertainties that remains, and it may be necessary to
conduct the study for more than a 12-week period tofurther scrutinize this matter.
Regarding SBP, the difference of the salt equivalent
between Reishi and Placebo may aﬀect the result. That isa matter of future study.

5. CONCLUSION
In conclusion, we found out that the ingestion of theprocessed food Reishi (Ganoderma lucidum ) containing βglucans for 12 weeks contributed to improving theimmunological vigor of human and the systolic bloodpressure. In addition, no safety-related matter occurred
during the 12-week test period.

診療と新薬・第 53 巻
CONFLICT OF INTEREST
All parts of this study were funded by LINKS Inc. Hiroyuki Sasaki is theprincipal. All authors state that the study was conducted in the absence of
any other relationships that could be interpreted as a conﬂict of interest.

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Appendix 1. Question of SEIV
Scale of 1 to 5, with lower scores indicating a better result.
#1 : Enjoyment of meal
#2 : Meal is often 3 times per day.
#3 : Nutritional balance of the meal is a considerable point.
#4 : Eat more meat than ﬁsh.
#5 : Meal is low in salt.
#6 : Eat moderately in quantity.
#7 : Eat mostly vegetables.
#8 : Limit intake of animal fat.
#9 : No food before sleep#10 : No alcohol#11 : Amount of drinking less than the standard quantity, i.e. beer < 500
ml, wine < 180 ml, sake < 180 ml, or whiskey < 50 ml#12 : Wake up energetically without fatigue from the previous night.
#13 : Feeling of fatigue is reduced by resting on weekends.
#14 : Going to bed before 12 pm.
#15 : Getting suﬃcient quantity of sleep.
#16 : No smoking#17 : Less frequency of stiﬀ shoulder and lower back pain
#18 : Catch a cold regularly.
#19 : Less symptoms of gastro-intestinal problem

第 11 号（2016 年 11 月）

77（1045）

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Function with Changes in Intestinal Microbiota by Salacia reticulata
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15) Peter Parham. The Immune System, 3rd edition. MEDSI. 201016) Nakamura Y, Saima S, Ishikawa H, et al. The relationship between
hypertension and immunoglobulin deposits in renal vascular wallamong the various renal diseases. Kidney and Dialysis. 22: 729-33;
1987.
17) Kabir Y, Kimura S, Tamura T. Dietary eﬀect of Ganoderma lucidum
mushroom on blood pressure and lipid levels in spontaneously
hypertensive rats (SHR). J Nutr Sci Vitaminol (Tokyo). 34: 433-8;
1988.
18) Butler J, Kalogeropoulos AP, Georgiopoulou VV, et al. Systolic bloodpressure and incident heart failure in the elderly. The Cardiovascular
Health Study and the Health, Ageing and Body Composition Study.
Heart. 97: 1304-11; 2011.
19) Miyazaki M, Yajima Y, Okita N, et al. Morphologgies of reishi(basidiocarp of Ganoderma licidium) containing high bioactive
elements. Medicine and Biology. 157: 1346-9; 2013.
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Treat Rev. 11: 131-55; 1984.
21) Taguchi T. Lentinan. Medicina. 16: 1026-7; 1979.
22) Wang J, Zhang L. Structure and chain conformation of five watersoluble derivatives of a β-d-glucan isolated from Ganoderma lucidum.
Carbohydr Res. 344: 105-12; 2009.
23) B a o X , F a n g J , L i X . S t r u c t u r a l C h a r a c t e r i z a t i o n a n d
Immunomodulating Activity of a Complex Glucan from Spores of
Ganoderma lucidum. 65: 2384-239; 2001.
24) Adachi Y. Role of the 1, 3-β-D-Glucan Receptor Dectin-1 in Fungal
Infection and Activation of Innate and Anti-Tumor Immunity. Trends
in glycoscience and glycotechnology. 19: 195-207; 2007.
25) Oohoshi W, Tenkawa M, Kato R. Eﬀects of β-glucan and lactic acidbacteria on gut immune system. 63: 673-9, 2014.
26) Kirmaz C, Bayrak P, Yilmaz O, et al. Eﬀects of glucan treatment on
the Th1/Th2 balance in patients with allergic rhinitis: a double-blind
placebo-controlled study. Eur Cytokine Netw. 16: 128-34; 200527) Queenan KM, Stewart ML, Smith KN, et al. Concentrated oat betag l u c a n , a f e r m e n t a b l e f i b e r, l o w e r s s e r u m c h o l e s t e r o l i n
hypercholesterolemic adults in a randomized controlled trial. Nutr J. 6:
6; 2007#20 : Less symptoms of stomatitis#21 : No record of the following diseases: diabetes mellitus, liver disease,kidney disease, hypertension, hyperlipidemia, cancer, heart disease,autoimmune disease, depression.
#22 : BMI < 25 BMI = BW{kg}/(BL{m} x BL{m})#23 : Normal bowel movement#24 : Try to take the stairs.
#25 : Try to walk instead of vehicles.
#26 : Fast pace walk
#27 : Indiﬀerence to walking#28 : Indiﬀerence to standing in the train#29 : Using pedometer#30 : Indiﬀerence to running when needed#31 : Have a hobby containing physical exercise.
#32 : Less distress / worry than usual#33 : Ability to forget problems / worries and move forward#34 : Enjoy talking with family and friends.
#35 : Have a friend listen to your negative feelings / thoughts.
#36 : Satisﬁed with your daily job.
#37 : Have optimism for the future.
#38 : Want to be helpful to people and society.
#39 : Have a hobby, not related with your job.
#40 : Daily activities except job decided by yourself.