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IMPROVEMENT IN IMMUNE FUNCTION
BY SUPPLEMENT CONTAINED TAHEEBO NAPHTHOQUINONE
AND TAHEEBO POLYPHENOL― A RANDOMIZED PLACEBO-CONTROLLED STUDY ―Masatomo NAJIMA1) and Taro SHIRAKAWA2)
1) JACTA (Japan Clinical Trial Association), 5-27-3 Sendagaya, Shibuya-ku, Tokyo, Japan
2) Institute for Frontier Medicine, Shirakane-kai Medical Association, 8-9-11 Ginza, Chuo-ku, Tokyo, Japan

Abstract
Objectives: The objective of this research was to investigate the effectiveness of daily
ingestion of a Taheebo tablet, which contains Taheebo naphthoquinone and Taheebo
polyphenol on immunological vigor.
Methods: In this randomized, placebo-controlled, double-blind trial, 28 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) was measured as
primary outcomes. The SEIV score (subjective reporting) was also tested as primary
outcomes.
Results: 5 subjects were withdrawn due to personal reasons and the remaining 23 subjects
completed the study. The SIV score of the subjects showed a signiﬁcant diﬀerence between
test and placebo samples after 12-week ingestion. Moreover, in the intergroup comparison ofSEIV, 8 items out of 40 illustrated a signiﬁcant diﬀerence after 12-week ingestion.
Conclusion: The present results suggest that daily ingestion of Taheebo tablets including
Taheebo naphthoquinone and Taheebo polyphenol can improve some respects ofimmunological vigor.
Key words: Taheebo, immunological vigor, immune

1. INTRODUCTION
Taheebo (the botanical name:) is atree that belongs to thespecies of the bignonia
family, and its place of origin is the Amazon river basin ofBrazil. Taheebo has been used for more than 1.5
thousand years, and in the era of the ancient Inca
Empire, the Indians made the Taheebo tea by brewing
the inner bark of Taheebo and drank it for the cure ofdiseases and the health maintenance. In the ancientaboriginal language, Taheebo means gift from God orlight of God , and the Taheebo trees were said to becalled as the tree of gift from God .
The recent studies applying the animal testing reported
that Taheebo owns various functionalities such as
analgesic and anti-inﬂammatory eﬀects1)2), antidepressantlike action 3) and anti-obesity effect 4). A part of theseeffects are thought to have a close relationship withhuman immune function. In addition, there is a reportthat the ingestion of Taheebo inhibits the progress ofcancer and the improvement of CD4+/CD8+ T-cell ratio5),
and this illustrates the possibility that Taheebo
contributes to the activation of the immune function.

Immunity is a self-protection system of human body.
Although it is an essential factor for maintaining ourhealth, its level decreases due to inevitable matters ofdaily life such as aging, stress and irregular lifestyle
habit. Therefore, the ingestion of foods with the capacity
to activate the immune function is thought to be aneﬀective measure against the weakening of immunologicalvigor.
Although Taheebo is thought to have a function ofactivating human immune function as illustrated above,
there are few reports that discuss the functionality ofTaheebo for the immune function of healthy Japanese
men and women with daily tiredness and fatigue; suchreports include the study utilizing animal testing, or the
study focuses on the medical functions of certain
ingredients contained in Taheebo. The objective of thisresearch was to investigate the eﬀectiveness of ingestionof a Taheebo tablet, which includes Taheebo
naphthoquinone and Taheebo polyphenol, on
immunological function of healthy human. As themeasurement, we adopted the immune score
measurement method by Hirokawa and Utsuyama6). The
test targets were healthy Japanese men and women who

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feel tiredness and fatigue on a day-to-day basis, and thetest method was a randomized, placebo-controlled,
double-blind study. We also examined the safety of thetest product.

2. METHOD
2.1. Trial Design
A randomized, placebo-controlled, double-blind study was
conducted with the aid of a fund from TAHEEBO JAPANCO., LTD. (Osaka) at two centers (OZ clinic, Tokyo, and
JACTA, Tokyo). The study period was 12 weeks, from
August 3rd to October 26th, 2015.
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.
2.2.1. Inclusion criteria(1) Healthy Japanese men and women aged between 35
and 59 years with daily tiredness and fatigue;(2) With relatively low self-examination of immunologicalvigor (SEIV) > 90.
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 anddiseases 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 test by
the doctor responsible for the present study.
2.3. Randomization
Recruited subjects were 42 persons. Subjects who
fulﬁlled eligibility criteria were 28 persons. The inclusion
was judged by the principle investigator. All subjects
were sequentially assigned based on a random number
table to one of the masked products and randomized togroup T (Test sample: 14) and group P (Placebo: 14).
The allocation was pre-assigned on the basis ofrandomized numbers.
2.4. Description of test foods and blinding
The test food, Taheebo NFD Premium ( TNP ) is atablet containing Taheebo naphthoquinone and Taheebo
polyphenol. The amount of a daily intake is 6 tablets (1

第 4 号（2016 年 4 月）

Table 1

Nutritional content of the sample per 100 g

Item

TNP

Placebo

Energy404 kcal

321 kcalProtein
Lipid
Ash
Carbohydrates
Salt equivalent

1.3 g
5.0 g
1.2 g
88.5 g0.0605 mg

0.8 g
3.8 g
21.0 g70.9 g0.404 mgtablet weighs 350 mg, therefore 6 tablets weigh 2.1 g).
Placebo does not contain Taheebo naphthoquinone andTaheebo polyphenol. Table 1 shows the nutritional
content of the sample. Both tablets were indistinguishable
in shape, color or taste. Tablets were managed by theidentiﬁcation symbol. All involved were blinded.
2.5. Experimental procedures
2.5.1. Experimental protocol
Subjects consumed 6 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
every Friday by mobile email.
2.5.2. Outcome
The objective of this study is to verify immunologicalvigor of ingesting food containing Taheebo
naphthoquinone and Taheebo polyphenol. Immunologicalvigor was set as the primary outcome. SIV and SEIV
were used to evaluate that. SIV is the scoring systemthat can combine seven immunological parameters, thenumber of T cells, naive T cells, CD8+CD28+ T cells, B
cells, and NK cells, and ratios of CD4/CD8 T cell andnaive/memory T cell, and express the immune status ofindividuals as a simple numeral. This system also shows
T lymphocyte age. Due to this, we can compare the real
age with the age 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 6), 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 7). SEIV is a selfexamination of immunological vigor with Likert scales.
Blood biochemical and urine parameters were recorded toevaluate the safety of the test foods as the secondary
outcome. These assessments were conducted upon entry
into the study (pre-intervention) and after 12 weeks

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Scoring of
immunologicalvigor1）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

Table 2
Item

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Term

SIV

Schedule for the study.
Screening

SEIV
Informed consent
Selection and/or allocation
immunological parameters
Biochemical analysis of blood
Urine analysis
Ingestion of test foods
Log

Pre Trial Test

Test period (12 w)
●

●
●
●
●
●
●

●
●
●
←―――――――→←―――――――→● : Implementation↔ : Daily practice during the test period(post-intervention).
To evaluate the safety of the test foods, adverse eventswere collected by means of a written questionnaireduring the study.
According to the schedule shown in Table 2, we
measured parameters on eﬃcacy and safety.
2.6. Data Analysis
The full analysis set principal was adopted in thepresent study and no sample size was used.
Data is expressed as mean ± SD. For SIV,
immunological parameters of blood, T lymphocyte age
and biochemical analyses of blood and urine, changes
from the baseline in the same group were assessed using
the paired t-test. Student s t-test was used for intergroupcomparisons of changes from the baseline. For SEIV,
changes from the baseline in the same group wereassessed using the Wilcoxon signed-rank test. The MannWhitney U test was used for intergroup comparisons ofchanges from the baseline. Student s t-test was used tocompare subject s backgrounds between groups.
Statistical analyses were performed using Statcel 3(Yanai, 2011). The results were considered signiﬁcant at
the < 5% level in the two-sided test.

3. RESULTS
3.1. Participant Demographics
From all of 42 applicants, 14 were eliminated according to
the SEIV criteria (< 90). 28 subjects were randomly

assigned to an intervention group and made a start withingestion. 5 were withdrawn due to personal reasons andremaining 23 subjects completed the study. These 5
subjects (all in the Placebo) were withdrawn for thefollowing reasons: urgent work commitment (3 subjects);
due to a cold (2 subjects).
Thus, data obtained from the 23 subjects was used forthe analysis of eﬃcacy (Fig. 2). There were no signiﬁcantdifferences in the mean age, gender ratio or SEIV
between groups (Table 3).
3.2. SIVThe results of the statistical analysis of SIV, otherimmunological parameters and T lymphocyte age areshown in Table 4. In TNP, the SIV score increased
significantly after 12-week ingestion. Furthermore
significant difference of ⊿ SIV was observed between
two groups after 12-week ingestion. Also, the withingroup analysis showed that only in the TNP the numbersof T cells and naive T cells increased signiﬁcantly after
12-week ingestion. As for CD8+CD28+ T cells, B cells andT lymphocyte age, there were significant tendency in
TNP after 12-week ingestion. In other items, any
signiﬁcant changes or diﬀerences were shown neither in
TNP nor in Placebo.
3.3. SEIV
Table 5 shows the results of SEIV. After 12-weekingestion, 8 items out of 40 illustrated a significant
changes in values of intergroup comparison: 1,

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Recruited (n ＝ 42)(M: 16, F: 26)
Excluded (n ＝ 14) (M: 5, F: 9)［SEIV ＜ 90］
Randomized (n ＝ 28)(M: 11, F: 17)

TNP (n ＝ 14)(M: 6, F: 8)

Placebo (n ＝ 14)(M: 5, F: 9)
Withdraw (n ＝ 5) (M: 1, F: 4)［personal reason］
Full analysis set

TNP (n ＝ 14)(M: 6, F: 8)

Placebo (n ＝ 9)
(M: 4, F: 5)

Fig. 2

Flow diagram of subject disposition

Table 3 Subject demographics
Item

Unit

TNP

Placebo

Subjects*
Male: female*
Age
SEIV

−
−
years
scores14
6:8
45.0 ± 4.6
115.1 ± 9.6

94:5
47.8 ± 6.7
110.9 ± 10.0＊

Number of subjects
mean ± SD

enjoyment of meal ; 12, wake up energetically without
fatigue from the previous night ; 13, feeling of fatigue isreduced by resting on weekends ; 17, less frequency ofstiﬀ shoulder and lower back pain ; 18, catching a cold ;20, less symptoms of stomatitis ; 28, indifference tostanding in the train ; 38, want to be helpful to people
and society .
3.4. Blood Test and Urine Test
Table 6 and 7 shows blood biochemical and urine
parameters.
With respect to blood test, a signiﬁcant diﬀerence wasobserved in Total Cholesterol, Potassium, Inorganic
Phosphorus, Urea Nitrogen, Creatinine (Female) andBlood Sugar serum of TNP after 12-week ingestion. The
same diﬀerence was found in urinary speciﬁc gravity after
12-week ingestion. In either case, since the difference
was minor one, the investigator judged it as the range ofphysiological variation (or clinically safe).
3.5. Adverse Event
No adverse event was reported during this trial.

4. DISCUSSION
We conducted a randomized, placebo-controlled, doubleblind study to verify the effects of the Taheebo tablet
which contains Taheebo naphthoquinone and Taheebo
polyphenol, on immunological vigor of human. As theprimary outcome, the study showed significant changes
in values of several items of SIV (Scoring of
Immunological Vigor), a comprehensive index of immune
function, and SEIV (Self-examination of immunologicalvigor), a subjective assessment, after 12-week ingestion
period. At the same time, as the secondary outcome theobservation of clinical ﬁndings such as medical interview,
blood and urine test revealed no abnormal change had
been triggered by the ingestion of test product.
In this study, we evaluated the effect of the test
product containing Taheebo naphthoquinone and Taheebo
polyphenol for the immunological vigor, by comparing
scores of SIV and SEIV between the test group (TNP)and the placebo group (Placebo).

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

SIV

T cells

Naive T cells

CD8+CD28+ T cells

B cells

NK cells

Unitscoresnumbers/μl

numbers/μl

numbers/μl

numbers/μl

numbers/μl

CD4/CD8 T cell
ratio

ratio

Naive/memory
T cell ratio

ratio

T lymphocyte age

years

Scores/Values

Time

P-valuepointsTNP (n = 14)

Placebo (n = 14)

Baseline
Week 12
Change15.5 ± 1.8
16.8 ± 1.6 **1.3 ± 1.1

16.3 ± 2.4
16.6 ± 2.1
0.2 ± 1.0

0.025 #

Baseline
Week 12
Change1226.1 ± 370.8
1406.9 ± 353.4 *180.8 ± 232.1

1291.6 ± 370.4
1451.3 ± 499.5
159.8 ± 355.6

0.865

Baseline
Week 12
Change276.8 ± 173.3
350.0 ± 179.4 *73.2 ± 112.3

363.6 ± 121.7
411.1 ± 176.6
47.6 ± 123.8

0.612

Baseline
Week 12
Change195.4 ± 68.4
226.5 ± 94.2 †31.1 ± 54.3

214.9 ± 147.4
202.3 ± 91.7
− 12.6 ± 108.4

0.286

Baseline
Week 12
Change236.4 ± 105.1
279.9 ± 96.2 †43.6 ± 85.8

264.0 ± 87.8
348.9 ± 129.7
84.9 ± 139.4

0.387

Baseline
Week 12
Change249.9 ± 67.8
241.6 ± 110.8− 8.4 ± 87.3

285.2 ± 183.8
282.2 ± 152.4− 3.0 ± 111.2

0.898

Baseline
Week 12
Change2.77 ± 1.50
3.17 ± 2.31
0.41 ± 1.84

5.05 ± 5.03
3.16 ± 1.11
− 1.89 ± 5.31

0.208

Baseline
Week 12
Change0.52 ± 0.26
0.63 ± 0.33
0.11 ± 0.24

0.80 ± 0.43
0.76 ± 0.29
− 0.04 ± 0.33

0.220

Baseline
Week 12
Change52.3 ± 6.7
49.9 ± 8.4 †− 2.4 ± 4.3

52.6 ± 12.9
54.1 ± 10.0
1.4 ± 6.8

0.176

Scores and values are expressed as the mean ± SD.
†

p ＜ 0.1, * p ＜ 0.05, ** p ＜ 0.01 against baseline.

#p ＜ 0.05 between-group diﬀerences in change from baseline.

SIV score is a comprehensive index of immune function
and it means that the higher the score, the more theimmune function is comprehensively good. The result
showed that in TNP the score of SIV increased after 12week ingestion, and this suggests there was a signiﬁcant
improvement in the immune function of TNP. As forPlacebo, on the other hand, there was no significant
change in the score, and therefore it indicates there was
no improvement in the immune function. T lymphocyte
age is an index which matches the immune function to theactual age, and it means the lower the year is, theyounger the immune function, is equipped. In this study,
although we could not statistically find any significant
difference, we observed that T lymphocyte age isyounger in TNP (i.e. improvement tendency) whereasthat of Placebo did not change. In addition, the number ofT cells and their subsets (such as Naive T cells,
CD8+CD28+ T cells and B cells) increased signiﬁcantly or
tended to increase in TNP. This study used healthy
Japanese men and women with daily tiredness and fatigue
as its test subject, therefore it is likely that the immune
function of the subject among Placebo deteriorated during
the test period. However, this result supports thepossibility that the ingestion of TNP activated theimmune function of subjects, especially among T-type
cells. At the same time, in SEIV (an index for theawareness of immune system), significant improvement
was observed in the items that may be related to fatigue,
stress or QOL. Since it is generally said that the fatigue
or stress have a major effect on the human immune
function8), this result of SEIV should have a relationshipwith the improvement of SIV score as discussed above.

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Table 5

第 4 号（2016 年 4 月）

SEIV ①

Item

Time points#

Placebo (n = 9)

1.6 ± 0.5
1.1 ± 0.4 *− 0.4 ± 0.5

1.3 ± 0.5
2.1 ± 0.8 *0.8 ± 0.7 ##1

Enjoyment of meal

Baseline
Week 12
Change2

Meal is often 3 times per day.

Baseline
Week 12
Change2.0 ± 1.4
1.9 ± 1.3
− 0.1 ± 0.7

2.0 ± 1.5
1.2 ± 0.4
− 0.8 ± 1.6

3

Nutritional balance of the meal is a considerable point.

Baseline
Week 12
Change2.6 ± 1.2
2.3 ± 1.1
− 0.3 ± 1.0

2.3 ± 1.3
1.9 ± 0.6
− 0.4 ± 1.1

4

Eat more meat than ﬁsh.

Baseline
Week 12
Change3.1 ± 1.2
3.1 ± 1.0
0.0 ± 1.3

3.1 ± 0.9
2.9 ± 0.9
− 0.2 ± 0.8

5Meal is low in salt.

Baseline
Week 12
Change2.9 ± 1.4
2.5 ± 0.9
− 0.4 ± 1.4

2.8 ± 1.4
2.7 ± 0.9
− 0.1 ± 1.2

6

Eat moderately in quantity.

Baseline
Week 12
Change2.9 ± 1.1
2.6 ± 0.9
− 0.3 ± 1.2

3.1 ± 1.5
2.7 ± 1.4
− 0.4 ± 1.0

7

Eat more vegetables.

Baseline
Week 12
Change2.6 ± 1.5
1.9 ± 0.7
− 0.7 ± 1.5

1.9 ± 0.9
1.7 ± 0.9
− 0.2 ± 1.08Limit intake of animal fat.

Baseline
Week 122.7 ± 1.2
2.5 ± 1.0

2.9 ± 1.3
1.9 ± 0.8 *Change− 0.2 ± 1.1− 1.0 ± 1.0

3.1 ± 1.0
3.0 ± 1.0
− 0.1 ± 1.0

2.8 ± 1.3
2.0 ± 0.7
− 0.8 ± 1.4

9

No food before sleep

Baseline
Week 12
Change10

No alcohol

Baseline
Week 12
Change2.6 ± 1.7
2.6 ± 1.5
0.0 ± 1.2

3.0 ± 1.8
3.0 ± 1.7
0.0 ± 1.8

11

Amount of drinking less than the standard quantity
i.e. beer < 500 ml, wine < 180 ml, sake < 180 ml, or whiskey< 50 ml

Baseline
Week 12
Change1.3 ± 1.1
1.6 ± 0.7
0.4 ± 0.9

1.9 ± 1.8
2.4 ± 1.9
0.6 ± 1.3

12

Wake up energetically without fatigue from the previous night.

Baseline
Week 12
Change3.5 ± 1.5
2.3 ± 0.8 **− 1.2 ± 1.1

3.2 ± 1.3
3.8 ± 1.0
0.6 ± 0.9 ##13

Feeling of fatigue is reduced resting on weekends.

Baseline
Week 12
Change4.3 ± 0.8
2.4 ± 1.0 **− 1.9 ± 1.2

2.7 ± 1.1
3.6 ± 1.0
0.9 ± 0.6 ##14

Going to bed before 12 pm

Baseline
Week 12
Change3.6 ± 1.5
3.3 ± 1.4
− 0.4 ± 0.9

3.1 ± 1.4
2.2 ± 1.0 †− 0.9 ± 1.2

15

Getting suﬃcient quantity of sleep.

Baseline
Week 12
Change3.6 ± 0.9
2.9 ± 0.9 *− 0.7 ± 1.1

2.8 ± 1.5
2.1 ± 1.1 †− 0.7 ± 0.9

16No smoking

Baseline
Week 12
Change1.3 ± 1.1
1.3 ± 1.1
0.0 ± 0.0

2.3 ± 2.0
2.2 ± 1.9
− 0.1 ± 2.0

17Less frequency of stiﬀ shoulder and lower back pain

Baseline
Week 12
Change3.9 ± 1.3
2.9 ± 1.5 *− 1.0 ± 1.2

3.6 ± 1.3
4.0 ± 0.9
0.4 ± 0.7 #18Catching a cold.

Baseline
Week 12
Change2.6 ± 1.1
1.7 ± 1.1 *− 0.9 ± 1.0

3.3 ± 1.5
3.4 ± 1.4
0.1 ± 0.3 #19Less symptoms of gastro-intestinal problem

Baseline
Week 12
Change2.2 ± 1.1
1.9 ± 1.0
− 0.4 ± 0.9

3.0 ± 1.5
3.1 ± 1.6
0.1 ± 0.3

20

Less symptoms of stomatitis

Baseline
Week 12
Change2.2 ± 1.1
1.6 ± 0.6 *− 0.6 ± 0.7

2.6 ± 1.1
3.0 ± 1.2
0.4 ± 1.0 #21

No record of the following diseases: diabetes mellitus, liverdisease, kidney disease, hypertension, hyperlipidemia, cancer,
heart disease, autoimmune disease, depression.

Baseline
Week 12
Change1.3 ± 1.1
1.5 ± 1.2
0.2 ± 1.7

1.0 ± 0.0
1.7 ± 1.4
0.7 ± 1.4

Scores are expressed as the mean ± SD.
†

ScoresTNP (n = 14)

p ＜ 0.1, * p ＜ 0.05, ** p ＜ 0.01 against baseline.
p ＜ 0.05, ## p ＜ 0.01 between-group diﬀerences in change from baseline.

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Table 5

第 4 号（2016 年 4 月）

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SEIV ②Item

Time points

BMI = BW{Kg}/(BL{m}x BL{m})ScoresTNP (n = 14)

Placebo (n = 9)

Baseline
Week 12
Change2.4 ± 2.0
2.4 ± 1.6
0.0 ± 1.7

2.3 ± 2.0
2.0 ± 1.0
− 0.3 ± 1.4

22

BMI ＜ 25

23

Normal bowel movement

Baseline
Week 12
Change2.2 ± 1.1
2.1 ± 1.1
− 0.1 ± 0.9

2.9 ± 1.4
3.2 ± 1.2
0.3 ± 0.5

24

Try to take the stairs.

Baseline
Week 12
Change3.5 ± 1.1
2.7 ± 1.1 †− 0.8 ± 1.4

3.7 ± 1.2
3.9 ± 0.9
0.2 ± 0.7 ‡25

Try to walk instead of vehicles.

Baseline
Week 12
Change2.5 ± 1.3
1.7 ± 0.8 †− 0.8 ± 1.5

3.0 ± 1.4
3.1 ± 1.3

26

Fast pace walk

Baseline
Week 12
Change2.9 ± 1.4
2.3 ± 1.0 †− 0.6 ± 1.2

3.0 ± 1.3
2.1 ± 1.3 †− 0.9 ± 1.4

27

Indiﬀerence to walking

Baseline
Week 12
Change2.8 ± 1.3
1.8 ± 0.6 *− 1.0 ± 1.2

2.9 ± 1.3
2.4 ± 1.1
− 0.4 ± 1.0

28

Indiﬀerence to standing in the train

Baseline
Week 12
Change3.4 ± 1.6
2.3 ± 1.1 *− 1.1 ± 1.4

3.7 ± 1.0
3.6 ± 0.9
− 0.1 ± 0.3 #Baseline
Week 12
Change3.6 ± 2.0
1.4 ± 1.1 *− 2.2 ± 2.0

4.1 ± 1.8
1.2 ± 0.4 *− 2.9 ± 1.7

Baseline
Week 12
Change3.5 ± 1.1
2.4 ± 1.2 *− 1.1 ± 1.5

3.3 ± 1.2
1.7 ± 0.9 *− 1.7 ± 1.1

0.1 ± 0.9

29

Using pedometer30

Indiﬀerence to running when needed31

Have a hobby containing physical exercise.

Baseline
Week 12
Change3.9 ± 1.6
3.4 ± 1.5
− 0.6 ± 1.6

4.0 ± 1.6
3.0 ± 1.0 †− 1.0 ± 1.6

32

Less distress / worry than usual

Baseline
Week 12
Change3.6 ± 1.2
3.0 ± 1.1 †− 0.6 ± 1.1

3.2 ± 0.7
3.0 ± 0.9
− 0.2 ± 0.7

33

Ability to forget problems / worries and move forward

Baseline
Week 12
Change3.7 ± 1.3
2.9 ± 1.0 *− 0.9 ± 1.3

2.9 ± 1.5
1.8 ± 0.8 *− 1.1 ± 1.2

34

Enjoy talking with family and friends.

Baseline
Week 12
Change2.4 ± 1.1
2.1 ± 1.1
− 0.3 ± 0.6

1.7 ± 1.1
1.7 ± 0.7
0.0 ± 1.0

35

Have a friend listen to your negative feelings / thoughts.

Baseline
Week 12
Change3.4 ± 1.4
2.5 ± 1.0 †− 0.9 ± 1.5

2.7 ± 1.6
1.8 ± 0.8 †− 0.9 ± 1.3

36Satisﬁed with your daily job.

Baseline
Week 12
Change3.4 ± 1.3
2.8 ± 1.1 †− 0.6 ± 1.2

3.4 ± 1.0
2.0 ± 0.9 *− 1.4 ± 0.937Have optimism for the future.

Baseline
Week 12
Change3.6 ± 1.3
2.6 ± 1.3 *− 1.0 ± 1.3

2.7 ± 1.2
2.0 ± 0.7
− 0.7 ± 1.2

38

Want to be helpful to people and society.

Baseline
Week 12
Change3.4 ± 1.2
2.6 ± 1.1 †− 0.7 ± 1.2

2.6 ± 1.1
2.9 ± 1.1
0.3 ± 0.5 #39Have a hobby, not related with your job.

Baseline
Week 12
Change2.4 ± 1.3
1.8 ± 1.1 †− 0.6 ± 1.2

2.3 ± 1.8
1.2 ± 0.4
− 1.1 ± 1.8

40Daily activities except job decided by yourself.

Baseline
Week 12
Change2.7 ± 1.4
2.7 ± 1.3
0.0 ± 1.4

1.9 ± 1.3
1.9 ± 0.6
0.0 ± 1.4−

Total score of SEIV

Baseline
Week 12
Change115.1 ± 9.6
92.0 ± 18.5 **− 23.1 ± 14.7

110.9 ± 10.0
98.0 ± 9.3 **− 12.9 ± 7.7 ‡Scores are expressed as the mean ± SD.
†
p ＜ 0.1, * p ＜ 0.05, ** p ＜ 0.01 against baseline.
‡p ＜ 0.1, # p ＜ 0.05 between-group diﬀerences in change from baseline.

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Table 6Item

Unit

第 4 号（2016 年 4 月）

Changes in biochemical blood test

Std. Value

GenderTime points

ValuesTNP (n = 14)

Placebo (n = 14)

0.66 ± 0.24
0.64 ± 0.27
− 0.02 ± 0.33

0.72 ± 0.31
0.66 ± 0.38
− 0.06 ± 0.25

Total Bilirubin

mg/dL

0.2‑1.2

M/F

Baseline
Week 12
ChangeTotal Protein

g/dL

6.3‑8.3

M/F

Baseline
Week 12
Change7.6 ± 0.4
7.6 ± 0.4
− 0.0 ± 0.2

7.6 ± 0.4
7.7 ± 0.4
0.1 ± 0.3

Albumeng/dL

3.8‑5.3

M/F

Baseline
Week 12
Change4.7 ± 0.2
4.6 ± 0.3
− 0.1 ± 0.2

4.6 ± 0.3
4.6 ± 0.2
0.0 ± 0.2

AST (GOT)

U/L

8‑38

M/F

Baseline
Week 12
Change21.4 ± 7.0
22.5 ± 6.1
1.1 ± 4.3

20.3 ± 5.5
20.0 ± 5.0− 0.3 ± 5.0

ALT (GPT)

U/L

4‑43

M/F

Baseline
Week 12
Change20.1 ± 9.3
21.7 ± 11.8
1.6 ± 6.1

21.2 ± 15.3
20.4 ± 10.8
− 0.8 ± 8.2

ALP

U/L

110‑354

M/F

Baseline
Week 12
Change182.6 ± 46.6
193.6 ± 54.3 †10.9 ± 23.0

198.2 ± 69.4
211.6 ± 89.1
13.4 ± 37.8

LD (LDH)U/L

121‑245

M/F

Baseline
Week 12
Change184.2 ± 33.9
179.8 ± 31.0
− 4.4 ± 17.5

183.8 ± 32.7
175.1 ± 32.7
− 8.6 ± 20.4

86 andunder

M

Baseline
Week 12
Change39.0 ± 13.9
37.5 ± 15.1
− 1.5 ± 6.4

41.4 ± 26.1
30.0 ± 13.0
− 11.4 ± 18.1

48 andunder

F

Baseline
Week 12
Change17.1 ± 6.2
16.9 ± 7.4− 0.3 ± 2.3

16.9 ± 6.5
17.7 ± 8.7
0.8 ± 3.6

38‑196

M

Baseline
Week 12
Change167.5 ± 112.7
154.3 ± 78.8
− 13.2 ± 119.1

154.6 ± 62.0
116.6 ± 69.5
− 38.0 ± 65.5

30‑172F

Baseline
Week 12
Change98.3 ± 72.9
90.4 ± 39.4
− 7.9 ± 41.7

84.6 ± 26.9
87.3 ± 38.6
2.8 ± 14.8

γ-GT (γ GTP)CK (CPK)

U/L

mg/dL

Total Cholesterolmg/dL

130‑219

M/F

Baseline
Week 12
Change195.6 ± 25.9
211.6 ± 22.1 **15.9 ± 19.4

222.7 ± 38.8
235.7 ± 42.4
13.0 ± 27.8

Neutral Fat (TG)mg/dL

30‑149M/F

Baseline
Week 12
Change127.9 ± 42.2
160.5 ± 114.2
32.6 ± 87.4

170.9 ± 91.4
171.4 ± 125.9
0.5 ± 107.5

SodiummEq/L

135‑150

M/F

Baseline
Week 12
Change144.5 ± 2.4
144.1 ± 2.0− 0.4 ± 1.9145.2 ± 1.6
144.2 ± 1.6 †− 1.0 ± 2.0

Chloride

mEq/L

98‑110

M/F

Baseline
Week 12
Change105.2 ± 1.7
104.5 ± 1.9− 0.7 ± 2.3

106.1 ± 2.6
104.7 ± 2.3 *− 1.4 ± 2.2

Potassium

mEq/L

3.5‑5.3

M/F

Baseline
Week 12
ChangeCalcium

mg/dL

8.4‑10.2

M/F

Baseline
Week 12
Change9.9 ± 0.2
9.8 ± 0.3
− 0.1 ± 0.3

9.8 ± 0.4
9.9 ± 0.4
0.1 ± 0.3

Inorganic
Phosphorus

mg/dL

2.5‑4.5

M/F

Baseline
Week 12
Change3.7 ± 0.5
3.4 ± 0.7 *− 0.3 ± 0.4

3.5 ± 0.4
3.3 ± 0.6
− 0.2 ± 0.6

Urea Nitrogen

mg/dL

8.0‑20.0

M/F

Baseline
Week 12
Change16.8 ± 5.8
14.1 ± 4.2 *− 2.8 ± 4.8

15.4 ± 4.7
13.8 ± 3.4− 1.5 ± 3.4

0.61‑1.04

M

Baseline
Week 12
Change0.91 ± 0.13
0.87 ± 0.13
− 0.04 ± 0.08

0.91 ± 0.12
0.90 ± 0.07
− 0.01 ± 0.09

0.47‑0.79

F

Baseline
Week 12
Change0.66 ± 0.06
0.63 ± 0.06 *− 0.03 ± 0.02

0.67 ± 0.08
0.66 ± 0.10
− 0.01 ± 0.05

60‑109M/F

Baseline
Week 12
Change68.6 ± 8.8
74.7 ± 8.5 *6.1 ± 6.9

69.7 ± 21.4
74.1 ± 13.4
4.4 ± 22.2

Creatinine

Blood Sugar(Serum)

mg/dL

mg/dL

Values are expressed as the mean ± SD.
†
p ＜ 0.1, * p ＜ 0.05, ** p ＜ 0.01 against baseline.

4.1 ± 0.3
4.3 ± 0.4 *0.2 ± 0.3

3.8 ± 0.2
4.1 ± 0.2 **0.3 ± 0.2

診療と新薬・第 53 巻

第 4 号（2016 年 4 月）

81 （351）

Table 7 Transition of Urinalysis
Item

Unit

Std. Value

GenderSpeciﬁc Gravity

mg/dL

1.010‑1.025

M/F

pH

g/dL

4.5‑8.0

M/F

ValuesTimepointsTNP (n = 14)

Placebo (n = 14)

Baseline
Week 12
Change1.026 ± 0.007
1.016 ± 0.007 **− 0.010 ± 0.007

1.022 ± 0.006
1.019 ± 0.007− 0.004 ± 0.009 #Baseline
Week 12
Change5.9 ± 0.9
6.0 ± 0.7
0.0 ± 1.1

5.9 ± 0.8
6.5 ± 1.0 *0.6 ± 1.0

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

The Taheebo tablet used for this study consists ofTaheebo bark extract and Taheebo-derived ingredientssuch as Taheebo naphthoquinone and Taheebo
polyphenol. Taheebo polyphenol contains acteoside,isoacteoside, echinacoside and salidroside9), all of which
are known to have strong anti-oxidative property10). In
addition, there are several study reports that emphasize
the function of Taheebo polyphenol such as its antiallergic effect which is achieved by its affection to
immunoglobulin E11), or its enhancement of the cellular/
humoral immune response by affection of salidroside to
T-cells, which is evaluated by the experiment using old
rats12). Taheebo naphthoquinone, on the other hand, is akind of quinone (plant pigment), and especially in
Taheebo 2-(1-hydroxyethyl)-5-hydroxy-naphtho [2,3-b]furan-4,9-dione (NQ801) is included13). Naphthoquinone
reportedly owns antitumor effect 14), anti-inflammatoryeﬀect and anti-oxidative eﬀect15), and as an indirect action,
immunostimulating effect 14)16) . In addition, it was
confirmed that Taheebo contains fat, tannin andminerals17), and these ingredients are thought to maintainbodily functions. Furthermore, there is a report that theingestion of Taheebo lowers the anti-oxidative effect ofmacrophage and enhances the cell-mediated immunity oflymphocyte 18). All of the above findings support the
hypothesis that the immunity was activated by theingestion of the test product (TNP) containing Taheebo
naphthoquinone and Taheebo polyphenol.
In this study we examined the safety of the test
product by blood and urine test. In the blood test,
significant difference was observed in total cholesterol,
potassium, inorganic phosphorus, urea nitrogen,creatinine (female) and blood sugar serum. On the other
hand, in the urine test we observed signiﬁcant diﬀerencein the change of urine specific gravity. In either case,since the difference was minor one, the investigator
judged it as the range of physiological variation (orclinically safe). During the study, 5 subjects were
excluded during the test due to personal reasons such as
work or a cold, and they were not related to the adverse

event caused by the test product. Therefore, based upon
the medical interview, blood and urine test, we observed
no harmful influence against biochemical and/or
physiological matters of the subjects. These results
indicated the safety of the ingestion of the test product(TNP) for the 12-week test period.
It is generally said that the immunity weakens withadvancing age. As Japanese society faces aging of
population, it is increasingly important to grow old while
maintaining good health. Non-prescription medicines
such as cold medicine are all symptomatic treatment andtherefore have a function of alleviating symptoms, but do
not boost disease resistance in a fundamental way.
Increasing natural immunity of human and boosting
disease resistance by ingesting snackable foods liketablet-type supplements may contribute to increase thepopulation of physical wellness, and eventually contributeto increase QOL and reduce the overall medical costs.
This study examined an immunostimulating effect ofhuman by the ingestion of the test product (TNP) for 12
weeks. However, the immune function of human tends tobe affected by their environment and/or stress. It may
also be affected depending upon the ingestion period.
Therefore, 12-week test period should be not enough for
obtaining solid evidence and we need to continue further
investigation with diﬀerent test arrangement, such as thelonger test period or the changing of season andenvironment. In addition, since there is a reportconcluding that the extracts of Taheebo is more eﬀective
than the individual ingredients from Taheebo 16), thefunctional mechanism of Taheebo ingredients inside thebody is still unknown, and this point should also be
further scrutinized in the future.
In conclusion, we found out that the ingestion of theTaheebo tablet (TNP) containing Taheebo
naphthoquinone and Taheebo polyphenol for 12 weeks
contributed to the immunostimulating eﬀect. In addition,no safety-related matter occurred during 12-week test
period.

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