Original Article

診療と新薬 2019; 56: 606‑613

Impact of Moringa Seed Extract on
Daily Fatigue and Low Back Pain:

診療と新薬 WebA Randomized, Parallel, Double-Blind, and Placebo-Controlled Study

Kazuo SHIMIZU／Aya ABE ＊／Mahendra P. KAPOOR／Zenta YASUKAWA／Makoto OZEKI
Nutrition Division, Taiyo Kagaku Co., Ltd.
1-3 Takaramachi, Yokkaichi, Mie 510-0844, Japan.

● Abstract
Objective: The objective of this study was to examine the effect of moringa seed extract containing
glucomoringin (GMG) on fatigue in healthy working men and women.
Methods: Healthy adult working men and women (forty participants, Male: 18; Female: 22) were enrolled inthis randomized, parallel, double-blind, and placebo-controlled study. The participants took 120 mg of moringa
seed extract (GMG; 12 mg) or placebo every day for four consecutive weeks. The severity of fatigue andphysical discomfort were evaluated with a Visual Analog Scale (VAS) and Chalder fatigue scale at baseline andevery week of the study duration. A medical interview with a study physician was conducted at the baseline
and end of the study.
Results: Intake of moringa seed extract led to the signiﬁcant decrease in VAS scores of fatigue, low backpain, stiﬀ shoulder, and eye strain. A diﬀerence in low back pain VAS scores from baseline was signiﬁcantly
higher in the treatment group than the placebo group after two weeks. Among the subjects with higher fatigue
VAS score subgroups, the change was considerably more signiﬁcant after four weeks in the treatment group.
In the higher low back pain VAS score subgroups, the diﬀerence from the baseline scores was considerably
more signiﬁcant after 2, 3, and 4 weeks among the subjects of treatment group.
Conclusion: The consumption of moringa seed extract is found eﬀective in lowering the severity of fatigue
and low back pain among the healthy working men and women of middle age subjects with somewhat severe
symptoms.
Key words: Moringa, Moringin, Glucomoringin, Fatigue, Low back pain

1. Introduction
Fatigue is a symptom caused by physical andpsychological stress, and it is a severe problem in modern
society that affects human health, work efficiency, andquality of life. In recent years, technological innovations
such as information communication have advanced, andchanges in working conditions have increased theopportunities for using computer devices, and that
resulted in the increased physical and mental fatigue.
According to a survey conducted in 2003 by Japan s
Ministry of Health, Labor and Welfare on 14,000 office
workers in Japan s privately-owned business offices andsales divisions; 86.2% of workers were using computerand 78% of workers felt physical fatigue and related
symptoms, and many workers felt eye strain (91.6%), stiﬀ
shoulder (70.4%), and low back pain (26.6%)1). Thus, theproblem of fatigue has become a serious problem not onlyin the working people, but also in the whole society, and＊Corresponding author; E-mail address:aabe@taiyokagaku.co.jp (A.Abe)the effective solution is needed. Since there are notenough pharmacological supplies for fatigue recovery,
therefore, non-pharmacological approaches such asfunctional foods are currently promising, and likely to
become of an increasing importance.
Moringa oleifera (Moringaceae) is a perennial tree
native to the northwestern part of India and is now widelydistributed in tropical areas. It is highly nutritive, andyoung fruits and leaves are mainly eaten as vegetables,
and leaves are utilized as supplements, besides, to use asa tea, and fruits containing seeds are locally used as curry
ingredients 2)3). Not only as a food, but moringa is also said
to have 300 medicinal effects in folk medicine
Ayurveda , and has been widely used since BC 4)〜6).
Recently, numerous pharmacological effects of moringa
has been shown in vivo and in vitro including
antibacterial, digestive aid, appetite suppression, antiinflammatory, immune improvement, cholesterol
reduction, blood pressure control, visual improvement,
antidepression, cognitive function improvement, antifatigue, and so on 7)〜14). Moringa oleifera is a rich source of
β -carotene, protein, vitamin C, calcium and potassium

診療と新薬・第 56 巻

and act as a good source of natural antioxidants. It also
contains unique bioactive compounds represented by
glucosinolates primarily glucomoringin (GMG; 4 (α-L-rhamnosyloxy)-benzyl glucosinolate)12). GMG undergoe n z y m a t i c c o n ve r s i o n t o m o r i n g i n , o n e t y p e o f
isothiocyanates by host gut microbiota 15). To date,moringin has been shown to have numerous
pharmacological effects including as chemoprotective
agent against cancer progression and direct antitumouraleffects along with antioxidant and anti-inflammatory
properties both in vivo and in vitro 7)16)〜19). Anti-fatigue
eﬀect of moringa leaves extract has already shown in rats
subjected to forced swimming endurance test 20), and we
conﬁrmed the same eﬀects of moringa seed extract in ourprevious study 21). Wherein, intake of feed containing
GMG at 0.2 mg/kg/day for four weeks was found to
improve fatigue during forced swimming. In this study,
we investigated the anti-fatigue effect of moringa seedextract in a clinical trial. We designed a randomized,
parallel, double-blind, and placebo-controlled study toinvestigate the anti-fatigue eﬀect of moringa seed extract.
2. Materials and Methods
2.1. Ethical approval of the study protocol
The study was conducted in accordance with the Helsinki
Declaration based on the Ethical Guidelines for Medicaland Health Research Involving Human Subjects(Notification by the Ministry of Health, Labor andWelfare, partially revised on February 28, 2017). The
institutional review board approved the study protocol at
Ueno-Asagao Clinic (Approval number: 2019-09; Date of
approval: January 24, 2019). The study protocol was
registered at the UMIN-CTR (Trial ID: UMIN 000035949).
The protocol was not modiﬁed from the time of ﬁnal setup
and during the study.
2.2. Supplementation and dosages
Tablets of moringa seed extract containing GMG (Taiyo
Kagaku Co., Ltd., Japan) were prepared as treatment
food. Based on our previous study 21), the eﬀective dosage
for human was estimated, and 12 mg of GMG/day waschosen for this study. Tablets without moringa seedextract, but containing dextrin as a substitute were used
as placebo. Composition of a single dose of treatment(moringa seed extract) and placebo are shown in Table 1.
There was no diﬀerence in appearance or ﬂavor between
the treatment and placebo tablets. Concerning to thesafety, a single-dose toxicity test (maximum dose 5,000
mg/kg), 90-days repeated dose toxicity test (maximum
dose 1,000 mg/kg/day), and teratogenicity test (maximum
dose 1,473 mg/kg/day) of studied moringa seed extract
showed no adverse effects. Further, a preliminary inhouse test with 120 mg of moringa seed extract (GMG;
12 mg) /day for two weeks also showed no adverse eﬀects(unpublished in-house data).

第 8 号（2019 年 8 月）

39 （607）

Table 1 Composition of single dose of treatment（Moringa
seed extract; MSE）and placebo（PLA）※.
Description（kcal）
Energy（g）
Protein（g）
Fat（g）
Carbohydrate
Sodium（mg）
Moringa seed extract（mg）└ Glucomoringin （mg）

Moringa seedextract
1.949
0.010
0.013
0.966
0.132
120
12

Placebo
1.956
0.001
0.013
0.978
0.034
0
0

※

Seven（7）tablets / day.
［MSE: 120 mg: 3 tablets（40 mg/ tablet）+
placebo 4 tablets］［PLA: placebo 7 tablets］

2.3. Participants
Healthy adult working men and women, aged 30-64 years
were recruited as paid volunteers. All participantsreceived explanatory documents and consent forms. The
purpose and the protocol procedures of the study were
thoroughly explained. Finally, the 112 subjects who
expressed consent were enrolled for the study.
As a preliminary examination, the subjects lifestyle
habit questionnaires, blood pressure, heart rate, height,
w e i g h t , b od y f a t , b od y m a s s i n d e x ( B M I ) w e r e
investigated. The severity of fatigue and physicaldiscomfort (low back pain, stiﬀ shoulder, and eye strain)
was rated on Visual Analog Scale (VAS) 22). Chalderfatigue scale ( Japanese version) 23) and Profile of Mood
States Short form 2 (POMS-2, Japanese version)24) werealso scored.
Inclusion criteria were (1) Japanese males and females
aged 30-64 years; (2) subjects who are healthy and are
not received treatment of disease; (3) subjects who have
daily fatigue; (4) subjects who have stiff shoulder, lowback pain, or eye strain derived from fatigue; (5) subjects
who work on daytime from Monday to Friday and have
Saturdays and Sundays off; (6) subjects whose written
informed consent has been obtained; (7) subjects who cancome to the designated venue for this study and be
inspected. (8) subjects judged appropriate for the study
by the principal investigator (Takahiro Ono, Ueno-Asagao
Clinic). Exclusion criteria were (1) subjects who havechronic fatigue; (2) subjects using medical products; (3)subjects who are patient or have a history of psychiatricdisease, high blood pressure, diabetes, andhyperlipidemia; (4) subjects who used a drug to treat a
disease in the past 1 month (except temporal usage forhay fever); (5) subjects who have a history of acute liverd y s f u n c ti o n , k i d n e y d a m a g e , h e a r t d i s e a s e a n dhematological disease; (6) subjects who are a patient or
have a history of or endocrine disease; (7) subjects whose40 （608）

診療と新薬・第 56 巻

第 8 号（2019 年 8 月）

Preliminary
examination（n ＝ 112）
Excluded（n ＝ 72）
Randomization（n ＝ 40）

Moringa seed extractgroup（T）（n ＝ 20）

Placebogroup（P）（n ＝ 20）

Completion of the study（n ＝ 40）
Eﬃcacy analysis
・（n ＝ 40）
〔T（n ＝ 20）; P（n ＝ 20）〕・Fatigue VAS scores ≧ median（63）（n ＝ 21）〔T（n ＝ 10）; P（n ＝ 11）〕
・Stiﬀ sholder VAS scores ≧ median（63）（n ＝ 22）〔T（n ＝ 11）; P（n ＝ 11）〕・Low Back pain VAS scores ≧ median（48）（n ＝ 20）〔T（n ＝ 12）; P（n ＝ 8）〕・Eye strain VAS scores ≧ median（66）（n ＝ 22）〔T（n ＝ 11）; P（n ＝ 11）〕
・Safty analysis（n ＝ 40）〔T（n ＝ 20）; P（n ＝ 20）〕

Figure 1

Systematic ﬂow chart of the study

BMI is over 30; (8) subjects with severe anemia; (9)subjects who are sensitive to a test product or otherfoods, and medical products; (10) subjects who
excessively take alcohol (expressed in an amount of
alcohol: over 60 mg/day); (11) subjects with possible
changes of life style, such as conducting a long-term
travel, during the test period; (12) subjects who had a
habit to ingest health-promoting foods, foods for speciﬁed
health uses, health foods, or supplements withcomponents contained in the test product in the past
three months or will ingest those foods during the test
period; (13) subjects who are or are possibly pregnant, or
are lactating; (14) subjects who participated in otherclinical studies in the past three months; (15) subjects
who are or whose family is engaged in functional foods orcosmetics company; (16) subjects judged inappropriate
for the study by the principal investigator.
2.4. Sample size
Based on the previous study that evaluated the eﬀects ofbroccoli-derived glucosinolates, structural analogs of
GMG on liver functions 25), we decided to recruit forty
participants (twenty in each intervention group) for thisstudy, which is theoretically necessary to detect a
diﬀerence (changes from baseline). The candidates werefirst screened according to the inclusion/exclusion
criteria, and then forty (n ＝ 40) subjects were recruitedin the order of total scores of VAS fatigue scores,
Chalder fatigue scale scores, and fatigue-inertia scoresof POMS-2.
2.5. Study design
The study was performed in a randomized, parallel,

double-blind, and placebo-controlled manner, and asystematical ﬂow chart of study protocol is illustrated in
Figure 1. The forty (n ＝ 40, M: 18; F: 22) participants
were randomly assigned to the moringa seed extract orplacebo supplementation groups using a stratified blockrandomization design stratified by age, fatigue VAS
scores, Chalder fatigue scale scores, and fatigue-inertia
scores of POMS-2. The allocation of subjects was
performed by TES Holdings Co., Ltd. (Tokyo, Japan),and the concerning information was concealed from boththe subjects as well as the investigators until thecompletion of the intervention study.
2.6. Schedule
The study was carried out at Ueno-Asagao Clinic (Taitok u, Tok yo) from F e b rua ry to Ma rc h 2019. The
participants took seven tablets every day after breakfast
for four weeks (see Table 1). During the study period,
subjects were instructed to maintain their usual lifestyleand refrain from taking pharmaceuticals (including
external preparation), quasi-drugs, Chinese medicine,and functional food, and in case of taking any of theabove, they were required to log in their daily log book.
Subjects were instructed to refrain from the excessive
exercise and alcohol consumption from the day before theclinic visit. The subjects were also instructed to log
details in the log book, including their tablets ingestion,
physical condition, use of pharmaceuticals, and any
adverse events.
During the study period of 1 to 3 weeks, the subjects
rated the severity of fatigue and physical discomfort on
VAS and Chalder fatigue scale at home every week after
the respective intervention. After four weeks, the診療と新薬・第 56 巻

第 8 号（2019 年 8 月）

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Table 2 Baseline characteristics of forty（n ＝ 40）subjects selected throughpreliminary examination.

（Male/Female）
Gender（years）
Age（kg）
WeightBody fat（％）（kg/m2）
Body Mass Index
Systolic blood pressure（mmHg）
Diastolic blood pressure（mmHg）
Heart rate
（bpm）
Fatigue VAS scores（mm）

Treatment group

Placebo group（n ＝ 20）（n ＝ 20）

9 / 1149.3 ± 3.5
62.5 ± 12.6
26.6 ± 6.6
22.6 ± 2.5
116.0 ± 12.9
71.8 ± 9.5
70.7 ± 9.1
63.1 ± 15.3

9 / 1148.9 ± 7.8
57.4 ± 9.5
24.4 ± 4.7
21.5 ± 2.0
116.7 ± 12.5
74.0 ± 9.0
72.0 ± 13.2
60.6 ± 11.9

Values represented as Mean ± SD.

subjects again visited the clinic and severity of fatigue(VAS, Chalder fatigue scale, POMS-2 questionnaires),blood pressure, heart rate, weight, body fat, BMI wasinvestigated, and a medical interview with study
physician was conducted.
The primary outcome was a subjective evaluation of
fatigue (rated with VAS, Chalder fatigue scale, POMS-2
questionnaires), and as the secondary outcome, thesafety of moringa seed extract was evaluated with bloodpressure, heart rate, weight, BMI, medical interview anddaily log book.
2.7. Methods of evaluation of fatigue
Visual Analog Scale (VAS): The subjects were instructed
to rate their fatigue level or physical discomfort level on
VAS from 0 (no fatigue) to 100 (extreme fatigue).
Chalder fatigue scale: A four-step questionnaire whichcontains 14 questions about the level of fatigue.
Profile of Mood States Short form 2 (POMS-2): A fivestep questionnaire which contains 65 questions that
describe seven different moods as follows: angerhostility , confusion-bewilderment , depressiondejection , fatigue-inertia , tension‒anxiety , vigoractivity and friendliness .
2.8. Statistical analysis
Values are presented as means ± standard deviations. As
a parametric test, we used the paired t -test for intragroupcomparison and the Student s t -test for intergroupcomparison. As the non-parametric test, the Wilcoxon
signed rank-test for intragroup comparison and the MannWhitney U -test for intergroup comparison were
employed. Additionally, to clarify the eﬀects of moringa
seed extract on the subjects with more severe symptoms,
we divided the subjects into subgroups with respect tothe median of each baseline VAS scores, and analyzed thegroups with abobe median baseline scores: higher fatigue
VAS scores subgroups, higher stiﬀ shoulder VAS scoressubgroups, higher low back pain VAS scores subgroups,

and higher eye strain VAS scores subgroups. Statisticalanalyses were performed using SAS (SAS 9.4) or SPSS
(Statistics 25) and p-value of ＜ 0.05 was considered to besigniﬁcant.
3. Results
3.1. The baseline characteristics of participants
The subjects were recruited from January 25, 2019 toFebruary 7, 2019. Of the forty subjects who participatedin this study, all subjects completed this trial, and no
subject was excluded from the analysis following the set
protocol (Figure 1). Table 2 lists the baselinecharacteristics of forty subjects selected thorough apreliminary examination (gender, age, weight, body fat,
BMI, systolic blood pressure, diastolic blood pressure,heart rate, fatigue VAS scores). There was no signiﬁcantdifference in any of the variables between the moringa
seed extract supplementation group and the placebogroup.
3.2. Eﬃcacy evaluation
Table 3 displays the VAS scores of fatigue, stiﬀ shoulder,
low back pain, and eye strain before the intake of moringa
seed extract treatment, and changes from the baseline at
1, 2, 3, and 4 weeks after the supplementation. Intake ofmoringa seed extract tablets led to the significantly
decreased respective VAS scores, whereas a certain levelof eﬀectiveness could also observed in the placebo group.
However, a signiﬁcant diﬀerence between the groups forthe estimated change in low back pain VAS scores frombaseline could be observed after 2 weeks; with themoringa seed extract group showing a marked decreasevalue (treatment: − 13.8 ± 23.2, placebo: 3.1 ± 16.4).
Also, the intervention of the treatment and the placebo
tablets led to the signiﬁcantly decreased many categories
of scores of Chalder fatigue scale and POMS-2, but there
was no significant difference between groups (data, notshown).

42 （610）

診療と新薬・第 56 巻

第 8 号（2019 年 8 月）

Table 3 VAS scores of fatigue and other physical discomfort parameters（n ＝ 40）
CategoryGroup

Baseline
ScoresChanges from the baseline（Median）

Week 1

Week 2

Week 3

Week 4

FatigueT（n ＝ 20） 63.1 ± 15.3
P（n ＝ 20） 60.6 ± 11.9

（63）

− 18.8 ± 21.1
− 10.2 ± 17.5

− 25.2 ± 18.4
− 14.4 ± 17.3

− 28.0 ± 19.4
− 16.6 ± 20.9

− 27.6 ± 22.5
− 17.4 ± 19.5

Stiﬀ shoulder

T（n ＝ 20） 61.7 ± 18.8
P（n ＝ 20） 61.7 ± 17.4

（63）

− 15.3 ± 21.0
− 15.7 ± 15.1

− 19.7 ± 19.6
− 14.4 ± 15.8

− 24.4 ± 21.2
− 17.0 ± 20.4

− 25.5 ± 22.8
− 22.7 ± 17.6

Low back pain

T（n ＝ 20） 49.1 ± 24.5
P（n ＝ 20） 36.7 ± 24.5

（48）

− 9.5 ± 21.6
− 2.1 ± 12.4

− 13.8 ± 23.2 ＊3.1 ± 16.4

− 18.3 ± 28.7
− 4.0 ± 16.5

− 17.5 ± 32.3
− 8.3 ± 15.0

Eye strain

T（n ＝ 20） 65.8 ± 17.1
P（n ＝ 20） 67.4 ± 11.1

（66）

− 9.6 ± 16.5
− 18.9 ± 20.1

− 19.3 ± 20.8
− 16.6 ± 19.7

− 19.4 ± 25.4
− 20.2 ± 21.6

− 28.2 ± 17.4
− 25.8 ± 21.7

Values represented as Mean ± SD.
T ＝ Moringa seed extract（Treatment）; P ＝ Placebo*p ＜ 0.05 between groups

Table 4 Analysis of VAS scores of the subjects with above median baseline scores※.
CategoryGroup

Baseline
ScoresChanges from the baseline
Week 1

Week 2

Week 3

Week 4

FatigueT（n ＝ 10） 74.9 ± 8.1
P（n ＝ 11） 68.8 ± 6.0− 31.5 ± 16.3
− 15.8 ± 20.5

− 33.2 ± 17.3
− 16.6 ± 20.3

− 36.6 ± 18.1
− 19.9 ± 24.6

− 43.4 ± 15.8 ＊− 18.7 ± 24.6

Stiﬀ shoulder

T（n ＝ 11） 75.3 ± 8.5P（n ＝ 11） 73.3 ± 9.4− 19.8 ± 22.3
− 17.0 ± 12.7

− 24.7 ± 22.8
− 18.8 ± 11.9

− 31.1 ± 24.9
− 26.0 ± 14.1

− 36.5 ± 23.9
− 27.8 ± 15.7

Low back pain

T（n ＝ 12） 65.9 ± 12.2
P（n ＝ 8） 60.3 ± 10.9

− 16.4 ± 19.4
− 7.6 ± 8.5− 23.1 ± 17.6 ＊＊− 6.0 ± 7.0− 32.4 ± 21.1 ＊− 10.4 ± 12.0

− 34.8 ± 19.5 ＊− 12.4 ± 14.8

Eye strain

T（n ＝ 11） 77.7 ± 8.1
P（n ＝ 11） 74.3 ± 9.8− 12.3 ± 12.9
− 26.8 ± 19.9

− 25.2 ± 16.3
− 20.7 ± 19.8

− 27.8 ± 20.5
− 19.9 ± 22.9

− 30.2 ± 18.0
− 31.2 ± 20.8

Values represented as Mean ± SD.
T ＝ Moringa seed extract（Treatment）; P ＝ Placebo※Baseline median values: Fatigue（63）, Stiﬀ shoulder（63）, Low back pain（48）, Eye strain（66）*p ＜ 0.05, **p ＜ 0.01 between groups

To clarify the eﬀects of moringa seed extract on subjects
with somewhat severe symptoms, we divided the subjects
into subgroups considering the median of each baseline
VAS scores and analyzed subjects with abobe medianbaseline scores. Table 4 shows the VAS scores of thesubjects with above median baseline scores. In the higher
fatigue VAS score subgroups, there was a significant
diﬀerence between the groups in respect to change fromthe baseline after 4 weeks; with the treatment group
showing a marked decrease value (treatment: − 43.4 ±
15.8, placebo: − 18.7 ± 24.6) (Figure 2). Whereas, in thehigher low back pain VAS score subgroups, there weresignificant differences between the groups in respect tochange from the baseline at week 2, 3, and 4; with thetreatment group showing a marked decrease values (atweek 2, treatment: − 23.1 ± 17.6, placebo: − 6.0 ± 7.0;
at week 3, treatment: − 32.4 ± 21.1, placebo: − 10.4 ±

12.0; at week 4, treatment: − 34.8 ± 19.5, placebo: −12.4 ± 14.8) (Figure 3). Therefore, it can be postulated
that the supplementation of moringa seed extract
mitigated the severity of fatigue and low back pain among
the subjects with somewhat severe symptoms.
3.3. Safety
There was no report of any adverse event resulting fromthe intake of the treatment tablets. Some relativechanges in body weight, BMI, heart rate were observedin the moringa seed extract treatment group. However,these were within normal limits of daily variation andwere not considered to be due to moringa seed extract by
the principal investigator.

診療と新薬・第 56 巻

Treatment

20
10

10

0

0

−10
−20
−30

*

−40
−50

43 （611）

Treatment

20

PlaceboΔLow back pain VAS

ΔFatigue VAS

第 8 号（2019 年 8 月）

Placebo

−10
**
−20

*

*

−30
−40
−50

−60

−60
Initial

1w

2w

3w

4w

InitialTreatment: moringa seed extract
Values represented as Mean ± SD.
*p ＜ 0.05 between groups

Figure 2 Changes in fatigue VAS scores of the subjects
with abobe median baseline scores during the study
period.

4. Discussion
In the present study, we evaluated the eﬀect of moringa
seed extract on daily fatigue in a randomized, parallel,
double-blind, and placebo-controlled study. The results
indicated that moringa seed extract mitigated fatigue andlow back pain in the subjects whose symptoms were
somewhat severe in the treatment group compared to theplacebo group. It has been demonstrated that oxidative
stress is one of the main factors leading to fatigue 26). In
the human body, the reactive oxygen species (ROS) are
generated and in normal condition usually disappears
rapidly. However, when cellular overproduction of ROS
overwhelms intrinsic antioxidant capacity, the oxidative
stress occurs, and the damage to the biomolecules ofnormal cells and tissues might occur 27). ROS increases
oxidized proteins, and lipid peroxides inhibit normal cellfunction and cause inﬂammation, which causes increased
fatigue and physical discomfort 28)29). This suggests that
supplementation of antioxidants that capable to reduce
ROS could potentially contribute to fatigue recovery.
Moringa seed extract used in this study contains GMG,
which is considered to be converted to moringin by hostgut microbiota. In the previous study, moringin has beenshown to mitigate the increase of intracellular oxidative
stress induced by H 2 O 2 on retinoic acid-induced
differentiated neuroblastoma cells 17). Moringin pretreated neuron cells showed signiﬁcant resistance to H2O2
-induced apoptotic cell death, revealing a high level of

1w

2w

3w

4w

Treatment: moringa seed extract
Values represented as Mean ± SD.
*p ＜ 0.05, **p ＜ 0.01 between groups

Figure 3

Changes in low back pain VAS scores of thesubjects with abobe median baseline scores during
the study period.

antioxidative effect 17). Moringin was also shown toincrease antioxidant Nrf2 expression, suppress theprimary inflammatory mediators, and regulate T-cell
activation in a mouse model of experimental autoimmune
encephalomyelitis 30). Moringin was also reported tomodulate not only the inflammatory pathway, but alsooxidative stress and apoptotic pathways in a mouse modelof subacute of Parkinson s disease 18). Related findings
suggest the antioxidant and anti-inflammatory effects ofmoringin could be considered as a postulated mechanismof the anti-fatigue effect of moringa. Anti-fatigue
characteristics of moringa leaves extract have alreadydemonstrated in rats subjected to a forced swimming
endurance test, along with enhancing the activity ofantioxidant enzymes, and lowering the bloodconcentration of malondialdehyde, a signiﬁcant marker ofoxidative stress 20). Additionally, in our previous in vitro
study with cell culture, wherein GMG extracted frommoringa seeds was further converted by the enzyme into
moringin, and showed activation of PPARβ/δ 21) .
Activation of PPARβ/δ has been reported to be involvedin the improvement of muscle endurance 31)〜33), and might
be considered as another mechanism of the anti-fatigue
eﬀect of moringa. In reference to the above reports, thefatigue and low back pain improvement eﬀects of moringa
seed extract of this human clinical study are likely due tothe combined effects of antioxidant, anti-inflammatory,
and activation PPARβ/δ activities of GMG contained inmoringa seed extract. Therefore, GMG is suggested to
be a primary component involved in lowering the severity44 （612）

診療と新薬・第 56 巻

of fatigue, and low back pain originated from antioxidant
activity.
Noteworthy to mention that a certain level of
effectiveness could be observed in the placebo group of
this study, which could be attributed to fatigue feelings
that were influenced by respective environmental andphysiological parameters. This could be a one of thepossible reason that the impact of moringa seed extract
was not appropriately evaluated due to the above
mentioned positive influence of placebo. Since thepresent study targeted at healthy subjects who feel
temporary fatigue, it might be difficult to assess thedesired effect. However, among the subjects withsomewhat severe fatigue symptoms, the placebo intake
did not influence fatigue and low back pain alleviating
effects over time, whereas moringa seed extract intake
showed a considerable impact. The ﬁnding supports theeﬀectiveness of moringa seed extract on fatigue and low
back pain.
Concerning the safety, no adverse events or any side
eﬀects could be noticed during the moringa seed extract
intervention period. Thus, considering the safety
viewpoint, the consumption of 120 mg of moringa seedextract (GMG; 12 mg) /day for four consecutive weeks isfound very safe.
5. Conclusion
The results of the present study demonstrated thatintervention of moringa seed extract was found eﬀective
in lowering the severity of fatigue as well as low backpain in the subjects whose symptoms were somewhat
severe among the healthy working men and women of
middle age. However, further comprehensive studies areneeded to design with a large sample size and diversity ofthe population to evaluate the potential of moringa seedextract and related products.
【Conﬂict of interest statement 】
Taiyo Kagaku Co., Ltd. provided the funding for this study, and there areno other conﬂicts of ﬁnancial interests to declare.

References
1) Ministry of Health L and W. An overview of the survey on actual
conditions concerning technological innovation and labor in 2003.
2003.
2) Gopalakrishnan L, Doriya K, Kumar DS. Moringa oleifera: A review
on nutritive importance and its medicinal application. Food Sci Hum
Wellness. 2016; 5: 49-56.
3) Mahmood KT, Mugal T, Haq IU. Moringa oleifera: A natural gift-a
review. J Pharm Sci Res. 2010; 2: 775-81.
4) Kuete V. Moringa oleifera. In: Medicinal Spices and Vegetables fromAfrica: Therapeutic Potential Against Metabolic, Inflammatory,
Infectious and Systemic Diseases. 2017.
5) Razis AFA, Ibrahim MD, Kntayya SB. Health benefits of Moringa
oleifera. Asian Paciﬁc Journal of Cancer Prevention. 2014.
6) Anwar F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: A food plantwith multiple medicinal uses. Phytotherapy Research. 2007.
7) Cirmi S, Ferlazzo N, Gugliandolo A, Musumeci L, Mazzon E, BramantiA, et al. Moringin from Moringa Oleifera Seeds Inhibits Growth,

第 8 号（2019 年 8 月）
Arrests Cell-Cycle, and Induces Apoptosis of SH-SY5Y Human
Neuroblastoma Cells through the Modulation of NF-κB and Apoptotic
Related Factors. Int J Mol Sci. 2019; 20: 1930.
8) Chan Sun M, Ruhomally ZB, Boojhawon R, Neergheen-Bhujun VS.
Consumption of Moringa oleifera Lam Leaves Lowers Postprandial
Blood Pressure. J Am Coll Nutr. 2019; 7: 1-9.
9) Mabrok HB, Mohamed MS. Induction of COX-1, suppression of COX-2
and pro-inflammatory cytokines gene expression by moringa leaves
and its aqueous extract in aspirin-induced gastric ulcer rats. Mol Biol
Rep. 2019; 46: 4213-24.
10) Dollah S, Abdulkarim SM, Ahmad SH, Khoramnia A, Mohd Ghazali H.
Physico-chemical properties of Moringa oleifera seed oil enzymaticallyinteresteriﬁed with palm stearin and palm kernel oil and its potential
application in food. J Sci Food Agric. 2016; 96: 3321-33.
11) Zeng K, Li Y, Yang W, Ge Y, Xu L, Ren T, et al. Moringa oleifera
seed extract protects against brain damage in both the acute anddelayed stages of ischemic stroke. Exp Gerontol. 2019; 122: 99-108.
12) Ogbunugafo HA, Eneh FU, Ozumba AN, Igwo-Ezikp MN, Okpuzor J,
Igwilo IO, et al. Physico-chemical and Antioxidant Properties ofMoringa oleifera Seed Oil. Pakistan J Nutr. 2011; 10: 409-14.
13) Shindano J, Kasase C. Moringa (Moringa oleifera): A source of foodand nutrition, medicine and industrial products. ACS Symp Ser. 2009;
1021: 421-67.
14) Galuppo M, Nicola G, Iori R, Dell Utri P, Bramanti P, Mazzon E.
Antibacterial Activity of Glucomoringin Bioactivated with Myrosinaseagainst Two Important Pathogens Aﬀecting the Health of Long-Term
Patients in Hospitals. Molecules. 2013; 18: 14340-8.
15) Tian S, Liu X, Lei P, Zhang X, Shan Y. Microbiota: a mediator totransform glucosinolate precursors in cruciferous vegetables to theactive isothiocyanates. J Sci Food Agric. 2018; 98: 1255-60.
16) Giacoppo S, Soundara Rajan T, De Nicola GR, Iori R, Bramanti P,
Mazzon E. Moringin activates Wnt canonical pathway by inhibiting
GSK3β in a mouse model of experimental autoimmune
encephalomyelitis. Drug Des Devel Ther. 2016; 10: 3291-304.
17) Jaafaru MS, Nordin N, Shaari K, Rosli R, Abdull Razis AF.
Isothiocyanate from Moringa oleifera seeds mitigates hydrogen
peroxide-induced cytotoxicity and preserved morphological features ofhuman neuronal cells. Gallyas F, editor. PLoS One. 2018; 13:e0196403.
18) Giacoppo S, Rajan TS, De Nicola GR, Iori R, Rollin P, Bramanti P, etal. The Isothiocyanate Isolated from Moringa oleifera Shows Potent
Anti-Inflammatory Activity in the Treatment of Murine Subacute
Parkinson s Disease. Rejuvenation Res. 2017; 20: 50-63.
19) Rajan TS, De Nicola GR, Iori R, Rollin P, Bramanti P, Mazzon E.
Anticancer activity of glucomoringin isothiocyanate in humanmalignant astrocytoma cells. Fitoterapia. 2016; 110: 1-7.
20) Lamou B, Taiwe GS, Hamadou A, Abene, Houlray J, Atour MM, et
al: Antioxidant and Antifatigue Properties of the Aqueous Extract ofMoringa oleifera in Rats Subjected to Forced Swimming Endurance
Test. Oxid Med Cell Longev. 2016; 2016: 1-9.
21) Shimizu K, Sugiura K, Nakata R, Inoue H. Anti-fatigue effects ofMoringa oleifera seed extract. 2019 Annu Meet Japan Soc Biosci
Biotechnol Agrochem. 2019;22) Maxwell C. Sensitivity and accuracy of the visual analogue scale: apsycho-physical classroom experiment. Br J Clin Pharmacol. 1978; 6:
15-24.
23) Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, WrightD, et al. Development of a fatigue scale. J Psychosom Res. 1993; 37:
147-53.
24) Heuchert J, McNair DM. POMS 2® - Proﬁle of Mood States Second
Edition® ¦ Multi Health Systems (MHS Inc.).
25) Kikuchi S, Aoki Y, Aizawa K, et al. Eﬀects of Broccoli Sprout Extract
Supplement on Liver Functions in Healthy Subjects ―A Multicenter,
Randomized, Double‒blind, Placebo‒controlled, Parallel‒group
Comparative Study―. Jpn Pharmacol Ther. 2018; 46: 81-95.
26) Reid MB. Reactive oxygen species as agents of fatigue. Med Sci
Sports Exerc. 2016; 48: 2239-46.
27) Dröge W. Free Radicals in the Physiological Control of Cell Function.
Physiol Rev. 2002; 82: 47-95.
28) Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL.
Blood parameters indicative of oxidative stress are associated withsymptom expression in chronic fatigue syndrome. Redox Rep. 2000;
5: 35-41.

診療と新薬・第 56 巻
29) Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch
JJF. Oxidative stress levels are raised in chronic fatigue syndrome andare associated with clinical symptoms. Free Radic Biol Med. 2005; 39:584-9.
30) Galuppo M, Giacoppo S, De Nicola GR, Iori R, Navarra M, Lombardo
GE, et al. Antiinﬂammatory activity of glucomoringin isothiocyanate
in a mouse model of experimental autoimmune encephalomyelitis.
Fitoterapia. 2014; 95: 160-74.
31) Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J,
Rassoulzadegan M, Grimaldi PA. Peroxisome proliferator-activated

第 8 号（2019 年 8 月）

45 （613）

receptor δ controls muscle development and oxidative capability.
FASEB J. 2003; 17: 2299-301.
32) Gan Z, Burkart-Hartman EM, Han D-H, Finck B, Leone TC, Smith
EY, et al. The nuclear receptor PPARβ/δ programs muscle glucose
metabolism in cooperation with AMPK and MEF2. Genes Dev. 2011;
25: 2619-30.
33) Fan W, Waizenegger W, Lin CS, Sorrentino V, He M-X, Wall CE, etal. PPARδ Promotes Running Endurance by Preserving Glucose.
Cell Metab. 2017; 25: 1186-1193.e4.