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Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies

Authors:
  • Innoscience Research

Abstract

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as “Eurycoma longifolia”, “EL”, “Tongkat Ali”, “male sexual health”, “sexual infertility”, “erectile dysfunction”, “male libido”, and “testosterone levels”. Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.
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Chinese Journal of Natural Medicines 2017, 15(1): 0071
0080
Chinese
Journal of
Natural
Medicines
Eurycoma Longifolia as a potential adoptogen of male sexual
health: a systematic review on clinical studies
Hnin Ei Thu 1, Isa Naina Mohamed 1, Zahid Hussain 2, Putri Ayu Jayusman 1, Ahmad Nazrun Shuid 1*
1 Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia (The National University of Malaysia),
Jalan Yaacob Latif 56000, Malaysia;
2 Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam
42300, Malaysia
Available online 20 Jan. 2017
[ABSTRACT] Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades,
numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in
managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testoste-
rone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clini-
cal significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following
databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using
search terms such as “Eurycoma longifolia”, “EL”, “Tongkat Ali”, “male sexual health”, “sexual infertility”, “erectile dysfunction”,
“male libido”, and “testosterone levels”. Notably, only human clinical studies published between 2000 and 2014 were selected and
thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were
randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL
on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the
treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary,
there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of
current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual
disorders.
[KEY WORDS] Eurycoma Longifolia; Male sexual disorders; Erectile dysfunction; Male infertility; Sexual libido; Testosterone
[CLC Number] R969 [Document code] A [Article ID] 2095-6975(2017)01-0071-10
Introduction
Sexual health impacts the quality of life of males and
females significantly, regardless of age, civil status, or sexual
orientation. Sexual activity involves systematic coordination
between various biological systems of the body. For example,
hormones and neurological pathways must be in sync to per-
form sexual activities. Males in addition require blood vessels,
[Received on] 17- Jan.-2016
[Research funding] This work was supported by the Ministry of
Agriculture for providing New Application for Herbal Research Grant
Scheme (NRGS) (No. NH1014D040).
[*Corresponding author] Tel: 6(0)391459567; Fax: 6(0)291459547;
E-mail: anazrun@yahoo.com
These authors have no conflict of interest to declare.
Copyright © 2017, China Pharmaceutical University.
Published by Elsevier B.V. All rights reserved
nerves, and penile integrity to be intact for an adequate erec-
tion and its continuance while performing sexual activities. Si-
milarly, physiological coordination among muscles and nerves
also play a pivotal role in regulating ejaculation of sperms
from the testicles [1-2].
Sexual dysfunction (inability to have pleasing sexual ac-
tivity) negatively affects the quality of life and can be the
leading cause of numerous medical or psychological dis-
tresses [3-4]. According to the Sexual Advice Association, one
in 10 men experiences sexual problems [5]. Hence, any sexual
complaint should be taken seriously and evaluated by partic-
ular health care specialist by assessing the entire possible
nuisance associated with sexual desire, penile erection, ejacu-
lation, and orgasm. In this chain of events, the most promi-
nent male sexual dysfunctions include erectile dysfunction
(ED), premature ejaculation (PE), low libido (reduced sexual
desire) as well as low level of testosterone (male sex hormone)
[6].
Hnin Ei Thu, et al. / Chin J Nat Med, 2017, 15(1): 7180
– 72 –
In male sexual well-being, one of the primary causes of
dissatisfaction in sexual performance is attributed to ED,
which is defined as frequent and persistent incapability of
male to retain penile erection during the course of performing
sexual activity [1-2, 7]. Previously published data have hig-
hlighted that the prevalence of ED is greatly influenced by
age [8]. ED affects approximately 30 million men in the Unit-
ed States, and among them, 18% are from 50 to 59 years of
age. The highest ED prevalence of 50% and 75% occurs in
70’s and 80’s of age worldwide [7-8]. There are numerous po-
tential causes of ED, including neurological, vascular, hor-
monal, pharmacological, and psychiatric causes. The thera-
peutic intervention of ED greatly depends on the identifica-
tion of precise cause of sexual dysfunction. However, before
considering pharmacological intervention, medical profes-
sionals often suggest lifestyle changes, such as anticipating regu-
lar exercise, a healthy diet, smoking cessation, and restraining
alcohol intake [9]. Lifestyle changes can also include the use
of a more genitalia-friendly bicycle seat [9]. Several pharma-
cological therapies are available for the symptomatic man-
agement of ED; among them, phosphodiesterase-5 (PDE-5)
inhibitors, such as sildenafil, verdenafil and tadalafil, have
gained remarkable attention [10-11]. These drugs improve and
maintain satisfactory penile erection by regulating the blood
flow to the penis. Several side effects, such as visual distur-
bances, flushing, back pain, and muscle pain associated with
the use of PDE-5, have left many men to turn to more natural
options for the management of sexual problems [12-13].
Another common ejaculatory disorder is PE, manifesting
as an inappropriate ejection of sperm, prostatic, and seminal
fluid via urethra. The prevalence of PE approximates 20% to
30% of men [9]. Among various potential causes of PE, the
prominent problems are associated with the central control of
ejaculation, innervations to the seminal tract, and sensory
innervations to the genitalia/prostate [1-2]. In addition, PE can
also appear as an early indicator of diabetes mellitus or may
develop following surgical intervention of benign prostatic
hyperplasia or can be associated with the use of certain medi-
cations such as alpha-blockers or antidepressants [10-12].
An additional sexual disorder affecting the quality of life
globally is male infertility. It is a multi-factorial disorder with
numerous causative factors manifesting as impaired sperma-
togenesis, low sperm count, erection or ejaculation issues, and
hormonal dysfunction [14-15]. The prevalence of the problem
which lies solely in the male partner, accounts for about one
in five infertile couples [16-17]. The numerous health issues and
medical problems associated with male infertility include
varicocele (swelling of veins that drain testicle), undescended
testes, infections, hormonal imbalance, sperm duct defects,
ejaculation issues, and sperm antibodies [18]. Certain lifestyles
such as the use of anabolic steroids, alcohol consumption,
tobacco smoking, emotional stress, obesity and prolonged
bicycling can also significantly contribute to the development
of male infertility [18]. Low libido which is solely associated
with low testosterone is another male sexual disorder. Most
males notice considerable downfall in testosterone levels and
thus sexual performance by the age 60 to 65. The penis takes
longer to erect and may not have normal hardness score,
which in turn affects male orgasm and ejaculatory cycle [19-23].
Eurycoma longifolia (EL) Jack, from family Simaroubaceae,
has attained remarkable recognition in Malaysia, Thailand
and Indonesia as a potential natural herbal medicine in the
improvement of male sexual disorders and infertility [24-27].
The remarkable attention of researchers to EL is based on its
aphrodisiac prospective, which is the ability to improve libido,
restore ED, and stimulate production of testosterone [28-29],
thus improving the overall male sexual well-being [30-32]. The
possible mechanism involved in improving male sexual per-
formance is associated with increased conversion of pregne-
nolone to progesterone, cortisol, 5-dehydroepiandrosterone
(DHEA), and testosterone in corpus cavernosum tissues [30-32].
In an attempt to better understand the underlying mechanism
of action, different fractions of EL root extract have been
tested for their effects on sexual function, using in vivo rat
models [30-31]. The extracted data highlight that eurypeptide, a
bioactive component of EL root extract, exhibits aphrodisiac
effects prominently by elevating the testosterone levels [30-31].
In addition, human clinical investigations on EL have also
shown other beneficial effects on male sexual health [26-27] as
well as its action as an “energy-booster” [33].
To date, there have been numerous studies highlighting
the clinical significance of EL in the treatment of male sexual
health disorders [26-27, 33, 35]. The impact of EL in managing
male sexual dysfunctions is mainly studied using in vivo ani-
mal models [28-32]; however, only limited clinical researches have
been carried out in human clinical trials [26-27, 34-38]. More clinical
data related to EL and male sexual health are required to draw
the attention of modern society and increase the awareness
towards EL. Thus, the present systematic review was de-
signed to summarize up-to-date researches on the clinical
significance of EL in the management of male sexual health
disorders. This systematic review would provide meaningful
baseline information for future work and commercialization.
Methods
Literature search strategy
The terms, including “Eurycoma Longifolia”, “EL”,
“Tongkat Ali” “male sexual health”, “male infertility”, “erectile
dysfunction”, “male libido” and “testosterone levels”, were
used to search the following databases: Medline, Wiley On-
line Library, BioMed Central, Hindawi, Web of Knowledge,
PubMed Central and Google Scholar. All the retrieved articles
were carefully screened for relevant citations in 2015.
Inclusion criteria
Original research articles, multiple cohort studies, ran-
domized and placebo-controlled trials and randomized cross
pilot studies regarding human clinical trials focusing on the
impact of EL on male sexual health were included. In order to
Hnin Ei Thu, et al. / Chin J Nat Med, 2017, 15(1): 7180
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assess the potential of EL on male sexual health, the principle
parameters focused in the present systematic review included
physical damage of sexual organ and clinical parameters such
as erectile dysfunction, male infertility, low male sexual libi-
do and low level of male sex hormone (testosterone).
Exclusion criteria
Case reports, case series, in vitro studies, in vivo animal
studies, news, letters to the editor, review articles and clinical
trials on women sexual health were excluded. In case of simi-
lar studies in concurrent publications, only the most recent
publications were included. The data presented in the current
systematic review is focused on the effect of EL on the male
sexual health; the data on its effect on other diseases were not
taken into account. Studies which also investigated other die-
tary supplements, herbal extracts, and the modern drugs used
as natural male sex boosters were also excluded.
Eligibility criteria
The searched articles and studies were reviewed for eli-
gibility based on their titles and abstracts and classified into
two categories. Category 1 included articles revealing
significant correlation between male sexual health and EL
with potential outcomes including biochemical parameters
and human clinical siginficance trials. Category 2 included
articles reporting disease mechanism, organ damage, and
major factors contributing to male sexual disorders. In
Category 1 there were variations in the study design, sample
size or aims towards the management of male sexual health
disorders via EL supplementation without serious side effects.
All the articles did not report on significant serious side
effects. All the searched articles in Category 1 and Category 2
were obtained in full text version and assessed by all authors
for relevant selection. Only articles which were agreed upon
by all authors were concomitantly included in the present
systematic review. Fig. 1 presents a summary of the process
for the selection of articles.
Review method
The articles potentially meeting the inclusion criteria
with independent citations were identified and screened by
the three reviewers (H.E.T, A.N.S, and I.N.M). The articles
with full text versions were included in the present review
after they were agreed upon by all the reviewers following
detailed discussion (H.E.T, P.A.J, Z.H, A.N.S, and I.N.M).
Any kind of disagreement with regard to inclusion criteria
was resolved by discussion with third and fourth reviewers
(A.N.S and I.N.M).
Data extraction
Following an inflexible selection, the published articles
were extracted and deliberated thoroughly. After an efficient
overview of the selected studies, the data such as country
name, year of publication, type of male sexual health disorder,
study design, type of study, sample size, and significant find-
ings were extracted. For systematic description, the scope,
components and key features of each of the selected studies
were also extracted. Additionally, for any other supplementary
information required, the authors were contacted via email or
telephone call. Regarding the articles which cited previous
publications, the original publication was retrieved, and the
relevant data were extracted. The extracted data with a P val-
ue less than 0.05 was recorded as statistically significant.
Results
More than 150 articles related to EL, male sexual disord-
ers, and pharmacodynamic profiles of EL in association with
male sexual health were obtained by computer search. The
majority of these articles were original research articles, sys-
tematic reviews, literature reviews, multiple cohort studies,
randomized and placebo-controlled trials, pilot studies, case
series, and case reports. Notably, the current systematic re-
view did not include articles published earlier than 2000.
Moreover, a significant number of articles on in vitro cell
culture studies and in vivo animal models were excluded.
The following articles were also excluded: (a) study design
that was not clearly described, (b) treatment of male sexual
disorders involving other herbal or dietary supplements, (c)
use of other modern drugs as male sex boosters, and (d) una-
ble to retrieve the full text version.
Eventually, a total of 7 human clinical trials [35-36, 38, 41, 47-49]
were found eligible to be included in the present systemic
review. Most of these studies were original research articles,
randomized and placebo-controlled trials, multiple cohort
trials and pilot studies. Notably, most of the reported stu-
dies were performed in Malaysia, followed by United
States of America (USA), China, and South Africa. The
sample sizes varied from 13 to 350 subjects with ages
ranging from young adults (30 years) to elderly (72 years).
Notably, the aim of the human clinical trials included in the
present systematic review was to evaluate the therapeutic
potential of EL for the treatment of male sexual disorders,
with penile erection, penile hardness, male sexual libido,
male infertility, and determination of the testosterone level
being the prime therapeutic concerns in the majority of
the studies. The key data of the selected studies are hig-
hlighted in Table 1.
Effect of EL on ED
Among the included human clinical trials, two were aimed
to determine the considerable association between the used EL
and the effects on ED [35-36]. Udani and co-workers [35] executed a
double-blind and placebo-controlled study in 40 to 65 years old
males having significant ED and followed them up for
12-weeks. The outcomes measured included penile erection,
sexual pleasure, sexual performance, erectile hardness
scores and sex intended frame of mind. A remarkable
improvement was found in the sexual intercourse attempt
diary, scores of penile erection hardness, and sexual
well-being of subjects (P < 0.05; paired t-test). Substantially,
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Fig. 1 Selection criteria: The algorithm for the selection of human clinical studies in the present systematic review
no significant abnormalities in the vital organs of the body
such as liver and kidney were noted by laboratory evalua-
tions.
Another randomized and placebo-controlled parallel de-
sign study also reported a positive effect of EL on ED [36].
Tambi and co-workers executed this study with the aim to
compare the clinical effects of EL in the management of
male sexual health with placebo groups. For that, 30
healthy male participants between the age of 40 and 65
years were recruited. Participants were required to be in a
stable heterosexual relationship for at least six months.
Both partners had to agree to attempt intercourse at least
once a week, on average, during the study. They observed
noteworthy improvement in sexual performance, including
erectile function, sexual intercourse performance, and
penile hardness score (P < 0.05, paired t-test).
Effect of EL on male infertility
In order to investigate the effect of EL on male infertility,
Tambi and co-workers [38] conducted a placebo-controlled
trial on 350 males with an average age of 32.7 years and hav-
ing a history of idiopathic infertility of 5.3 years. A daily dose
of 200 mg of soluble extract of EL was given to all patients
with subsequent analysis of semen every 3 months for a total
period of 9 months. The clinical significance of EL in male
infertility was evaluated by assessing the principle parameters
of fertility, such as semen volume, concentration of sperms,
proportion of sperms having normal morphology and motility
in accordance to World Health Organization (WHO) guide-
lines [39]. The results showed significant (P < 0.05, paired
t-test) improvement in all the seminal parameters and 11 (ap-
prox. 15%) spontaneous pregnancies. Tambi et al.[40] had also
highlighted an indirect effect of EL on men’s sexual health by
down-regulating stress hormone profile correlated with male
sexual performance.
In addition, Ismail and co-workers [41] had conducted a
12-week, randomized, and placebo-controlled trial on Malay
males according to the Good Clinical Practice (ICH-6) guide-
lines and Declaration of Helsinki. This placebo-controlled
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Table 1 Summary of the selected studies showing promising potential in improving male sexual disorders
Year
of
Publi-
cation
Country Major effect Sample size
and Age Subject state Study
duration
Study de-
sign EL form
EL
dosing
regimen
Outcomes Ref.
2014 Malaysia Improvement
in penile erec-
tion
109
(4065
years)
Healthy males +6
months
Double
blind/ Mul-
tiple cohort
study
Wat e r
extract
300 mg
daily
A significant (P < 0.05)
increment in penile erection
and sexual libido
(8.4%8.7%).
A remarkable improvement in
p
rinciple sexual parameters,
including penile hardness,
p
enile erection scores, and
sexual libido.
[35]
2012 Malaysia Increase in sex
hormone and
penile erection
320
(3064
years)
Hypogonadic
males
16
months
Multiple
cohort study
Wat e r
soluble
extract
200 mg
daily
A significant (P < 0.000 1)
increase in testosterone level.
N
oteworthy improvement in
sexual performance, including
erectile function, sexual
intercourse performance,
and penile hardness.
[36]
2010 Malaysia Male fertility 350
(4564
years)
Sub-fertile
couples with
idiopathic
infertility
9 months Pla-
cebo-control
led trial
Wat e r
soluble
extract
200 mg
daily
A significant (P < 0.05)
increase in principle
p
arameters of fertility such
as semen volumes, sperm
concentrations, percentage
of sperm morphology, and
sperm motility.
11 (approx. 15%) spontaneous
p
regnancies.
[38]
2012 Malaysia Male fertility 109
(3055
years)
Healthy male 6 months Double
blind / mul-
tiple cohort
study
Wat e r
extract
300 mg
daily
A significant (P < 0.05)
improvement in principle
seminal parameters, including
semen volume, sperm motility,
sperm concentration, and
sperm morphology.
[41]
2013 USA Increase in
testosterone
level and male
sexual libido
63
(4565
years)
Moderately
psychological
stressed male
24 weeks Multiple
cohort study
Hot water
soluble
extract
200 mg
daily
Protective effect of EL on
testicles and produce
ro-fertility effects.
A considerable (P < 0.05)
increase in testosterone level
in all sub-fertile men.
Improvement in male sexual
libido and sexual performance.
[47]
2014 South Af-
rica
Increase testos-
terone and
ergogonic effect
13
(5772
years)
Physically
stable
5 weeks Pilot study Wat e r
extract
400 mg
daily
A significant (P < 0.05)
increase in total and free
testosterone concentrations.
[48]
2014 Malaysia,
China and
South Af-
rica
Increase testos-
terone level
44
(> 60 years)
Hypogonadic
elderly male
12 weeks Pla-
cebo-control
led trial
Wat e r
soluble
extract
300 mg
daily
E
L as natural alternative to
conventional testosterone
replacement therapy.
Adaptogen to restore serum
testosterone level.
Significantly improved sex-
ual health in males older than
60 years.
[49]
2014 Malaysia Increase testos-
terone and male
sexual libido
109
(3064
years)
Healthy males +6 months Double
blind clini-
cal trial
Wat e r
extract
300 mg
daily
Substantial improvement in
male sexual libido.
A significant (P < 0.05)
increase in male sex hormone,
p
enile erection, and sexual
libido.
[35]
2012 Malaysia Increase in sex
hormone and
male sexual
libido
320
(3064
years)
Hypogonadic
male
16
months
Double
blind clini-
cal trial
Wat e r
soluble
extract
200 mg
daily
A significant (P < 0.000 1)
increase in testosterone level.
Improvement in sexual
Performance, including
erectile function, sexual
intercourse performance, and
p
enile hardness.
[36]
trial was performed on 109 randomized males between the ages
of 30 to 55 years. The subjects ingested 300 mg of EL daily.
They demonstrated significant improvement in sexual libido,
sexual activities, and sexual satisfaction with considerably
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positive effects on seminal parameters, including volume and
concentration of sperms in ejaculate and the proportion of
sperms having normal motility [41]. The outcomes of this ran-
domized trail demonstrate the positive effect of EL on male
fertility.
Effects of EL on testosterone level and male sex libido
Several studies were performed in men to evaluate the
effect of EL on testosterone levels and male sex libido [45-46].
Since there were a paucity of data supporting the potential
role of EL in boosting testosterone level and sexual well-
being, a clinical placebo-controlled trial was conducted by
Talbott et al. [47]. The trial was carried out in 63 subjects by
supplementing them with daily 200 mg of standardized
hot-water extract of EL daily for 4 weeks. Talbott and
co-workers noticed significant improvements in testosterone
status (+ 37%) in EL treated subjects with subsequent en-
hancement in sexual activities and well-being [47]. Another
clinical trial investigating the clinical effects of EL on testos-
terone level and age-related sexual impotence was performed
by Henkel et al. [48]. In this reported study, 400 mg of EL
(water extract) was supplemented daily to 13 physically ac-
tive males aged between 57 to 72 years for 5 weeks. Total free
and bound testosterone, cortisol, dihydroepiandrosterone and
sex hormone-binding globulin (SHBG) were analyzed as the
principle parameters. Henkel and co-worker [48] noticed re-
markable increases in the free and bound form of testosterone
in all patients. The increased level of male sex hormone, in
the later phase, produced considerable effects on male sexual
performance and sex libido.
The clinical significance of EL in improving male sexual
libido and testosterone levels has also been supported by other
published clinical studies [35-36, 49-50]. Udani et al. [35] hig-
hlighted noteworthy (P < 0.05; paired t-test) improvement in
the majority of sexual parameters, including sexual inter-
course performance, concentration of male sex hormone, sex
libido, and overall sexual well-being for all the subjects.
Tambi and co-workers [36] also supported the testosterone-
enhancing and sexual performance improving effects of
EL by emphasizing substantial (P < 0.05, paired t-test) im-
provement in testosterone level, erectile function, sexual in-
tercourse performance, and penile hardness. In addition,
George et al. [49] presented remarkable significance of EL an
adaptogen to restore serum testosterone levels, compared to
conventional regimen such as testosterone replacement thera-
py. George and co-workers further highlighted the feasibility
of EL in improving male sex libido in 60-years-old patients
having 40%50% lower testosterone level than young ones.
The clinical superiority of EL, compared to other testoste-
rone-enhancing and sexual boosting regimens, has also been
supported by Cyranoski [50].
Discussion
EL, a well-recognized herbal plant in the South-East
Asian countries, is used as a popular medicinal herb for the
treatment of sexual dysfunctions and improvement of sexual
health. Despite having many traditional evidences, it is still
lacking robust data from human clinical studies. It has been
used for the treatment of various sexual dysfunctions in males;
nevertheless it is noteworthy that the majority of research was
exclusively based on in vivo animal studies with limited data
available on human studies. Toxic effects, drug interactions or
negative clinical trial results may hamper human based clini-
cal studies being carried out on EL.
The data summarized in the present systematic review
revealed substantial evidences for the firm association be-
tween the use of EL and the effects on male sexual health
disorders in humans. It is noteworthy that the clinical signi-
ficance of EL has been demonstrated in term of managing
various male sexual disorders, including erectile dysfunction
[35-36], male infertility, and low sexual libido [38, 41], with rela-
tively bigger sample sizes of 109, 320, 350 and 109, respec-
tively. Apart from a significant direct correlation between the
use of EL and the treatment of male sexual disorders, there
are several clinical studies reporting indirect association of EL
in promoting male sexual well-being via enhancing testoste-
rone level in serum [47-49]. It may be agreed that the clinical
studies with EL on male sexual health is not common in
modern medical society. The population is unaware about the
outcomes relating to EL researches and to achieve the positive
findings with significant efficacy is definitely challenging.
Thus, the potential findings of these descriptive or observa-
tional studies are worthy to be acknowledged in generating
the hypotheses about the constructive effect of EL on the
treatment of male sexual disorders. Notably, all the human
clinical trials of EL presented in this review were recently
conducted from the year 2010.
EL has gained remarkable attention due to its strong
aphrodisiac effects observed in animals and humans in Asian
countries for many years [35-36, 51-53]. Udani et al. [35] hig-
hlighted a remarkable prospect of EL in improving penile
erection, penile hardness, and other principle parameters of
male sexual health, substantiating the therapeutic feasibility
of EL in the management of ED. Udani and co-workers [35]
further suggested that daily intake of EL can improve physical
health, erectile performance, sexual desire and satisfaction as
well as the meaningful improvement in overall male sexual
activities, compared to placebo groups. These results were
also in harmony with another human clinical trial by Tambi et
al. [36], which has also shown the potential effects of EL on
the treatment of ED. The findings of this study have also
demonstrated a significant improvement in sexual performance,
including erectile function, sexual intercourse performance,
and penile hardness. The exact mechanism behind the aphro-
disiac characteristics of EL is not well established. Neverthe-
less, researchers have proposed that the pro-aphrodisiac effects
of EL might be contributed by its glycoprotein and eurypep-
tide contents (via increasing testosterone levels) [54]. The
claim originated from a patent surrounding LJ100 (a concen-
Hnin Ei Thu, et al. / Chin J Nat Med, 2017, 15(1): 7180
– 77 –
trated EL extract of glycoproteins and eurypeptides) [54]. Other
investigators proposed that EL produced aphrodisiac effect
via direct action on corpus cavernosa and seminal vesicles
muscle tone [55]. In this study, researchers investigated the effect
of 9-hydroxycanthine-6-one (9-HC-6-one), a β- carboline
alkaloid isolated from EL, on penile hardness and seminal
ejaculate. The results obtained clearly identified that
9-HC-6-one cause relaxation of phenylephrine induced con-
traction of corpus cavernosim muscles. Furthermore, endo-
thelium disruption did not attenuate this response, precluding
the involvement of nitric oxide-dependant pathway. The pro-
posed mechanistic pathway highlighted that 9-HC-6- one, as
the prime component, might have major contribution to the
aphrodisiac effect of EL [55].
Male infertility is a multi-factorial syndrome, with numerous
factors down-regulating spermatogenesis, producing immotile
sperms, reducing sperm volume, and producing abnormality
in sperm morphology [15, 37]. The quantity and quality of the
sperms greatly influence male’s fertility. Low number or poor
quality of sperms in male’s ejaculate significantly influences
the ability of a man to cause pregnancy [15]. With regard to
male infertility, several studies have demonstrated a positive
influence of EL. Tambi et al. [38] reported a remarkable im-
provement in the principle seminal parameters, including
concentration of sperms, semen volume, and the percentile of
sperms with desired morphological characteristics. They fur-
ther demonstrated a dose-dependent effect of this herb on
seminal parameters, leading to the assumption that a daily
dose of 300 mg of EL root extract was prominent and effica-
cious in the treatment of idiopathic infertility in men. This
effect might be associated to testosterone-enhancing effect of
EL; that in turn, may trigger spermatogenesis in testicles and
improve the quality and quantity of sperms in ejaculate. In
addition, an increase in sperm concentration in sub-fertile
men might also be attributed to the suppression of apoptosis of
sperms in the presence of anti-sperm antibodies [22], which may
identify sperms as extraneous matters and attempt to eradicate
them.
Ismail and co-workers [41], on the other hand, have also
conducted a placebo-controlled trial in Malay males and hig-
hlighted a positive role of EL in improving male’s fertility in
sub-fertile couples. They observed a significant improvement in
sexual libido, sexual performance, and sexual satisfaction. They
have also noted prominent effects of EL on seminal parameters,
including concentration of sperms with normal morphology,
sperm motility, and semen volume [41]. Although the exact me-
chanism of EL at cellular level is not fully understood, other
researchers have correlated the positive effects of EL on male’s
fertility to the high level of male sex hormone as well as its
antioxidative properties [39-40]. Recent human clinical trials also
provide evidences by exploring that the extract of EL signifi-
cantly enhances testosterone and dihydroepiandrosterone levels in
the serum [56-59]. The same studies also highlighted antioxi-
dant characteristics of EL extract by showing superoxide
dismutase (SOD) activity. Several studies have shown that
antioxidant supplementation could improve male reproductive
functions [ 60-62]. Thus, the antioxidant properties of EL might
also contribute to the improvement of male’s fertility. Fol-
lowing each treatment cycle with EL, the semen analysis of
sub-fertile subjects whose partners had got pregnant, demon-
strated meaningful increment in percentages of sperm with
desired morphology, sperm motility as well as concentration
of normal sperms in semen [61-62]. The result of this study
indicated that the male’s fertility can be improved by treating
them with EL.
Testosterone is the principle male sex hormone that is
primarily secreted by testicles. The key roles of testosterone
in men are to develop male reproductive tissues such as
the testis and prostate and to promote secondary sex characteristics
including, increased muscle and bone mass and growth
of body hair. The inadequate functioning of the testicles,
caused by hypothalamic or pituitary disorder, results in lower
production of testosterone and thus, androgen deficiency [42].
Among the prime reasons for androgen deficiency are aging
and certain diseases such as Klinefelter’s syndrome, pituitary
and hypothalamic disorders [43], which eventually results in
reduced levels of testosterone [43-44]. The low levels of testos-
terone, as a result, manifest down-regulation of male sexual
libido and sexual activities [25]. On the topic of the potential
role of EL in boosting testosterone level and male sexual
well-being, Talbott et al. [47] had suggested a strong physio-
logical alliance between EL and testosterone levels. They
noticed a significant improvement in testosterone levels in all
the subjects treated with EL and subsequent enhancement in
sexual activities and overall sexual well- being [47] compared
to the placebo group. The precise mechanism contributing to
the increased levels of total testosterone in these males is not
fully understood. Nevertheless, the investigators have sug-
gested that EL (containing prime component, eurypeptides)
may have played notable role in releasing the bound-form of
testosterone from SHBG [37, 63] that might increase free form
of sex hormone in the serum. The free form of testosterone is
biologically active and able to enter into cells and activate the
associated androgen receptor signaling spermatogenesis in the
testis. They have also postulated that the supplementation of
EL might also reduce the metabolism of testosterone and thus
tend to enhance free form of sex hormone [37, 63]. The thera-
peutic feasibility of EL is further stressed by demonstrating
safety profile of EL after consumption of this natural product
[64-65]. The findings showed no significant changes in EL
treated patients in relevant to liver and kidney laboratory val-
ues including, albumin, alanine transaminase (ALT), alkaline
phosphatase (ALP), aspartate aminotransferase (AST), bilirubin,
blood urea nitrogen (BUN), creatinine clearance, and glome-
rular filtration rate (GFR), compared to the baseline or place-
bo group [64-65].
The corresponding effects observed by Henkel and
co-worker [48] are also found in accordance with the report of
Hnin Ei Thu, et al. / Chin J Nat Med, 2017, 15(1): 7180
– 78 –
Talbott et al. [47] which has shown noticeable increase in the
free as well as bound concentrations of testosterone in the
treated subjects. The increased concentration of male sex
hormone subsequently produces remarkable improvement in
male sexual performance. Thus, the data expressed in this
review present satisfactory picture exploring the positive im-
pact of EL in improving various male sexual health disorders.
The summary of effects of EL in improving male sexual dis-
orders is highlighted by Fig. 2.
Fig. 2 EL and male sexual disorders: Schematic illustration showing the effect of EL in improving male sexual disorders
Strengths and Limitations of This Review
Studies on the effects of EL on erectile dysfunction, de-
creased libido, low testosterone level, and hypogonadism
have shown promising results in terms of improving male
sexual health. In the quest of seeking newer alternative treat-
ments against male sexual disorders, the current review is
greatly relevant. Our search identified 7 clinical studies which
were highly relevant and were included in the present syste-
matic review. To the best of our knowledge, this was the first
critical review which focuses on the effects of EL on male
sexual disorders. The human clinical studies were focused in
this review with the aim to have a relevant overview of the
most recent and prospective evidences presented on this topic.
Admittedly, the present review had few limitations. The
articles in languages other than English were not included;
those articles may contain relevant information or supplementary
evidence related to this topic, which should be considered as
one of the potential limitations of our review. Concurrently,
the present review included the articles published from the
year 2000 to 2014, as our priority was to discuss about the
current health aspect and its impact on the general population.
The study design used in most of these human clinical studies
did not present a clear picture of underlying mechanism of
action and pharmacokinetic profile of EL on male sexual
health disorders. Future research on the effect of EL in male
sexual health disorder is expected to explore more relevant
concerns on its pharmacokinetic and pharmacodynamic pro-
files. In recent years, much emphasis has been placed on EL
in the treatment of male sexual disorders. Based on the pros-
pective clinical evidence presented in the current review, it
would be misleading to make any ultimate claims for the
therapeutic feasibility of EL in other human clinical aspects.
Hnin Ei Thu, et al. / Chin J Nat Med, 2017, 15(1): 7180
– 79 –
Conclusion
Eventually, the global scenario of numerous human clin-
ical trials screened in this review article, highlighted the role
of EL as a potential herbal supplement against various male
sexual health disorders, including erectile dysfunction, male’s
infertility, low libido, and male sex hormone associated com-
plications. Based on the evidences highlighted in the present
review, EL may have a remarkable potential in renewing male
sexual vitality and enhancing libido and overall sexual per-
formance. The clinical superiority of EL against male sexual
health disorders is associated with its broad safety profile and
patient compliance.
Acknowledgement
Authors would like to acknowledge Department of
Pharmacology, Faculty of Medicine, Universiti Kebangsaan
Malaysia (UKM) for providing resources and tremendous
support throughout the completion of present research project.
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Cite this article as: Hnin Ei Thu, Isa Naina Mohamed, Zahid Hussain, Putri Ayu Jayusman, Ahmad Nazrun Shuid. Eury-
coma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies [J]. Chin J Nat
M
ed, 2017, 15
(
1
)
: 71-80.
... It has been found that libido (sex drive) can be modulated by various factors including diet, seasons, age, environment, and genetics [105]. Low libido is categorized as male sexual dysfunction, caused by low testosterone levels [106]. e sex drive can be increased with the help of aphrodisiacs, for example, herbal and plant products. ...
... e Southeast Asian plant Eurycoma longifolia (EL) has been found to be a natural herbal remedy for male sexual dysfunction, including improving libido by increasing blood testosterone levels [82,106]. e effects of medicinal plants on male fertility, including libido, are mainly associated with antioxidant properties. According to u et al. [106], the action of this type of plants improves the process of spermatogenesis and steroidogenesis and may also have a protective effect against oxidative stress. ...
... e effects of medicinal plants on male fertility, including libido, are mainly associated with antioxidant properties. According to u et al. [106], the action of this type of plants improves the process of spermatogenesis and steroidogenesis and may also have a protective effect against oxidative stress. ...
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... This species is a traditional medicinal plant widely used in the improvement of sexual health (Thu et al. 2017). Plant extracts can be used to treat erectiledysfunction (Drewes et al. 2003). ...
... In males, the plant has been suggested as an adaptogen. Plant extracts can increase the sex hormone and libido, as well as semen quality which improves overall fertility (Thu et al. 2017). ...
... Eurycoma longifolia is a shrub plant under genus Eurycoma of Simaroubaceae, and it is widely distributed in Vietnam, Indonesia, and Malaysia (Thu, Hussain, Mohamed, & Shuid, 2017). E. longifolia is known as Malaysian ginseng, and the whole plants can be used as drugs and food additives, and the roots are mainly used (He et al., 2019). ...
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... Also, a significant elevation and decrease in bladder weight and testes weight respectively was noticed in the untreated control in comparison to the normal control. The changes noticed in the bladder may result in an inflamed prostate gland which obstructs bladder outflow thereby causing difficulties in urination and weakens the bladder muscles (Bhavsar and Verma 2014;Thu et al. 2017). ...
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... Eurycoma longifolia, also known as Malaysian ginseng, is one species of the Simaroubaceae family, and is mainly distributed in Indonesia, Vietnam, Malaysia, and other Southeast Asian countries [1,2]. In Malaysia, E. longifolia has long been used as medicines because of its extensive pharmacological functions, such as antimicrobial, antidiabetic, antipyretic, aphrodisiac, anti-cancer and anti-malaria properties, and is now regarded as a national treasure [3]. ...
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Chapter
Numerous factors influence human fertility and reproductive capability, and many of these factors are dictated by biochemical processes and early fetal development. Fertility factors are strongly impacted by endocrinological status, which in turn is influenced by oxidative stress. Oxidative stress occurs during cellular metabolism and results from the imbalance of reactive oxygen species, reactive nitrogen species, and antioxidant systems. These byproducts of oxidative processes, while necessary for many aspects of reproductive functioning, including maturation and release of oocytes and spermatozoa, can become toxic when present in excess. Disease states characterized by endocrinological disruption, oxidative stress, and inflammation often correspond with subfertility and infertility. Treatments that incorporate antioxidant supplementation offer an exciting, promising, easy, and affordable approach; however, the research remains inconsistent in the application of supplementation with phytonutrients and nutraceuticals. This chapter provides an overview of factors influencing male and female infertility and subfertility and the role that phytonutrients and nutraceutical supplementations may play in supporting fertility.
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Some of the areas of concern in andrology are erectile dysfunction, late onset hypogonadism, benign prostatic hyperplasia, and infertility. Often these are associated with depletion in androgens, particularly the testosterone hormone. Lack of physical, mental, and sexual vitality, particularly in elderly men, is recognized as a worldwide health problem, which is challenging medically as well as in healthcare. There are numerous traditional herbal products that claim to enhance male overall well-being and restore reproductive health. Proof of acceptance and relevance of herbal treatment in men’s health management are underlined by the tremendous number of publications as well as clinical data, which meet the highest quality, safety, and efficacy standards. This chapter reviews scientific evidence from clinical trials performed with well-known traditional herbs, claiming therapeutic benefits in men’s health: Eurycoma longifolia (tongkat ali), Lepidium meyenii (maca), Withania somnifera (ashwagandha), and Trigonella foenum-graecum (fenugreek). Furthermore, information of acceptance in terms of regulatory issues is summarized.
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Several medicinal plants are traditionally used in different regions of Africa for the treatment of male infertility, sexual asthenia, erectile dysfunction, and impotency or used as an aphrodisiac. Scientific studies, mostly conducted in vitro or in animals, have proven the acclaimed traditional use of these plants to enhance sexual activities or sperm concentration, motility, and viability. Some of the mechanisms of actions associated with these plants include increased level of testosterone and the relaxation of the smooth cavernosal muscles. However, some plants were also shown to have detrimental effects on the male reproductive system. This may be due to the varying modes of plant extraction, duration of treatment, experimental design, dosage used, quality of the plant, or toxic effects. There is a need to standardize the protocols as well as to better understand the mechanism of actions of the respective plants. Further studies should be conducted using human subjects.
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This study aims to analyze the effects of a concurrent training (CT) associated with Eurycoma longifolia (EL) supplementation on the muscle strength, cardiorespiratory fitness, and symptomatology score of men with the androgen deficiency of aging male (ADAM). Forty-five subjects (47.6±5.2 years) were included in the study. The randomized, double-blinded, placebo controlled clinical trial lasted for 6 months. Participants were randomized into four groups, control (C; n=12); EL (n=11); CT (n=11); and CT+EL (n=11). Along this period, the isokinetic peak torque of the knee extensors increased in the CT (14%) and CT+EL (17%) groups (p=0.040; p=0.006, respectively), while the isokinetic peak torque of knee flexion increased in the CT+EL group only (p<0.05). For all participants, testosterone levels were correlated with isokinetic peak torque of knee extension (r=0.517, p=0.001) and flexion (r=0.362, p=0.028). Subjects of the CT (27.3%) and CT+EL (36.1%) groups decreased the symptomatology of ADAM (p=0.005). This study demonstrated the benefits of CT and EL consumption as a non-pharmacological treatment for ADAM.
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This study investigated the effects of supplementation of the nutraceutical product Eurycoma longifolia Jack on recreational athletes’ endurance running capacity and physiological responses in the heat. Twelve Malaysian healthy male recreational athletes (Age: 23.3 (3.7) years old; VO2max: 45.1 (8.1) ml.kg-1.min-1) were recruited in this double blind, placebo-controlled, cross-over study. Subjects completed two endurance running trials in the heat (31°C, 70% relative humidity), performed on separate days, after consuming either 2 capsules of Eurycoma longifolia Jack (75 mg per capsule) or a placebo per day for 7 days before and one hour prior to the experimental trial. On trial day, after 5 minutes of warm-up at 50 % VO2max, the subjects were requested to run on the treadmill at 60 % VO2max for 60 minutes. This was immediately followed by a 20-minute time trial for determining endurance running capacity. Blood samples were taken before warm up, after warm-up, and every 20 minutes during the trial. Statistical analysis was performed using one-way ANOVA with repeated measures. Results showed that the endurance running capacity of E. longifolia was not significantly different from that of the placebo trial. Similarly, oxygen uptake, heart rate, skin temperature, tympanic temperature, ratings of perceived exertion, haemoglobin concentration, haematocrit level, plasma glucose concentration, and plasma free fatty acid concentration were not significantly different between the trials. These findings suggested that supplementation of the E. longifolia product at a dosage of 150 mg.day-1 for 7 days has not provided beneficial effects on endurance running capacity and physiological responses of recreational athletes in the heat. Higher dosage and longer duration of supplementation of the product may be warranted to evaluate further its endurance capacity during exercise.
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Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40-65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.
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Testosterone is important in the physiology of various organs and tissues. The serum testosterone concentration gradually declines as one of the processes of aging. Thus, the concept of late-onset hypogonadism has gained increasing attention in the last few years. Reported symptoms of late-onset hypogonadism are easily recognized and include diminished sexual desire and erectile quality, particularly in nocturnal erections, changes in mood with concomitant decreases in intellectual activity and spatial orientation, fatigue, depression and anger, a decrease in lean body mass with associated decreases in muscle volume and strength, a decrease in body hair and skin alterations, and decreased bone mineral density resulting in osteoporosis. Among these various symptoms, sexual dysfunction has been the most common and necessary to treat in the field of urology. It is well known that a low serum testosterone level is associated with erectile dysfunction and hypoactive sexual libido and that testosterone replacement treatment can improve these symptoms in patients with hypogonadism. Recently, in addition to sexual dysfunction, a close relationship between metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, and late-onset hypogonadism has been highlighted by several epidemiologic studies. Several randomized control trials have shown that testosterone replacement treatment significantly decreases insulin resistance in addition to its advantage for obesity. Furthermore, metabolic syndrome is one of the major risk factors for cardiovascular disease, and a low serum testosterone level is closely related to the development of atherosclerosis. Presently, it is speculated that a low serum testosterone level may increase the risk for cardiovascular disease. Thus, testosterone is a key molecule in men's health, especially that of elderly men.
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The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age-depending decline in serum testosterone levels with concentrations being about 40-50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT.