Content uploaded by Ralf Henkel
Author content
All content in this area was uploaded by Ralf Henkel on May 09, 2019
Content may be subject to copyright.
ORIGINAL ARTICLE
Standardised water-soluble extract of Eurycoma
longifolia, Tongkat ali, as testosterone booster for
managing men with late-onset hypogonadism?
M. I. B. M. Tambi
1,2
, M. K. Imran
2
& R. R. Henkel
3
1 Wellmen Clinic, Damai Service Hospital, Kuala Lumpur, Malaysia;
2 Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kbg Kerian, Kelantan, Malaysia;
3 Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa
Introduction
Natural therapy in the form of natural herbal supplemen-
tation has been the acceptable form of therapy for many
people in most countries in the Orient as well as in
Africa, South America and the Far East (Van Wyk et al.,
1997; Ernst, 2000; Gonzales et al., 2002; Bratman &
Girman, 2003; Valerio & Gonzales, 2005; Gonzales &
Valerio, 2006; Tambi, 2009; Henkel et al., unpublished).
Such plants and/or herbal extracts are also used in man-
aging wellness and general well-being related to ageing.
However, in modern medicine very little is known about
these alternative traditional approaches to combat diseases
although 25% of prescriptions contain active ingredients
extracted from plants (Castleman, 1995). In addition, very
little is known about possible side effects of long-term
treatments with these herbs as some of them also contain
toxic substances. Therefore, an immense need exists to
investigate the mode of molecular action of these herbs,
their extracts and phytochemicals as conflicting results are
published in literature reports.
Most of these plants like Mountain Ginseng (Panax
ginseng) including a variety of their compounds were clas-
sified as adaptogens, meaning that these herbs or herbal
compounds assist in combating stress and disease,
improving physical strength without adverse effects. Com-
pounds of P. ginseng have been found not to exert any
effect to testosterone levels in the body (Perry & Metzger,
1980; Nocerino et al., 2000; Bratman & Girman, 2003;
MacKay, 2004). On the other hand, ‘Malaysian ginseng’
Keywords
Adaptogen—Eurycoma longifolia—
Hypogonadism—late-onset hypogonadism—
testosterone—Tongkat ali
Correspondence
Prof. Mohd Ismail Bin Mohd Tambi, Wellmen
Clinic, Damai Service Hospital, Kuala Lumpur
52100, Malaysia.
Tel.: +603 4043 4900 (Ext 791);
Fax: +603 4043 5399;
E-mail: dr_tambi@yahoo.com
Accepted: December 7, 2010
doi: 10.1111/j.1439-0272.2011.01168.x
Summary
In most countries, millions of people are relying on herbal medicines as
remedy for numerous ailments. In South-East Asia, Eurycoma longifolia Jack,
also known as ‘Malaysian ginseng’ or Tongkat ali, is used to combat stress and
disease and to improve physical strength. Moreover, the compounds of the
roots of this plant are reported to have aphrodisiac and testosterone enhancing
effects in the rat. Considering that human studies are not available, 76 of 320
patients suffering from late-onset hypogonadism (LOH) were given 200 mg of
a standardised water-soluble extract of Tongkat ali for 1 month. The Ageing
Males’ Symptoms (AMS) according to the standardised rating scale and the
serum testosterone concentration were taken. Results show that treatment of
LOH patients with this Tongkat ali extract significantly (P< 0.0001) improved
the AMS score as well as the serum testosterone concentration. While before
treatment only 10.5% of the patients did not show any complaint according to
the AMS scale and 35.5% had normal testosterone levels, after the completed
treatment 71.7% and 90.8% of the patients showed normal values, respectively.
Thus, Tongkat ali extract appears to be useful as a supplement in overcoming
the symptoms of LOH and for the management of hypogonadism.
ª2011 Blackwell Verlag GmbH ÆAndrologia xx,1–5 1
(Eurycoma longifolia Jack; Simaroubaceae) or Tongkat ali,
as it is known in Malaysia and indigenous to South-East
Asia, is also regarded as adaptogen (Tambi, 2006).
Tongkat ali is an evergreen plant (Bhat & Karim,
2010), which is slowly growing up to 15–18 m in height
on jungle slopes where they receive adequate shade and
water (Bhat & Karim, 2010). The tree starts bearing fruits
after 2–3 years, yet complete maturation takes up to
25 years. Its long, twisted roots are harvested, and aque-
ous concoctions are used by the local people to restore
energy and vitality (Bhat & Karim, 2010) or for its aphro-
disiac properties (Zanoli et al., 2009).
Particularly, the roots of E. longifolia contain a wide
variety of chemical compounds including alkaloids,
quassinoids, quassinoid diterpenoids, eurycomaoside, eur-
ycolactone, laurycolactone or eurycomalactona (Morita
et al., 1993; Ang et al., 2002; Bedir et al., 2003). Apart
from these compounds, a bioactive peptide of 4.3 kDa
with aphrodisiac properties has been identified (Ali &
Saad, 1993; Sambandan et al., 2006; Asiah et al., 2007).
The bioactive complex polypeptides from the Tongkat ali
root extract, labelled as eurypeptides, exert and enhance
their effects on the biosynthesis of various androgens (Ali
& Saad, 1993). Unlike for other adaptogens, a wealth of
animal studies is available pointing out aphrodisiac and
testosterone enhancing effects of the root extract of
Tongkat ali (Ang & Sim, 1998a,b). In contrast, properly
conducted human studies are not available, except for a
few short notices (Hamzah & Yusof, 2003; Tambi, 2006,
2009; Tambi & Imran, 2010).
As, according to traditional healers, Tongkat ali is sup-
posed to be a suitable herbal supplement in treating
male infertility and alleviating chronic low testosterone
levels, this study aimed at investigating the usefulness of
a treatment of hypogonadic men suffering from late-
onset hypogonadism (LOH) with a patented standardised
water-soluble extract of Tongkat ali in a retrospective
analysis.
Materials and methods
This study had received ethical clearance from the Ethics
Committee of the Ministry of Health of Malaysia.
In the period from 2005 until 2009, a total of 850 male
subjects of different ethnicity attended the Wellmen
Clinic at Damai Service Hospital, Kuala Lumpur,
Malaysia, for hypogonadism. Of these, 320 patients gave
informed consent and opted for the treatment of symp-
toms of hypogonadism and LOH (Jockenho
¨vel, 2004;
Wang et al., 2008) with Tongkat ali. Patients were identi-
fied using the Ageing Males’ Symptoms (AMS) Rating
Scale (Heinemann et al., 1999) as well as serum testoster-
one levels (below 6 nmol testosterone per litre; normal
range: 6–30 nm). The AMS score was categorised as fol-
lows: score ‘0’ from 17 to 26: ‘no complaints’; score ‘1’
from 27 to 36: ‘few complaints’; score ‘2’ from 37 to 49:
‘mild complaints’; and score ‘3’ at or above 50: ‘severe
complaints’. Similarly, the serum testosterone concentra-
tion was categorised into category ‘0’ (normal: testoster-
one concentration 6–30.0 nm); ‘1’ (low: testosterone
concentration <5.99 nm). Serum testosterone levels were
determined using a competitive immunoassay using direct
chemiluminescent technology (ADVIA Centaur Testoster-
one assay; Bayer, Newbury, UK) according to the manu-
facturer’s instructions.
Patients were treated with 200 mg (two capsules with
100 mg) of the standardised water-soluble extract of
Tongkat ali (Sambandan et al., 2006; Phytes Bioteks, Bio-
tropics Malaysia, Berhad, Malaysia) daily. After 1 month
of treatment, follow-up examinations were conducted
where AMS scores and the serum testosterone levels were
recorded again. Of the 320 patients recruited for the
study, only 76 subjects (Malay: n= 64, Indian: n= 9 and
Chinese: n= 3) with LOH had regularly taken the Tong-
kat ali supplement and came for regular follow-up exam-
inations. For this report, only data of men who
completed a full course of Tongkat ali supplementation
with a dose of 200-mg standardised water-soluble extract
were taken into consideration.
Statistical analysis of the data was performed by using
medcalc (Ver. 11.3.3), MedCalc Software, Mariakerke,
Belgium. Data were checked for normal distribution by
means of the Kolmogorov–Smirnov test and expressed as
mean ± standard deviation and Median ± range respec-
tively. For analysis of categorical variables, patients were
categorised regarding the results for AMS score and
serum testosterone concentration: AMS: no complaints
(AMS score 0) versus any complaint (AMS scores 1, 2
and 3); no/few complaints (AMS scores 0 and 1) versus
mild/severe complaints (AMS scores 2 and 3). Similarly,
the serum testosterone concentration was categorised
into categories ‘normal’ (testosterone concentration 6–
30.0 nm) versus ‘low’ (testosterone concentration <5.99 nm).
For comparisons, appropriate statistical tests were applied
and McNemar test was used, and P-values <0.05 were
considered significant.
Results
Table 1 depicts the summary statistics for the parameters
taken in this study. Data also revealed no difference
between the different ethnic groups for any of the param-
eters taken.
As expected, significant correlations were observed
between the patients’ age, the AMS scores and testoster-
one concentrations before and after the treatment with
Treatment of hypogonadism with Tongkat ali M. I. B. M. Tambi et al.
2ª2011 Blackwell Verlag GmbH ÆAndrologia xx,1–5
Tongkat ali (Table 2). Correlations between AMS score
and the serum testosterone concentration are even highly
significant (P< 0.0001).
Comparison of the parameters, AMS score and testos-
terone concentration before and after treatment revealed
highly significant differences for both parameters (Figs 1
and 2). While the AMS score decreased from
38.05 ± 9.25 to 23.67 ± 5.11 after treatment, the testoster-
one concentration increased from 5.66 ± 1.52 to
8.31 ± 2.47 nm, which represents an average increase of
46.8%. These changes are highly significant (P< 0.0001).
These improvements were seen in all individuals (results
not shown).
After categorisation of the patients (Table 3) for the
AMS scores and serum testosterone concentrations, the
differences between paired proportions were calculated
with the McNemar test. In fact, while before the treat-
ment with the water-soluble Tongkat ali extract, only
10.5% (n= 8) of the patients did not show any com-
plaints; this proportion increased to 71.7% (n= 54)
after the treatment. The same improvement was
observed for the serum testosterone concentration, which
was normal in 35.5% (n= 27) before and in 90.8%
(n= 69) of the patients after the treatment. Results of
the McNemar tests show highly significant (P< 0.0001)
improvements for both AMS score and serum testoster-
one concentration.
Table 1 Summary statistics of age, Ageing Males’ Symptoms (AMS) score and serum testosterone concentrations before and after treatment of
patients with late-onset hypogonadism with 200 mg of the standardised water-soluble extract of Tongkat ali (Eurycoma longifolia) for 1 month
Parameter nMean SD Median Minimum Maximum
Age (years) 76 51.00 10.06 52.00 28.00 70.00
AMS (before) (score) 76 38.05 9.25 38.00 23.00 58.00
AMS (after) (score) 76 23.67 5.11 24.00 17.00 38.00
Testosterone (before) (nm) 76 5.66 1.51 5.60 2.54 9.80
Testosterone (after) (nm) 76 8.31 2.47 7.60 4.20 18.00
Table 2 Spearman rank correlations between age, Ageing Males’ Symptoms (AMS) scores and serum testosterone (nm) in 76 late-onset hypog-
onadism (LOH) patients before and after intervention with 200-mg standardised water-soluble extract of Tongkat ali (Eurycoma longifolia) for
1 month. Significant positive and negative correlations between parameters are obvious, particularly between the AMS scores and testosterone
concentrations before and after treatment of the LOH patients with 200-mg standardised water-soluble extract of Tongkat ali (E. longifolia) for
1 month
AMS (before)
(score)
AMS (after)
(score)
Testosterone
(before) (nm)
Testosterone
(after) (nm)
Age (years) Correlation coefficient
Significance level (P)
n
0.271
0.0178
76
0.260
0.0236
76
)0.317
0.0053
76
)0.211
0.0670
76
AMS (before score) Correlation coefficient
Significance level (P)
n
0.710
<0.0001
76
)0.904
<0.0001
76
)0.463
<0.0001
76
AMS (after score) Correlation coefficient
Significance level (P)
n
)0.717
<0.0001
76
)0.740
<0.0001
76
2
4
6
8
10
12
14
16
18
Testosterone (nM)
(before treatment)
Testostosterone (nM)
(after treatment)
Fig. 1 Serum testosterone concentration in 76 late-onset hypogona-
dism patients before and after treatment with 200-mg standardised
water-soluble extract of Tongkat ali (Eurycoma longifolia) for
1 month. A highly significant increase in the testosterone concentra-
tion was calculated by means of the Wilcoxon test (P< 0.0001).
M. I. B. M. Tambi et al. Treatment of hypogonadism with Tongkat ali
ª2011 Blackwell Verlag GmbH ÆAndrologia xx,1–5 3
Discussion
Eurycoma longifolia Jack (Malaysian ginseng), locally
known as Tongkat Ali, is traditionally used to treat a variety
of illnesses including fever, aches, hypertension, tuberculo-
sis, vermifuge and sexual insufficiency and erectile dysfunc-
tion. With regard to its said aphrodisiac properties, several
animal studies using the rat as model revealed increased
sexual motivation and performance (Ang & Sim, 1997,
1998a; Ang and Sim, 1998b; Ang & Ngai, 2001; Ang & Lee,
2002; Ang et al., 2000, 2003) including increased serum tes-
tosterone concentrations in treated rats (Zanoli et al.,
2009). On the contrary, Lin et al. (2001) reported that a
crude ethanol extract of Tongkat ali roots decreased the
basal testosterone release, but increased the hCG-induced
synthesis of the male sex hormone in rat Leydig cells.
Considering that the herbal extract of Tongkat Ali is
used by traditional healers to treat sexual dysfunctions
including erectile dysfunction and scientific studies in
humans are lacking (Low & Tan, 2007), this is the first
study that aimed at investigating the extract’s effects on
patients suffering from LOH and confirming the testos-
terone stimulating properties of the standardised water-
soluble extract of Tongkat ali in the human. Increased
testosterone levels also alleviated AMS according to the
AMS rating scale (Heinemann et al., 1999).
The molecular mechanism, by which root extract from
E. longifolia is acting, is most probably through the bioac-
tive complex eurypeptides that exert and enhance their
effect on the biosynthesis of various androgens (Ali & Saad,
1993). The eurypeptide works by activating the CYP17 (17
a-hyroxylase/17, 20 lyase) enzyme to enhance the metabo-
lism of pregnenolone and 17-OH-pregnenolone to yield
more dehyroepiandrosterone (DHEA) as well as the metab-
olism of progesterone and 17-OH-progesterone to 4-
androstenedione and to testosterone (Ali & Saad, 1993).
In conclusion, the standardised water-soluble extract of
Tongkat ali proved to be a suitable herbal supplement in
overcoming symptoms of LOH and managing hypogona-
dism. Similarly, men with other causes of hypogonadism
may also benefit by taking the herbal extract as an adjunct
to their testosterone replacement therapy to enhance their
DHEA. Moreover, a treatment like this may be a reasonable
therapy for numerous patients, particularly in Third World
or emerging countries as such herbal extracts are often
cheaper than Western pharmaceutical medicines. In Malay-
sia, for instance, the supplement is available in most leading
pharmacies and popular as a male health supplement. Yet,
Table 3 Distribution of Ageing Males’ Symptoms (AMS) categories and the serum testosterone concentration in 76 late-onset hypogonadism
patients before and after intervention with 200-mg standardised water-soluble extract of Tongkat ali (Eurycoma longifolia) for 1 month. Calcula-
tion of McNemar tests for the differences between paired proportions (AMS: no complaints versus any complaint and no/few complaints versus
mild/severe complaints; testosterone concentration: normal versus low) before and after the treatment with Tongkat ali resulted in highly signifi-
cant (P< 0.0001) improvements for both the AMS score and serum testosterone concentration
Before treatment After treatment Category
AMS score
n(%)
Testosterone concentration
n(%)
AMS score
n(%)
Testosterone concentration
n(%) AMS Testosterone
8 (10.5) 27 (35.5) 54 (71.1) 69 (90.8) 0 No complaints
a,c
Normal
e
25 (32.9) 49 (64.5) 21 (27.6) 7 (9.2) 1 Few complaints
b,c
Low
f
33 (43.4) 0 (0.0) 1 (1.3) 0 (0.0) 2 Mild complaints
b,d
10 (13.2) 0 (0.0) 3 Severe complaints
b,d
Low = testosterone concentration <5.99 nm; normal = testosterone concentration is between 6.00 and 30.0 nm.
McNemar tests:
a,b
No complaint (AMS: 0) versus any complaint (AMS: 1, 2, 3): P< 0.0001.
c,d
No/few complaints (AMS: 0, 1) versus mild/severe complaints (AMS: 2, 3): P< 0.0001.
e,f
Normal testosterone concentration versus low testosterone concentration: P< 0.0001.
15
20
25
30
35
40
45
50
55
60
AMS score
(before treatment)
AMS score
(after treatment)
Fig. 2 Ageing Males’ Symptoms (AMS) rating score in 76 late-onset
hypogonadism patients before and after treatment with 200-mg
standardised water-soluble extract of Tongkat ali (Eurycoma longifolia)
for 1 month. A highly significant decrease in the AMS score was
calculated by means of the Wilcoxon test (P< 0.0001).
Treatment of hypogonadism with Tongkat ali M. I. B. M. Tambi et al.
4ª2011 Blackwell Verlag GmbH ÆAndrologia xx,1–5
randomised placebo-controlled studies investigating the
positive effects of Tongkat ali on ageing male well-being
including its effects on the prostate are missing in the liter-
ature thus far and are currently underway.
References
Ali JM, Saad JM (1993) Biochemical effect of Eurycoma Longi-
folia Jack on the sexual behavior, fertility, sex hormone and
glycolysis [Dissertation]. Department of Biochemistry,
University of Malaya.
Ang HH, Lee KL (2002) Effect of Eurycoma longifolia Jack on
orientation activities in middle-aged male rats. Fundam Clin
Pharmacol 16:479–483.
Ang HH, Ngai TH (2001) Aphrodisiac evaluation in non-
copulator male rats after chronic administration of Euryco-
ma longifolia Jack. Fundam Clin Pharmacol 15:265268.
Ang HH, Sim MK (1997) Eurycoma longifolia Jack enhances
libido in sexually experienced male rats. Exp Anim 46:287–
290.
Ang HH, Sim MK (1998a) Eurycoma longifolia increases sexual
motivation in sexually naive male rats. Arch Pharm Res
21:779–781.
Ang HH, Sim MK (1998b) Eurycoma longifolia Jack and
orientation activities in sexually experienced male rats.
Biol Pharm Bull 21:153–155.
Ang HH, Cheang HS, Yusof AP (2000) Effects of Eurycoma
longifolia Jack (Tongkat Ali) on the initiation of sexual
performance of inexperienced castrated male rats. Exp Anim
49:35–38.
Ang HH, Hitotsuyanagi Y, Fukuya H, Takeya K (2002) Quassi-
noids from Eurycoma longifolia.Phytochemistry 59:833–837.
Ang HH, Ngai TH, Tan TH (2003) Effects of Eurycoma
longifolia Jack on sexual qualities in middle aged male rats.
Phytomedicine 10:590–593.
Asiah O, Nurhanan MY, Ilham MA (2007) Determination of
bioactive peptide (4.3 kDa) as an aphrodisiac marker in six
Malaysia plants. J Tropical Forest Sci 19:61–63.
Bedir E, Abou-Gazar H, Ngwendson JN, Khan IA (2003)
Eurycomaoiside: a new quassinoid-type glycoside from the
root of Eurycoma longifolia.Chem Pharm Bull (Tokyo)
51:1301–1303.
Bhat R, Karim AA (2010) Tongkat ali (Eurycoma longifolia
Jack): a review on its ethnobotany and pharmacological
importance. Fitoterapia 10:1–11.
Bratman S, Girman A (2003) Mosby’s Handbook of Herbs
and Supplements and their Therapeutic Uses. Mosby Inc.,
St. Louis, MO, pp 976–978.
Castleman M (1995) Healing Herbs. Bantam Books,
New York, pp 1–5.
Ernst E (2000) The role of complementary and alternative
medicine. BMJ 321:1133–1135.
Gonzales GF, Valerio LG Jr (2006) Medicinal plants from
Peru: a review of plants as potential agents against cancer.
Anticancer Agents Med Chem 6:429–444.
Gonzales GF, Cordova A, Vega K, Chung A, Villena A, Gonez
C, Castillo S (2002) Effect of Lepidium meyenii (MACA) on
sexual desire and its absent relationship with serum testos-
terone levels in adult healthy men. Andrologia 34:367–372.
Hamzah S, Yusof A (2003) The ergogenic effects of Tongkat
Ali (Eurycoma longifolia). Br J Sports Med 37:465–466.
Heinemann LAJ, Zimmermann T, Vermeulen A, Thiel C
(1999) A new ‘Aging Male’s Symptoms’ (AMS) rating scale.
The Aging Male 2:105–114.
Jockenho
¨vel F (2004) Male Hypogonadism. Uni-Med Verlag,
Bremen, Germany, pp 118–134.
Lin LC, Peng CY, Wang HS, Lee KWW (2001) Reinvestigation
of the chemical constituents of Eurycoma longifolia.
Chin Pharm J 53:97–106.
Low WY, Tan HM (2007) Asian traditional medicine for
erectile dysfunction. JMHG 4:245–250.
MacKay D (2004) Nutrients and botanicals for erectile
dysfunction: examining the evidence. Altern Med Rev 9:4–16.
Morita H, Kishi E, Takeya K, Itokawa H, Iitaka Y (1993)
Squalene derivatives from Eurycoma longifolia.
Phytochemistry 4:765–771.
Nocerino E, Amato M, Izzo AA (2000) The aphrodisiac and
adaptogenic properties of ginseng. Fitoterapia 71:S1–S5.
Perry LM, Metzger J (1980) Medicinal Plants of Southeast
Asia: Attributed Properties and Uses. MIT Press, Cambridge.
Sambandan TG, Rha C, Aminudim N, Saad JM, Kadir AA
(2006) Bioactive fraction of Eurycoma longifolia. Patent
number: WO0217946; Other reference numbers:
JP2004521075, US2004087493, EP1313491, DK1313491,
DE60125955.
Tambi MI (2006) Eurycoma Longifolia Jack: a potent adapto-
gen in the form of water-soluble extract with the effect of
maintaining men’s health. Asian J Androl 8(Suppl. 1):49–50.
Tambi MI (2009) Nutrients and botanicals for optimizing
men’s health. Examining the evidence for Eurycoma longifo-
lia Jack, the Malaysian Ginseng in men. Asian J Androl
11(Suppl. 5):37–38.
Tambi MI, Imran MK (2010) Eurycoma longifolia Jack in man-
aging idiopathic male infertility. Asian J Androl 12:376–380.
Valerio LG Jr, Gonzales GF (2005) Toxicological aspects of the
South American herbs cat’s claw (Uncaria tomentosa) and
Maca (Lepidium meyenii): a critical synopsis. Toxicol Rev
24:11–35.
Van Wyk B, Van Oudtshoorn B, Gericke N (1997) Medicinal
Plants of South Africa. Briza Publishers, Pretoria, South
Africa.
Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ,
Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A,
Morley JE, Schulman C, Thompson IM, Weidner W, Wu
FCW (2008) Investigation, treatment and monitoring of
late-onset hypogonadism in males. ISA, ISSAM, EAU, EAA
and ASA recommendations. Eur J Endocrinol 159:507–514.
Zanoli P, Zavatti M, Montanari C, Baraldi M (2009) Influence of
Eurycoma longifolia on the copulatory activity of sexually slug-
gish and impotent male rats. J Ethnopharmacol 126:308–313.
M. I. B. M. Tambi et al. Treatment of hypogonadism with Tongkat ali
ª2011 Blackwell Verlag GmbH ÆAndrologia xx,1–5 5
