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R E S E A R C H A R T I C L E Open Access
Evaluation of a multi-herb supplement for erectile
dysfunction: a randomized double-blind,
placebo-controlled study
Gaurang R Shah
1
, Manojkumar V Chaudhari
2
, Suresh B Patankar
3
, Shrikant V Pensalwar
4
, Vilas P Sabale
5
and Navneet A Sonawane
6*
Abstract
Background: Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual
dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) –a proprietary polyherbal preparation
for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups,
multi-centre study.
Methods: 78 men aged 25–50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated
in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for
12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other
efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone,
Semen analysis, Investigator’s Global assessment and Subjects’opinion.
Results: In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to
placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to
25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results
were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse
satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean
(sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P< 0.001. Thirty-five
out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the
treatment they received. Investigator’s global assessment rated VXP therapy as very good to excellent in more
than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and
subject’s rating for tolerability of treatment was similar in both groups.
Conclusions: VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men.
Trial Registration: Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009
Background
Erectile dysfunction (ED) or impotence is defined as the
persistent inability to attain and maintain an erection
sufficient to permit satisfactory sexual performance [1].
One of the oldest diseases known to mankind, ED
affects 52% of 40- to 70-year-old men [2] with estimates
predicting the incidence to rise to over 320 million by
the year 2025 [3]. The earliest reports of medical
therapies for ED are found in ancient medical literature
prescribing the use of numerous herbs and natural
ingredients for sexual rejuvenation and a healthy
progeny. As sexual medicine evolved, introduction of
intracavernous injection therapy followed by phospho-
diesterase type-5 (PDE type-5) inhibitors revolutionized
the treatment of ED. Despite the enormous success of
pharmacological agents and a wide variety of treatment
choices currently available, the ED sufferer continues to
* Correspondence: medical@vediclifesciences.com
6
Clinical Operations, Vedic Lifesciences Pvt. Ltd., B-118, Morya House, Link
Road, Andheri (West), Mumbai 400 053, India
Full list of author information is available at the end of the article
© 2012 Shah et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Shah et al. BMC Complementary and Alternative Medicine 2012, 12:155
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resort to natural alternatives or herbal supplements to
regain his sexual vigor.
Clinicians on the other hand, do not wholeheartedly
recommend herbal or alternative therapies, mainly due
to a lack of adequate evidence from robustly designed
scientific studies [4-6]. In the absence of any regulatory
obligations to undertake rigorous testing for safety and
efficacy of dietary supplements [7], there is no impetus
for evaluation of herbal or dietary supplements before
they are sold over-the-counter. Manufacturers base the
advertising or labeling claims for such products on the
testing of individual ingredients rather than the whole
composition [8]. There are also risks attendant upon
self-medication and unmonitored use of these products
[9]. Evidence of contamination of herbal products with
PDE type-5 inhibitors [10] further prompts the need for
companies to act responsibly and encourage third-party
scientists to conduct efficacy and safety studies on nat-
ural products claiming therapeutic health benefits.
In the present study, we evaluated the safety and effi-
cacy of a multi-herb formulation marketed as VigRx Plus
(Leading Edge Herbals), created for enhancement of sex-
ual health in men. Development of this product was
based on the preliminary evaluation of a first generation
product, VigRX, consisting of a proprietary blend of
Panax ginseng,Serenoa repens,Gingko biloba,Crataegus
laevigata,Ptychopetalum olacoides,Erythroxylum
catuaba,Cuscuta chinensis, and Epimedium sagittatum
extract. In two different studies in male Sprague–
Dawley rats, VigRX was shown to engender a marked
improvement in sexual behaviour including decreased
intromission and ejaculation latencies, and increased
intromission, ejaculation and mounting frequencies [11].
In the same study, assays for pharmaceutical adulter-
ation found that VigRX did not contain any detectable
levels of known PDE-5 inhibitors including sildenafil,
tadalafil, vardenafil or related analogues. In vitro assays
also determined that VigRX is able to inhibit the Rho-
kinase. Rho-kinase is an enzyme that plays an important
role in maintaining the flaccid state of the penis through
cavernosal vasoconstriction [12] and is being increas-
ingly considered as emerging target for the treatment of
erectile dysfunction [13]. VigRX, however, exhibited a
relatively high inhibition concentration in the Rho-
kinase inhibition assay, indicating that a large dose
would be necessary to achieve similar results in a living
system. Hence, three more ingredients Tribulus terres-
tris,Turnera diffusa and Bioperine
W
(piperine) were
added to the formulation. The resulting new formula-
tion, named VigRX Plus (Table 1), was evaluated for its
aphrodisiac properties in male albino Wistar rats. Treat-
ment with VigRX Plus at the dose of 450 mg/kg showed
a significant increase in ejaculation frequency on day 7
and a non-significant increase on day 14 with a marginal
increase in testosterone concentration in serum and
number of spermatogonia cells in seminiferous tubules
of testes (Unpublished data; Available upon request). An
acute oral toxicity study of VigRX Plus tablet blend
observed no lethality, nor adverse effects at single oral
doses up to 4,000 mg/kg in female rats (Unpublished
data, Available upon request).
With the accrued preclinical evidence, VigRx Plus
demonstrated potential as a novel agent for management
of ED. It was thus imperative to evaluate its safety and
efficacy in humans.
Methods
Administration
The study was registered at the Clinical Trials Registry
India (Registration No: CTRI/2009/091/000099, 31-03-
2009) and received approval from an independent ethics
committee (IEC) of Noble Hospital, and AMAI Charit-
able Trust, Pune, India. The study was conducted at out-
patient clinics of participating urologists and general
physicians, from May 2009 to December 2009. The trial
conduct was monitored to ensure compliance to the eth-
ical principles of Declaration of Helsinki, International
Conference on Harmonisation (ICH) - Good Clinical
Practice (GCP) guidelines and IEC approved protocol.
Independent quality assurance auditors verified the qual-
ity of the data generated from the study.
Participants
Men aged 25–50 years, seeking treatment for sexual dys-
function, at the outpatient clinics of investigators, were
offered participation in this study. The volunteers gave
written informed consent before being assessed on the
IIEF scale. Those with a score of 11–23 on the EF do-
main of the IIEF were eligible. Major illnesses (including
Table 1 Composition of VigRX Plus
Ingredients
(Botanical names)
Part used Quantity per
capsule (mg)
Panax ginseng Root 100
Serenoa repens Berry 100
Crategus rivularis Berry 100
Ginkgo Biloba Leaf 100
Turnera diffusa Leaf 100
Tribulus terrestris Vine 075
Erythroxylum catuaba Bark 050
Ptychopetalum olacoides Bark 050
Cuscuta chinensis Seed 025
Epimedium sagittatum Leaf 015
Bioperine (extract from
Piper nigrum fruit)
- 005
Total amount 720
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diabetes and cardiovascular diseases) and sexual dys-
function due to anatomical, surgical or pharmacological
causes were excluded.
Randomisation and blinding
Subjects were randomized to receive VXP or placebo at
a dose of 2 capsules twice daily (each capsule containing
360 mg of active or placebo composition) for 12 weeks.
The randomization sequence was generated manually, in
blocks of four, by drawing chits of paper from a bag, by
a person not involved in the execution of the study or
the analysis of its results. Investigator, patient and statis-
tician were blinded to the random assignment. Ran-
domization sequence was concealed in tamper-evident
envelopes maintained in the custody of investigators.
Envelope integrity was checked at each monitoring visit
to ensure concealment of random allocation.
The study medications were indistinguishable in terms
of appearance, weight and taste. Both active and placebo
were packed in identical containers with identical labels
carrying patient ID and treatment week as distinctive
markers for dispensing and monitoring compliance. Use
of any other substance or product for treatment of male
sexual dysfunction was prohibited during the study.
Prior use of conventional or alternative medicine
required a wash out of 7 and 15 days respectively.
Outcome measures
The IIEF questionnaire was used to evaluate the treat-
ment effect on the sexual functioning in subjects of this
study. The questionnaire described by Rosen et al. is a
self-reported, validated instrument for measuring erectile
dysfunction and monitoring response to treatment [14].
It evaluates several aspects of sexual function over five
important domains: Erectile Function (EF), Sexual Desire
(SD), Orgasmic Function (OF), Intercourse satisfaction
(IS), and Overall satisfaction (OS). The IIEF was admi-
nistered at baseline and 4-week intervals.
Treatment satisfaction of subjects and their female
partners was assessed through responses to the Erectile
Dysfunction Inventory of Treatment Satisfaction (EDITS)
questionnaire. Seminal parameters and serum testoster-
one levels were assessed at baseline and end of study.
Safety was evaluated through incidence of adverse events,
changes in laboratory parameters and subject’s rating for
tolerability of treatment. Subjects were also asked to de-
clare whether they wished to continue with the trial
medication. Additionally, at study end, investigators
rated response to therapy as excellent, good, fair or poor.
Statistical analysis
Analysis for safety was done on an intent-to-treat (ITT)
population of subjects who received at least one dose
and had at least a single post-baseline measurement.
Efficacy analysis was done on a per protocol (PP) data
set consisting of subjects completing all protocol-
required visits. Statistical analyses were performed using
SAS
W
for windows (version 9.2; SAS Institute, Cary, NC,
USA), True Epistat version 5.0; and MS Excel XP. Mean
changes in IIEF-EF, IS,OF,SD and OS domains, and total
IIEF scores from baseline to end of treatment were eval-
uated by analysis of covariance (ANCOVA) with baseline
scores as the covariate. Data on EDITS (patient
and partner versions), seminal parameters and serum
testosterone were analyzed by independent sample ttest.
Chi-square test was used to analyze investigators’global
assessment and subject’s opinion. All statistical tests
were applied at a 5% level of significance.
Results
Patient disposition and baseline characteristics
A total of 78 subjects were recruited into the study.
While all men receiving VXP completed the study dur-
ation of 12 weeks, one in the placebo group was with-
drawn due to his unwillingness to continue participation,
and two others were lost to follow-up (Figure 1). Baseline
characteristics of the participants including severity of
sexual dysfunction were comparable across the two
Screened
(N=108)
Screening failures
(N=30)
IIEF scores (N=8)
Laboratory testing (N=14)
Pre-existing illness (N=1)
Others (N=7)
Randomized
(N=78)
Received
Placebo
(N=39)
Received VigRX
Plus
(N=39)
Week 4
(N=39)
Week 4
(N=39)
Week 8
(N=39)
Week 8
(N=38)
Week 12
(N=39)
Week 12
(N=36)
Total
completed
(N=75)
Lost to
follow-up
(N=01)
Lost to
follow-up
(N=02)
Figure 1 Flow of participants.
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groups (Table 2). Almost all patients in the VXP (38/39)
and placebo (36/36) group were finding it difficult to ex-
tremely difficult maintaining their erection to completion
of intercourse. In both groups, attempts to intercourse
ranged from 3–4 or5-6 in the four weeks prior to enter-
ing the study.
Efficacy
Primary efficacy parameters
IIEF-EF domain
Treatment with VXP showed a statistically significant
(P< 0.0001) increase of IIEF–EF domain scores from
baseline to end of study (12 weeks) as compared to pla-
cebo (Table 3). Mean (sd) increase in EF score was of 9
(4.95) points in the VXP group and 0.61 (2.43) points in
the placebo group. In 13/ 39 (34%) patients in the VXP
group and one (3%) in the placebo group, the erections
were almost always or always hard enough for penetra-
tion (Q2 IIEF).The ability to penetrate the partner (Q3
IIEF) and maintain erection after penetration (Q4 IIEF)
increased by 59% and 63% in subjects receiving VXP
and by 4% and 9% in those receiving placebo, respect-
ively. Almost all subjects receiving VXP, and two receiv-
ing placebo rated their confidence to get and keep
erection as high to very high. 14 subjects in the VXP
group and one in the placebo group achieved >25 (no
dysfunction) scores at the end of study.
IIEF- Other domains
Following 12 weeks of treatment, there was a signif-
icant improvement from baseline in all other IIEF do-
mains (SD, OF, IS and OS) in the VXP group as
compared to placebo (Table 3). Percentage increase in
each of the domains was greater with VXP therapy
than with placebo (Figure 2).Greatest increases were
observed in the erectile function and intercourse satis-
faction domains.
Frequency of intercourse attempts increased in both
groups with 15 patients in the VXP group and 10 in the
placebo group making 11+ attempts in the last four
weeks of the study. However, a majority of patients in
the VXP group said that their sexual intercourse was
highly to very highly enjoyable whereas for most patients
in the placebo group sexual intercourse was either fairly
enjoyable or not enjoyable.
Sexual desire was frequently rated as high to very high
in the VXP group, and moderate to high in patients re-
ceiving placebo. More patients in the VXP than in the
placebo group were very satisfied with their overall sex
life sexual relationship with their partner. The mean (sd)
increase in total IIEF was 20.10(11.08) in the VXP group
and 1.0(5.73) in the placebo group (P< 0.001).
Table 2 Baseline characteristics
Characteristics VigRX Plus Placebo
(N = 39) (N = 39)
Age in years
Mean (SD) 35.23 (6.62) 34.33 (5.89)
Range 25-48 25-44
Duration (years)
Mean (SD) 2.27 (1.80) 2.01(1.35)
Range 0.25-10 0.25-6
Mild to moderate
†
ED (n) 21 23
Moderate ED (n) 18 16
ED, erectile dysfunction; IIEF-EF, international index of erectile function-erectile
function.
†
Mild-to-moderate ED and moderate ED were defined as IIEF-EF:17–21 and IIEF
scores 11–16 respectively.
Table 3 Effect of VigRX Plus on the IIEF domains
IIEF Domains VigRX Plus Placebo
Baseline EoT Change 95%CI Baseline EoT Change 95%CI
EF,Q1-5,15 16.08 (2.87) 25.08 (4.56)* 9 (4.95) 7.40,10.60 15.86 (3.24) 16.47 (4.25) 0.61(2.43) −0.21,1.43
Q1 3.38 (0.67) 4.64 (0.67) 1.26 (0.88) 0.98,1.54 3.33 (0.53) 3.38 (0.77) 0.06 (0.58) −0.14,0.25
Q2 2.71(0.65) 4.17 (0.82) 1.46 (0.94) 1.16,1.76 2.66 (0.63) 2.80 (0.75) 0.14 (0.42) −0.0,0.28
Q3 2.69 (0.57) 4.12 (0.80) 1.43 (0.85) 1.15,1.70 2.63 (0.59) 2.75 (0.69) 0.11(0.46) −0.05,0.26
Q4 2.56 (0.50) 4.02 (0.81) 1.46 (0.91) 1.16, 1.76 2.44 (0.56) 2.66 (0.68) 0.22 (0.48) 0.06, 0.38
Q5 2.23 (0.78) 3.94 (0.89) 1.71 (1.02) 1.38, 2.04 2.27 (0.85) 2.33 (0.89) 0.06 (0.47) −0.10, 0.21
Q15 2.48 (0.56) 4.15 (0.87) 1.66 (1.03) 1.33, 1.99 2.5 (0.56) 2.52 (0.84) 0.03 (0.56) −0.16, 0.21
IS, Q6-8 7.28 (1.70) 11.58 (2.46)* 4.3 (2.47) 3.50,5.10 7.13 (1.76) 7.72(1.98) 0.58 (1.44) 0.09,1.07
OF, Q9-10 7.84 (0.93)9( 9.23 (1.13)* 1.38 (1.24) 0.98,1.78 7.77 (1.20) 7.77 (1.53) 0.0 (0.92) −0.31,0.31
SD,Q11-12 6.35 (1.11) 9.05 (1.36)* 2.69 (1.73) 2.13,3.25 6.47 (1.28) 6.41 (1.5) −0.05 (1.62) −0.60,0.50
OS, Q13-14 5.46 (1.10) 8.17 (1.73)* 2.71 (1.86) 2.10,3.31 5.61 (0.96) 5.47 (1.50) −0.14 (0.90) −0.45,0.16
Total IIEF,Q1-15 42.56 (5.09) 63.13 (10.06)* 20.10 (11.08) 16.51,23.69 42.54 (5.10) 43.86 (8.45) 1.0 (5.73) −0.93,2.93
IIEF scores are expressed as Mean (SD), *P <0.001 is statistically significant for change from baseline as compared to placebo.CI, confidence intervals; EF, erectile
function; EoT, end of treatment; IS, intercourse satisfaction; OF, orgasmic function; OS, overall satisfaction; SD, sexual desire.
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Overall, the significant rise in every domain of the IIEF
indicates that VXP had improved various aspects of sex-
ual functioning in men.
Secondary efficacy parameters
Subjects and female partners in the VXP group reported
significantly higher (P< 0.0001) scores of treatment satis-
faction by EDITS than those in the placebo group
(Table 4). The fact that both patient and partners were
highly satisfied is a reflection of the improved quality of
sexual life after treatment with VXP.
There was no significant difference in the changes in
sperm count, semen volume and sperm motility between
the two treatment groups. Serum Testosterone levels
were not altered significantly in any of the study groups
(Table 5). VXP received greater number of favorable
(p < 0.001) responses in investigator’s global assessment
of efficacy, as compared to placebo. VXP therapy was
rated as excellent in 8, very good in 18 and good in 11
subjects. In a majority of subjects (26 out of 36) in the
placebo group, efficacy was rated as poor. Thirty-five out
of 39 (90%) subjects (P< 0.0001) in the VXP group
answered ‘yes’to the question, ‘Would you take the same
product in the future if you suffer from the same condi-
tion?’Only one subject (3%) from the placebo group
responded positively to this question.
Safety
VXP was generally well tolerated in this study. Out of a
total of 23 adverse events occurring in the study, 11
were reported from the VXP group and 12 from the pla-
cebo group. The most common (7/23) adverse event was
fever of mild severity, with the incidence of the event
being similar in both. A single serious adverse event oc-
curred in this study when one subject from VXP group
was hospitalized due to malarial infestation and subse-
quently withdrawn from the study. No significant differ-
ence was observed in the tolerability of treatment as a
majority of subjects in both groups (31 in VXP and 28
in placebo) rated the tolerability as very good.
Discussion
Over recent years, the use of complementary and alter-
native medicines has become increasingly popular [15],
and ED is one condition for which herbal supplements
are heavily promoted and easily accessible [16]. ED suf-
ferers often seek alternatives, since many are reticent to
express their sexual problems to physicians [17], or are
dissatisfied with current therapies. Even after restoration
of erectile function, successful treatments have neverthe-
less been abandoned for such reasons as fear of possible
side effects, aversion to drug-dependent erections, high
drug cost, dislike of need to plan sexual activity, and lack
of sexual interest [18].
The present study evaluated VigRX Plus, a poly-herbal
supplement purported to offer natural sexual enhance-
ment in men. The efficacy results of this first-in-human
study were generally consistent with the effects demon-
strated by VXP in animal experiments. VXP was found
to be effective in improving the erectile function in men
with sexual dysfunction. Statistically significant increases
in IIEF scores showed that VXP had a therapeutic bene-
fit that was superior to placebo. From the improvement
displayed in all five domains of the IIEF (erection qual-
ity, sexual desire, orgasm quality, intercourse satisfaction
and overall satisfaction), it appears that VXP may help
in enhancing the overall quality of sexual experience in
men.
Multi-herb combination: synergistic efficacy or
compromised safety?
Efficacy
Often, multi-herb supplements are formulated with the
aim of achieving a net additive or synergistic effect of in-
dividual ingredients with similar clinical or pharmaco-
logical actions. Practitioners of traditional medicine
believe that combinations of herbs improve efficacy and
reduce adverse effects [19]. But whether such combina-
tions synergize or even simulate the therapeutic action
of their components remains largely unknown.
Figure 2 Percentage change from baseline in IIEF domains.
Treatment with VigRX Plus significantly improved all important
domains of sexual functioning in men. Note that an increase in the
ability to achieve and maintain an erection (erectile function) was
accompanied by increases in intercourse and overall satisfaction.
*P < 0.001 for% change (mean ± sem) from baseline to end-of-
treatment with VigRX Plus as compared to placebo.
Table 4 Effect on EDITS scores
VigRX Plus Placebo
Patient 82.31 (20.23) 36.78 (22.53)
(N = 39) (N = 36)
Partner 88.75 (9.80) 18.50 (9.44)
(N = 12) (N = 10)
EDITS scores are expressed as Mean (SD).
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Among the herbal constituents of VXP, only Korean
red ginseng has been previously evaluated on the IIEF
scale, in two double-blind, randomized, controlled stud-
ies. Of the two, a similar study in 60 patients with mild
to moderate ED showed an increase in the IIEF-five item
scores from a baseline of 16.4 ± 2.9 to 21.0 ± 6.3, after re-
ceiving 1000 mg (3 times daily) of ginseng for 12 weeks
[20]. The increase of 9 points in IIEF- EF with VXP in
our study is comparable to the approximately 5-point in-
crease in the ginseng study. In the other 45-patient study
designed as cross-over, mean increases in IIEF scores in
the Ginseng (900 mg. 3 times daily) group were signifi-
cantly higher than in those who received placebo (base-
line 28.0 +/−16.7 and 38.1 +/−16.6 versus 30.9 +/−
15.7, p <0.01) [21]. In response to the global efficacy
question, 60% of the patients answered that Korean red
ginseng improved erection, which is in agreement with
the 72% (26 out of 36) patients global response observed
in our study.
The aphrodisiac properties of tribulus were demon-
strated in animal models [22-24] and in a human study
[25] where tribulus extract (3x250 mg/day for 3 weeks)
increased the sexual drive in 60% of diabetic and non-
diabetic ED men. This was accompanied by a significant
improvement in the levels of dehydroepiandrosterone-
sulphate (DHEA) - a hormone necessary for the matur-
ation process of spermatozoa; however no significant dif-
ferences were observed in testosterone.
Serenoa repens (Saw Palmetto) in an open study for
longer than 48 weeks in 155 men with clinically diag-
nosed BPH, prostate symptoms and quality of life
improved significantly from baseline over the 2 years
while sexual function improved in the second year
[26]. Turnera diffusa (Damiana)’s sexually invigorating
properties were evidenced from studies in sexually
exhausted male rats [27,28]. Gingko biloba has been
shown to relax vascular smooth muscle and this mech-
anism of action is thought to contribute to an im-
provement in ED [29]. Icariin, the active ingredient
from Epimedium sagitattum, improved the erectile
function and expression of nitric oxide synthase in
castrated rats [30,31].
Thus, overall, the VXP multiple-herb preparation
appears to have exhibited the properties of its individual
ingredients. But whether the blend was more potent
than single herbs is unlikely to be ascertained from this
study, mainly due to different study methodologies and
populations of individual herb studies, causing difficulty
in comparison of results.
Safety
Safety deserves no less attention than efficacy, while
choosing an appropriate therapy for ED. Negative conse-
quences associated with treatment, have been identified
as important to patients receiving treatment for ED [32].
VXP was apparently safe and well-tolerated in this study.
This is consistent with the long history of safe use of
herbs present in VXP. Contrary to the general belief, re-
cent reports have questioned the safety of some herbs
including Ginkgo biloba which has concerns over blood-
thinning effects [33] and ocular toxicity [34]. That none
of these adverse effects were reported for VXP is assur-
ing; however, caution should be exercised while inter-
preting the safety results as they are not determined
over the long-term.
ED: Through the patient’s perspective
Unlike many other medical disorders, ED is a condition
for which nobody other than the patient can decide
upon a treatment option or interpret its success [35].
Both patient and partner satisfaction are considered to
be relevant to understanding and predicting treatment
continuation in ED [32,36].The growing importance of
patient choice in clinical decision-making is evident from
several trials that have attempted to evaluate patient
preference or treatment-switching patterns amongst
available PDE-5 inhibitors: the first-line ED treatment.
Long-term adherence to PDE-5 inhibitors seems to be
low despite their high efficacy, good tolerability, and
ease of administration [37].
Our study primarily focused on obtaining the patients’
perspective on treatment success, mainly by employing
patient-reported measures like the IIEF and EDITS.
We found that improvements in sexual function recorded
Table 5 Effect on seminal parameters and serum testosterone
Variable VigRX Plus Placebo
Baseline 12 weeks Baseline 12 weeks
Sperm count (million/ml) 49.45 (27.85) 47.15 (25.31) 58.29 (30.02) 63.97 (20.83)
(N = 22) (N = 22) (N = 18) (N = 18)
Semen volume (ml) 1.75 (0.63) 2.11 (0.53) 1.97 (0.70) 2.22 (0.88)
(N = 22) (N = 22) (N = 18) (N = 18)
Serum testosterone (ng/Dl) 544.46 (207.64) 527.66 (155.47) 518.10 (197.51) 471.75 (160.38)
(N = 37) (N = 37) (N = 25) (N = 25)
Data are expressed as Mean (SD).
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by IIEF were corroborated by patient and partner satisfac-
tion, as evidenced by significantly greater EDITS (patient
and partner) scores reported for VXP as compared to pla-
cebo. Additionally, subjects’opinions and investigators’
rating were also in favor of VXP.
Limitations and future action
First of all, the study sought to examine the effects of
VigRx Plus in young men who had no apparent co-
morbid conditions. ED on the other hand, is recognized
as a disorder of older adults suffering from systemic dis-
eases such as diabetes mellitus, cardiovascular disease
and hypertension [38,39]. The seemingly atypical patient
characteristics limit the extrapolation of the clinical
benefit of VXP to that in the presence of concurrent dis-
eases and medications that are commonly seen in a lar-
ger ED population of older adults.
However, young patients reporting erectile difficulties
are not unknown of. Heruti et al. reported that at least
one out of three young men could be suffering from ED,
emphasizing that this condition is a major health concern
of the young as well [40]. Another study has observed that
young men with ED have comparatively more difficulty in
adjusting to life influenced by less relationship satisfaction,
greater depressive symptomatology, more negative reac-
tion from partners and less job satisfaction [41]. Moreover,
unlike the ‘asexual older men’who perceive ED as a nor-
mal and irreversible part of the ageing process [42], young
men may find ED a serious impediment to an active and
perfect sexual life, and are hence likely to seek help more
often than their older counterparts.
Secondly, the study does not gather enough evidence
to conclude whether the ED was of organic, psychogenic
or mixed origin. Even in the absence of any detectable
underlying condition or risk factor, an organic aetiology
cannot be refuted as ED is known to share common
endothelial dysfunction pathways with many vascular
diseases [43] and manifests 2–3 years beforehand [44] to
serve as an early warning of such diseases, particularly
in men 45 years or younger [45]. Experts therefore rec-
ommend that physicians consider a man with ED and
no cardiac symptoms as a cardiac or vascular patient
until proved otherwise [46]. Thus, we hypothesize that
vascular and other conditions though noticeably absent
could have existed in a latent or subclinical phase when
patients entered the study. Only long- term follow-up
programs can help verify if ED had actually served as a
predictor of vascular abnormalities in these patients.
Then again, we did not specifically rule out psychogenic
ED by the use of psychometric assessments or by evaluating
the intactness of sleep-time erections through nocturnal
penile tumescence and rigidity testing. Given that psycho-
genic ED should be confirmed only after ascertaining the
presence of psychosocial factors as the predominant or
exclusive cause [47], a definitive statement that the patients
in our study were mainly suffering from psychogenic ED
would remain unjustified. Future studies with VXP should
aim at differentiating between various forms of ED in order
to acquire a better understanding of the intervention in
treating ED of diverse aetiology.
An intriguing finding of the study was the small sized
placebo effect observed for patient reported outcomes. It
is a clear departure from the usually observed placebo re-
sponse rate of 25% (1 out of every 4 men benefits) in ED
trials [48]. Here again, the finding suggests a preponder-
ance of organic ED and also a tendency for non-response
towards placebo. The fact that patients had a history of
over two years of erectile difficulties before enrolling
themselves for the study indicates that they were not treat-
ment naive and had exhausted their placebo response to a
new treatment option .The learning that occurs after ex-
periencing the benefits and side effects (or the lack
thereof) from a previous medication may have shaped
patients’expectations about a therapeutic effect, allowing
them to decipher whether or not they received the active
treatment during the study. This partly explains why pa-
tient responses in the placebo group were poor while
those in the active group were comparable to that of
pharmacological drugs for ED. However, considering the
small sized placebo effect observed in this study, the
results described should be viewed with caution. It may
have benefited the treatment results as significantly better,
even if minimal. In clinical trials of drug treatments, pla-
cebo responses have often been substantial, usually signifi-
cantly and statistically better than no treatment (baseline).
Patient expectations could also be influenced by fore-
knowledge of the treatment assignment. Differences in
color or size of pills can serve as cues in differentiating
the active treatment from placebo to introduce a re-
sponse bias. However, this possibility is eliminated from
our study as the indistinguishable treatments and strict
implementation of operational measures ensured ad-
equate concealment of allocation sequence and pre-
vented any lapses in the integrity of study blinding.
To summarize, results obtained from evaluation in
young men with no overt organic causes may offer limited
generalizability, nevertheless, represent an important sub-
set of ED patients who are potentially amenable to therapy
and at the same time are least likely to exhibit a placebo
response that can confound the determination of active
treatment effects. The study has set grounds for further
evaluation of VXP in patients with well-recognized risk
factors and distinctly identified forms of ED.
Conclusions
VigRX Plus was well-tolerated and effective in improving
erectile function in men. Confirmation of the beneficial
effect in a broader ED population is recommended.
Shah et al. BMC Complementary and Alternative Medicine 2012, 12:155 Page 7 of 9
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Abbreviations
EF, Erectile function; IS, Intercourse satisfaction; OF, Orgasmic function;
OSD, Overall satisfaction; SD, Sexual desire.
Competing interests
Authors GRS, MVC, SBP, SVP and VPS were compensated for their
participation as study planners, organizers, investigators, and writers. NAS is
an employee of an organization that received funds for monitoring the
study. The funders had no influence on the scientific integrity of the
preparation for research, the study execution, and the preparation of the
manuscript for publication.
Authors' contributions
All authors made substantial contributions to study conception, acquisition
of data, and preparation of the manuscript. All authors read and approved
the final manuscript.
Authors’information
GRS: M.S., M.Ch (Urology), is a consulting urologist at leading hospitals in
Mumbai, and a member of the Mumbai Urology Society. Areas of special
interest include male infertility and impotence. MVC: M.D., PhD, is an
associate professor and practitioner of herbal medicine, Ashtang Ayurved
college and hospital, Pune. SBP: M.S., M.Ch (Urology) is Professor and Head
of Department at B.J.Medical College, Pune; chief urologist, Institute of
Urology; and a member of Urology society of India. SBP was an investigator
for clinical trials of PDE5 inhibitors in sexual dysfunction; and is the author of
several international peer-reviewed publications in urology. SVP: MBBS, is a
general medical practitioner in Mumbai and has been actively involved in
clinical trials of herbal medications. VPS: M.Ch. (Urology) is a practicing
urologist at Pune. NAS: B.A.M.S., is Manager, clinical operations,
Vediclifesciences Pvt. Ltd. Mumbai; has executed numerous phase II to III
clinical trials; and is also a practitioner of herbal medicine.
Acknowledgements
The authors acknowledge Leading Edge Herbals for funding the trial
medications and other requisites for the conduct and publication of the
study, including the article processing charges.
Author details
1
Jivdaya Hospital, Dharmoday bldg, Jivdaya lane, L.B.S. Marg, Ghatkopar
(West), Mumbai 400 086, India.
2
Bhaghirathi Medical Foundation, 169, Parvati
gaon, Pune 400 009, India.
3
Institute of Urology, 32/2A, Erandwane, Gulwani
Maharaj Road, Pune 400 009, India.
4
Balaji Clinic, Devi Pada, Main Road,
Borivali (East), Mumbai 400 066, India.
5
Sabale Multispeciality Clinic, First floor,
Vithal Acrade, Bhosari, Pune 411 039, India.
6
Clinical Operations, Vedic
Lifesciences Pvt. Ltd., B-118, Morya House, Link Road, Andheri (West),
Mumbai 400 053, India.
Received: 4 August 2011 Accepted: 16 August 2012
Published: 15 September 2012
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doi:10.1186/1472-6882-12-155
Cite this article as: Shah et al.:Evaluation of a multi-herb supplement for
erectile dysfunction: a randomized double-blind, placebo-controlled study.
BMC Complementary and Alternative Medicine 2012 12:155.
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