Microsoft word - addyzoa vaze.doc
Double-Blind Comparative Trial of Herbomineral Antioxidant Formulation with Ubiquinone (Coenzyme Q10) in Oligoasthenospermia
Consultant Urologist and Andrologist, Lilawati Hospital and Research Centre
104, “Cornelian”, August Kranti Marg,
Telephone: 91-22-2386 0126, 91-22-2387 7923
Key words: Oligoasthenospermia, Ubiquinone (Coenzyme Q10), Herbomineral Antioxidant Formulation, Addyzoa
Aim: To evaluate the efficacy of an antioxidant herbomineral formulation, Addyzoa
(Charak Pharma Pvt. Ltd., Mumbai, India) in oligospermia in comparison with
Methods: A double-blind, randomised controlled trial was conducted at Dr Vaze’s clinic,
Mumbai. A total of sixty patients, 30 in each group, were studied. Cap Addyzoa was
administered in a dose of two capsules twice a day for three months and Cap Ubiquinone
(Coenzyme Q10) 30 mg, one capsule thrice a day. The main study outcomes were an
increase in sperm count and improvement in motility and morphology of sperms.
Results: In the Addyzoa group, an average increase of 2.74 million sperm was observed,
whereas in the Ubiquinone (Coenzyme Q10) group sperm count increased by 2.27
million. In both groups, the increase in motility was on average 1.5 to 2 times. Though
the observed difference between the two groups is not statistically significant (p > 0.1),
the 0.47 million difference appears to be clinically significant.
Conclusion: The study concluded that treatment with Addyzoa is effective in improving
the semen quality by increasing the sperm count and sperm motility. The results are
comparable with that of Ubiquinone (Coenzyme Q10) on semen parameters.
The author thanks Charak Pharma Pvt. Ltd., Mumbai, India, for providing a research
Male infertility, with its clinical and psychosocial implications, poses a significant
challenge to the physician and to the society as a whole. Recent studies have indicated
that the prevalence of oligospermia is extremely high in metropolis as well as in smaller
towns of India. According to the results of one such study, in Kurnool in Andhra Pradesh
(a state in India), the prevalence of oligospermia was 51%; it was 31% in Mumbai and
between 15% and 30% in other three cities like Jalandhar, Jodhpur and Bangalore (1).
The alarmingly high prevalence of oligospermia has resulted in an increase in male
infertility. Almost in 50% of couple infertility, male partner suffers from oligospermia.
In 15% of subfertile couples, in approximately 30% of the cases, abnormality is identified
in the male partner and in another 20%, abnormalities are detected in both the partners.
For the majority of men with infertility, no specific causal factor can be identified.
In majority of cases, defective sperm function is the commonest cause for male infertility
(2). Defects in sperms are associated with low sperm concentration (oligospermia), poor
sperm motility (asthenospermia) or abnormal sperm morphology (teratospermia). These
defects are collectively called as oligoasthenoteratospermia (3). Recent research suggests
that large proportion of infertile men have elevated levels of seminal reactive oxygen
species (ROS). Various ROS like superoxide, hydroxyl, nitric oxide, peroxide, and
peroxynitrile are generated in excess by immature and abnormal spermatozoa and by
contaminating leukocytes associated with genitourinary tract inflammation. These ROS
have been associated with oligoasthenoteratospermia. As spermatozoa membranes are
rich in poly-unsaturated fatty acids (PUFA), sperms are more susceptible to the damage
caused by ROS by lipid peroxidation. Environmental factors like pesticides, exogenous
estrogens and the process of aging itself, further induce oxidative stress (4, 5, 6). Free
radical-induced sperm damage can occur within the semen, in the epididymis or in the
testis. By damaging the membrane integrity, free radicals impair sperm motility as well
Normally, semen contains antioxidant mechanisms, which protect spermatozoa from
oxidative stress by neutralizing ROS. However, when there is an improper balance
between ROS and antioxidant mechanisms, spermatozoa are damaged leading to male
In addition, the intracellular antioxidant enzymes cannot protect the plasma membrane
that surrounds the acrosome and the tail, forcing spermatozoa to supplement their limited
intrinsic antioxidant defenses by depending on the protection afforded by the seminal
Oxidative stress attacks not only the fluidity of the sperm plasma membrane, but also the
Since ROS induced lipid peroxidation in sperm cells is an important factor affecting male
infertility, antioxidants could assume a significant therapeutic role in these patients.
Therefore, the present study was carried out to evaluate efficacy of Addyzoa (Charak
Pharma Pvt. Ltd., Mumbai, India), a herbomineral formulation (Table 1), in comparison
with Ubiquinone (Coenzyme Q10) 30 mg in oligospermia.
This clinical study was undertaken at Dr. Vaze’s clinic, Mumbai. This was a double blind,
randomized, comparative study. The protocol was approved by the ethics committee.
Before enrolling patients in the study, written informed consent was obtained after
Patients with infertility persisting longer than 2 years were examined twice before
recruitment in the study. The main inclusion criteria were oligospermia (less than 20
million sperm counts) and asthenospermia (less than 50% motile sperms).
Complete physical examination and biochemical tests like CBC, ESR, blood sugar, renal
function tests, liver function tests and semen examinations were performed in the
screening examinations. Two semen samples were collected after abstinence of 4 days at
2.2 Patients: Sixty patients in the age group of 25-42 were included in the trial.
2.3 Dose and Duration: Thirty patients received Addyzoa, two capsules twice a day and
30 patients received Ubiquinone (Coenzyme Q10), one capsule three times a day for 3
2.4 Semen analysis: Semen analysis was performed according to WHO guidelines and
included physical parameters as well as sperm count, motility and morphology. Semen
analysis (and all the other biochemical investigations) was performed at the same
2.5 Statistical evaluation: Student’s t-test was applied to evaluate the average sperm
count increase from the baseline at the end of the trial.
Of the 60 patients, 30 received Addyzoa and 30 patients received Ubiquinone (Coenzyme
Q10). The sperm count at baseline and on completion of the therapy with corresponding
increasing sperm count is shown in Table No. 2. The main expected improvement was
the sperm count increase. No adverse effects were reported during the treatment.
In the Addyzoa group, an average increase of 2.74 million in sperm count was observed,
whereas in Ubiquinone (Coenzyme Q10) group, sperm count increased by 2.27 million.
Though the observed difference between the two is not statistically significant (p > 0.1),
the 0.47 million difference in sperm count appears to be clinically significant (Figure 2).
Overall, the motility showed a significant increase in both groups. The increase in
Marginal improvement in morphology was observed in both groups.
Discussion: Advances in medical sciences for the last three decades have identified the
presence of excessive oxidative stress responsible for male infertility. Sperms are made
up of unsaturated fatty acids and are very sensitive to free radical damage by lipid
peroxidation. Many environmental, physiological and genetic factors have been identified
as a cause of poor sperm function and infertility. All these factors lead to reactive oxygen
species (ROS). Therefore, the role of anti-oxidants in the treatment of male infertility is
In view of free radical damage to the sperms, anti-oxidant mechanisms are important in
the maintenance of sperm motility, the spermatogenesis and the ability of sperms to
The ingredients of Addyzoa such as Amalaki (Emblica officinalis) (9), Ashwagandha
(Withania somnifera) (10), Guduchi (Tinospora cordifolia) (11,12), Shatavari (Asparagus
racemosus) (13), Safed Musli (Chlorophytum tuberosum) (14), Kapikachhu (Mucuna
pruriens) (15), Balamool (Sida cordifolia) (16) and Vidarikand (Ipomoea digitata) (17)
are all reputed anti-oxidants. These ingredients are used in a number of antiageing,
rejuvenating and virilizing formulations.
Various studies suggest that these medicinal plants might be potent and novel therapeutic
agents for scavenging of NO and the regulation of pathological conditions caused by
excessive generation of NO and its oxidation product, peroxynitrite.
The individual constituent herbs in Addyzoa have been extensively studied for their
spermatogenic and antioxidant effects. For example, the antioxidant activity of tannoid
active principles of Amalaki (E. officinalis) consisting of emblicanin A (37%),
emblicanin B (33%), punigluconin (12%) and pedunculagin (14%), was investigated on
the basis of their effects on rat brain frontal cortical and striatal concentrations of the
oxidative free radical scavenging enzymes, superoxide dismutase (SOD), catalase (CAT)
and glutathione peroxidase (GPX), and lipid peroxidation, in terms of thiobarbituric acid-
reactive products. The results also indicate that the antioxidant activity of E. officinalis
may reside in the tannoids of the fruits of the plant, which have vitamin C-like properties,
Ashwagandha (W. somnifera), the other important ingredient, has direct spermatogenic
effect. The effect of lyophilized aqueous extract of Withania somnifera on testicular
development and on serum levels of testosterone, ICSH and FSH has been studied in
immature male Wistar rats. A notable increase was observed in the testicular weight of
animals treated with the extract. Histological examination revealed an apparent increase
in the diameter of seminiferous tubules and the number of seminiferous tubular cell
layers in the testes of treated rats as compared with control ones. The extract of Withania
somnifera elicited notable spermatogenesis in immature rats. Serum testosterone and FSH
levels were lower in animals treated with the plant extract than controls, whereas ICSH
level was higher in treated animals. It was concluded that the extract of Withania
somnifera has a direct spermatogenic influence on the seminiferous tubules of immature
rats presumably by exerting a testosterone-like effect (18).
In previous studies, the efficacy and safety of Addyzoa in improving seminal parameters
has been studied extensively. The effect of 6 month’s therapy with Addyzoa on sperm
parameters was investigated in a randomized, placebo-controlled study of 200 men with
idiopathic subfertility. The results indicated that Addyzoa resulted in statistically
significant improvements in sperm density (368%), motility (197%) and morphology
(183%) as well as other routine sperm tests. Pregnancy rates among the subfertile
couples, to which these men belonged, were found to be 25% with Addyzoa over a two-
year follow-up period as compared to 2% with placebo (19).
The effects of Addyzoa on male factor subfertility have also been compared with
clomiphene citrate. In a 6-month, randomized study of Addyzoa in 100 men in
comparison with clomiphene, treatment with Addyzoa resulted in statistically significant
improvements in sperm density, motility, morphology as well as other routine sperm
tests. Pregnancy rates among the subfertile couples, to which these men belonged, were
22% and 19% in the Addyzoa and clomiphene groups, respectively, over a one-year
As such, significantly high proportion of male subfertility is unexplained. In such a
scenario, infertility can significantly affect their relationship as it often becomes the
central issue in their lives. Even in the era of assisted reproductive techniques (ART),
therapy with anti-oxidants like Addyzoa helps in improving the semen parameters.
Further, Addyzoa also provides an advantage in terms of cost of therapy compared to
Recent advances in cellular biology have indicated the presence of the facilitative glucose
transporter GLUT-5 in sperms. GLUT-5 helps in transporting glucose into the sperm cell,
which is then used as a substrate for energy production. Expression of GLUT-5 is
susceptible to hormonal and environmental factors such as oxidative stress. Differential
expression of this molecule is associated with several physiological abnormalities (21).
We now know that ingredients of Addyzoa such as Shilajit, Amalaki and Guduchi have a
significant role in the regulation of glucose metabolism. It is postulated that by virtue of
these ingredients, Addyzoa regulates the expression of GLUT-5 in sperm cells, thereby
The positive effect of anti-oxidants in improving the sperm quality and quantity will
restrict indiscriminative use of assisted fertility treatments like intra-cytoplasmic sperm
CONCLUSION: This double-blind, comparative trial of the herbomineral antioxidant
formulation Addyzoa in oligoasthenospermia concludes that treatment with Addyzoa is
effective in improving the semen quality by increasing the sperm count and enhancing
sperm motility and morphology. Treatment with Addyzoa resulted in a larger increase in
sperm count as compared to Ubiquinone (Coenzyme Q10), though the difference was not
statistically significant. In addition, a significant increase of 1.5 to 2 times in motility was
observed with Addyzoa and Ubiquinone (Coenzyme Q10) treatment. Improvement in
morphology was also observed in both groups. Thus, Addyzoa is a better option for
treating male infertility as it also provides an advantage over Ubiquinone (Coenzyme
Q10) in terms of cost of therapy. Further trials in a larger number of patients are required
to corroborate the findings of this study.
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subfertility. Obs Gyn Comm 2001; 3: 55-60.
20. Singh I, Kumar A, Bhandari P. Comparison of the efficacy of Addyzoa and
clomiphene in male factor subfertility. Int J Gyn Obs Ind 2001; 4(6).
21. Medina RA, Owen G. Glucose transporters: expression, regulation and cancer.
Sperm count in individual patients at baseline and on completion of trial.
Figure 1 Comparison of the mean sperm count (in millions) between Addyzoa and
Ubiquinone (Coenzyme Q10) group after 3 months of therapy
Are means signif. different? (P < 0.05)
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