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Sexual Dysfunction and Infertility
255
Urology Journal Vol 5 No 4 Autumn 2008
Effect of Saffron on Semen Parameters of Infertile Men
Mohammad Heidary,1 Jahanbakhsh Reza Nejadi,2 Bahram Delfan,2 Mehdi Birjandi,2
Hossein Kaviani,3 Soudabeh Givrad4
Introduction: We conducted this study to determine the effects of saffron
(Crocus sativus) on the results of semen analysis in men with idiopathic
infertility.
Materials and Methods: In this clinical trial, 52 nonsmoker infertile men
whose problem could not be solved surgically were enrolled. They were
treated by saffron for 3 months. Saffron, 50 mg, was solved in drinking milk
and administered 3 times a week during the study course. Semen analysis was
done before and after the treatment and the results were compared.
Results: The mean percentage of sperm with normal morphology was 26.50
± 6.44% before the treatment which increased to 33.90 ± 10.45%, thereafter
(P < .001). The mean percentage of sperm with Class A motility was
5.32 ± 4.57% before and 11.77 ± 6.07% after the treatment (P < .001). Class B
and C motilities were initially 10.09 ± 4.20% and 19.79 ± 9.11% which increased
to 17.92 ± 6.50% (P < .001) and 25.35 ± 10.22% (P < .001), respectively.
No significant increase was detected in sperm count; the mean sperm count
was 43.45 ± 31.29 × 106/mL at baseline and 44.92 ± 28.36× 106/mL after the
treatment period (P = .30).
Conclusion: Saffron, as an antioxidant, is positively effective on sperm
morphology and motility in infertile men, while it does not increase sperm
count. We believe further studies on larger sample sizes are needed to elucidate
the potential role and mechanism of action of saffron and its ingredient in the
treatment of male infertility.
Urol J. 2008;5:255-9.
www.uj.unrc.ir
Keywords: male infertility, Crocus
sativus, antioxidants, sperm motility,
sperm count
1Department of Urology, Lorestan
University of Medical Sciences,
Khorramabad, Iran
2Department of Anesthesiology,
Lorestan University of Medical
Sciences, Khorramabad, Iran
3Shohada-e-Ashayer Hospital,
Lorestan University of Medical
Sciences, Khorramabad, Iran
4Urology and Nephrology Research
Center, Shahid Beheshti University
(MC), Tehran, Iran
Corresponding Author:
Mohammad Heidary, MD
Urology and Nephrology Research
Center, No 44, 9th Boustan St,
Pasdaran Ave, Tehran, Iran
Phone: +98 21 2256 7222
Fax: +98 21 2256 7282
E-mail: drheidary@yahoo.com
Received February 2008
Accepted July 2008
INTRODUCTION
Approximately, 8% of the Iranian
couples suffer from infertility after
2 years of attempting conception.(1)
Where the issue lies with the male
partner, 2 groups of patients are
seeking treatment, namely those
suffering from idiopathic infertility
and those in whom the etiology
of infertility is known. Various
therapeutic agents including
clomiphene citrate, tamoxifen,
kallikreins, and antioxidant agents
such as vitamin E and glutathione
are used to help these patients;
nevertheless, none is a definite
treatment.(2-4) This necessitates
utilization of other alternative
agents.
Recent studies have investigated
the role of reactive oxygen species
(ROS) on sperm. Even though, small
amounts of ROS are necessary for
sperm activation, these agents can
cause damage to the sperm in higher
concentrations.(5-7) Increased levels
of ROS are related to decreased
motility of the spermatozoa and
DNA damage, and may even lead
to germ cell apoptosis.(8-12) In fact,
studies have shown that more than
Saffron and Semen Parameters of Infertile Men—Heidary et al
256 Urology Journal Vol 5 No 4 Autumn 2008
40% of infertile men have augmented levels of
ROS in their seminal plasma.(13) Therefore, many
studies have focused on antioxidant agents in order
to prevent this damage on sperm metabolism,
motility, morphology, and as a consequence,
fertilizing capacity.
Crocus sativus (saffron) is a perennial herb of the
Iridaceae family with antioxidative prosperities.(14-16)
It is widely cultivated in Iran, India, Greece,
Spain, and France. Its dried red stigma is
commercially used as a food spice. Saffron has
also been widely used in folk medicine as an
antispasmodic, eupeptic, pain killer, anticatarrhal,
carminative, diaphoretic, expectorant, stimulant,
stomachic, aphrodisiac, and emmenagogue.(17,18) In
some countries such as India, Spain, and China,
saffron has been used to treat infertility and
impotence from long ago.(19,20) We undertook this
study to investigate the effect of saffron on semen
parameters and infertility.
MATERIALS AND METHODS
Between 2006 and 2007, we evaluated infertile
men referring to the urology clinic of Shohada-
e-Ashayer Hospital in Khorramabad, Iran. All
patients were initially interviewed and questioned
about their sexual behavior, history of prior
surgical interventions or childhood diseases such
as cryptorchidism that affect fertility, and family
history of infertility. Complete drug history
was obtained; the patients were specifically
asked about administration of sulfasalazine,
cimetidine, marijuana, cocaine, and tobacco.
Moreover, history of contact with chemicals
and ionizing radiation was acquired. All patients
were then assessed for systemic diseases such
as fever, viremia, and acute infections (eg,
mumps). Finally, the participants underwent
full urologic examination. Smokers and patients
whose problems could be solved surgically were
excluded. Eligible patients provided informed
consent and entered the study. The study
protocol was approved by the ethics committee
of the Urology and Nephrology Research Center,
Shahid Beheshti University (MC).
Before initiating the treatment with saffron,
semen analysis was performed. Samples were
obtained 48 to 72 hours after the patient’s last
sexual contact. Analyses were performed by the
aid of the Computer-Assisted Sperm Analysis in
less than 1 hour after sample collection. Using
this method, sperm motility was determined
in 4 classes defined by the World Health
Organization.(21) These 4 classes are characterized
as follows: class A, fast progressively motile sperm
(4th degree); class B, progressively motile sperm
(3rd degree); class C, nonprogressively motile
sperm (2nd degree); and class D, immotile sperm
(1st degree).
By the end of initial evaluation and semen
analysis, the patients were asked to administer 50
mg of saffron solved in milk, 3 times a week for 3
months. A specific brand of the available saffron
in Khorramabad was obtained for all the patients.
The amount to be used was weighed and divided
in separate doses by the trained research assistants.
No other treatment options were considered
during the study period. After finishing the
treatment course, semen analysis was again
carried out by Computer-Assisted Sperm Analysis
method. Results were compared and analyzed by
paired t test.
RESULTS
A total of 52 eligible patients were enrolled in the
study, all of whom finished the study course and
underwent a secondary semen analysis. The mean
age of the patients was 31.0 ± 4.6 years (range, 21
to 48 years). The mean percentage of sperm with
normal morphology was 26.50 ± 6.44% before
the treatment which increased to 33.90 ± 10.45%,
thereafter (P < .001), which corresponded to
a 7.4% improvement in this index. Significant
increases were also seen in the percentages of class
A to class C morphology of the sperm. The mean
percentage of sperm with Class A motility was
5.32 ± 4.57% before and 11.77% ± 6.07% after
the treatment (P < .001). Class B and C motilities
were initially 10.09 ± 4.20% and 19.79 ± 9.11%
which increased to 17.92 ± 6.50% (P < .001) and
25.35 ± 10.22% (P < .001), respectively. Overall,
6.4%, 7.8%, and 5.6% increases were detected
in the percentage of sperm with class A, B, and
C motility, respectively. We could not detect
a significant increase in terms of sperm count
with saffron therapy; the mean sperm count was
Saffron and Semen Parameters of Infertile Men—Heidary et al
Urology Journal Vol 5 No 4 Autumn 2008 257
initially 43.45 ± 31.29 × 106/mL which changed
to 44.92 ± 28.36× 106/mL, afterwards (P = .30).
DISCUSSION
About 8% of the Iranian couples are infertile, and
male factor accounts for nearly 40% of infertility
cases.(1,22) Recent advances in fertility medicine are
indicative of ROS, which impairs sperm function,
as one of the reasons behind this dilemma.(1,8-13,23)
As mentioned earlier, in contrast to the semen
of a healthy man, seminal plasma of up to 40%
of infertile men shows increased amounts of
ROS.(13) Thus, reducing the ROS may help in
the treatment of male-factor infertility. Pursuing
this hypothesis, we examined saffron stigma as
an antioxidant and found that semen parameters
improved after a period of saffron administration.
Reactive oxygen species consist of a wide range
of molecules including radicals, nonradicals, and
oxygen derivatives.(22) A small amount of ROS
is necessary for the function of cells including
germ cells. However, in increased levels,
these molecules are capable of damaging cell
membranes and genetic content. Polyunsaturated
fatty acids found in the sperm cell membrane are
one of the primary targets of ROS due to their
lipid nature. Reactive oxygen species cause lipid
peroxidation in the sperm cell membrane, and as
a result, impair sperm motility and its ability to
fuse with the oocyte.(24,25) Moreover, ROS may
induce DNA damage, which in turn will result
in poor fertilization. This DNA damage happens
through modification of all bases, production
of base-free sites, deletions, frame shifts, DNA
cross links, and chromosomal re-arrangements.
Also, they may induce high frequencies of single-
strand and double-strand DNA breaks.(11,12,24)
Finally, high levels of ROS disrupt the inner
and outer membranes of the mitochondria; as
a consequence, cytochrome c is released and
caspases are activated which lead to apoptosis.(24)
Antioxidants preserve fatty acids from oxidation,
and therefore, may play an important role in
male fertility.(25) Many studies have investigated
the role of different antioxidants on infertility. In
an investigation by Lenzi and colleagues, it was
shown that utilizing glutathione (600 mg/d for
2 months) had a significant effect on increasing
sperm motility and morphology.(26) They carried
out another study in 1993 on 20 infertile men
and re-established the role of glutathione in
improving sperm motility and morphology.(27)
In 1996, Suleiman and coworkers determined
the role of vitamin E in the treatment of infertile
men. They treated 82 infertile men with vitamin
E and demonstrated that sperm motility increased
from 31.1% to 48.9%, compared to a slighter
increase from 30.6% to 35.9% in the control
group of infertile men.(28) In the group receiving
vitamin E, 11 pregnancies took place, 9 of which
led to birth; however, no pregnancies happened
in the control group. In another research project,
Martin-Du Pan and Sakkas treated 14 infertile
men with vitamin E and gave another 20 infertile
men glutathione.(29) They concluded that vitamin
E improved sperm count, while glutathione
increased sperm motility. Five years later,
Ibrahim and colleagues investigated the effect of
vitamin E on 65 infertile men.(30) Sperm motility
and sperm count increased from 32.46% and
11.9 × 106/mL to 37.2% and 12.15 × 106/mL
in their patients, respectively. Eskenazi
and associates performed another study on
96 healthy male participants in California
University in 2005.(31) They established the fact
that using antioxidants (vitamin E, vitamin C,
L-carnitine, and beta carotene) had beneficial
effects on concentration and motility of the
sperm; especially, class A motility. Increased
absorption of antioxidants led to increased effect
on concentration and motility of the sperm.
Therefore, those with higher absorption, had
80 × 106/mL more sperm than those with lower
absorption; furthermore, the number of sperm
with class A motility was 36 × 106/mL more in
those with a high absorption rate.(32)
Crocetin and dimethylcrocetin are derived from
crocin which is a water-soluble carotenoid found
in the stigmas of saffron.(16) Their antioxidant
effect has been documented in several studies.(14-16)
We tested this effect on the sperm of infertile
men and found no significant change in sperm
count after a period of treatment with saffron;
however, significant alterations were observed
in sperm morphology and motility. The normal
morphology of the sperm increased from a mean
of 26.5% to 33.9%; class A motility was initially
Saffron and Semen Parameters of Infertile Men—Heidary et al
258 Urology Journal Vol 5 No 4 Autumn 2008
5.3% that later increased to 11.8%. As for class
B and C motility, the preliminary amounts of
10.1% and 19.8% changed to 17.9% and 25.4%
after the treatment course, respectively. Overall,
the introductory amount of motile sperm
(35.2%) increased to the final amount of 55.1%.
Although the study did not have the strength
of a randomized controlled trial, results were
promising and the effect of saffron on semen
parameters was documented. This can be a basis
of further investigation on saffron ingredients in
infertility research.
CONCLUSION
Saffron has a positive effect on semen parameters
in terms of sperm motility in men suffering
from idiopathic infertility. It comprises several
ingredients and even though its antioxidative
effect may be the reason behind its positive
value on spermatic parameters, further studies
are required to define its exact mechanism of
action. Moreover, we acknowledge the need for
further studies on larger groups of patients. We
also believe that a longer period of follow-up,
possibly up to 1 year, will be more beneficial in
determining the role of saffron on seminal fluid.
CONFLICT OF INTEREST
None declared.
REFERENCES
1. Safarinejad MR. Infertility among couples in a
population-based study in Iran: prevalence and
associated risk factors. Int J Androl. 2008;31:303-14.
2. Isidori AM, Pozza C, Gianfrilli D, Isidori A. Medical
treatment to improve sperm quality. Reprod Biomed
Online. 2006;12:704-14.
3. Kumar R, Gautam G, Gupta NP. Drug therapy for
idiopathic male infertility: rationale versus evidence. J
Urol. 2006;176:1307-12.
4. Schiff JD, Ramírez ML, Bar-Chama N. Medical and
surgical management male infertility. Endocrinol Metab
Clin North Am. 2007;36:313-31.
5. De Lamirande E, Gagnon C. Capacitation-
associated production of superoxide anion by human
spermatozoa. Free Radic Biol Med. 1995;18:487-95.
6. De Lamirande E, Gagnon C. A positive role for the
superoxide anion in triggering hyperactivation and
capacitation of human spermatozoa. Int J Androl.
1993;16:21-5.
7. Ford WC. Regulation of sperm function by reactive
oxygen species. Hum Reprod Update. 2004;10:387-99.
8. Agarwal A, Said TM. Oxidative stress, DNA damage
and apoptosis in male infertility: a clinical approach.
BJU Int. 2005;95:503-7.
9. Wang X, Sharma RK, Sikka SC, Thomas AJ Jr,
Falcone T, Agarwal A. Oxidative stress is associated
with increased apoptosis leading to spermatozoa DNA
damage in patients with male factor infertility. Fertil
Steril. 2003;80:531-5.
10. Rao AV, Shaha C. Role of glutathione S-transferases
in oxidative stress-induced male germ cell apoptosis.
Free Radic Biol Med. 2000;29:1015-27.
11. Barroso G, Morshedi M, Oehninger S. Analysis of
DNA fragmentation, plasma membrane translocation
of phosphatidylserine and oxidative stress in human
spermatozoa. Hum Reprod. 2000;15:1338-44.
12. Kemal Duru N, Morshedi M, Oehninger S. Effects of
hydrogen peroxide on DNA and plasma membrane
integrity of human spermatozoa. Fertil Steril.
2000;74:1200-7.
13. Zini A, De Lamirande E, Gagnon C. Reactive oxygen
species in semen of infertile patients: levels of
superoxide dismutase- and catalase-like activities
in seminal plasma and spermatozoa. Int J Androl.
1993;16:183-8.
14. Pham TQ, Cormier F, Farnworth E, Tong VH, Van
Calsteren MR. Antioxidant properties of crocin from
Gardenia jasminoides Ellis and study of the reactions
of crocin with linoleic acid and crocin with oxygen. J
Agric Food Chem. 2000;48:1455-61.
15. Botsoglou NA, Florou-Paneri P, Nikolakakis I, et
al. Effect of dietary saffron (Crocus sativus L.) on
the oxidative stability of egg yolk. Br Poult Sci.
2005;46:701-7.
16. Kanakis CD, Tarantilis PA, Tajmir-Riahi HA, Polissiou
MG. Crocetin, dimethylcrocetin, and safranal bind
human serum albumin: stability and antioxidative
properties. J Agric Food Chem. 2007;55:970-7.
17. Basker, D, Negbi, M. Uses of saffron Crocus sativus.
Econ Bot. 1983;37:228-36.
18. Ríos JL, Recio MC, Giner RM, Máñez S. An Update
Review of Saffron and its Active Constituents.
Phytotherapy Research. 1996;10:189-93.
19. Chatterjee S, Poduval TB, Tilak JC, Devasagayam TP.
A modified, economic, sensitive method for measuring
total antioxidant capacities of human plasma and
natural compounds using Indian saffron (Crocus
sativus). Clin Chim Acta. 2005;352:155-63.
20. Abdullaev FI. Cancer chemopreventive and
tumoricidal properties of saffron (Crocus sativus L.).
Exp Biol Med (Maywood). 2002;227:20-5.
21. World Health Organization. Laboratory manual for the
examination of human semen and semen-cervical
mucus interaction. 4th ed. New York, NY: Cambridge
University Press; 1999.
22. Giudice LC. Infertility and the environment: the
medical context. Semin Reprod Med. 2006;24:129-33.
23. Agarwal A, Prabakaran SA. Oxidative stress and
antioxidants in male infertility: a difficult balance. Iran J
of Reprod Med. 2005;3:1-8.
Saffron and Semen Parameters of Infertile Men—Heidary et al
Urology Journal Vol 5 No 4 Autumn 2008 259
24. Agarwal A, Makker K, Sharma R. Clinical relevance of
oxidative stress in male factor infertility: an update. Am
J Reprod Immunol. 2008;59:2-11.
25. Bolle P, Evandri MG, Saso L. The controversial
efficacy of vitamin E for human male infertility.
Contraception. 2002;65:313-5.
26. Lenzi A, Lombardo F, Gandini L, Culasso F, Dondero
F. Glutathione therapy for male infertility. Arch Androl.
1992;29:65-8.
27. Lenzi A, Culasso F, Gandini L, Lombardo F, Dondero
F. Placebo-controlled, double-blind, cross-over trial
of glutathione therapy in male infertility. Hum Reprod.
1993;8:1657-62.
28. Suleiman SA, Ali ME, Zaki ZM, el-Malik EM, Nasr
MA. Lipid peroxidation and human sperm motility:
protective role of vitamin E. J Androl. 1996;17:530-7.
29. Martin-Du Pan RC, Sakkas D. Is antioxidant therapy
a promising strategy to improve human reproduction?
Are anti-oxidants useful in the treatment of male
infertility? Hum Reprod. 1998;13:2984-5.
30. Ibrahim OM, Al-Azab GA, Kolkaila AA, Hegazy SK.
Clinical & biochemical study on the role of free radicals
& antioxidants in male infertility. J Pan-Arab League
Dermatol. 2004;15:211-7.
31. Eskenazi B, Kidd SA, Marks AR, Sloter E, Block
G, Wyrobek AJ. Antioxidant intake is associated
with semen quality in healthy men. Hum Reprod.
2005;20:1006-12.
32. Verma SK, Bordia A. Antioxidant property of Saffron in
man. Indian J Med Sci. 1998;52:205-7.
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