A systematic review and meta-analysis of clinical trials on saffron (Crocus sativus) effectiveness and safety on erectile dysfunction and semen parameters

Document Type : Review Article


1 Student Research Committee, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran

2 Faculty of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: We performed this systematic review and meta-analysis study to determine saffron (Crocus sativus) effectiveness and safety in male infertility problems.
Materials and Methods: The databases PubMed, Scopus, Cochrane, Google Scholar, SID, IranMedex and Magiran until July 2016 and reference section of relevant articles, were searched to find both English and Persian clinical trials on male infertility issues that used saffron as medical treatment. Also, the quality of these trials was evaluated by Oxford Center for Evidence Based Medicine checklist. A total of six trials was ultimately included. All statistical analyses were done by Comprehensive Meta-analysis (CMA) Version 2.
Results: Only in one study conducted on sperm parameters, the mean percentage of sperm with normal morphology (p<0.001) and sperm motility (p<0.001) were increased. Quantitative analysis showed that saffron had a significantly positive effect on all dimensions of Erectile Function questionnaire (MD for Erectile function=5.36(p=0.00), Orgasmic function=1.12 (p=0.007), Overall satisfaction=1.23 (p=0.005), Satisfaction with intercourse=2.18 (p=0.00) and Sexual desire=0.78 (p=0.00), Fixed effects model using 3 trials). The result of subgroup analysis based on dimensions of Erectile Function questionnaire showed statistically significant differences among subgroups (p=0.00).
Conclusion: saffron has a positive effect on erectile dysfunction. However, our study showed contradictory results about semen parameters. So, interpretation of results is limited because of methodological flaws of the included studies, erectile dysfunction status and a large heterogeneity among them. Further trials are still needed to confirm the current findings.


Main Subjects

Abdullaev F, and Espinosa-Aguirre J. 2004. Biomedical Properties of Saffron and Its Potential Use in Cancer Therapy and Chemoprevention Trials. Cancer Detect Prev, 28: 426-432.
Abdullaev  I. 2002. Cancer Chemopreventive and Tumoricidal Properties of Saffron (Crocus Sativus L.). Exp Biol Med, 227: 20-25.
Agarwal A. and Said M. 2005. Oxidative Stress, Dna Damage and Apoptosis in Male Infertility: A Clinical Approach. Bju International, 95:503-507.
Alavizadeh H, and Hosseinzadeh H. 2014. Bioactivity Assessment and Toxicity of Crocin: A Comprehensive Review. Food Chem Toxicol, 64: 65-80.
Andersson E. 2011. Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction. Pharmacol Rev, 63: 811-859.
Basker, D. & Negbi, M. 1983. Uses of Saffron. Econ Bot, 37: 228-236.
Botsoglou  N, Florou-Paneri  P, Nikolakakis  I, Giannenas  I, Dotas  V , Botsoglou  E, Aggelopoulos S. 2005. Effect of Dietary Saffron (Crocus Sativus L.) On The Oxidative Stability of Egg Yolk. Br Poult  Sci, 46:701-707.
Burnett A. 2012. Evaluation and Management of Erectile Dysfunction. Wein Aj, Kavoussi Lr, Partin Aw, Et Al., Eds.
Chatterjee S, Poduval B, Tilak C, Devasagayam P. 2005. A Modified, Economic, Sensitive Method for Measuring Total Antioxidant Capacities of Human Plasma and Natural Compounds Using Indian Saffron (Crocus Sativus). Clin  Chim Acta, 352: 155-163.
De Liz  T, and Strauss  B. 2005. Differential Efficacy of Group and Individual/Couple Psychotherapy with Infertile Patients. Hum Reprod, 20: 1324-1332.
Downey  J , Yingling  S , Mckinney  M , Husami  N , Jewelewicz  R, Maidman J. 1989. Mood Disorders, Psychiatric Symptoms, and Distress in Women Presenting For Infertility Evaluation. Fertil Steril, 52: 425-432.
Hamada A, Esteves  C, Nizza  M, Agarwal  A. 2012. Unexplained Male Infertility: Diagnosis and Management. Int Braz J Urol, 38: 576-594.
Hatzimouratidis K, Amar E, Eardley  I, Giuliano  F, Hatzichristou  D, Montorsi  F, Vardi Y,Wespes  E. 2010. Guidelines on Male Sexual Dysfunction: Erectile Dysfunction and Premature Ejaculation. Eur Urol, 57: 804-814.
Heidary M, Vahhabi S, Reza-Nejadi J, Delfan B, Birjandi M, Kaviani H, Givrad S. 2008. Effect of Saffron on Semen Parameters of Infertile Men. J Urol, 5: 255-259.
Heidelbaugh J. 2010. Management of Erectile Dysfunction. Am Fam Physician, 81: 305-312.
Hosseinzadeh  H, and Jahanian  Z. 2010. Effect of Crocus Sativus L. (Saffron) Stigma and Its Constituents, Crocin and Safranal, on Morphine Withdrawal Syndrome in Mice. Phytother Res, 24: 726-730.
Hosseinzadeh  H, and Nassiri‐Asl  M. 2013. Avicenna's (Ibn Sina) the Canon of Medicine and Saffron (Crocus Sativus): A Review. Phytother Res, 27: 475-483.
Hosseinzadeh  H, Sadeghnia  R, Ghaeni    A, Motamedshariaty  S, Mohajeri  A. 2012. Effects of Saffron (Crocus Sativus L.) And it’s Active Constituent, Crocin, on Recognition and Spatial Memory after Chronic Cerebral Hypoperfusion in Rats. Phytother Res, 26: 381-386.
Hosseinzadeh H, and  Younesi  M. 2002. Antinociceptive and Anti-Inflammatory Effects of Crocus Sativus L. Stigma and Petal Extracts in Mice. BMC Pharmacology, 2: 1-8.
Hosseinzadeh  H, Ziaee  T, Sadeghi A. 2008. The Effect of Saffron, Crocus Sativus Stigma, Extract and Its Constituents, Safranal and Crocin on Sexual Behaviors in Normal Male Rats. Phytomedicine, 15:491-495.
Howick J, Chalmers I, Glasziou P, Greenhalgh T , Heneghan  C , Liberati  A , Moschetti I, Phillips B, Thornton H. 2011. The 2011 Oxford Cebm Levels Of Evidence (Introductory Document). Oxford CEBM. Retrieved January, 20, 2011.
 Irani M, Amirian M, Sadeghi R, Le-Lez J,  Latifnejad-Roudsari R.2017.The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis.ourology . Urol J, 14: 4069-4078
Isidori  M, Pozza C , Gianfrilli  D, Isidori A. 2006. Medical Treatment to Improve Sperm Quality. Reprod Biomed Online, 12:704-714.
Kanakis  D, Tarantilis A , Tajmir-Riahi A, Polissiou G. 2007. Crocetin, Dimethylcrocetin, and Safranal Bind Human Serum Albumin: Stability and Antioxidative Properties. J  Agric Food Chem, 55: 970-977.
Khori V, Alizadeh  M, Yazdi  H, Rakhshan E, Mirabbasi  A, Changizi S, Mazandarani  M, Nayebpour  M. 2012. Frequency‐Dependent Electrophysiological Remodeling of the Av Node By Hydroalcohol Extract of Crocus Sativus L. (Saffron) During Experimental Atrial Fibrillation: The Role of Endogenous Nitric Oxide.  Phytother Res, 26: 826-832.
Kumar R, Gautam G, Gupta  P. 2006. Drug Therapy for Idiopathic Male Infertility: Rationale Versus Evidence. J Urol, 176: 1307-1312.
Modabbernia  A, Sohrabi  H, Nasehi A, Raisi  F,Saroukhani S, Jamshidi  A, Tabrizi  M, Ashrafi M, Akhondzadeh  S. 2012. Effect Of Saffron On Fluoxetine-Induced Sexual Impairment In Men: Randomized Double-Blind Placebo-Controlled Trial. Psychopharmacology, 223:381-388.
Mohammadzadeh-Moghadam H, Nazari    M, Shamsa  A, Kamalinejad  M, Esmaeeli  H, Asadpour  A, Khajavi  A. 2015. Effects of A Topical Saffron (Crocus Sativus L) Gel on Erectile Dysfunction in Diabetics A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial. J  Evid Based Complement  Altern  Med, 20: 283-286.
Mollazadeh H, Emami  A, Hosseinzadeh H. 2015. Razi’s Al-Hawi and Saffron (Crocus Sativus): A Review. IJBMS, 18: 1153.
Mosher  D. 1988. Fecundity and Infertility in the United States. Am J Public Health, 78:181-182.
Mousavi Z, and Bathaie  Z. 2011. Historical Uses of Saffron: Identifying Potential New Avenues for Modern Research. Avicenna J Phytomed, 1:57-66.
Pham  Q, Cormier F, Farnworth E, Tong   H,Van Calsteren R. 2000. 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, 48: 1455-1461.
Porst H, Padma-Nathan H, Giuliano F, Anglin G , Varanese L, Rosen  R. 2003. Efficacy of Tadalafil for the Treatment of Erectile Dysfunction at 24 and 36 Hours after Dosing: A Randomized Controlled Trial. J Urol, 62: 121-125.
Rezaee R, and Hosseinzadeh H. 2013. Safranal: From an Aromatic Natural Product to A Rewarding Pharmacological Agent.  IJBMS, 16: 12-26.
Rios  J, Recio  M, Giner  R, Manez  S. 1996. An Update Review of Saffron and Its Active Constituents. Phytother Res, 10: 189-193.
Safarinejad M , Shafiei N, Safarinejad S. 2010. An Open Label, Randomized, Fixed-Dose, Crossover Study Comparing Efficacy And Safety of Sildenafil Citrate and Saffron (Crocus Sativus Linn.) For Treating Erectile Dysfunction in Men Naïve To Treatment. Int J Impot Res, 22:240-250.
Safarinejad  R, Shafiei  N, Safarinejad  S. 2011. A Prospective Double‐Blind Randomized Placebo‐Controlled Study of the Effect of Saffron (Crocus Sativus Linn.) on Semen Parameters and Seminal Plasma Antioxidant Capacity in Infertile Men with Idiopathic Oligoasthenoteratozoospermia. Phytother Res, 25, 508-516.
Shamsa  A, Hosseinzadeh H, Molaei M, Shakeri  T, Rajabi  O. 2009. Evaluation of Crocus Sativus L.(Saffron) on Male Erectile Dysfunction: A Pilot Study. Phytomedicine, 16: 690-693.
Sina  I. 2005. Al-Qanun Fi Al-Tibb [The Canon of Medicine]. Alaalami Library, Beirut, 437, 48.
Smith  R, Tanagho  A, Mcaninch  W. 2008. Smith's General Urology, Lange Medical Books/Mcgraw-Hill.
Tonkaboni  M. 2011. Tohfato-Almomenin (Tohfehe-Hakim Momen).
Verma  S, and  Bordia  A. 1998. Antioxidant Property of Saffron in Man. IJBMS, 52:205-207.
Wang X, Sharma K, Sikka  C, Thomas J, Falcone T, Agarwal  A. 2003. Oxidative Stress is Associated with Increased Apoptosis Leading to Spermatozoa Dna Damage in Patients with Male Factor Infertility. Fertil Steril, 80: 531-535.
Whiteford  M, and  Gonzalez  L. 1995. Stigma: The Hidden Burden of Infertility. Soc Sci Med, 40: 27-36.
Zini  A, Lamirande E, Gagnon  C. 1993. Reactive Oxygen Species in Semen of Infertile Patients: Levels of Superoxide Dismutase‐And Catalase‐Like Activities in Seminal Plasma and Spermatozoa. Int J Androl, 16: 183-188.