Mohammadzadeh-Moghadam H, Nazari SM, Shamsa A, et. al. 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 Complementary Altern Med. 2015 Oct;20(4):283-286.
To investigate the effects of a topical saffron gel on erectile dysfunction in diabetic men.
Randomized, double-blind, placebo-controlled clinical trial
Fifty married diabetic men, 40 years of age or older, with erectile dysfunction. Participants were randomized to either the active treatment (n=25) or placebo (n=25) groups. The exclusion criteria included history of central neurological and psychological disorders, drug allergy, or patients’ willingness to withdraw from the study.
Study Parameters Assessed
The intervention group was given a starch-based gel containing 1% saffron while the placebo group received a starch-based gel colored golden-yellow (similar to color of saffron) with a food coloring agent. Both groups were trained to rub a pea-sized amount of the gel on their penis 30 minutes prior to sexual intercourse for a period of 1 month.
The participants were asked to complete the 15-item International Index of Erectile Function Questionnaire (IIEF-15) prior to the intervention and then one month later.
There were significant (P<0.001 for each) improvements in total IIEF-15 scores and its five dimensions (erectile function, sexual desire, orgasmic function, intercourse satisfaction, and overall satisfaction) compared to baseline in the intervention group but not in the placebo group.
In addition to being a highly valued spice known for its ability to both flavor and color food, saffron (Crocus sativus) also has a long history of use in traditional Persian medicine. Historically it has been used in a wide variety of conditions, including as an aphrodisiac.1
Several recent clinical trials have suggested that saffron may be an effective option for treating sexual dysfunction. While topical saffron-containing creams and lotions have previously been studied for their direct therapeutic effects on the skin,2 to my knowledge this is the first study investigating a systemic effect of topical saffron administration. There have been 4 previous human clinical trials on the use of oral saffron for the treatment of sexual dysfunction. The first was an uncontrolled pilot study of 20 men with erectile dysfunction who received 200 mg of saffron a day for 10 days.3 The results showed statistically significant (P<0.0001) improvements in both penile tip and base rigidity and tumescence. Moreover, mean scores for erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction on the IIEF-15 were all significantly higher (P<0.0001 for each) after taking the saffron for just 10 days.
Subsequently, 2 randomized, double-blind, placebo-controlled trials investigated the effect of saffron on fluoxetine-induced sexual impairment. The first gave 30 male patients who were currently taking fluoxetine for major depressive disorder 15 mg of saffron orally twice a day for 4 weeks.4 The saffron resulted in significantly greater improvements in erectile function, intercourse satisfaction, and total IIEF-15 scores (P≤0.001 for each) compared to placebo. In a similar study, 34 female patients with major depression taking fluoxetine were given 15 mg of saffron orally twice a day for 4 weeks. Patients in the saffron group experienced significantly more improvement in arousal, lubrication, pain, and total scores on the Female Sexual Function Index (FSFI) (P<0.05 for each) compared to placebo.5
However, not all studies have been positive. The fourth clinical trial was a larger (N=307) randomized, open-label, crossover study comparing sildenafil and saffron (30 mg twice a day for 12 weeks) in the treatment of erectile dysfunction. This study found no significant effect of saffron on any of the IIEF-15 scores.6
A therapeutic trial of such a simple, noninvasive, safe, relatively low cost, and potentially beneficial intervention for erectile dysfunction could be easily justified in clinical practice.
Saffron is well known to have antioxidant and anti-inflammatory effects,2 but this does not explain how it could impact sexual function. A recent animal study has attempted to elucidate this mechanism. Rats injected with a saffron extract were found to have increased intracellular cyclic GMP (cGMP) concentrations in their corpus cavernosum.7 Increased cavernosal cGMP levels will result in cavernosal smooth muscle relaxation, increased penile blood flow, and consequent erection. These fluctuations in cGMP occurred without any change in plasma testosterone or dihydrotestosterone levels. Therefore, the effects of saffron on erectile function appear to be mediated through a nonhormonal pathway. This fact may be particularly important in treating erectile dysfunction in men with prostate cancer because testosterone is known to stimulate prostate cancer cell growth. Additionally, the antineoplastic effects of saffron are currently another area of investigation8 and several of its constituents, including crocin, crocetin, and safranal, have been shown to possess antiproliferative effects in prostate cancer cell lines.9-11 This may provide another advantage to using saffron in this patient population.
Saffron has also been shown to have antidepressant activity in several randomized controlled clinical trials,2 and it has been suggested that this mood-enhancing effect may also contribute to the effects of saffron on sexual function.3 Its antidepressant action may be an additional advantage particularly in the treatment of selective serotonin reuptake inhibitor-induced sexual dysfunction in patients with depression.
Investigators have also attempted to determine which constituent of saffron is most active in its sexual effects. Hosseinzadeh et al. injected rats receiving sildenafil with either safranal or crocin.12 While safranal was not found to have any effect on sexual behavior, crocin significantly increased the frequency of erections and sexual desire in the rats. This raises the question of whether some of the variable results in the clinical trials of saffron on erectile function could be due to varying crocin levels in different batches of the spice. Consequently, could its efficacy be increased by creating saffron extracts with a higher concentration of this particular constituent (crocin)?
The advantages of an effective natural topical treatment for erectile dysfunction are significant. Currently, the standard available options for the treatment of erectile dysfunction are associated with substantial adverse effects. Standard treatments include oral phosphodiesterase type 5 (PDE-5) inhibitors and significantly more invasive options such as intraurethral aprostadil, intracavernosal injections, and penile prosthesis implants. Although PDE-5 inhibitors are currently the first-line therapy for erectile dysfunction, their high cost, adverse effect profile (including headache, flushing, nasal congestion, heartburn, vision changes, and palpitations), and potential for several drug interactions make them undesirable for many men. In this study, none of the participants reported any adverse effects or complications associated with the saffron gel.
This trial has a few notable limitations: the sample size was small, and the study only included diabetic men with erectile dysfunction. For these reasons it is too early to make any firm statements about the efficacy of topical saffron in the treatment of erectile dysfunction in diabetic men or to generalize these results to other populations. However, a therapeutic trial of such a simple, noninvasive, safe, relatively low-cost, and potentially beneficial intervention for erectile dysfunction could be easily justified in clinical practice.
- Hausenblas HA, Heekin K, Mutchie HL, Anton S. A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes. J Integr Med. 2015;13(4):231-240.
- Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical applications of saffron (Crocus sativus) and its constituents: A review. Drug Res (Stuttg). 2015;65(6):287-295.
- Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O. Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: A pilot study. Phytomedicine. 2009;16(8):690-693.
- Modabbernia A, Sohrabi H, Nasehi AA, et. al. Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo controlled trial. Psychopharmacology (Berl). 2012;223(4):381-388.
- Kashani L, Raisi F, Saroukhani S, et. al. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. Hum Psychopharmacol. 2013;28(1):54-60.
- Safarinejad MR, Shafiei N, Safarinejad S. 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. 2010;22(4):240-250.
- Al-Rehaily AJ, Alhowiriny TA, El-Tahir KE, Al-Taweel AM, Perveen S. Molecular mechanisms that underlie the sexual stimulant actions of Avicennia marina (Forssk.) Vierh. and Crocus sativus L. Pak J Pharm Sci. 2015;28(1):49-58.
- Bhandari PR. Crocus sativus L. (saffron) for cancer chemoprevention: A mini review. J Tradit Complement Med. 2015;5(2):81-87.
- D'Alessandro AM, Mancini A, Lizzi AR, et. al. Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer. Nutr Cancer. 2013;65(6):930-942.
- Samarghandian S, Shabestari MM. DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian J Urol. 2013;29(3):177-183.
- Festuccia C, Mancini A, Gravina GL, et. al. Antitumor effects of saffron-derived carotenoids in prostate cancer cell models. Biomed Res Int. 2014;2014:135048.
- Hosseinzadeh H, Ziaee T, Sadeghi A. The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behavior in normal male rats. Phytomedicine. 2008;15(6-7):491-495.