Saffron is the dried elongated stigmas and styles of the blue-purple saffron flower (Crocus sativus L.). At a retail price of up to $11 000 per kg, it is the world’s most expensive spice, reflected by the labour intensiveness associated with its production. It is estimated that it takes approximately 150 000 crocus blossoms or 450 000 hand-picked stigmas to produce just 1 kg of this unique spice (1,2).
Saffron stigmas contain four major bioactive compounds: crocins (family of six mono-glycosyl or di-glycosyl polyene esters), crocetin (a natural carotenoid dicarboxylic acid precursor of crocin), picrocrocin (monoterpene glycoside precursor of safranal and product of zeaxanthin degradation) and safranal. Crocins and crocetin are responsible for the colour, pricrocrocin the taste and safranal the aroma, although collectively, these compounds are responsible for the health-enhancing properties associated with saffron (2,3).
In addition to these compounds, saffron contains in excess of 150 volatile and aroma-yielding compounds and many non-volatile active components, many of which are carotenoids, including zeaxanthin, lycopene, beta-carotenes and polysaccharides (4). As a result of its characteristic bitter taste, pungent hay-like aroma and luminous yellow-orange colour, saffron is used in fragrances, flavourings, colouring agents and medicines (2).
In traditional medicine, saffron has been used as an anticonvulsive, analgesic, aphrodisiac, antispasmodic and expectorant (5). Modern pharmacological studies have demonstrated that extracts of saffron stigmas have anticancer, anti-inflammatory, antioxidant and antiplatelet effects (6,7). Recent clinical trials have also suggested a potential for saffron in the treatment and prevention of Alzheimer’s disease (8,9) and macular degeneration (10,11). Saffron also has the potential to enhance mental health through its antidepressant properties and, in a recent meta-analysis, was confirmed to be effective for the treatment of depression (12).
Depression
In two randomised, double-blind, placebo-controlled trials, saffron was effective for the treatment of mild to- moderate depression (6,13). At a daily dosage of 30 mg/day of C. sativus, stigma or petal, a large effect size (Cohen’s d of 1.51 (6) and 1.76 (13)) was determined.
When compared with antidepressant medication, reflected by four published randomised, double-blind, placebo-controlled trials, saffron had similar efficacy (14-16). In a 6-week trial, at a dosage of 30 mg/day, extracts of saffron stigma were as effective as fluoxetine (20 mg/day) for the treatment of mild-to-moderate depression (16). Similar findings were obtained with petal extracts of C. sativus following an 8-week trial compared with fluoxetine (15). In another trial, extracts of saffron stigma (30 mg/day) had similar antidepressant effects to imipramine (100 mg/day). In a recently published randomised, double-blind study, saffron was also as effective as fluoxetine in reducing symptoms of depression in patients who had recently undergone percutaneous coronary intervention (17).
Duration of treatment
In five studies, the intervention period was 6 weeks, and in one, it was 8 weeks (15). Statistically significant improvements in depressive symptoms were reported after the first week, although depressive symptoms continued to subside as treatment progressed. Weekly improvements generally continued throughout the length of treatment; however, progress after 8 weeks is unknown as no long-term follow-up studies have been conducted. When compared with the antidepressants imipramine and fluoxetine, saffron had a similar recovery profile over time (14-17).
In a human trial, the ingestion of saffron for 7 days was associated with slight changes in haematological and biochemical parameters, although these remained within the normal range and were not considered medically significant (18). However, a different investigation into the short-term safety and tolerability of crocin tablets (20 mg/day) was also undertaken in healthy adult volunteers. The 1-month ingestion of crocin tablets had little effect on haematological, biochemical or hormonal parameters apart from moderately decreasing levels of amylase, mixed white blood cells and partial thromboplastin time (PTT) (19).
As saffron has shown some effect on blood coagulation and platelet aggregation in in vitro and in vivo studies (18), however, a recent double blind, placebo-controlled investigation was undertaken using a larger sample size. One week of treatment with 200 and 400 mg saffron tablets did not change plasma levels of fibrinogen, factor VII (as coagulant agent), C and S protein (an anticoagulant agent), prothrombin time or PTT (20).
On the whole, it seems that daily doses of up to 1.5 g of saffron are generally considered safe (21). The efficacious dosage for the treatment of depression (30 mg/day) is in accordance with the amount of saffron used in various cuisines, so there is a very large margin of safety (22).
References
1. Schmidt M, Betti G, Hensel A. 2007. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 157: 315–319.
2. Melnyk JP, Wang S, Marcone MF. 2010. Chemical and biological properties of the world’s most expensive spice: Saffron. Food Res Int 43: 1981–1989.
3. Moghaddasi MS. 2010. Saffron chemicals and medicine usage. J Med Plants Res 40: 427–430.
4. Sampathu SR, Shivashankar S, Lewis YS, Wood AB. 1984. Saffron (Crocus sativus Linn.) — cultivation, processing, chemistry and standardization. Cr Rev Food Sci 20: 123–157.
5. Hosseinzadeh H, Nassiri-Asl M. 2013. Avicenna’s (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res 27: 475–483.
6. Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. 2006. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebocontrolled trial. Phytomedicine 13: 607–611.
7. Wang Y, Han T, Zhu Y, et al. 2010. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med 64: 24–30.
8. Akhondzadeh S, Sabet MS, Harirchian MH, et al. 2010. Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16- week, randomized and placebo-controlled trial. J Clin Pharm Ther 35: 581–588.
9. Akhondzadeh S, Shafiee Sabet M, Harirchian MH, et al. 2010. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl) 207: 637–643.
10. Falsini B, Piccardi M, Minnella A, et al. 2010. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 51: 6118–6124.
11. Piccardi M, Marangoni D, Minnella AM, et al. 2012. A longitudinal followup study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evid Based Complement Alternat Med 2012: 429124
12. Hausenblas HA, Saha D, Dubyak PJ, Anton SD. 2013. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med 11: 377–383.
13. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. 2005. Crocus sativus L. in the treatment of mild to moderate depression: a doubleblind, randomized and placebo-controlled trial. Phytother Res 19: 148–151.
14. Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F. 2004. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med 4: 12.
15. Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. 2007. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry 31: 439–442.
16. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. 2005. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol 97: 281–284.
17. Shahmansouri N, Farokhnia M, Abbasi SH, et al. 2014. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affect Disord 155: 216–222.
18. Modaghegh MH, Shahabian M, Esmaeili HA, Rajbai O, Hosseinzadeh H. 2008. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine 15: 1032–1037
19. Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H. 2013. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 16: 39–46.
20. Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M, Hosseinzadeh H. 2014. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother Res 28: 593–543.
21. Schmidt M, Betti G, Hensel A. 2007. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 157: 315–319.
22. Hosseinzadeh H, Nassiri-Asl M. 2013. Avicenna’s (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res 27: 475–483
