The use of saffron as a medicinal plant dates back to ancient times, with its reported therapeutic applications ranging from complaints of the eye, skin, respiratory, digestive, and genitourinary tracts, in mood disorders and as a general tonic. However, the medicinal portion of saffron is traditionally derived from the dried stigmas of Crocus sativus L. – it takes the stigmas from about 100,000 flowers to make one kilogram of pure dried saffron – thus, making it one of the world’s most expensive medicinal substances known throughout time.[1] Consequently, many of its traditional uses have been forgotten to history. Nevertheless, in recent years saffron has been the subject of numerous studies, with excellent results shown in many areas of health, particularly mood disorders.
Saffron in Europe
It is not known where saffron was first grown and harvested, but there are historical records of its use in several European countries, the Middle East, India and China. In Europe, antique frescos uncovered in Greece depict medicinal application of saffron over 3,600 years ago.[2] Greek physicians and botanists including Hippocrates, Erasistratus, Diokles and Dioscorides believed that saffron had styptic and soothing properties and used it to treat eye disorders (painful eye, purulent eye infections, corneal disease and cataracts), earache, tooth ache, and ulcers (skin, mouth and genital tract).[1] In ancient Rome, saffron was used to treat coughs and was added to wine in the belief that it would prevent hangover.[1]
Middle East
Renowned Persian physician and philosopher Avicenna (980-1037AD) described the pharmacological activities of saffron in Book II, Canon of Medicine (al-Quanum fi al-tib) as antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilatory, aphrodisiac, inducer of labour, emmenagogue and others.[3] Most of these effects have been studied in modern pharmacology and are well documented. Moreover, ancient Persians were one of the first people to cultivate saffron rather than relying on wild flower supply.[1]
In Traditional Iranian Medicine (TIM) saffron is considered hot and dry and was prescribed to invigorate the body, strengthen the senses, and elevate mood. It was also used for swellings, headaches, insomnia, eye problems, as a cardiotonic, to strengthen the respiratory system, liver and stomach, decrease appetite, as a diuretic to purify the kidneys and bladder, to regulate the menstrual cycle and facilitate labour, and as an aphrodisiac. Externally, ground saffron was used for major bleeding.[1]
In addition to medicinal applications, saffron was also valued as a spiritual item and was used in incense and scented oils for kings and ritual leaders, as a dye for shoes and clothing for the king, and in cooking.[1]It has been said that the Egyptian Queen Cleopatra used to bath in milk with saffron.[1]
India
According to Buddhist legend, saffron was first planted in Kashmir in the 5th century BC. [Dalby, pp 95] In Ayurvedic medicine, saffron is considered an immunostimulant, aphrodisiac, cardiotonic, liver tonic, nervine tonic, carminative, diaphoretic, diuretic, emmenagogue, galactogogue, febrifuge, sedative, relaxant and anxiolytic.[1]
China
The use of saffron in China dates back to at least the 3rd century BC.[1] Traditional Chinese medicine (TCM) utilised saffron in similar ways as the other cultures described above, including cardiovascular applications, as an immune stimulant, diuretic, anti-inflammatory, emmenagogue, for ailments of the respiratory tract (including pertussis and asthma) and to protect the brain from oxygen deprivation.[1]
Brief selection of current research supporting the traditional uses of saffron
Recent studies have validated the potential of saffron and several of its active components, including crocetin, crocins and safranal, to lower the risk of numerous diseases. Many of the medicinal properties of saffron and its constituents are attributed to their strong antioxidant and free radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines.[4]
Antidepressant
One of the most well recognised effects of saffron is its anti-depressant activity as recorded historically as well as demonstrated in modern clinical studies. Suggested mechanisms of action include serotonergic, antioxidant, anti-inflammatory and neuroprotective effects.[6]
In a four-week randomised, placebo-controlled, double-blind study published late last year, researchers investigated the efficacy of affron®, a standardised stigma extract from saffron for improving mood, stress, anxiety and sleep quality in healthy adults.[7] Analysis of the results demonstrated a significant decrease in negative mood and symptoms related to stress and anxiety at a 28mg/d dose. Thus, it was concluded that affron® increased mood, reduced anxiety and managed stress – without side effects – offering a natural alternative to standard treatments.
The same extract has also been tested for its mood-related effects in teenagers.[8] In an eight-week, randomised, double-blind, placebo-controlled study, youth aged 12-16 years, with mild-to-moderate anxiety or depressive symptoms were given affron® (14mg twice daily) or placebo. Based on self-reports, the treatment was associated with greater improvements in overall internalising symptoms, separation anxiety, social phobia, and depression. affron® was well tolerated and there was a trend of reduced headaches in participants on the active treatment.
Comparing saffron to standard drug treatment for mild to moderate depression, researchers have reported that short term administration (30mg/d in two divided doses) for six weeks is as effective as fluoxetine (Prozac; a selective serotonin reuptake inhibitor).[9] The efficacy of saffron has also been found equivalent to imipramine (a tricyclic antidepressant).[10]
Neurodegenerative disorders
The antioxidant and anti-inflammatory effects of saffron and its constituents have shown therapeutic potential in the management of neurodegenerative disease.[11]
Exposure to high levels of glucocorticoids or chronic stress may lead to oxidative injury in the hippocampus, which may impair memory and learning. It has been demonstrated that saffron can prevent oxidative stress in the hippocampus and prevent deficits in spatial learning and memory.[11]
Administration of saffron, 15mg twice daily, has been shown to be as effective as donepezil (an acetylcholinesterase inhibitor) for the treatment of mild-to-moderate Alzheimer disease (AD) in patients 55 years and older.[12] In another study of patients with mild-to-moderate AD, 16 weeks of supplementation with saffron (15mg twice daily) produced a significantly better outcome on cognitive function than placebo.[13] Moreover, there were no significant differences in the saffron and placebo groups in terms of observed adverse events.
Respiratory ailments
As previously mentioned, saffron has been traditionally used to improve respiratory ailments and asthmatic problems. In this context, animal research suggests that the bronchodilatory effects of saffron may be equal to theophylline,[14] a bronchodilator used to treat symptoms such as shortness of breath and wheezing caused by asthma, bronchitis, and emphysema.
The bronchodilatory effects of saffron may be attributed to a stimulatory effect on beta-2-adrenergic and H1 histaminergic receptors while blocking the muscarinic receptors.[15]
Cardioprotective effects
Cardioprotective and anti-atherosclerotic effects have been reported for saffron-derived crocin and crocetin.[15] Mechanisms responsible for these properties include anti-hyperlipidemic and insulin sensitising effects, inhibition of foam cell formation, aortic intima thickening, oxidised low-density lipoprotein uptake, lipid absorption and vascular cell adhesion molecule-1 expression.[15,16]
Ocular disoders
Ischaemic retinopathy and age-related macular degeneration are leading causes of blindness. The aetiology of these disorders is due in part to the reduction of blood flow in the retina and/or choroid. Crocin analogs isolated from saffron have been found to significantly increase the blood flow in the retina and choroid and to facilitate retinal function recovery.[17]
While there are many more clinical applications for saffron, it is beyond the scope of this article to mention them all. However, numerous reviews are readily available online. Even though saffron is well tolerated with very few adverse effects reported in literature, it is advisable that it should be used under professional supervision when treating mental health conditions to promote safety.
References
- Mousavi SZ, Bathaie SZ. Historical uses of saffron: Identifying potential new avenues for modern research. AJP 2011;1(2):57-66. [Abstract]
- Dwyer AV, Whitten DL, Hawrelak JA. Herbal medicines, other than St. John’s Wort, in the treatment of depression: a systematic review. Altern Med Rev 2011;16(1):40-49.[Abstract]
- Hosseinzadeh H, Nassiri-Asl M. Avicenna’s (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res 2013;27(4):475-483.[Abstract]
- Dalby A. Dangerous tastes, the story of spices. Berkley: California Press, 2000.[Source]
- Poma A, Fontecchio G, Carlucci G, et al. Anti-inflammatory properties of drugs from saffron crocus. Antiinflamm Antiallergy Agents Med Chem 2012;11(1):37-51.[Abstract]
- Lopresti AL, Drummond PD. Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum Psychopharmacol 2014;29(6):517-527.[Abstract]
- Kell G, Rao A, Beccaria G, et al. affron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomized, placebo-controlled clinical trial. Complement Ther Med 2017;33:58-64.[Abstract]
- Lopresti AL, Drummond PD, Inarejos-Garcia AM, et al. affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study. J Affect Disord 2018;232:349-357.[Abstract]
- Noorbala AA, Akhondzadah S, Tahmacebi-Pour N, et al. 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 2005;97(2):281-284.[Abstract]
- Akhondzadeh S, Fallah-Pour H, Afkham K, et al. 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 2004;4:12.[Abstract]
- Khazdair MR, Boskabady MH, Hosseini M, et al. The effects of Crocus sativus (saffron) and its constituents on nervous system: review. Avicenna J Phytomed 2015;5(5):376-391.[Abstract]
- Akhondzadeh S, Shafiee Sabet M, Harirchaian MH, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Phytopharmacology (Berl) 2010;207(4):637-643.[Abstract]
- Akhondzadeh S, Sabet MS, Harirchaian MH, et al. 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 2010;35(5):581-588.[Abstract]
- Mokhtari-Zaer A, Khazdair MR, Boskabady MH. Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms. Avicenna Journal of Phytomedicine 2015;5(5):365-375.[Abstract]
- Javadi B, Sahebkar A, Emami SA. A survey on saffron in Major Islamic Traditional medicine books. Iran J Bas Med Sci 2013;16(1):1-11.[Abstract]
- Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review. J Tehran Heart Cent 2011;6(2):59-61.[Full Text]
- Xuan B, Zhou YH, Li N, et al. Effects of crocin analogs on ocular blood flow and retinal function. J Ocul Pharmacol Ther 1999 Apr;15(2):143-152.[Abstract]
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