Table 2.
The detail of saffron clinical trials.
| Role of Saffron | Country | Year | Concentration | Participants | Clinical Trial # | Ref. |
|---|---|---|---|---|---|---|
| SLEEP QUALITY | ||||||
| Reports have shown that saffron intake was associated with improvements in sleep quality in adults with self-reported sleep complaints. | Belgium | 2021 | 15.5 mg per day for 6 weeks | 34 | NCT04750681 | [164] |
| Australia | 2020 | 14 mg twice daily for 28 days | 33 | ACTRN12619000863134 | [165] | |
| NEUROPSYCHIATRIC CONDITIONS | ||||||
| Several lines of evidence have shown that supplementation with saffron showed potential SSRI-like activity and neuroprotective properties, implying that saffron could serve as a safe adjunctive medication to alleviate symptoms, particularly in MDD and postpartum depression, with a notable impact on anxiety disorders and a minimal occurrence of side effects. | Australia | 2019 | 14 mg b.i.d. for 8 weeks | 72 | NA | [166] |
| Australia | 2018 | 14 mg b.i.d. for 8 weeks | 40 | ACTRN12617000155392 | [167] | |
| Australia | 2017 | 28 mg/day and 22 mg/day for 4 weeks | 121 | NA | [168] | |
| Iran | 2017 | 30 mg/day for 6 weeks | 30 | NA | [169] | |
| Iran | 2017 | 15 mg twice daily for 6 weeks | 34 | NA | [170] | |
| Iran | 2016 | 50 mg twice daily for 12 weeks | 54 | NA | [167] | |
| Iran | 2015 | 30 mg/day and 15 mg b.i.d. for 4 weeks | 23 | IRCT20130418013058N11 | [171] | |
| Iran | 2005 | 30 mg/day (b.i.d.) for 6 weeks | 20 | NA | [172] | |
| Iran | 2005 | 30 mg/day capsule for 6 weeks | 20 | NA | [173] | |
| Australia | 2020 | 28 mg daily for 6 weeks | 31 | ACTRN12621000501842 | [174,175] | |
| Studies have shown that saffron exhibited efficacy equivalent to methylphenidate in treating ADHD in children, suggesting its potential as a candidate for ADHD therapy due to its ability to impact both monoaminergic and glutamatergic systems, yielding satisfactory outcomes. | Iran | 2019 | 20–30 mg/day for 6 weeks | 27 | IRCT201701131556N94 | [176] |
| Other reports have shown saffron to be both safe and effective in the short-term for individuals with mild-to-moderate AD, attributed to its ability to inhibit the aggregation and deposition of amyloid β in the human brain, thereby potentially treating neurodegenerative damage caused by oxidative stress. | Iran | 2009 | 30 mg/day (15 mg twice per day) | 27 | IRCT138711051556N1 | [177] |
| Iran | 2010 | 30 mg/day for 16 weeks | 23 | NA | [178] | |
| CARDIOVASCULAR EFFECTS | ||||||
| Saffron, possessing antioxidant, anti-inflammatory, antihyperlipidemic, hypotensive, and weight-lowering properties, can aid in supporting cardiovascular health and ameliorating symptoms in atherosclerosis patients, including physical disability, sexual dysfunction, and psychological disorders, enhancing quality of life. | Iran | 2014 | 30 mg/day capsule for 6 weeks | 22 | NA | [179] |
| Iran | 2022 | 100 mg/day for 6 weeks | 33 |
NA IRCT201511192017N25 |
[180] | |
| METABOLIC DISORDERS | ||||||
| Saffron’s potent antidiabetic, antiobesity, hypotensive, and hypolipidemic effects suggest its potential importance in managing MetS, with studies demonstrating improvements in FBG, hemoglobin A1C, glycemic status, lipid profile, oxidative status, and liver function tests in diabetic profiles. | Iran | 2022 | 100 mg/day for 8 weeks | 35 | NA | [181] |
| Iran | 2014 | 30 mg daily for 12 weeks | 44 | NA | [182] | |
| RHEUMATOID ARTHRITIS | ||||||
| A study showed the potential benefits of saffron supplementation in enhancing disease activity and clinical outcomes in RA by decreasing inflammatory ILs, highlighting its anti-inflammatory properties and ability to alleviate acute and chronic pain. | Iran | 2020 | 100 mg/day for 12 weeks | 31 | NA | [183] |
| REPRODUCTIVE HEALTH | ||||||
| Studies have explored saffron’s aphrodisiac effects in men, indicating improvements in erectile function and overall sexual health, especially in diabetes. Similarly, in women, saffron has proven effective in alleviating sexual dysfunction and relieving symptoms of premenstrual syndrome, dysmenorrhea, and irregular menstruation, potentially modulating the secretion of steroid hormones. | Iran | 2022 | 15 mg twice daily for 2 weeks | 34 | IRCT20090117001556N110 | [184] |
| Iran | 2015 | 1% topical saffron gel | 25 | IRCT ID: 201404071769N1 | [185] | |
| Iran | 2008 | 30 mg/day for 2 menstrual cycles | 25 | NA | [186] | |
| Inflammatory Bowel Disease | ||||||
| Reports have shown that saffron supplementation among patients with UC may be effective in improving antioxidant status and reducing disease severity. Our multiple-center IBD clinical trial has suggested that saffron treatment led to a decrease in pro-inflammatory (TNFα, INF-γ, IL-6, IL-2, and IL-17a) and an increase in anti-inflammatory (IL-10 and TGF-β) cytokines, along with reduced fecal calprotectin (CP) and serum CRP levels in patients with mild-to-moderate UC |
Iran USA |
2020 Presently active |
100 mg/daily 50mg/b.i.d |
40 62 |
NA NCT04749576 |
[163] [122,187] |
| IMMUNOREGULATORY | ||||||
| Saffron may have effects on the immune system and hematological parameters. | Iran | 2011 | 100 mg daily for 6 weeks | 45 | NA | [188] |
| Saffron may have mental and physical effects in healthy recreationally active adults | Australia | 2020 | 28 mg daily for 6 weeks | 31 | ACTRN12621000501842 | [174] |
| OCULAR DISEASES | ||||||
| Saffron supplementation modestly improved visual function in participants with AMD, including those using AREDS supplements. Additionally, saffron supplementation shows promise in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF. | Italy | 2019 | 20 mg over 180 days | 14 | NCT01278277 | [189] |
| Australia and New Zealand | 2019 | 20 mg/day for 3 months | 50 | ACTRN 12612000729820 | [190] | |
Note: SSRI (selective serotonin reuptake inhibitor), major depressive disorder (MDD), ADHD (attention deficit hyperactivity disorder), Alzheimer’s disease (AD), metabolic syndrome (MetS), FBG (fasting blood glucose), hemoglobin A1C (Hb A1C), b.i.d (twice a day), rheumatoid arthritis (RA), interleukins (ILs), AMD (age-related macular degeneration), including those using AREDS (Age-Related Eye Disease Study), ABCA4-related STG/FF (Stargardt disease and fundus flavimaculatus), and IBD (inflammatory bowel disease), NA (not available, due to multiple reasons—outside USA and other).