Saf8.0

Saffron Research

42 peer-reviewed studies · Evidence score: 8/10

Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis

Cheng YC et al. • Psychological medicine (2025)

This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.

Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response.
This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.
Further research warranted to confirm findings

Meta-Analysisn=17,437

DOI

Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials

Long Z et al. • Frontiers in immunology (2023)

Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc.

Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc.
However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols.
Further research warranted to confirm findings

Meta-Analysisn=3,852

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The Effects of Crocus sativus (Saffron) on ADHD: A Systematic Review

Seyedi-Sahebari S et al. • Journal of attention disorders (2024)

The results manifested an efficient role of saffron as either an adjuvant therapy to MPH or a single therapy against ADHD, without significant safety issues.

Systematic review examining Saffron efficacy
Further research warranted to confirm findings

Systematic Reviewn=118

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Systematic Review and Network Meta-Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients

Li J et al. • Phytotherapy research : PTR (2025)

Future longer follow-up, larger samples, and more methodologically rigorous randomized controlled trials are recommended to clearly establish the effects of different dosages on cognitive function and quality of life in stroke patients.

John's Wort extract (SUCRA 71.2%) was the most effective in reducing NIHSS scores, Berberine (SUCRA 84.1%) was most effective in reducing mRS scores, and St.
John's Wort extract (SUCRA 99.1%) showed the highest efficacy in enhancing ADL scores.
Ginsenosides were the most effective in improving Barthel Index (SUCRA 74.7%), MMSE (SUCRA 93%), and MOCA (SUCRA 79.7%) scores.

Meta-Analysis

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Effect of Aromatic Herbs and Spices Present in the Mediterranean Diet on the Glycemic Profile in Type 2 Diabetes Subjects: A Systematic Review and Meta-Analysis

Garza MC et al. • Nutrients (2024)

Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin.

Our results showed that cinnamon, turmeric, ginger, black cumin, and saffron significantly improved the fasting glucose levels in T2DM subjects.
The most significant decreases in fasting glucose were achieved after supplementation with black cumin, followed by cinnamon and ginger, which achieved a decrease of between 27 and 17 mg/dL.
Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin.

Meta-Analysisn=77

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Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review

Hasheminasab FS et al. • Phytotherapy research : PTR (2024)

This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress.
Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction.
Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers.

Systematic Reviewn=50

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Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials

Tóth B et al. • Phytomedicine (2019)

Saffron supplementation significantly reduced depressive symptoms compared to placebo and showed comparable efficacy to conventional antidepressants.

Significant antidepressant effect vs placebo across 11 RCTs
Comparable efficacy to SSRIs (fluoxetine, citalopram) and imipramine
Both crocin and safranal components contributed to antidepressant effects

Meta-Analysisn=531

DOI

Effect of Saffron Versus Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment of Depression and Anxiety: A Meta-analysis of Randomized Controlled Trials

Shafiee A et al. • Nutrition reviews (2025)

Saffron could be a potential SSRI alternative to reduce depressive and anxiety symptoms with fewer adverse events.

Saffron could be a potential SSRI alternative to reduce depressive and anxiety symptoms with fewer adverse events.
Further research with larger sample sizes and in diverse populations is warranted to validate these findings and explore potential moderators of treatment response.
Further research warranted to confirm findings

Meta-Analysis

DOI

Crocus Sativus for Insomnia: A Systematic Review and Meta-Analysis

Munirah MP et al. • International journal of environmental research and public health (2022)

This non-pharmacological intervention may reduce the chance of adults with insomnia taking sedative-hypnotic medication, thus reducing dependency and withdrawal symptoms.

Eight articles were included, involving 431 participants.
Although there is limited evidence of a very low- to moderate-quality, Crocus sativus may benefit people with insomnia.
This non-pharmacological intervention may reduce the chance of adults with insomnia taking sedative-hypnotic medication, thus reducing dependency and withdrawal symptoms.

Meta-Analysisn=431

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Effect of saffron and fenugreek on lowering blood glucose: A systematic review with meta-analysis

Correia AGDS et al. • Phytotherapy research : PTR (2023)

Further high-quality studies should be conducted to establish the clinical efficacy of herbal medicines.

The mean difference (MD) and the standardized MD (SMD) were adopted, and subgroup analyses were performed according to patient's clinical condition.
Saffron supplementation reduced FBG (MD: -9.06 mg/dl; 95%CI: -16.25 to -1.86; I2 = 40%; p = 0.12) and HbA1c (MD: -0.19%; 95%CI: -0.23 to -0.14; I2 = 0%; p > 0.99).
Our results show that using saffron and fenugreek can reduce FBG, PPBG, and HbA1c; however, there are some shortcomings that require attention for these results.

Meta-Analysis

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New horizons for the study of saffron (Crocus sativus L.) and its active ingredients in the management of neurological and psychiatric disorders: A systematic review of clinical evidence and mechanisms

Han S et al. • Phytotherapy research : PTR (2024)

Saffron may exert protective roles for neurological and psychiatric disorders and represents a relatively favorable and safe treatment.

A random-effects or fixed-effects model was used to calculate the pooled effect sizes.
Saffron was more effective than placebo in improving cognition, depression with an overall effect size of -4.26 (95% CI: -5.76, -2.77), anxiety of -3.75 (95% CI: -5.83, -1.67), and sleep disorders of -1.91 (95% CI: -2.88, -0.93).
Forty-six RCTs were enrolled, and the duration of these trials ranged from 4 to 48 weeks with saffron or its extracts, both alone or in combination with conventional drugs.

Systematic Review

DOI

The effect of saffron supplementation on symptoms of depression and anxiety: A systematic review and meta-analysis

Marx W et al. • Nutrition Reviews (2019)

Saffron supplementation had a large positive effect on depression symptoms and a moderate effect on anxiety symptoms compared to placebo.

Large effect size (Hedges g = 0.99) for reducing depressive symptoms
Significant anxiolytic effects also observed in pooled analysis
Doses of 30mg/day of standardized extract were most commonly effective

Meta-Analysisn=420

DOI

Saffron and its major constituents against neurodegenerative diseases: A mechanistic review

Abdian S et al. • Phytomedicine : international journal of phytotherapy and phytopharmacology (2024)

Saffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs.

Saffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs.
However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs.
More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials.

Systematic Review

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Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials

Ahmad S et al. • Metabolic brain disease (2023)

The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD.
Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment.
Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.

Systematic Review

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Clinical Use of Curcumin in Depression: A Meta-Analysis

Ng QX et al. • Journal of the American Medical Directors Association (2017)

Curcumin appears to be safe, well-tolerated, and efficacious among depressed patients.

Curcumin appears to be safe, well-tolerated, and efficacious among depressed patients.
More robust randomized controlled trials with larger sample sizes and follow-up studies carried out over a longer duration should be planned to ascertain its benefits.
Further research warranted to confirm findings

Meta-Analysisn=377

DOI

Saffron for depression: A meta-analysis

Hausenblas HA et al. • Journal of Integrative Medicine (2013)

Saffron supplementation significantly reduced symptoms of depression compared to placebo.

Large effect size for depression
Comparable to pharmaceutical antidepressants
Well tolerated

Meta-Analysisn=200

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Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

Sarris J et al. • The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry (2022)

Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders.

Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders.
However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use.
It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Meta-Analysis

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Medicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis

Zhang W et al. • Pharmacological research (2022)

Medicinal herbs may be promising for the treatment of anxiety.

Kava was found to be an effective anxiolytic (MD: -2.46, 95% CrI: -4.47 to -0.32) but possibly ineffective in patients with generalized anxiety disorder (MD: -0.17, 95% CrI: -2.55 to -1.97).
Ginkgo biloba (MD: -4.63, 95% CrI: -9.01 to -0.23) and Withania somnifera (MD: -4.90, 95% CrI: -9.70 to -0.17) were efficacious, as measured by HAMA scores but the trials were limited by their small sample sizes.
Conversely, although Passionflower (MD: -4.20, 95% CrI: -8.82 to 0.16) and Saffron (MD: -2.71, 95% CrI: -6.06 to 0.57) did not reduce HAMA scores significantly in the summary network, both were worthy of further study because of support from separate networks.

Meta-Analysisn=29

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Effects of saffron (Crocus sativus L.) on anthropometric and cardiometabolic indices in overweight and obese patients: A systematic review and meta-analysis of randomized controlled trials

Tahmasbi F et al. • Phytotherapy research : PTR (2022)

Despite bearing several limitations, mainly as a result of heterogeneity among included studies, the available evidence indicates saffron supplementation shows promising effects on some cardiometabolic factors among overweight to obese patients; however, further investigations and high-quality evidence are required for more generalizable and comprehensive results.

A random-effects meta-analysis was used to pool estimates across studies, and standardized mean difference (SMD) was used to synthesize quantitative results.
Twenty-five RCTs met the inclusion criteria.
Further research warranted to confirm findings

Meta-Analysis

DOI

Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta-analysis

Asbaghi O et al. • Phytotherapy research : PTR (2021)

Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.

Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin.
Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day.
We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03).

Meta-Analysis

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