Saffron (Eye)

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

OBJECTIVE: To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS AND ANALYSIS: Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption.Participants were given oral saffron supplementation (20 mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these.Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry. RESULTS: At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3-6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1-6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected. CONCLUSION: Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits. © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PURPOSE: Comparing visual outcomes after use of a novel binocular eye-tracking-based home treatment (CureSight; NovaSight, Ltd) with patching. DESIGN: Prospective, multicenter, randomized, masked, controlled, noninferiority pivotal trial. PARTICIPANTS: One hundred three children 4 to < 9 years with anisometropic, small-angle strabismic or mixed-mechanism amblyopia were randomized 1:1 to either CureSight treatment or patching. METHODS: The CureSight treatment uses combined anaglyph glasses and an eye tracker to induce real-time blur around the fellow eye fovea in dichoptic streamed video content. Participants used the device for 90 minutes/day, 5 days/week for 16 weeks (120 hours). The patching group received 2 hours of patching 7 days/week (224 hours). The prespecified noninferiority margin was 1 line. MAIN OUTCOME MEASURES: The primary outcome was the improvement in the amblyopic eye visual acuity (VA), modeled with a repeated measures analysis of covariance. Secondary outcomes included stereoacuity, binocular VA, and treatment adherence rates, analyzed by a 1-sample Wilcoxon test within each group and a 2-sample Wilcoxon test comparing groups. Safety outcomes included the frequency and severity of study-related adverse events (AEs). RESULTS: CureSight group VA improvement was found to be noninferior to patching group improvement (0.28 ± 0.13 logarithm of the minimum angle of resolution [logMAR] [P < 0.0001] and 0.23 ± 0.14 logMAR [P < 0.0001], respectively; 90% confidence interval [CI] of difference, -0.008 to 0.076). Stereoacuity improvement of 0.40 log arcseconds (P < 0.0001) and improved binocular VA (0.13 logMAR; P < 0.0001) were observed in the binocular treatment group, with similar improvements in the patching group in stereoacuity (0.40 log arcseconds; P < 0.0001) and binocular VA (0.09 logMAR; P < 0.0001), with no significant difference between improvements in the 2 groups in either stereoacuity (difference, 0; 95% CI, -0.27 to -0.27; P = 0.76) or binocular VA (difference, 0.041; 95% CI, -0.002 to 0.085; P = 0.07). The binocular treatment group had a significantly higher adherence than the patching group (91% vs. 83%; 95% CI, -4.0% to 21%; P = 0.011).

OBJECTIVE: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). METHODS: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software. RESULTS: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events. CONCLUSION: 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. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

INTRODUCTION: Some medicinal plants have shown promising therapeutic potential for the management of the diseases. We aimed to systematically review the literature wherein the therapeutic effects of saffron have been studied on eye disorders. METHODS: A systematic literature search was performed in PubMed, Scopus, Web of Science, Google scholar and other databases using eye disorders and saffron as key terms. No strict inclusion criteria were defined, and almost all clinical studies, as well as in vivo and in vitro studies were included. The reported data in each study were extracted and then qualitatively described. RESULTS: Finally, 78 articles were found but only 29 relevant articles were included. Nine articles were clinical trials and 20 articles were studies conducted on cellular and molecular aspects of saffron on eye disorders. According to the included studies, crocin prevented the pro-inflammatory response in retinal cells and decreased glucose levels in diabetic mice. Also, crocetin prevented retinal degeneration and saffron protected photoreceptors from light-induced damage in retinal cells. Saffron also improved visual function in age-related macular edema and decreased intraocular pressure in patients with glaucoma. In addition, it was shown that crocin can improve best corrected visual acuity and decrease central macular thickness in patients with diabetic maculopathy. CONCLUSION: The results of this review indicated that saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease especially eye inflammation; however, further clinical studies are needed to confirm such efficiency.

Background: Regarding the antioxidant content of saffron, it could be beneficial for diseases linked to oxidative stress, such as Parkinson's disease (PD). However, there were limited human studies on the efficacy of saffron supplements on PD. Therefore, we aimed to investigate this subject. Method: The current study is a triple-blind, randomized, parallel clinical trial, which investigated the effect of 100 mg d-1 saffron powder or placebo on 92 patients with PD for 12 weeks. The analyses were conducted based on an intention-to-treat approach. Results: The age and BMI (mean ± SE) were 68.36 ± 1.0 years and 27.09 ± 0.45 kg m-2, respectively. Comparing the mean changes of the saffron and placebo groups confirmed significant favorable effects of saffron on C-reactive protein (CRP) values (adjusted mean difference: -3.84 mg L-1 and 95% CI: -5.61, -2.08; PANCOVA < 0.001), distress (adjusted mean difference: -4.40 and 95% CI: -8.43, -0.37; PANCOVA = 0.03), anxiety (adjusted mean difference: -4.75 and 95% CI: -8.30, -1.20; PANCOVA = 0.009), depression (adjusted mean difference: -4.58 and 95% CI: -8.34, -0.81; PANCOVA = 0.01), cognitive status (adjusted mean difference: 0.78 and 95% CI: 0.16, 1.40; PANCOVA = 0.01), sleep quality (adjusted mean difference: 14.76 and 95% CI: 3.20, 26.32; PANCOVA = 0.01), fatigue (adjusted mean difference: -9.20 and 95% CI: -13.76, -4.65; PANCOVA < 0.001) and indices of quality of life including mobility (adjusted mean difference: -6.43 and 95% CI: -12.32, -0.54; PANCOVA = 0.03), daily activity (adjusted mean difference: -6.62 and 95% CI: -12.89, -0.34; PANCOVA = 0.03), cognitive impairment (adjusted mean difference: -8.07 and 95% CI: -14.39, -1.75; PANCOVA = 0.01), bodily discomfort (adjusted mean difference: -7.50 and 95% CI: -13.93, -1.06; PANCOVA = 0.02), and Parkinson's Disease Summary Index (PDSI) (adjusted mean difference: -4.86 and 95% CI: -7.48, -2.25; PANCOVA < 0.001). Additionally, the saffron group in comparison with the placebo group showed marginal decreases in the values of malondialdehyde (adjusted mean difference: -0.32 nmol mL-1 and 95% CI: -0.69, 0.03; PANCOVA = 0.07). No side effect was observed in the groups. Conclusi

BACKGROUND: Premenstrual syndrome (PMS) is a prevalent and often debilitating health conditions affecting women of reproductive age. The natural PMSoff supplement contains several active ingredients, including spirulina, whey protein, calcium citrate, vitamin B1, chamomile, turmeric, marigold, lavender, saffron, valerian, and aftimoon. This clinical trial aimed to assess the efficacy and safety of PMSoff, a natural supplement, in alleviating the symptoms of PMS. METHODS: In this double-blind, randomized trial, women diagnosed with PMS were randomly assigned to receive either PMSoff or placebo. The primary objective of the study was to evaluate the impact of PMSoff on symptom severity, with secondary objectives focusing on safety and adherence. The primary outcome of this study was the severity of PMS symptoms, evaluated using the Daily Record of Severity of Problems (DRSP) questionnaire. The secondary outcome focused on the presence of premenstrual dysphoric disorder (PMDD), a more severe and debilitating form of PMS. Symptom severity was assessed at multiple time points: pre-intervention, one month post-intervention, and two months post-intervention. RESULTS: Of the 255 randomized participants, 218 (85.4%) patients aged 14 to 30 years were enrolled and completed the clinical trial. No significant difference was observed between groups at baseline characteristics. Medication adherence in the first and second month of treatment was reported 72%. Following one month of treatment, the intervention group showed a significant reduction in DRSP scores compared to the control group (P-value = 0.043). This reduction became even more pronounced after two months of taking the supplement (P-value = 0.001). In patients with PMDD, a more severe form of PMS, a statistically significant difference emerged two months after the intervention (P-value = 0.04), indicating that the PMSoff was effective in alleviating PMDD-related symptoms, particularly during the second month of treatment. CONCLUSION: The results of this randomized placebo-controlled clinical trial were suggestive of the use of PMSoff in patients with PMS and PMDD to ameliorate its unpleasant symptoms, with sustaine

PURPOSE: Poor sleep is closely associated with obesity and contributes to hormonal dysregulation and weight gain. This meta-analysis aimed to evaluate the effects of nutritional interventions on the sleep quality of individuals with obesity, focusing on strategies, such as calorie restriction, high-protein diets, and plant-based supplementation. METHODS: A systematic literature search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library, covering publications from inception up to January 2025. Randomized controlled trials (RCTs) assessing nutritional interventions and sleep quality were also included. The risk of bias (ROB) was assessed using Cochrane's ROB 2 tool, and a meta-analysis was performed using the Comprehensive Meta-Analysis software. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs), and heterogeneity was evaluated using the I² statistic. RESULTS: Eleven RCTs involving 637 participants demonstrated that compared with the controls, the nutritional intervention significantly improved sleep quality (OR = 2.52, 95% CI [1.57, 4.03], P = 0.000). Specific interventions, such as saffron supplementation (OR = 11.10, P = 0.000), showed varying degrees of effectiveness. Long-term interventions (≥ 16 weeks) yielded consistent benefits, whereas moderate heterogeneity was observed (I² = 67.43%, P = 0.027). CONCLUSION: Nutritional interventions, especially those that include calorie restriction, high-protein diets, and plant-based supplementation, have the potential to improve sleep quality in adults with obesity. Long-term interventions (≥ 16 weeks) may offer the most effective benefits. © 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

BACKGROUND: Subclinical depressive symptoms, including low mood, fatigue and anxiety, refer to clinically relevant depressive manifestations that do not meet the criteria for major depressive disorder. These symptoms affect quality of life and can lead to chronic mental health issues. Nutritional interventions, such as saffron extract supplementation, may help modulate mood and inflammation, potentially alleviating these symptoms. OBJECTIVES: This study evaluated the efficacy of a 6-wk saffron extract supplementation on mood in healthy individuals with subclinical neuropsychiatric symptoms and explored the underlying mechanisms. METHODS: This randomized, double-blind, placebo-controlled study involved 51 adult healthy individuals who received oral administration of either saffron extract or a placebo for 6 wk. The primary outcome was a composite z-score averaging standardized scores of depression (Beck Depression Inventory-II), anxiety (State-Trait Anxiety Inventory-YA), and fatigue (Multidimensional Fatigue Inventory 20). Secondary outcomes included neuropsychiatric scores, quality of life, inflammatory markers, and hypothalamic-pituitary-adrenal axis reactivity. Amino acid derivatives were analyzed in blood samples. RESULTS: Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score) nor individual symptoms. However, it improved autoperceived mental health, as reflected in increased mental health scores over time on the Medical Outcome Study Short-Form 12 questionnaire, compared with placebo (mean at 6 wk: 53.8 ± 12.7 vs 44.6 ± 11.4 for placebo and saffron group, respectively; time × treatment, P = 0.04). There were no significant effects on inflammatory parameters or hypothalamic-pituitary-adrenal axis reactivity. Metabolomic analysis revealed that saffron extract significantly modulated N-acetyl-phenylalanine. CONCLUSIONS: Saffron extract supplementation do not affect subclinical depressive symptoms, either as a composite score or individual symptom categories. A potential effect on improved mental health outcomes cannot be excluded but requires further replication in future well-powered tr

INTRODUCTION: Osteoarthritis (OA) is a prevalent joint disorder with a significant global impact. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used for OA treatment but can have adverse effects. This study aimed to investigate the potential anti-inflammatory and analgesic effects of saffron in patients with OA. METHODS: A randomized, double-blind, controlled trial was conducted in patients with OA aged 50 to 70 years. The intervention group received saffron tablets (containing 50 mg of saffron extract, administered orally once daily) for 12 weeks, while the control group received a matched placebo. Pain severity, physical activity, and levels of IL-1 beta and TNF-alpha were assessed using validated measures and quantitative methods. NSAID treatment was monitored. RESULTS: The saffron group exhibited a significant decrease in IL-1β levels, indicating an anti-inflammatory effect. Both groups demonstrated improvements in pain severity and physical activity scores. However, the saffron group exhibited a significant reduction in NSAID use over time. DISCUSSION: This study suggests that saffron may be an effective and safe supplement for managing osteoarthritis by reducing inflammation, improving symptoms, and lowering NSAID use. These results support previous research on saffron's anti-inflammatory properties. However, limitations such as a small, mostly female sample, high dropout in the control group, and self-reported adherence highlight the need for larger, more rigorous studies. CONCLUSION: Saffron consumption may have potential anti-inflammatory and analgesic effects in OA patients. Furthermore, saffron supplementation may reduce the need for NSAIDs, potentially minimizing associated complications. Further research is needed to explore the full benefits and mechanisms of saffron in OA management. CLINICAL TRIAL REGISTRATION NUMBER: IRCT2016091029777N1.

Sleep disturbances are associated with an increased risk of neurodegenerative diseases and alterations in gut microbiota composition. Saffron (Crocus sativus) has been shown to improve sleep and modulate the gut microbiome, but its effect on sleep quality via the gut microbiota-brain axis remains largely unexplored. This randomised, placebo-controlled pilot study investigated the impact of four weeks of saffron supplementation (30 mg day-1) on sleep quality and gut microbiota in older adults (ages 55-85) with self-reported sleep complaints (N = 52). Subjective sleep quality was assessed using validated questionnaires, while objective measures were captured via an electroencephalography-based sleep tracker. Gut microbiota composition was analysed in a subgroup (N = 26). Saffron supplementation significantly improved subjective sleep quality (p = 0.02) and sleep efficiency (p = 0.04). Objective outcomes included reduced latency to persistent sleep (p = 0.003) and shorter sleep onset latency (p = 0.03). Microbiome analysis using linear discriminant analysis effect size (LEfSe) revealed significant increases in Faecalibacterium (q = 0.013), Lachnoclostridium (q = 0.045), Prevotella (q = 0.022), UBA1819 (q = 0.020) and Oscillibacter (q = 0.045), alongside a decrease in Dialister (q = 0.028). Univariate analysis further identified increases in Lachnospiraceae-UGC-001 (p = 0.020) and Roseburia (p = 0.03), with a reduction in Turicibacter (p = 0.045) in the saffron group. Correlational analyses revealed that Oscillibacter and UBA1819 were positively associated with subjective sleep efficiency (r = 0.63, p = 0.0007) and inversely associated with sleep latency (r = -0.39, p = 0.04). Alterations in in Dialister, Turicibacter and UBA1819 correlated with objective sleep quality parameters including wake duration, latency to persistent sleep and wake-after-sleep-onset. In summary, four-weeks saffron supplementation improved both subjective and objective sleep quality in older adults with sleep complaints, and modulated gut microbiota composition, particularly increasing short-chain fatty acids producing bacteria. These findings pave the way for further randomised controlled t

BACKGROUND: Saffron, derived from the stigmas of the Crocus sativus flower, has been shown in previous trials to have antidepressant effects in clinically diagnosed adults. However, the recruitment of small sample sizes, short treatment periods, and variability in the quality of studies have negatively impacted the strength of conclusions. OBJECTIVES: The purpose of this 2-arm, 12-wk, parallel-group, randomized, double-blind, placebo-controlled trial was to examine the effects of supplementation with a saffron extract (Affron) on mood and sleep in adults experiencing subclinical depressive symptoms. METHODS: Two hundred and two adults aged 18-70 with depressive symptoms were supplemented with 28 mg saffron daily or a placebo. Outcome measures included the Depression, Anxiety, and Stress Scale - 21, Sleep Disturbance and Sleep-Related Impairment Scale, World Health Organization-Five Well-Being Scale, and daily depression, stress, and anxiety ratings. RESULTS: On the primary outcome measure, compared to the placebo, saffron was associated with greater improvements in the Depression, Anxiety, and Stress scale - 21 depression score (β: -2.92 points; 95% confidence interval: -5.13, -0.71 points; Cohen's d = 0.39), with 72.3% of participants in the saffron group achieving a clinically significant change (a reduction of ≥ 7 points) compared to 54.3% of participants in the placebo group (P = 0.010). However, in the other secondary outcomes, there was no evidence of between-group differences. In exploratory analyses across various strata and assumptions, improvements in sleep disturbances (β: -2.72 points; 95% confidence interval: -4.99, -0.46 points; Cohen's d = 0.44) were identified in a subset of participants with a greater severity of sleep disturbance. There were no serious adverse reactions reported. CONCLUSIONS: This study, the largest conducted to date on saffron, provides evidence supporting the beneficial effects of 3 mo of saffron supplementation on depressive symptoms in adults. Large placebo responses were evident in this study, which require consideration in future trials. This trial was registered at Australian and New Zealand clinical trials registry as A

Background: Coronary artery disease (CAD) is a common heart disease characterized by plaque buildup in the coronary arteries. Saffron, which is rich in active compounds, has strong antioxidant properties that help reduce free radicals and plasma malondialdehyde (MDA) levels. This study aimed to evaluate the effects of crocetin supplementation on antioxidant and inflammatory markers, as well as serum leptin levels, in CAD patients. Methods: In this double-blind, placebo-controlled trial conducted in Ahvaz, Iran, 50 clinically diagnosed CAD patients, including men and women aged 40-65, were randomly assigned to two parallel groups to receive either one tablet of 10 mg crocetin (n = 25) or one placebo (n = 25) daily for eight weeks. The primary outcome was high-sensitivity C-reactive protein (hs-CRP) levels, and the secondary outcomes included the activities of superoxide dismutase (SOD) and catalase (CAT), malondialdehyde (MDA) levels, the atherogenic index of plasma (AIP), leptin levels, anthropometric measurements, and body composition. Both groups followed similar dietary and exercise regimens. Results: We found no significant differences between the intervention and placebo groups regarding C-reactive protein (CRP) levels, as indicated by ANCOVA (P = 0.695). Similarly, ANCOVA results for leptin (P = 0.854), superoxide dismutase (SOD) (P = 0.520), malondialdehyde (MDA) (P = 0.178), and the atherogenic index of plasma (AIP) (P = 0.409) also did not show significant differences. However, a significant result was observed for catalase (CAT) (P = 0.008). The comparison of mean differences within the intervention and placebo groups showed clinical improvements for several measurements. Importantly, hs-CRP levels were -119.62 in the intervention group compared to -156.91 in the placebo group. Other mean differences included SOD (41.72 vs. -7.33), MDA (-0.99 vs. -0.16), AIP (-0.13 vs. 0.04), leptin (-1.86 vs. -0.09), systolic blood pressure (SBP) (-0.25 vs. 0.13), and diastolic blood pressure (DBP) (-0.24 vs. -0.01). Conclusions: Crocetin supplementation significantly improved inflammation, oxidative stress status, and leptin levels in CAD patients. Although further s

BACKGROUND: Critically ill patients suffering from sepsis are at an increased risk of morbidity and mortality due to its serious complications. Saffron as an herbal medicine has been proven to have anti-inflammatory and anti-oxidative stress effects previously. Hence, this study aimed to determine how saffron supplementation affected inflammatory and hematological factors in patients admitted to the intensive care unit (ICU) with sepsis. METHODS: In this double-blind clinical trial, 90 ICU sepsis patients with GCS lower than 13 were randomized to receive either an intervention tablet containing 100 mg of saffron or a placebo tablet containing 100 mg of corn starch for seven days. Before and after the intervention, clinical, inflammatory, hematological, and mortality parameters were assessed. RESULTS: After seven days, the saffron group showed a significantly decline from baseline compared to the placebo group in inflammatory markers, including CRP (-24.58 ± 22.16 vs. -2.42 ± 30.86; P < 0.001), ESR (-5.36 ± 28.75 vs. 24.29 ± 28.24; P < 0.001), IL-6 (-22.09 ± 25.22 vs. -4.02 ± 20.04; P < 0.001), IL-18 (-9.56 ± 9.31 vs. -0.89 ± 3.38; P < 0.001), and TNF-α (-2.52 ± 3.79 vs. -0.035 ± 2.35; P < 0.001). Regarding clinical outcomes, significant improvements were observed in APACHE II (-2.55 ± 5.47 vs. 0.78 ± 3.37; P = 0.003), SOFA (-1 ± 1.07 vs. -0.05 ± 1.53; P < 0.001), NUTRIC score (-1.2 ± 1.01 vs. 0.2 ± 0.87; P < 0.001), and WBC count (-4176.34 ± 4063.01 vs. 61.57 ± 4118.97; P < 0.001). Moreover, the effect sizes (Cohen's d) for these factors ranged from moderate to large, except for IL-6, which had a small effect size (d = -0.38). However, no significant differences were found between the groups in the Glasgow Coma Scale, FOUR Score, 28-day and 90-day mortality rates, or other hematological parameters (P > 0.05). CONCLUSIONS: Saffron administration in sepsis patients admitted to the ICU led to significant improvements in inflammatory markers and some clinical parameters. However, the clinical significance of these findings remains to be fully established. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20201129049534N8. It was registered on 17 March 202

Background: A nutritional supplement based on medicinal plants (saffron and ashwagandha), tryptophan, and vitamin B6 could contribute to alleviating/improving mood and associated disorders. The aim of this study was to evaluate the potential benefits of this combination supplement. During the study period, participants underwent a period of forced home confinement due to the COVID-19 pandemic, which represented an unexpected impact factor. Methods: This open-label prospective trial enrolled a cohort of female employees who reported mild to moderate anxiety. The primary objective was to evaluate changes in the level of anxiety using the adapted Hamilton Anxiety Rating Scale (HARS) after 12 weeks of regular supplementation with Safromotive (two tablets daily, for 12 weeks). The secondary objectives were to evaluate health-related quality of life (HRQoL) and tolerability. Results: In total, 46 women with a mean age of 45.0 (6.5) years were included. A statistically significant improvement in HARS was observed, with a 7.5-unit decrease from baseline to 12 weeks (p < 0.0001) and from 4 to 12 weeks of supplement intake (p=0.0058). However, no significant changes were found during the lockdown period (between weeks 8 and 12 of the study). No relationship was found between women's sociodemographic characteristics and the HARS total score. A significant reduction in the HRQoL questionnaire score of 1.2 units was observed between baselines and 12 weeks of treatment (p=0.0273). At the end of the study, 78.6% of the women reported consistency the supplement intake during the study course. Conclusion: This nutritional supplement composed of saffron, ashwagandha, tryptophan, and vitamin B6 appears to improve anxiety and HRQoL, but confinement could have impacted the evolution of the outcome.

Background/Objectives: The global prevalence of mental health disorders, particularly anxiety and depression, has increased significantly, with rates further elevated by the COVID-19 pandemic. Conventional pharmacological treatments, while effective, often lead to side effects that can impact patient adherence and quality of life. This has driven interest in safer, natural adjunctive therapies. Crocus sativus L. (Iridaceae) (saffron) and Scutellaria baicalensis Georgi (Lamiaceae) (scutellaria) have individually shown potential, in humans and animals, respectively, as mood regulators, with bioactive compounds that modulate neurotransmitter systems and possess anti-inflammatory and anxiolytic effects. This study aimed (1) to explore the efficacy and safety of scutellaria extracts in humans and (2) to test a possible synergistic effect when combining scutellaria and saffron on mood regulation in individuals experiencing mild-to-moderate depressive symptoms. Methods: In a randomized, double-blind, placebo-controlled trial, 180 participants with mild-to-moderate depressive symptoms were assigned to receive either scutellaria extract alone (SCUTELL'UP®), saffron extract alone (SAFFR'ACTIV®), a combination of scutellaria and saffron extracts (SAFFR'UP®), or a placebo for six weeks. The primary outcome was assessed using a standardized depression scale (Beck Depression Inventory). The secondary outcomes, including anxiety, emotional state, well-being level, and sleep quality, were all assessed using validated questionnaires. Safety and tolerability were evaluated throughout the study period. Results: The results confirmed the beneficial effects of saffron extract on depressive and anxious symptoms, as well as its role in improving sleep quality. For the first time in humans, scutellaria extract demonstrated a positive effect on mood regulation. Furthermore, a synergistic effect of the combination of these two extracts was identified, leading to enhanced improvements in depressive and anxious symptoms and emotional well-being among individuals with mild-to-moderate depression, compared to the placebo group. Minimal adverse effects were reported across all treatment group

Saffron is a traditional herbal medicine used to treat conditions associated with metabolic syndrome (MetS). However, the conclusions of relevant clinical studies have been inconsistent. This study aimed to assess the impact of saffron supplementation on the metabolism of glycolipids and blood pressure in individuals with MetS and related disorders. Web of Science, PubMed, Cochrane Library, Scopus, and Embase were comprehensively searched for studies investigating saffron supplementation for MetS and related disorders up to February 2024. Stata 17.0 was used to conduct the Meta-analysis. Twenty-five randomized controlled trials (RCTs) were included in this study, involving 1486 participants with MetS and related conditions. Compared to placebo, saffron supplementation triggered significant reductions in fasting blood glucose (FBG) (WMD: -6.67 mg/dL; 95% CI: -10.55, -2.78; p = 0.001; I 2 = 50.0%), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.25%; 95% CI: -0.35, -0.14; p < 0.001; I 2 = 0.0%), total cholesterol (TC) (WMD: -4.77 mg/dL; 95% CI: -8.83, -0.71; p = 0.021; I 2 = 31.8%), systolic blood pressure (SBP) (WMD: -1.15 mmHg; 95% CI: -1.66, -0.64; p < 0.001; I 2 = 41.8%), and diastolic blood pressure (DBP) (WMD: -1.61 mmHg; 95% CI: -1.88, -1.34; p < 0.001; I 2 = 7.0%). However, no significant changes were observed for homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and waist circumference (WC). Saffron supplementation has an improving effect on FBG, HbA1c, TC, DBP, and SBP in patients with MetS and related disorders. Nonetheless, additional high-quality RCTs involving diverse ethnic populations are necessary to validate this effect. © 2025 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.

Saffron has been traditionally used for various health benefits, but its effects on biomarkers of liver function, kidney function, and blood pressure in diabetes are not well understood. This meta-analysis aims to evaluate the impact of saffron supplementation on systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), liver enzymes (ALT, AST), and kidney function markers (BUN, creatinine) in patients with diabetes and prediabetes. A comprehensive search was conducted across multiple databases to identify randomized controlled trials (RCTs) assessing saffron/crocin supplementation on glycemic control, hepatic and renal function, and blood pressure regulation in patients with diabetes and prediabetes. Data were extracted and analyzed using random effects model to determine the effect sizes and 95 % confidence intervals (CIs) for each biomarker. The GRADE framework was employed to assess the certainty of the evidence for each outcome. Thirteen studies were included in the meta-analysis. Saffron supplementation significantly reduced SBP (SMD = -0.57, 95 % CI: -0.8 to -0.34, p = 0.036) with the high certainty of evidence, FBG (SMD = -0.57, 95 % CI: -0.93 to -0.22, p = 0.001) with the low certainty of evidence, and AST (SMD = -0.49, 95 % CI: -0.97 to -0.00, p = 0.049) with the low certainty of evidence. Other studied biomarkers were not affected significantly by saffron/crocin supplementation. Saffron/crocin supplementation is effective in decreasing AST, SBP, and FBG levels in patients with diabetes and prediabetes. However, it has no significant effect on ALT, renal function, and DBP. Our observed effect sizes on AST, SBP, and FBG are not clinically important.

Saffron is the dried stigma of Crocus sativus L. flowers. The yellow-orange color of saffron comes from crocin, a water-soluble carotenoid that can be ingested. Crocin is known for its anti-inflammatory and antioxidant potential. It is believed to affect inflammation and oxidative stress, making it a promising therapeutic option. However, research on its impact is inconclusive. This meta-analysis aimed to assess the benefits of crocin supplementation and its specific effects on inflammation and oxidative stress markers. A comprehensive search of the literature was conducted up to February 2024 in PubMed/Medline, Scopus, and Web of Science to find suitable randomized clinical trials (RCTs). All participants were adults who were supplemented with crocin as part of the study intervention. The selected trials were subjected to heterogeneity tests using the I 2 statistic. Random effects models were examined based on the heterogeneity tests, and the pooled data were calculated as weighted mean differences (WMD) with a 95% confidence interval (CI). Of the 519 papers that remain after duplications were removed, 13 eligible RCTs were included in the present meta-analysis. Our findings indicated that crocin supplementation significantly reduced c-reactive protein (CRP) levels (SMD: -0.50; 95%CI: -0.86 to -0.13; p = 0.008), tumor necrosis factor-α (TNF-α) (SMD: -1.96; 95%CI: -2.72 to -1.19; p < 0.001), and interleukin-6 (IL-6) (SMD: -3.52; 95%CI: -6.84 to -0.20; p = 0.03). Also, crocin supplementation led to a significant increase in total antioxidant capacity (TAC) (SMD: 1.48; 95%CI: 0.52 to 2.43; p = 0.002). Overall effect size showed that crocin intake failed to change the erythrocyte sedimentation rate (ESR) and malondialdehyde (MDA) levels significantly. Crocin reduces inflammatory markers and increases TAC. The effect of crocin on inflammatory markers was greater in a dose ≥ 30 mg/day and an intervention duration ≥ 12 weeks. However, more studies are needed for definitive conclusions. © 2024 John Wiley & Sons Ltd.