Lopresti AL, Smith SJ. The Effects of a Saffron Extract (affron®) on Menopausal Symptoms in Women during Perimenopause: A Randomised, Double-Blind, Placebo-Controlled Study.J Menopausal Med. 2021;27(2):66-78. doi:10.6118/jmm.21002

Publication Date: "Published online 2021 Jun 2."

Peer Reviewed: Yes

Study Design: "12-week, parallel-group, double-blind, randomised controlled trial"

Methodology: Parallel-group, randomised controlled trial; 86 perimenopausal women; placebo or 14 mg saffron extract twice daily; outcome measures GCS, PANAS, SF-36.

Sample Size: "86 perimenopausal women"

Controls Used: "placebo"

Dose Used: "14 mg of a saffron extract (affron®), twice daily"

Statistical Significance Declared: "significantly greater reduction in the GCS psychological score (P = 0.032)" "significantly greater reduction in the PANAS negative affect score (P = 0.043)" "a 33% reduction in anxiety and a 32% reduction in depression scores from baseline to week 12."

Adverse Events: "no major adverse events were reported by participants" "one participant in the saffron group withdrew due to mild digestive complaints/bloating" "the frequency of reported adverse effects revealed an overall similar frequency in reported adverse events between the two groups. However, there was a tendency to suggest greater digestive complaints in the saffron group (e.g., flatulence and nausea)."

Conflict of Interest: "This study was funded by Pharmactive Biotech Products, SL." "Dr. Lopresti is the managing director of Clinical Research Australia, a contract research organisation that received funding from Pharmactive Biotech Products, SL for this study." "Dr. Lopresti has received either presentation honoraria or clinical trial grants from nutraceutical companies to complete previous clinical trials." "Mr. Smith is an employee of Clinical Research Australia and declares no other conflicts of interest."

Delam H, Keshtkaran Z, Shokrpour N, Eidi A, Bazrafshan MR. The effect of Crocus sativus L. (saffron) herbal tea on happiness in postmenopausal women: a randomized controlled trial. BMC Complementary Medicine and Therapies. 2023;23(1):176. doi:10.1186/s12906-023-04014-8.

Publication Date: "June 1, 2023"

Peer Reviewed: Yes

Study Design: "randomized controlled trial"

Methodology: 72 postmenopausal women; 30 mg dried stigmas of saffron plant boiled in 300 ml water; daily consumption of saffron tea with white rock candy; Oxford Happiness Questionnaire used; control group used lukewarm water with white rock candy.

Sample Size: "72 postmenopausal women"

Controls Used: "control group used lukewarm water with white rock candy"

Dose Used: "30 mg of dried stigmas of the saffron plant"

Statistical Significance Declared: "the happiness mean score in the intervention group increased significantly (p < 0.001)" "there was no significant difference between the happiness mean score at the beginning and end of the study in the control group (p = 0.861)" "a significant difference between the two groups in terms of the happiness mean scores (p < 0.001)"

Adverse Events: "no side effects"

Conflict of Interest: "The present study is the result of a research project with the code number of 1399-64 in Larestan University of Medical Sciences. Authors would like to thank and appreciate the Larestan University of Medical Sciences for financial support of the project."

Hasheminasab FS, Azimi M, Raeiszadeh M. Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review. Phytother Res. 2024. doi:10.1002/ptr.8186.

Publication Date: "First published: 01 April 2024"

Peer Reviewed: Yes

Study Design: "systematic review"

Methodology: Scientific databases (PubMed, Web of Sciences, Google Scholar, Scopus, Scientific Information Database) searched for in vivo, in vitro, and human studies on C. sativus effects on female reproductive system until July 2023. 50 studies included.

Sample Size: 50 studies

Controls Used: Not specified

Dose Used: "15 mg/twice a day" "30 mg/day" "250 mg" "15 mg/twice daily for 2 weeks" "14 mg/twice daily for 12 weeks"

Statistical Significance Declared: Not specified

Adverse Events: "C. sativus stigma powder (30 mg/daily) caused red skin and mild pruritus" "lung and liver toxicity was observed in the petal extract group" "some degree of nephrotoxicity was reported in excessive dosages in mice offspring" "consumption of C. sativus decoction in pregnant mice reduced the number of live infants compared with the control group" "some blindness cases were reported in the treatment group, which may be due to the teratogenic effect of C. sativus"

Conflict of Interest: "The authors declare that they have no conflict of interest in this study."

Babaev KF, Shukurova PA, Ibragimov AS, Abbasov RY, Ibragimova JM, Alieva RI, Gasimova GZ. The Effect of Saffron (Crocus sativus L. Iridaceae) Orally Administration on Blood Level of Sex Hormones in Rats. J Dis Med Plants. 2022;8(2):24-27. doi:10.11648/j.jdmp.20220802.11

Publication Date: "Published: April 14, 2022"

Peer Reviewed: Yes

Study Design: "The objective of the research was to study the effects of the Crocus sativus L. Iridaceae stigma extract on blood level of follicle-stimulating hormone in female rats, and blood level of testosterone in male rats."

Methodology: 45 Wistar rats; saffron stigma extract obtained by percolation method; female rats given 120 mg/kg for 14 or 21 days; male rats given 120 mg/kg for 21 days; blood samples collected; FSH and testosterone levels measured using hormonal test kits.

Sample Size: "45 Wistar rats"

Controls Used: "control groups included 6-month-old (the 1st controls) and 12-month old (the 2nd controls); animals were treated with physiological saline in the same manner."

Dose Used: "120 mg/kg for 21 days"

Statistical Significance Declared: "statistically significant increase in the level of total testosterone in experimental animals (p<0.001)" "21-day treatment with saffron extract led to almost 33% decrease in FSH level in the animals (p <0.01)"

Adverse Events: Not specified

Conflict of Interest: Not specified

Izadi S, Mohammad-Alizadeh-Charandabi S, Yadollahi P, Mirghafourvand M. Effect of vitamin E with and without saffron on the sexual function in women of reproductive age with sexual dysfunction: a randomized controlled trial. BMC Women's Health. 2024;24(1):143. doi:10.1186/s12905-024-02980-w.

Publication Date: "Feb. 26, 2024"

Peer Reviewed: Yes

Study Design: "triple-blind randomized controlled trial"

Methodology: A triple-blind randomized controlled trial with 50 participants experiencing sexual dysfunction, allocated into two groups using block randomization. Experimental group received 15 mg saffron capsule in the morning and 15 mg saffron with 50 mg vitamin E in the evening. Control group received placebo saffron capsule in the morning and 50 mg vitamin E with placebo saffron in the evening. Female Sexual Function Index and Depression, Anxiety, and Stress Scale-21 were used to assess outcomes at baseline, four weeks, eight weeks, and four weeks post-intervention.

Sample Size: "50 participants"

Controls Used: "placebo of saffron and vitamin E"

Dose Used: "15 mg saffron capsule (safrotin) in the morning and a combination capsule containing 15 mg saffron and 50 mg vitamin E (safradide) in the evening"

Statistical Significance Declared: "overall mean score of sexual function compared to the control group (adjusted mean difference (AMD): 4.6; 95%CI: 3.1 to 6.1; p < 0.001)" "mean scores for sexual function dimensions, namely libido, arousal, orgasm, and satisfaction, except for pain, were consistently higher (p < 0.001)" "mean score for lubrication was significantly higher only at the eighth-week measurement (p = 0.004)" "mean depression score in the experimental group was significantly lower than in the control group at all-time points, i.e., four (p = 0.011) and eight weeks after the intervention (p = 0.005), and four weeks after the end of the intervention (p = 0.007)" "experimental group exhibited a statistically significant decrease in mean anxiety score compared to the control group at four weeks into the intervention (p = 0.016) and four weeks following the end of the intervention (p = 0.002)" "significant reduction in the overall mean stress score compared to the control group after the intervention (AMD: -2.3; 95%CI: -3.1 to -1.5; p < 0.001)"

Adverse Events: "one person reported headache in the intervention group" "one person reported dry mouth in the control group"

Conflict of Interest: Not specified in the provided text.

Liu X, Wang Z, Song X, Chang X, Zu E, Ma X, Sukegawa M, Liu D, Wang DO. Crocetin Alleviates Ovariectomy-Induced Metabolic Dysfunction through Regulating Estrogen Receptor β. J Agric Food Chem. 2021 Dec 15;69(49):14824-14839. doi: 10.1021/acs.jafc.1c04570.

Publication Date: "Publication Date: December 1, 2021"

Peer Reviewed: Yes

Study Design: "randomised, double-blind, placebo-controlled trial"

Methodology: Recruited participants through social media, administered saffron extract or placebo, assessed outcomes using standardized scales, and measured biochemical markers.

Sample Size: "The number of participants required per group to find an effect on the Greene Climacteric Scale (GCS) total score was estimated as 36."

Controls Used: "Placebo"

Dose Used: "14 mg twice daily"

Statistical Significance Declared: "*, #P < 0.05; ##, **P < 0.01; and ***, ###P < 0.001."

Adverse Events: "Saffron intake was well tolerated with no reported major adverse events."

Conflict of Interest: "This study was funded by Pharmactive Biotech Products, SL. Pharmactive Biotech Products, SL was not involved in the design of the research, analysis of data, or the writing of the report."

Lin WC, Cao PC, Xiao WX, Yan YB, Zhao X, Liu S, Feng J, Zhang W, Wang J, Feng YF, Lei W. Preventive Effect of Crocin on Osteoporosis in an Ovariectomized Rat Model. Evidence-Based Complementary and Alternative Medicine. 2014;2014:825181. doi:10.1155/2014/825181

Publication Date: "Published 14 August 2014"

Peer Reviewed: Yes

Study Design: "The purpose of this study was to investigate the therapeutic effects of crocin on ovariectomy-induced osteoporosis in rats."

Methodology: Female Sprague-Dawley rats, randomly assigned to sham-operated and five ovariectomy subgroups, daily oral administration of E2 or crocin started 4 weeks after OVX and lasted for 16 weeks, measured BMD, trabecular microarchitecture, oxidative stress status, biochemical parameters, and bone turnover markers.

Sample Size: "sham, n=10; OVX, n=50; OVX with 17β-estradiol (E2, 25 µg/kg/day), and OVX with graded crocin doses (5, 10, or 20 mg/kg/day), n=10 each."

Controls Used: "sham-operated group (sham) and OVX with vehicle (OVX)"

Dose Used: "OVX with graded crocin doses (5, 10, or 20 mg/kg/day)"

Statistical Significance Declared: "P < 0.05 considered significant"

Adverse Events: "crocin exhibits high efficacy and no major toxicity in experimental models"

Conflict of Interest: "The authors declare that there is no conflict of interests regarding the publication of this paper."

Abedimanesh N, Bathaie SZ, Abedimanesh S, Motlagh B, Separham A, Ostadrahimi A. Saffron and crocin improved appetite, dietary intakes and body composition in patients with coronary artery disease.J Cardiovasc Thorac Res. 2017;9(4):200-208. doi:10.15171/jcvtr.2017.35

Publication Date: "published: 30 December 2017"

Peer Reviewed: Yes

Study Design: "8 weeks randomized, double-blind, and placebo-controlled trial"

Methodology: 84 patients with CAD, ages 40-65, randomly divided into groups to receive 30 mg saffron aqueous extract (SAE), 30 mg crocin, or placebo daily. Appetite, dietary intake, anthropometry, body composition, biochemical analysis assessed before and after the study.

Sample Size: "84 patients with CAD"

Controls Used: "placebo"

Dose Used: "30 mg saffron aqueous extract (SAE) or 30 mg crocin or placebo daily"

Statistical Significance Declared: "Decrease in body mass index (BMI), waist circumference and fat mass values in SAE group was significantly more than crocin group (P<0.001)." "Both SAE and crocin yielded significant decrease in energy and dietary intake mean values (P<0.001 and P=0.046)." "The appetite decreased significantly in SAE and crocin group (P<0.001 and P=0.029, respectively)."

Adverse Events: "one person reported headache in the intervention group" "one person reported dry mouth in the control group"

Conflict of Interest: "The authors declare no competing financial interests exist."

Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, M Tsatsakis A. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review.Avicenna J Phytomed. 2015;5(5):376-391.

Publication Date: "Sep-Oct 2015"

Peer Reviewed: Yes

Study Design: "a review"

Methodology: A review of studies investigating the effects of C. sativus and its constituents on the nervous system.

Sample Size: Not applicable

Controls Used: Not applicable

Dose Used: Not applicable

Statistical Significance Declared: Not applicable

Adverse Events: "The median lethal doses (LD50) of C. sativus are 200 mg/ml and 20.7 g/kg in vitro and in animal studies, respectively." "Increased the frequency of saffron extract side effects similar to those of donepezil except for vomiting, which occurred more frequently in the donepezil group." "Some degree of nephrotoxicity was reported in excessive dosages in mice offspring." "Consumption of C. sativus decoction in pregnant mice reduced the number of live infants compared with the control group." "Some blindness cases were reported in the treatment group, which may be due to the teratogenic effect of C. sativus." "Saffron at the dose of 200 mg/kg did not significantly suppress PTZ-induced seizures." "Safranal, reduced PTZ-induced seizure duration, delayed the onset of tonic convulsions and protected mice from death but crocin (200 mg/kg, i.p.) did not show anticonvulsant activity." "Poor bioavailability of crocetin through oral administration is likely due to its low solubility; therefore, increasing administration frequency and/or modifying delivery systems are required."

Conflict of Interest: Not specified in the provided text.

Chen AY, Chen YC. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention.Food Chem. 2013;138(4):2099-2107. doi:10.1016/j.foodchem.2012.11.139

Publication Date: "Published online 2021 Jun 2."

Peer Reviewed: Yes

Study Design: "This review summarizes the findings of various clinical and preclinical studies on the therapeutic effects of saffron and its active constituents."

Methodology: Review of clinical and preclinical studies investigating the effects of saffron and its constituents on various health conditions, including depression, sexual function, cognitive function, cardiovascular health, and cancer.

Sample Size: Not applicable

Controls Used: Not applicable

Dose Used: Not applicable

Statistical Significance Declared: Not applicable

Adverse Events: "The most common side effects reported were digestive complaints, such as nausea and vomiting." "Some studies reported mild adverse effects such as headache and dizziness." "A few clinical trials indicated an increased risk of bleeding with high doses of saffron." "There were occasional reports of allergic reactions, including itching and rashes." "High doses of saffron may cause hypotension and central nervous system depression." "A rare side effect noted was the development of hypomania in individuals with bipolar disorder." "Some studies mentioned the risk of toxicity at very high doses, but these doses are significantly higher than those used in therapeutic settings."

Conflict of Interest: "The authors declare no conflict of interest."

Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials.J Integr Med. 2013;11(6):377-383. doi:10.3736/jintegrmed2013056

Publication Date: "Available online June 28, 2014."

Peer Reviewed: Yes

Study Design: "The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD."

Methodology: Electronic and non-electronic searches for randomized, double-blind controlled trials; calculated weighted mean effect sizes for saffron vs placebo control groups and saffron vs antidepressant groups; assessed methodological quality using the Jadad score.

Sample Size: "Five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials)"

Controls Used: "Placebo control or antidepressant comparison group"

Dose Used: "All the trials used a 30 mg/d dose of saffron."

Statistical Significance Declared: "A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001)." "A null effect size was evidenced between saffron supplementation and the antidepressant groups (M ES = -0.15, 95% CI: -0.52-0.22, P = 0.42)."

Adverse Events: "None of the trials reported any severe adverse events associated with the use of saffron supplementation." "The most common adverse effects reported for saffron supplementation were headache, nausea, anxiety, and decreased appetite."

Conflict of Interest: "Drs. Anton and Hausenblas serve as scientific advisors and as consultants for the company ReBody, LLC., which is an affiliate of Reserve Life Organics, LLC. d/b/a Reserveage Organics, the developer and marketer of a product in which saffron is used. Neither author has received personal financial gain from sales of this product. All findings and views expressed in this paper are those of the authors and do not necessarily reflect the views of the Reserve Life Organics, LLC., d/b/a Reserveage Organics that funded this trial."

Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. 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. doi:10.1016/j.jep.2004.11.004

Publication Date: "Available online 6 January 2005."

Peer Reviewed: Yes

Study Design: "6-week double-blind, randomized trial"

Methodology: "Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study."

Sample Size: "Forty adult outpatients"

Controls Used: "No placebo group"

Dose Used: "30 mg/day (BD) of saffron or 20 mg/day (BD) of fluoxetine"

Statistical Significance Declared: "F = 0.13, d.f. = 1, P = 0.71" (for the comparison between saffron and fluoxetine)

Adverse Events: "No significant differences in the two groups in terms of observed side effects." "Saffron at this dose did not induce any abnormal bleeding."

Conflict of Interest: "None declared."

Shafiee M, Arekhi S, Omranzadeh A, Sahebkar A. Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action.J Affect Disord. 2018;227:330-337. doi:10.1016/j.jad.2017.11.020

Publication Date: "Published online 2021 Jun 2."

Peer Reviewed: Yes

Study Design: "This review summarizes the findings of various clinical and preclinical studies on the therapeutic effects of saffron and its active constituents."

Methodology: Review of clinical and preclinical studies investigating the effects of saffron and its constituents on various health conditions, including depression, sexual function, cognitive function, cardiovascular health, and cancer.

Sample Size: Not applicable

Controls Used: Not applicable

Dose Used: Not applicable

Statistical Significance Declared: Not applicable

Adverse Events: "Saffron intake was well tolerated with no reported major adverse events, although there was a greater number of reports of mild digestive complaints (e.g., flatulence and nausea)."

Conflict of Interest: "The authors declare no conflict of interest."

Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial.Phytomedicine. 2006;13(9-10):607-611. doi:10.1016/j.phymed.2006.08.006

Publication Date: "Nov. 2006"

Peer Reviewed: Yes

Study Design: "6-week double-blind, randomized and placebo-controlled trial"

Methodology: "Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM IV) for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients were randomly assigned to receive capsule of petal of C. sativus 30 mg/day (BD) (Group 1) and capsule of placebo (BD) (Group 2) for a 6-week study. Patients were assessed by a psychiatrist at baseline and after 1, 2, 4 and 6 weeks after the medication started."

Sample Size: "Forty adult outpatients"

Controls Used: "Placebo control"

Dose Used: "Capsule of petal of C. sativus 30 mg/day (BD)"

Statistical Significance Declared: "At 6 weeks, petal of C. sativus produced a significantly better outcome on Hamilton Depression Rating Scale than placebo (d.f. = 1, F = 16.87, p<0.001)."

Adverse Events: "There were no significant differences in the two groups in terms of observed side effects."

Conflict of Interest: Not specified.

Gout B, Bourges C, Paineau-Dubreuil S. Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women.Nutr Res. 2010;30(5):305-313. doi:10.1016/j.nutres.2010.04.008

Publication Date: "Available online 15 June 2010."

Peer Reviewed: Yes

Study Design: "randomized, double-blind, placebo-controlled, parallel-group study"

Methodology: "Randomized controlled trial; 60 healthy, mildly overweight women participated; received either Satiereal (176.5 mg extract per day) or placebo for 8 weeks; body weight and snacking frequency were assessed."

Sample Size: "60 healthy, mildly overweight women"

Controls Used: "placebo control"

Dose Used: "176.5 mg extract per day"

Statistical Significance Declared: "P < .01" (body weight reduction), "P < .05" (snacking frequency reduction)

Adverse Events: "The frequency of adverse events in the Satiereal group (5/31 patients, 16%) was low, and they were mild in intensity and transient in nature. Adverse events affected the digestive tract (nausea, diarrhea, and reflux)."

Conflict of Interest: "This research was funded by Inoreal, Ltd (Plerin, France), the supplier of Satiereal extract. Inoreal Ltd did not contribute to the reporting of the results or the preparation of the manuscript."

Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review.J Tehran Heart Cent. 2011;6(2):59-61.

Publication Date: "Published online 2011 May 31."

Peer Reviewed: Yes

Study Design: "This paper reviews the studies regarding the beneficial effects of saffron in cardiovascular health."

Methodology: Review of studies investigating the effects of saffron on cardiovascular health, including cholesterol levels, antioxidant properties, anti-inflammatory properties, and clinical trials involving saffron's impact on heart disease.

Sample Size: Not applicable

Controls Used: Not applicable

Dose Used: Not applicable

Statistical Significance Declared: Not applicable

Adverse Events: None explicitly stated in the text provided.

Conflict of Interest: None explicitly stated in the text provided.

Kang C, Lee H, Jung ES, et al. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.Food Chem. 2012;135(4):2350-2358. doi:10.1016/j.foodchem.2012.06.092

Publication Date: "Published online 2012 July 2."

Peer Reviewed: Yes

Study Design: "randomized controlled trial"

Methodology: "Randomized controlled trials; C2C12 (mouse myoblasts cell line) were maintained in DMEM supplemented with 10% heat inactivated FBS and 1% antibiotics at 37 °C in a humidified atmosphere with 5% CO2. Differentiated into myotubes, then treated with saffron and their glucose uptakes were measured by 2-Deoxy-D [3H] glucose uptake assay. Various biochemical and molecular analyses were performed."

Sample Size: Not applicable

Controls Used: "Control group without saffron treatment."

Dose Used: "The concentrations up to 2.5 μg/ml of saffron were used in subsequent experiments."

Statistical Significance Declared: "The glucose uptake of myotubes was considerably stimulated by the treatment of saffron in a concentration-dependent manner with a maximal increase occurring at 2.5 μg/ml." "The results are expressed as mean ± S.D. for three independent experiments, *P < 0.05, #P < 0.01, as compared with the control value."

Adverse Events: "The frequency of adverse events in the Satiereal group (5/31 patients, 16%) was low, and they were mild in intensity and transient in nature. Adverse events affected the digestive tract (nausea, diarrhea, and reflux)."

Conflict of Interest: "This research was funded by Inoreal, Ltd (Plerin, France), the supplier of Satiereal extract. Inoreal Ltd did not contribute to the reporting of the results or the preparation of the manuscript."

Lashay A, Sadough G, Ashrafi E, Lashay M, Movassat M, Akhondzadeh S. Short-term Outcomes of Saffron Supplementation in Patients with Age-related Macular Degeneration: A Double-blind, Placebo-controlled, Randomized Trial.Med Hypothesis Discov Innov Ophthalmol. 2016;5(1):32-38.

Publication Date: "Published online 2016 Spring."

Peer Reviewed: Yes

Study Design: "Double-blind, placebo-controlled, randomized trial."

Methodology: Sixty patients with wet or dry age-related macular degeneration (AMD) were randomly assigned to receive oral saffron 30 mg/d or placebo supplementation for 6 months. Optical coherence tomography (OCT), electroretinography (ERG), fluorescein angiography, and visual acuity testing were performed at baseline and 3 and 6 months after treatment. The main outcome measures were OCT, ERG amplitude, and implicit time.

Sample Size: "Sixty patients with wet or dry age-related macular degeneration (AMD)."

Controls Used: "Placebo control."

Dose Used: "30 mg of saffron daily."

Statistical Significance Declared: "No statistically significant decrease in OCT results was observed between the groups with dry AMD (P = 0.282)." "A statistically significant increase in ERG results between the groups at 3 months after treatment (P = 0.027)." "A significant decrease in OCT results between groups with wet AMD at the follow-up (P = 0.05)." "A significant increase in ERG findings between the groups with wet AMD at 3 months after treatment (P = 0.01), but these changes decreased at 6 months after treatment (P = 0.213)."

Adverse Events: "No major side effects were observed among patients in either the saffron or the placebo group, and no patient reported severe complications, such as bleeding." "There were no significant differences in the two groups in terms of observed side effects."

Conflict of Interest: "None declared."

Fernández-Sánchez L, Lax P, Noailles A, Angulo A, Maneu V, Cuenca N. Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration.Molecules. 2015;20(8):13875-13893. Published 2015 Jul 31. doi:10.3390/molecules200813875

Publication Date: "Published online 31 July 2015."

Peer Reviewed: Yes

Study Design: "This review summarizes the findings of various studies on the neuroprotective effects of natural compounds used in the ancient pharmacopoeia, specifically focusing on saffron and bear bile constituents."

Methodology: Review of various clinical and preclinical studies investigating the effects of saffron and its constituents on retinal health, including studies on animal models of retinal degeneration and human clinical trials.

Sample Size: Not applicable

Controls Used: Not applicable

Dose Used: Not applicable

Statistical Significance Declared: Not applicable

Adverse Events: "None explicitly stated in the text provided."

Conflict of Interest: "The authors declare no conflict of interest."

Kashani L, Raisi F, Saroukhani S, Sohrabi H, Modabbernia A, Nasehi AA, Jamshidi A, Ashrafi M, Mansouri P, Ghaeli P, Akhondzadeh S. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. Hum. Psychopharmacol Clin Exp. 2013;28(1):54-60. doi:10.1002/hup.2282

Publication Date: "Published online 20 December 2012"

Peer Reviewed: Yes

Study Design: "randomized, double-blind, placebo-controlled study"

Methodology: "This was a randomized double-blind placebo-controlled study. Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks and had experienced subjective feeling of sexual dysfunction entered the study. The patients were randomly assigned to saffron (30 mg/daily) or placebo for 4 weeks. Measurement was performed at baseline, week 2, and week 4 using the Female Sexual Function Index (FSFI). Side effects were systematically recorded."

Sample Size: "Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day."

Controls Used: "Placebo control."

Dose Used: "30 mg/daily."

Statistical Significance Declared: "Two-factor repeated measure analysis of variance showed significant effect of time treatment interaction [Greenhouse–Geisser’s corrected: F(1.580, 50.567) = 5.366, p = 0.012] and treatment for FSFI total score [F(1, 32) = 4.243, p = 0.048]. At the end of the fourth week, patients in the saffron group had experienced significantly more improvement in total FSFI (p < 0.001), arousal (p = 0.028), lubrication (p = 0.035), and pain (p = 0.016) domains of FSFI."

Adverse Events: "Eight side effects were recorded during the course of the trial." "Frequency of side effects did not differ between the two groups."

Conflict of Interest: "No competing financial interests exist."

Kell G, Rao A, Beccaria G, Clayton P, Inarejos-García AM, Prodanov M. 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. Complementary Therapies in Medicine. 2017;33:58-64. doi:10.1016/j.ctim.2017.06.001.

Publication Date: "Available online 13 June 2017."

Peer Reviewed: Yes

Study Design: "Double-blind, parallel, randomized, placebo-controlled clinical trial."

Methodology: In this 3-arm study, 128 participants self-reporting low mood but not diagnosed with depression, were given affron® at 28 mg/day, 22 mg/day, or a placebo treatment in a randomized, double-blind, placebo-controlled trial for 4 weeks. Mood was measured at baseline and at the end of the study, using the POMS (primary outcome measure) and PANAS questionnaires, and the DASS-21 scale. Sleep was monitored using Sleep Quality Index (PSQI).

Sample Size: "128 participants"

Controls Used: "Placebo control"

Dose Used: "affron® at 28 mg/day, 22 mg/day"

Statistical Significance Declared: "A significant decrease in negative mood and symptoms related to stress and anxiety at a 28 mg/day dose (with a significant difference between 28 mg/day and placebo on the POMS Total Mood Disturbance scale, p < 0.001, d = −1.10), but no treatment effect at the 22 mg/day dose."

Adverse Events: "One participant in the placebo group reported a singular event of symptoms of diarrhea."

Conflict of Interest: "The authors have declared there is no conflict of interest."

Pachikian BD, Copine S, Suchareau M, Deldicque L. Effects of Saffron Extract on Sleep Quality: A Randomized Double-Blind Controlled Clinical Trial.Nutrients. 2021; 13(5):1473. https://doi.org/10.3390/nu13051473

Publication Date: "Published online 27 April 2021."

Peer Reviewed: Yes

Study Design: "Double-blind, randomized, placebo-controlled parallel study."

Methodology: Sixty-six subjects with mild to moderate sleep disorder associated with anxiety were randomized to receive either placebo (maltodextrin) or saffron extract (15.5 mg per day) for 6 weeks. Sleep quality was assessed using actigraphy, LSEQ and PSQI questionnaires, and quality of life by SF-36 questionnaire.

Sample Size: "Sixty-six subjects"

Controls Used: "Placebo control"

Dose Used: "15.5 mg per day of saffron extract"

Statistical Significance Declared: "At the end of the fourth week, patients in the saffron group had experienced significantly more improvement in total FSFI (p < 0.001), arousal (p = 0.028), lubrication (p = 0.035), and pain (p = 0.016) domains of FSFI." "Saffron extract supplementation improved ease of getting to sleep, sleep quality, sleep latency, sleep duration, and global scores as evaluated by the PSQI questionnaire." "Six weeks of saffron supplementation led to an increased time in bed assessed by actigraphy (p = 0.051)."

Adverse Events: "No major side effects were observed among patients in either the saffron or the placebo group, and no patient reported severe complications, such as bleeding." "One mild adverse event was reported in the saffron group, i.e., palpitations in the evening after the consumption of the product."

Conflict of Interest: "The funders participate to the setup of the study design and to the redaction of the publication. However, the funder had no role in data collection, analyses and interpretation of the data."

Falsini B, Piccardi M, Minnella A, Savastano C, Capoluongo E, Fadda A, Balestrazzi E, Maccarone R, Bisti S. Influence of Saffron Supplementation on Retinal Flicker Sensitivity in Early Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2010;51(12):6118-6124. doi:10.1167/iovs.09-4995.

Publication Date: "Published online 2010 Aug 4."

Peer Reviewed: Yes

Study Design: "Randomized Controlled Trial"

Methodology: "Twenty-five patients with AMD were randomly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months. Focal electroretinograms (fERGs) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation. fERGs were recorded in response to a sinusoidally modulated (41 Hz), uniform field presented to the macular region (18°) at different modulations between 16.5% and 93.5%."

Sample Size: "Twenty-five patients with AMD"

Controls Used: "Placebo control"

Dose Used: "oral saffron 20 mg/d"

Statistical Significance Declared: "P < 0.01" (fERG amplitude increase), "mean change after saffron, -0.26 log units; mean change after placebo, 0.0003 log units" (fERG thresholds decrease)

Adverse Events: "Eight side effects were recorded during the course of the trial." "Frequency of side effects was similar between the two groups."

Conflict of Interest: "None declared."

Kashani L, Aslzadeh S, Shokraee K, et al.Crocus sativus(saffron) in the treatment of female sexual dysfunction: a three-center, double-blind, randomized, and placebo-controlled clinical trial.Avicenna J Phytomed. 2022;12(3):257-268. doi:10.22038/AJP.2022.19714

Publication Date: "Published online 2022 May-Jun."

Peer Reviewed: Yes

Study Design: "Parallel-group, double-blind, randomized, placebo-controlled trial."

Methodology: "Participants were randomized to receive either 15 mg Crocus sativus capsules twice daily or placebo. The treatment continued for 6 weeks, and patients were evaluated every 2 weeks. The primary outcome was the change in the female sexual function index score."

Sample Size: "Seventy-four patients were equally randomized to each group, and 34 in each group completed the trial."

Controls Used: "Placebo control."

Dose Used: "15 mg Crocus sativus capsules twice daily."

Statistical Significance Declared: "A repeated-measures ANOVA revealed that time treatment differed between groups in favor of the saffron group (p=0.050)."

Adverse Events: "The most frequently observed adverse events (approximately 10% of the participants) in this trial were headaches and nausea." "Frequency of side effects was similar between the groups." "None of the participants deemed any of the adverse events intolerable."

Conflict of Interest: "The authors have declared that there is no conflict of interest."