A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes

doi:10.1016/S2095-4964(15)60176-5

Abstract

Background
Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression.
Objective
The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes.
Search strategy
Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).” Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed.
Inclusion criteria
Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome.
Data extraction and analysis
The methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression).
Results
Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n = 6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n = 4), and weight loss/snacking behaviors (n = 1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior.
Conclusion
Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.

Key words: Crocus, Health-related outcomes, Systematic review

Heather Ann Hausenblas, Kacey Heekin, Heather Lee Mutchie, Stephen Antonb. A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes. Journal of Integrative Medicine, 2015, 13(4): 231-240.

/ / Recommend

Add to citation manager EndNote| Reference Manager|ProCite|BibTeX|RefWorks

URL: http://www.jcimjournal.com/EN/10.1016/S2095-4964(15)60176-5

http://www.jcimjournal.com/EN/Y2015/V13/I4/231

[1]	Capasso F, Gaginella TS, Grandolini G, Izzo AA . Phytotherapy: a quick reference to herbal medicine. Berlin: Spriger-Verlag. 2003. doi: 10.1111/j.2042-7166.2004.tb04305.x
[2]	Williamson EM, Okpako DT, Evans FJ . Pharmacological methods in phytotherapy. John Wiley & Sons. 1996.
[3]	Gohari AR, Saeidnia S, Mahmoodabadi MK . An overview on saffron, phytochemicals, and medicinal properties. Pharmacogn Rev, 2013,7(13):61-66 doi: 10.4103/0973-7847.112850 pmid: 3731881
[4]	Moghaddasi MS . Saffron chemicals and medicine usage. J Med Plants Res, 2010,4:427-430 doi: 10.1002/cbic.200900706
[5]	Srivastava R, Ahmed H, Dixit RK, Dharamveer, Saraf S . Crocus sativus L.: A comprehensive review. Pharmacogn Rev, 2010,4(8):200-208 doi: 10.4103/0973-7847.70919 pmid: 22228962
[6]	Kianbakht S, Ghazavi A . Immunomodulatory effects of saffron: a randomized double-blind placebo-controlled clinical trial. Phytother Res, 2011,25(12):1801-1805 doi: 10.1002/ptr.v25.12
[7]	Abdullaev FI, Espinosa-Aguirre JJ . Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev, 2004,28(6):426-432 doi: 10.1016/j.cdp.2004.09.002
[8]	Bathaie SZ, Mousavi SZ . New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr, 2010,50(8):761-786 doi: 10.1080/10408390902773003 pmid: 20830635
[9]	Kamalipour M, Akhondzadeh S . Cardiovascular effects of saffron: an evidence-based review. J Tehran Heart Cent, 2011,6(2):59-61 pmid: 3466873
[10]	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
[11]	Lopresti AL, Drummond PD . Saffron(Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum Psychopharmacol, 2014,29(6):517-527 doi: 10.1002/hup.v29.6
[12]	Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med, 2009,151(4):264-269 doi: 10.7326/0003-4819-151-4-200908180-00135
[13]	Ulbricht C, Conquer J, Costa D, Hollands W, Iannuzzi C, Isaac R, Jordan JK, Ledesma N, Ostroff C, Serrano JM, Shaffer MD, Varghese M . An evidence-based systematic review of saffron(Crocus sativus) by the Natural Standard Research Collaboration. J Diet Suppl, 2011,8(1):58-114 doi: 10.3109/19390211.2011.547666
[14]	Nahid K, Fariborz M, Ataolah G, Solokian S . The effect of an Iranian herbal drug on primary dysmenorrhea: a clinical controlled trial. J Midwifery Womens Health, 2009,54(5):401-404 doi: 10.1016/j.jmwh.2008.12.006 pmid: 19720342
[15]	Modaghegh MH, Shahabian M, Esmaeili HA, Rajbai O, Hosseinzadeh H . Safety evaluation of saffron(Crocus sativus) tablets in healthy volunteers. Phytomedicine, 2008,15(12):1032-1037 doi: 10.1016/j.phymed.2008.06.003 pmid: 18693099
[16]	Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ . Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996; 17(1):1-12. doi: 10.1016/0197-2456(95)00134-4
[17]	Heidary M, Vahhabi S, Reza Nejadi J, Delfan B, Birjandi M, Kaviani H, Givrad S . Effect of saffron on semen parameters of infertile men. Urol J, 2008,5(4):255-259 pmid: 19101900
[18]	Akhondzadeh Basti A, Ghoreishi S, Noorbala AA, Akhondzadeh SH, Rezazadeh SH . Petal and stigma of Crocus sativus L. in the treatment of depression: a pilot double-blind randomized trial. J Med Plants, 2008,7(4):29-36
[19]	Marangoni D, Falsini B, Piccardi M, Ambrosio L, Minnella AM, Savastano MC, Bisti S, Maccarone R, Fadda A, Mello E, Concolino P, Capoluongo E . Functional effect of saffron supplementation and risk genotypes in early age-related macular degeneration: A preliminary report. J Transl Med, 2013,11:228 doi: 10.1186/1479-5876-11-228
[20]	Piccardi M, Marangoni D, Minnella AM, Savastano MC, Valentini P, Ambrosio L, Capoluongo E, Maccarone R, Bisti S, Falsini B . A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evid Based Complement Alternat Med, 2012,2012:429124
[21]	Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O . Evaluation of Crocus sativus L.(saffron) on male erectile dysfunction: a pilot study. Phytomedicine, 2009,16(8):690-693 doi: 10.1016/j.phymed.2009.03.008 pmid: 19427775
[22]	Akhondzadeh S, Shafiee Sabet M, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SS, Yousefi MH, Alimardani R, Jamshidi A, Rezazadeh SA, Yousefi A, Zare F, Moradi A, Vossoughi A . A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl), 2010,207(4):637-643 doi: 10.1007/s00213-009-1706-1
[23]	Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SSh, Yousefi MH, Alimardani R, Jamshidi A, Zare F, Moradi A . Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther, 2010,35(5):581-588 doi: 10.1111/j.1365-2710.2009.01133.x
[24]	Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M, Hosseinzadeh H . Effect of Crocus sativus L.(saffron) on coagulation and anitcoagulation systems in healthy volunteers. Phytother Res, 2013,28(4):539-543
[25]	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
[26]	Verma SK, Bordia A . Antioxidant property of saffron in man. Indian J Med Sci, 1998,52(5):205-207 pmid: 9808914
[27]	Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH, Khani M . Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res, 2005,19(2):148-151 doi: 10.1002/(ISSN)1099-1573
[28]	Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S . Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry, 2007,31(2):439-442 doi: 10.1016/j.pnpbp.2006.11.010
[29]	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, 2006,13:607-611 doi: 10.1016/j.phymed.2006.08.006
[30]	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
[31]	Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F . Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med, 2004,4:12 doi: 10.1186/1472-6882-4-12
[32]	Shahmansouri N, Farokhnia M, Abbasi SH, Kassaian SE, Noorbala Tafti AA, Gougol A, Yekehtaz H, Forghani S, Mahmoodian M, Saroukhani S, Arjmandi-Beglar A, Akhondzadeh S . A randomized, double-blind, clinical trial comparing the efficacy and safety of Cocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affect Disord, 2014,155:216-222 doi: 10.1016/j.jad.2013.11.003
[33]	Modabbernia A, Sohrabi H, Nasehi AA, Raisi F, Saroukhani S, Jamshidi A, Tabrizi M, Ashrafi M, Akhondzadeh S . Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial. Psychopharmacology (Berl), 2012,223(4):381-388 doi: 10.1007/s00213-012-2729-6
[34]	Safarinejad MR, Shafiei N, Safarinejad S . A prospective double-blind randomized placebo-controlled study of the effect of saffron(Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. Phytother Res, 2011,25(4):508-516 doi: 10.1002/ptr.3294
[35]	Safarinejad MR, Shafiei N, Safarinejad S . An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron(Crocus sativus Linn.) for treating erectile dysfunction in men naïve to treatment. Int J Impot Res, 2010,22:240-250 doi: 10.1038/ijir.2010.10
[36]	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, 2013,28(1):54-60 doi: 10.1002/hup.v28.1
[37]	Agha-Hosseini M1, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, Akhondzadeh S . Crocus sativus L.(saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. BJOG, 2008,115(4):515-519 doi: 10.1111/bjo.2008.115.issue-4
[38]	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
[39]	Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A . Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol, 2011,21(12):841-860 doi: 10.1016/j.euroneuro.2011.04.002

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

Comments

Recommended 10

[1]	Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2]	Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3]	Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4]	SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5]	Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6]	Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7]	Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8]	Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9]	Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10]	Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239