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Effects of saffron (Crocus sativus L.) on cognitive function. A systematic review of RCTs



Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer’s disease (AD) or mild cognitive impairment (MCI). The aim of this systematic review is to investigate the cognitive effects of oral saffron intake, in patients with MCI/AD and/or in non-demented individuals, by following the PRISMA guidelines.


We performed a literature search on MedLine, Cochrane library, and to identify randomized controlled trials (RCTs) investigating the effects of oral saffron administration in patients with MCI/AD and/or in non-demented individuals.


Five studies (enrolling 325 individuals) met our inclusion criteria. Four studies included patients with MCI/AD, and one study included cognitively normal individuals. Saffron was well-tolerated in all groups. Regarding cognitively impaired patients, scores on Alzheimer’s Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine. Saffron effects on functional status were similar with its effects on cognition.


Saffron was shown to be equally effective to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects, when compared with placebo or drugs. The promising results should be seen cautiously, since the evidence was derived from studies with potentially high risk of bias (ROB). RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment.

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  1. 1.

    Keuck L (2017) Slicing the cortex to study mental illness: Alois Alzheimer’s pictures of equivalence. Prog Brain Res 233:25–51

    PubMed  Google Scholar 

  2. 2.

    Fiest KM, Roberts JI, Maxwell CJ, Hogan DB, Smith EE, Frolkis A, Cohen A, Kirk A, Pearson D, Pringsheim T, Venegas-Torres A, Jetté N (2016) The prevalence and incidence of dementia due to Alzheimer’s disease: a systematic review and meta-analysis. Can J Neurol Sci 43(Suppl 1):S51–S82

    PubMed  Google Scholar 

  3. 3.

    Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58(12):1985–1992

    CAS  PubMed  Google Scholar 

  4. 4.

    Becker RE, Kapogiannis D, Greig NH (2018) Does traumatic brain injury hold the key to the Alzheimer’s disease puzzle? Alzheimers Dement 14(4):431–443

    PubMed  Google Scholar 

  5. 5.

    Gauthier S, Schlaefke S (2014) Efficacy and tolerability of Ginkgo biloba extract EGb 761(R) in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials. Clin Interv Aging 9:2065–2077

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Yang M, Xu DD, Zhang Y, Liu X, Hoeven R, Cho WC (2014) A systematic review on natural medicines for the prevention and treatment of Alzheimer’s disease with meta-analyses of intervention effect of ginkgo. Am J Chin Med 42(3):505–521

    PubMed  Google Scholar 

  7. 7.

    Enderami A, Zarghami M, Darvishi-Khezri H (2018) The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review. Neurol Sci 39(10):1667–1675

    PubMed  Google Scholar 

  8. 8.

    Chen N, Yang M, Zhou M, Xiao J, Guo J, He L (2017) L-carnitine for cognitive enhancement in people without cognitive impairment. Cochrane Database Syst Rev 3:CD009374

    PubMed  Google Scholar 

  9. 9.

    Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D (2018) Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials. Exp Gerontol 108:166–173

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Bathaie SZ, Mousavi SZ (2010) New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr 50(8):761–786

    CAS  PubMed  Google Scholar 

  11. 11.

    Christodoulou E, Kadoglou NP, Kostomitsopoulos N, Valsami G (2015) Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol 67(12):1634–1649

    CAS  PubMed  Google Scholar 

  12. 12.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 343:d5928

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SS, Yousefi MH, Alimardani R, Jamshidi A, Zare F, Moradi A (2010) 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 35(5):581–588

    CAS  PubMed  Google Scholar 

  15. 15.

    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 (2010) A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology 207(4):637–643

    CAS  PubMed  Google Scholar 

  16. 16.

    Farokhnia M, Shafiee Sabet M, Iranpour N, Gougol A, Yekehtaz H, Alimardani R, Farsad F, Kamalipour M, Akhondzadeh S (2014) Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer’s disease: a double-blind randomized clinical trial. Hum Psychopharmacol 29(4):351–359

    CAS  PubMed  Google Scholar 

  17. 17.

    Tsolaki M, Karathanasi E, Lazarou I, Dovas K, Verykouki E, Karacostas A et al (2016) Efficacy and safety of Crocus sativus L. in patients with mild cognitive impairment: one year single-blind randomized, with parallel groups, clinical trial. J Alzheimers Dis 54(1):129–133

    PubMed  Google Scholar 

  18. 18.

    Moazen-Zadeh E, Abbasi SH, Safi-Aghdam H, Shahmansouri N, Arjmandi-Beglar A, Hajhosseinn Talasaz A, Salehiomran A, Forghani S, Akhondzadeh S (2018) Effects of saffron on cognition, anxiety, and depression in patients undergoing coronary artery bypass grafting: a randomized double-blind placebo-controlled trial. J Altern Complement Med 24(4):361–368

    PubMed  Google Scholar 

  19. 19.

    Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS (2011) A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 77(6):556–563

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Group ADC, Bentham P, Gray R, Sellwood E, Hills R, Crome P et al (2008) Aspirin in Alzheimer’s disease (AD2000): a randomised open-label trial. Lancet Neurol 7(1):41–49

    Google Scholar 

  21. 21.

    Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A et al (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63(10):1402–1408

    PubMed  Google Scholar 

  22. 22.

    Modabbernia A, Akhondzadeh S (2013) Saffron, passionflower, valerian and sage for mental health. Psychiatr Clin North Am 36(1):85–91

    PubMed  Google Scholar 

  23. 23.

    Sarris J (2007) Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother Res 21(8):703–716

    PubMed  Google Scholar 

  24. 24.

    Mattson MP (2008) Hormesis defined. Ageing Res Rev 7(1):1–7

    CAS  Google Scholar 

  25. 25.

    Mattson MP (2008) Dietary factors, hormesis and health. Ageing Res Rev 7(1):43–48

    PubMed  Google Scholar 

  26. 26.

    Calabrese V, Cornelius C, Trovato A, Cavallaro M, Mancuso C, Di Rienzo L et al (2010) The hormetic role of dietary antioxidants in free radical-related diseases. Curr Pharm Des 16(7):877–883

    CAS  PubMed  Google Scholar 

  27. 27.

    Premkumar K, Thirunavukkarasu C, Abraham SK, Santhiya ST, Ramesh A (2006) Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice. Hum Exp Toxicol 25(2):79–84

    CAS  PubMed  Google Scholar 

  28. 28.

    Premkumar K, Abraham SK, Santhiya ST, Ramesh A (2003) Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother Res 17(6):614–617

    CAS  PubMed  Google Scholar 

  29. 29.

    Berger F, Hensel A, Nieber K (2011) Saffron extract and trans-crocetin inhibit glutamatergic synaptic transmission in rat cortical brain slices. Neuroscience. 180:238–247

    CAS  PubMed  Google Scholar 

  30. 30.

    Geromichalos GD, Lamari FN, Papandreou MA, Trafalis DT, Margarity M, Papageorgiou A, Sinakos Z (2012) Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies. J Agric Food Chem 60(24):6131–6138

    CAS  PubMed  Google Scholar 

  31. 31.

    Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M, Lamari FN (2006) Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 54(23):8762–8768

    CAS  PubMed  Google Scholar 

  32. 32.

    Montoro P, Maldini M, Luciani L, Tuberoso CI, Congiu F, Pizza C (2012) Radical scavenging activity and LC-MS metabolic profiling of petals, stamens, and flowers of Crocus sativus L. J Food Sci 77(8):C893–C900

    CAS  PubMed  Google Scholar 

  33. 33.

    Lyketsos CG, Olin J (2002) Depression in Alzheimer’s disease: overview and treatment. Biol Psychiatry 52(3):243–252

    PubMed  Google Scholar 

  34. 34.

    Scaricamazza E, Colonna I, Sancesario GM, Assogna F, Orfei MD, Franchini F, Sancesario G, Mercuri NB, Liguori C (2019) Neuropsychiatric symptoms differently affect mild cognitive impairment and Alzheimer’s disease patients: a retrospective observational study. Neurol Sci 40:1377–1382

    PubMed  Google Scholar 

  35. 35.

    Starkstein SE, Mizrahi R, Power BD (2008) Depression in Alzheimer’s disease: phenomenology, clinical correlates and treatment. Int Rev Psychiatry 20(4):382–388

    PubMed  Google Scholar 

  36. 36.

    Spalletta G, Caltagirone C, Padovani A, Sorbi S, Attar M, Colombo D, Cravello L, on behalf of the E V O L U T I O N study Working Group (2014) Cognitive and affective changes in mild to moderate Alzheimer’s disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study. PLoS One 9(2):e89216

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Spalletta G, Gianni W, Giubilei F, Casini AR, Sancesario G, Caltagirone C, Cravello L (2013) Rivastigmine patch ameliorates depression in mild AD: preliminary evidence from a 6-month open-label observational study. Alzheimer Dis Assoc Disord 27(3):289–291

    CAS  PubMed  Google Scholar 

  38. 38.

    Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwin R, Bentham P, Fox C, Holmes C, Katona C, Knapp M, Lawton C, Lindesay J, Livingston G, McCrae N, Moniz-Cook E, Murray J, Nurock S, Orrell M, O'Brien J, Poppe M, Thomas A, Walwyn R, Wilson K, Burns A (2011) Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet. 378(9789):403–411

    CAS  PubMed  Google Scholar 

  39. 39.

    Dudas R, Malouf R, McCleery J, Dening T (2018) Antidepressants for treating depression in dementia. Cochrane Database Syst Rev 8:CD003944

    PubMed  Google Scholar 

  40. 40.

    Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F (2004) 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 4:12

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH, Khani M (2005) Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res 19(2):148–151

    PubMed  Google Scholar 

  42. 42.

    Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH (2005) 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 97(2):281–284

    CAS  PubMed  Google Scholar 

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The present study was supported in part by the Intramural Program of the National Institute on Aging, National Institutes of Health.

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Correspondence to Dimitrios Kapogiannis.

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Avgerinos, K.I., Vrysis, C., Chaitidis, N. et al. Effects of saffron (Crocus sativus L.) on cognitive function. A systematic review of RCTs. Neurol Sci 41, 2747–2754 (2020).

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  • Saffron
  • Crocus Sativus L.
  • Cognitive
  • Alzheimer’s disease
  • Mild cognitive impairment
  • Systematic review