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Efficacy and Safety of Crocus Sativus L in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial

September 12, 2016
Greek researchers and clinicians demonstrated the potential of Crocus Sativus L. (saffron) as a therapeutic pharmaceutical natural compound for older adults with amnestic Mild Cognitive Impairment (aMCI). MCI is a condition that often predates Alzheimer’s disease (AD) and is characterized by memory loss and inability to execute complex Activities of Daily Living. While there is no treatment for MCI and symptomatic only treatment for AD, the global effort against cognitive disorders is focused on early detection and management of AD at the stage of MCI.

Scientists from the Aristotle University of Thessaloniki (AUTH), the Greek Association of Alzheimer’s Disease and Related Disorders (GAADRD) and the Centre for Research and Technology Hellas/Information Technologies Institute (CERTH/ITI) have succeeded in making the shift to MCI therapy via robust natural remedies that can be used in order to forestall cognitive deterioration. In an article published in the Journal of Alzheimer’s Disease, the researchers have indicated that 0,125 gr/ per day lead to better cognitive performance after 12 months as revealed in neuropsychological assessment, ERP response, and 3 Tesla MRI. P300 latency was measured by a HD-EEG [EGI 300 Geodesic EEG system (GES 300) using a 256-channel HydroCel Geodesic Sensor Net (HCGSN)]. A small volume increase on the left inferior temporal gyrus, an area close to medial temporal lobe (MTL) and hippocampus, was found in experimental group. Thus, this study highlighted how Crocus can change brain activation, striatal volume of specific brain regions, neuropsychological performance and cognitive processing in aMCI patients whereas control group exhibited worse performance after 12 months. Consequently, patients with MCI can hopefully have better cognitive functioning by taking Crocus Sativus L. on a daily basis.

It is widely known that no conventional or alternative therapy is currently available and approved to treat MCI patients. Current therapeutic strategies for cognitive impairment in AD, is symptomatic with cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine, galantamine, and the N-methyl-D-aspartate (NMDA) receptor antagonist memantine. The discovery of new natural compounds with neuroactive properties for the management of Neurodegenerative diseases (NDs) has gained much attention recently. Since no drug treatment is available to prevent the development of NDs, studies have shown that diet or plant-based extracts with antioxidant properties may have beneficial effects on improving brain function in NDs.

Nevertheless, preclinical and clinical pharmacological studies have demonstrated that Crocus sativus crude extracts and purified chemicals of it have anti-tumor effects, radical scavenging activity, anti-nociceptive and anti-inflammatory properties, inhibitory activity on Amyloid beta aggregation, reduce atherosclerosis and hepatic damage, counteract hyperlipidemia, protect from myocardial injury, display antihypertensive action, and finally it is safe and effective in mild to moderate AD as revealed from this study. More specifically, crocins and crocetin (molecules of Crocus sativus L.) have a wide range of activities including antioxidant effects, neuroprotective activities in memory impairment and antioxidant capacities. Also, crocin acts on NMDA receptors and on tracheal muscles β2-adrenoceptors, with a possible inhibitory effect on histamine (H1) receptors. More specifically, in vitro and in silico studies also suggest that crocetin can inhibit acetylcholinesterase, a main AD medicinal target.

Our study revealed in all measures we used better performance of treatment group compared with control group in the second assessment after 12 months of follow-up. Until today there is no other study which has proved that any kind of medication can be considered as an effective solution for patients with MCI. The same organizations are also focused on developing other novel pharmaceutical natural compounds that respond to a number of clinical needs in the effort against neurocognitive disorders.


Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. Tsolaki M, Karathanasi E, Lazarou I, Dovas K, Verykouki E, Karacostas A, Georgiadis K, Tsolaki A, Adam K, Kompatsiaris I, Sinakos Z. J Alzheimers Dis. 2016 Jul 27;54(1):129-33. doi: 10.3233/JAD-160304. PMID: 27472878

Contact-Principal Investigator:
Magda Tsolaki
Professor of 3rd Department of Neurology, Aristotle University of Thessaloniki, Greece
Chair of Greek Federation of Alzheimer’s disease in Greece
Scientific Director of Daily Alzheimer’s centers in Thessaloniki, Greece
Tel: +306942918933, +302310234239
Fax: +30 2313 307332

About the Aristotle University of Thessaloniki (AUTH)
The Aristotle University of Thessaloniki is the largest university in Greece. It comprises 7 faculties that consist of 33 schools, 5 faculties that consist of one school each, as well as 4 independent schools. About 81,500 students study at the Aristotle University (72,140 in undergraduate programs and 8,360 in postgraduate programs). There are 2,150 faculty members: 739 professors, 435 associate professors, 634 assistant professors, and 342 lecturers. There are also 11 teaching assistants, 58 research fellows, 248 members of the Special Laboratory Teaching Personnel (S.L.T.P.), as well as 15 foreign language teachers and 4 foreign instructors. Faculty members are also assisted by 213 members of the Special Technical Laboratory Personnel (S.T.L.P.).

The Aristotle University of Thessaloniki conducts research projects, participates in European research programs, cooperates with international institutions and organizations and attracts outstanding researchers from within Greece and abroad. The Aristotle University supports research projects in a wide variety of disciplines related to the environment (natural and built), computing, new technologies and nanotechnology, telecommunications, industrial technologies, transport, biotechnology, biomedicine and health, agriculture, forestry and fishery, education and language, history and archaeology, social studies and economics.

About the Greek Association of Alzheimer’s disease and Related Disorders (GAADRD)
The Greek Association of Alzheimer’s Disease and Related Disorders is a non-profit organization that was founded in 1995 by relatives of patients suffering from Alzheimer’s disease, doctors of all specialties (mainly neurologists and psychiatrists) and other experts (such as psychologists, social workers, physiotherapists, etc.) who deal with the problems caused by this disease and other types of dementia. The Association operates 2 day centers in Thessaloniki and has over 4.000 members. It is a member of Alzheimer Europe and Alzheimer’s disease International (ADI) and has successfully participated in various national and European research projects producing new scientific knowledge and innovative interventions for cognitive disorders.

The aim of the Association is to offer information and advice concerning the care of patients with cognitive disorders and provide services for patients and their families. It also strives to offer help and support to caregivers in order to reduce the social, economic and emotional burden deriving from the long term care of people suffering from dementia. Lastly, the Association attempts to publicize the social needs of the affected population and inform the public on issues related to dementia and cognitive disorders in general.

About the Information Technologies Institute (ITI)-Centre for Research and Technology Hellas (CERTH)
The Information Technologies Institute, formerly Informatics and Telematics Institute, was established in 1998 in Thessaloniki as a non-profit research organization under the auspices of the General Secretariat of Research and Technology (GSRT) of the Greek Ministry of Development. Since 2000, ITI has joined the Centre for Research and Technology Hellas (CERTH). The main objective of the Institute is to be a research institution of excellence, identifying promising fields for the future and creating an environment that will allow the transfer of basic, applied and technological research in the growth of the digital economy of the 21st century. CERTH/ITI has developed spheres of excellence and critical mass in research and technology in several strategically important fields in a number of areas: Image and Signal Processing, Computer Vision, Human Computer Interaction, Virtual and Augmented Reality, Artificial Intelligence, Security and Surveillance, Biomedicine – Bioinformatics, Robotics, ICT for Environment Monitoring, Geosciences and Remote Sensing, Social Network Analysis, Networks and Communications, Cultural and Educational Technology.

About Journal of Alzheimer’s disease (JAD)
The Journal of Alzheimer’s Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer’s Disease has an Impact Factor of 4.151 according to Thomson Reuters’ 2014 Journal Citation Reports. The Journal is published by IOS Press.

[1] Pitsikas N (2015) The effect of Crocus sativus L. and its constituents on memory: basic studies and clinical applications. Evid Based Complement Alternat Med 2015, 926284.
[2] Howe AS, Bani-Fatemi A, De Luca V (2014) The clinical utility of the auditory P300 latency subcomponent event-related potential in preclinical diagnosis of patients with mild cognitive impairment and Alzheimer’s disease. Brain Cogn 86, 64–74.