Abstract

Aim Natural interventions for sleep disturbances, such as saffron extract, are gaining scientific and clinical interest. This 3-arm, randomized, double-blind, placebo-controlled trial examined the effect of a standardized saffron extract (Safr’InsideTM) on sleep, stress, and other associated psychological outcomes in 165 men and women reporting moderate insomnia.

Methods Participants received a daily capsule containing 30 mg saffron extract, 20 mg saffron extract, or placebo (maltodextrin) for 4 weeks. The primary endpoint was the change in insomnia symptoms measured by the Athens Insomnia Scale (AIS). Secondary outcomes included the Single-Item Sleep Quality Scale (SQS), Perceived Stress Scale (PSS), Patient Health Questionnaire-4 (PHQ-4), Positive and Negative Affect Schedule (PANAS), Epworth Sleepiness Scale (ESS), and World Health Organization Quality of Life (WHOQOL). Analyses followed an intention-to-treat (ITT) approach, with per-protocol (PP) confirmation.

Results Compared to placebo, saffron extract significantly improved insomnia symptoms (AIS, P < .05), with the most pronounced effects on sleep onset and duration. Sleep quality (SQS) improved significantly after 3 weeks (P < .05 for 30 mg, P < .01 for 20 mg). Both doses of saffron extract reduced perceived stress (PSS) more than placebo (P = .01). Psychological symptoms (PHQ-4) improved significantly with 30 mg saffron compared to placebo (P < .05), while all other measures showed no significant differences. No serious adverse events were reported.

Conclusions Four weeks of 20 or 30 mg saffron extract may reduce insomnia and stress in middle-aged adults. Future research should assess longer interventions, reliable objective sleep measures, and complementary effects of saffron on stress and sleep.

Competing Interest Statement

The authors declare that this study was financially supported by Activ'Inside, who were involved in the study design and provided feedback on the manuscript. Data collection and statistical analysis were performed independently by the academic investigators. The authors report no additional financial or personal conflicts of interest related to the content of this article.

Clinical Trial

DRKS00033435

Funding Statement

This study was funded by Activ'Inside (Beychac et Caillau, France), who provided financial support for the study and were involved in the study design and manuscript feedback. Data collection and statistical analysis were conducted independently by the academic investigators.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee of the Medical Association of Lower Saxony (Ärztekammer Niedersachsen, Hannover, Germany) waived ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

AbbreviationsAISAthens Insomnia ScaleANCOVAAnalysis of CovarianceANOVAAnalysis of VarianceBMAL1Brain and Muscle Arnt-Like Protein 1ESSEpworth Sleepiness ScaleGABAGamma-aminobutyric acidHPAHypothalamic-Pituitary-AdrenalHRVHeart Rate VariabilityITTIntention-To-TreatLMMLinear Mixed ModelNREMNon-Rapid-Eye-MovementPANASPositive and Negative Affect SchedulePHQ-4Patient Health Questionnaire 4PPPer-ProtocolPSSPerceived Stress ScaleREMRapid-Eye-MovementRISRegensburg Insomnia ScaleROSReactive Oxygen SpeciesSQSSingle-item Sleep Quality ScaleWHOQOL-BREFWorld Health Organization Quality of Life-BREF