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Effect of saffron extract supplementation on mood in healthy adults with subclinical symptoms of depression: a randomized, double-blind placebo-controlled study.

  • 2025-12
  • The American journal of clinical nutrition 122(6)
    • Camille Amadieu
    • Quentin Leyrolle
    • Milena Farneti
    • Andrea Anesi
    • Eva Bruchet
    • Juliette Montet
    • Sandra Dexpert
    • David Gaudout
    • Fulvio Mattivi
    • Line Pourtau
    • Nathalie Castanon
    • Lucile Capuron

Study Design

Type
Randomized Controlled Trial (RCT)
Population
51 healthy adults with subclinical neuropsychiatric symptoms
Methods
Randomized, double-blind, placebo-controlled; 6 wk of oral saffron extract or placebo
Blinding
Double-blind
Duration
6 wk
Funding
Unclear

Background

Subclinical depressive symptoms, including low mood, fatigue and anxiety, refer to clinically relevant depressive manifestations that do not meet the criteria for major depressive disorder. These symptoms affect quality of life and can lead to chronic mental health issues. Nutritional interventions, such as saffron extract supplementation, may help modulate mood and inflammation, potentially alleviating these symptoms.

Objectives

This study evaluated the efficacy of a 6-wk saffron extract supplementation on mood in healthy individuals with subclinical neuropsychiatric symptoms and explored the underlying mechanisms.

Methods

This randomized, double-blind, placebo-controlled study involved 51 adult healthy individuals who received oral administration of either saffron extract or a placebo for 6 wk. The primary outcome was a composite z-score averaging standardized scores of depression (Beck Depression Inventory-II), anxiety (State-Trait Anxiety Inventory-YA), and fatigue (Multidimensional Fatigue Inventory 20). Secondary outcomes included neuropsychiatric scores, quality of life, inflammatory markers, and hypothalamic-pituitary-adrenal axis reactivity. Amino acid derivatives were analyzed in blood samples.

Results

Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score) nor individual symptoms. However, it improved autoperceived mental health, as reflected in increased mental health scores over time on the Medical Outcome Study Short-Form 12 questionnaire, compared with placebo (mean at 6 wk: 53.8 ± 12.7 vs 44.6 ± 11.4 for placebo and saffron group, respectively; time × treatment, P = 0.04). There were no significant effects on inflammatory parameters or hypothalamic-pituitary-adrenal axis reactivity. Metabolomic analysis revealed that saffron extract significantly modulated N-acetyl-phenylalanine.

Conclusions

Saffron extract supplementation do not affect subclinical depressive symptoms, either as a composite score or individual symptom categories. A potential effect on improved mental health outcomes cannot be excluded but requires further replication in future well-powered trials. This trial (Saffromfood study) is registered at clinicaltrial.gov as NCT05690126 (https://clinicaltrials.gov/study/NCT05690126?term=NCT05690126&rank=1).

Research Insights

  • Saffron→Improved HPA Axis Reactivity

    There were no significant effects on inflammatory parameters or hypothalamic-pituitary-adrenal axis reactivity.

    Effect
    Neutral
    Effect size
    Small
  • Saffron→Improved Mental Health Score

    it improved autoperceived mental health, as reflected in increased mental health scores over time on the Medical Outcome Study Short-Form 12 questionnaire, compared with placebo (mean at 6 wk: 53.8 ± 12.7 vs 44.6 ± 11.4 for placebo and saffron group, respectively; time × treatment, P = 0.04).

    Effect
    Beneficial
    Effect size
    Small
  • Saffron→Reduced Anxiety

    Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score) nor individual symptoms.

    Effect
    Neutral
    Effect size
    Small
  • Saffron→Reduced Composite Depression, Anxiety, and Fatigue Score

    Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score)

    Effect
    Neutral
    Effect size
    Small
  • Saffron→Reduced Depression Symptoms

    Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score) nor individual symptoms.

    Effect
    Neutral
    Effect size
    Small
  • Saffron→Reduced Fatigue

    Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score) nor individual symptoms.

    Effect
    Neutral
    Effect size
    Small
  • Saffron→Reduced Inflammatory Parameter

    There were no significant effects on inflammatory parameters or hypothalamic-pituitary-adrenal axis reactivity.

    Effect
    Neutral
    Effect size
    Small
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