Effect of saffron extract supplementation on mood in healthy adults with subclinical symptoms of depression: a randomized, double-blind placebo-controlled study.
The American Journal of Clinical Nutrition. 2025-12-01; 122(6): 1625-1635
DOI: 10.1016/j.ajcnut.2025.09.050
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https://www.bordeaux-neurocampus.fr/12581
Amadieu C(1), Leyrolle Q(1), Farneti M(1), Anesi A(2), Bruchet E(1), Montet J(1), Dexpert S(1), Gaudout D(3), Mattivi F(2), Pourtau L(3), Castanon N(1), Capuron L(4).
Author information:
(1)University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, Bordeaux, France.
(2)Department of Food Quality and Nutrition, Research and Innovation Centre,
Fondazione Edmund Mach (FEM), San Michele all’Adige, Italy.
(3)Activ’Inside, Beychac et Caillau, France.
(4)University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, Bordeaux, France.
Electronic address: .
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).
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ajcnut.2025.09.050
PMID: 41047129 [Indexed for MEDLINE]
Conflict of interest statement: Conflict of interest The authors declare no
conflicts of interest.