Effects of Saffron Extract Supplementation on Mood, Well-Being, and Response to a Psychosocial Stressor in Healthy Adults: A Randomized, Double-Blind, Parallel Group, Clinical Trial

Abstract

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron-identified as promising following preliminary beneficial effects in major depressive disorder-represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18-54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders. Clinical trials number: NCT03639831.

Keywords: anxiety; crocetin; depression; heart rate variability; saffron.

Figure 1

Participant disposition flowchart. ITT, intent to treat population; PP, per protocol population; POMS, Profile of Mood States questionnaire; BMI, body mass index.

Figure 2

Testing timeline of the study visits. Participants completed a battery of questionnaires predose on arrival; the State–Trait Anxiety Inventory (STAI)-State, visual analog scales (VAS), and saliva samples were completed preobserved multitasking stressor (OMS). Galvanic skin response (GSR) and heart rate were collected for 5 min during completion of the questionnaire battery and again during the OMS. Collection of saliva samples and completion of VAS was repeated immediately and at 15-min intervals poststressor, respectively; the STAI-State was completed immediately and at 30-min intervals. POMS-2, Profile of Mood States 2; PSWQ, Penn State Worry Questionnaire; PSS-10, Perceived Stress Scale-10; WHOQOL-BREF, World Health Organization Quality of Life questionnaire; HADS, Hospital Anxiety and Depression Scale.

Figure 3

Change from baseline day 1 responses on the primary outcome measure (A) Profile of Mood States (POMS) Total mood disturbance and (B) the POMS Depression subscale by treatment and visit. No effects were observed on the primary outcome measure. A main effect of treatment was observed for depression (p = 0.05). Estimated means ± standard error are shown.

Figure 4

Change from baseline day 1 responses on the chronic mood/well-being questionnaires by treatment and visit; (A) World Health Organization Quality of Life Questionnaire (WHOQOL) Social relationships subscale, (B) COPE questionnaire Positive reinterpretation subscale, and (C) COPE questionnaire Denial subscale. Estimated means ± standard error are shown. **p < 0.01; t, p < 0.10.

Figure 5

Urinary crocetin levels collected at baseline and at 14, 28, and 56 days post-supplementation. Data are means ± standard deviation of raw values. Urinary crocetin levels were expressed by milligrams of creatinine.

Figure 6

Effect of the Observed Multitasking Stressor (OMS) on (A) State–Trait Anxiety Inventory (STAI) (State), (B) anxiety measured using visual analog scale (VAS), (C) salivary cortisol, and (D) salivary α amylase. Data are pooled across treatment groups and visits. Estimated means ± standard error are shown derived from a linear mixed model including the terms treatment, visit, and assessment.

Figure 7

Effect of treatment on heart rate variability (root mean square of the successive differences) during the resting 5-min baseline and observed multitasking stressor (OMS). Estimated means ± standard error are shown. **p < 0.01.

Figure 8

Effect of treatment on the Relaxed visual analog scale (VAS) at each assessment point. Estimated means ± standard error are shown. t, p < 0.10.