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.

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission

“…Moreover, the behavioral effect of stress remained significant in mice treated after stress, whereas the two saffron-treated groups only differed by the time of saffron administration. In addition, the current results fit with compelling clinical and preclinical studies reporting its ability to improve mood and depressive symptoms [26,31,34,35,70,71], including in stressful conditions, although the number of studies is much less in this case [68,69,72]. Taken together, these findings highlight the need of investigating further the behavioral impact of saffron under stress conditions.…”

“…Further studies would be required to obtain a dynamic overview of the effect of stress on each of these 5-HT factors and their potential interdependence, but this was not the question addressed in the present study. Importantly, we show that the pre-administration of saffron prevents ARS-induced impairment of 5-HT neurotransmission, including by acting on the same targets than conventional ADs [72]. Indeed, it blocks the increase of 5-HIAA levels and 5-HIAA/5-HT ratio in the FCx, as well as SERT upregulation in the HPC.…”

Crocins for Ischemic Stroke: A Review of Current Evidence

“…Crocins (CRs) are a group of carotenoid compounds isolated from SF that also contain other active compounds, including picrocrocin and safranal (Suchareau et al, 2021). Seven different natural CR analogues have been identified from SF, namely CR (crocin 1, CR, CR1), CR 2 (crocin 2, CR II), CR 3 (crocin 3), CR 4 (Giaccio, 2004;Jackson et al, 2021;Qin et al, 2021) Dimethyl Crocetin (crocin 4), CR 5 (crocin 5), CR 6 (crocin 6), and CR 7 (crocin 7) (Zhang et al, 2004;Mehrnia et al, 2017;Song et al, 2021b). All are mono or di glycosyl polyene esters of CC (Mohajeri et al, 2010a;Nam et al, 2010;Pang et al, 2020).…”

Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr’InsideTM) Protect Neurons from Oxidative Stress: Consideration for Depressive Disorders

“…Although a large variety of antidepressant medications is currently available, a significant proportion of patients does not respond to them adequately, highlighting the need to continue to search for alternative solutions. Saffron, a spice obtained from the stigmas of Crocus sativus L., a Mediterranean plant belonging to the Iridaceae family, is used as a highly valued plant for traditional medicinal purposes [ 12 ] and, in particular, for its positive effects on mood and depression [ 13 , 14 , 15 , 16 , 17 ]. Saffron stigmas are rich in crocins and crocetins, two carotenoid pigments responsible for its color; in picrocrocin, which is responsible for its flavor and bitter taste; and in safranal, a volatile compound responsible for its aroma and smell.…”