Standardized Saffron Extract Formulation for Low Mood and Subclinical Depressive Symptoms: A Randomized,...

Background and aim Low mood with subclinical to mild depressive symptoms represents an early stage of mood disorders with risk of progression to major depression. This study was conducted to evaluate the efficacy and safety of a standardized saffron extract formulation (UO SAF 02, 15 mg) in adults with self-reported low mood and subclinical to mild depressive symptoms. Methods In this randomized, double-blind, placebo-controlled trial, 56 adults aged 18-65 years with self-reported low mood and Beck Depression Inventory (BDI) scores of 10-20 were randomized (1:1) to receive UO SAF 02 or placebo for 56 days. The trial was registered with the Clinical Trials Registry of India (CTRI/2023/11/059603). The primary outcome was the change in total Profile of Mood States (POMS) scores. Secondary outcomes included measures of affective state (Positive and Negative Affect Schedule (PANAS)), depression, anxiety, and stress (Depression Anxiety Stress Scales (DASS-21)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), and serum cortisol levels. Results Compared with placebo, UO SAF 02 demonstrated significant and consistent improvements in mood-related outcomes, with statistically significant effects observed at Day 28 and maintained through Day 56. POMS scores decreased markedly in the UO SAF 02 group at Day 56 (-48.46 ± 5.39, p < 0.0005) versus the placebo group (-5.67 ± 3.44, p > 0.05). Significant improvements were also observed in affective states, with greater increases in positive affect and reductions in negative affect (p < 0.05), along with reductions in DASS-21 scores (p < 0.001) and improvements in sleep quality (PSQI; p < 0.05). Serum cortisol levels were significantly reduced at both Day 28 and Day 56 (p < 0.05). The intervention was well tolerated, with no serious adverse events reported. Conclusions UO SAF 02 significantly improved psychological and physiological mood-related outcomes in individuals with low mood and subclinical to mild depressive symptoms, supporting its potential as an effective and well-tolerated intervention for mood regulation.