Beneficial effects of a standardised saffron extract (SafrInside™) on premenstrual syndrome: a multicentric, double-blind, randomized, placebo-controlled trial

Background: Premenstrual syndrome (PMS) affects nearly half of women of reproductive age and can substantially impair quality of life, daily functioning, and psychological well-being. Although saffron extract has been proposed as a potential non-pharmacological approach for PMS management, clinical evidence remains limited. This randomized, multicentric, double-blind, placebo-controlled trial evaluated the efficacy and tolerability of saffron extract in reducing PMS symptoms. Methods: A total of 110 healthy women aged 18-45 years with mild-to-moderate PMS were randomized to receive saffron extract (30 mg/day; SafrInside™) or placebo for three menstrual cycles. The primary endpoint was the Premenstrual Assessment Form-Short Form (PAF-SF) total score. Secondary endpoints included PAF-SF affect, pain, and water retention subscales, and the Patient Health Questionnaire-4 (PHQ-4) total score. Efficacy analyses were performed in the intention-to-treat (ITT) and per-protocol populations using linear mixed-effects models. Results: Saffron supplementation resulted in a significantly greater reduction in overall PMS symptoms than the placebo (difference in slope for PAF-SF total score: -1.88; 95% confidence interval [CI] -2.64 to -1.12; p<0.001). Between-group differences in change from baseline were significant at 7 days (-2.42; 95% CI -4.79 to -0.04; p=0.046), 35 days (-3.40; 95% CI -5.78 to -1.02; p=0.010), and 63 days of supplementation (-5.96; 95% CI -8.34 to -3.58; p<0.001). Significant improvements were also observed for affective symptoms (p=0.003), pain (p<0.001), water retention (p<0.001) from the PAF-SF, and psychological distress as assessed by the PHQ-4 total score (p=0.011). No adverse events were reported. Conclusions: Daily supplementation with saffron extract over three menstrual cycles significantly improved overall PMS symptom severity compared with placebo in women with mild-to-moderate PMS. Benefits were also observed for affective, pain, and water retention symptoms. Saffron extract was well-tolerated and may represent a promising non-pharmacological option for women experiencing bothersome PMS symptoms.