REVIEW OF: Lopresti AL et al, J Nutr 2025;155(7):2300–2311; Schuster J et al, Sleep Med X 2025;10:100147 STUDY TYPE: Two randomized, double-blind, placebo-controlled trials
Low mood and poor sleep often go together, and many patients look for “natural” ways to address both. Two recent industry-funded RCTs investigated saffron for each of these.
Lopresti and colleagues randomized 202 adults with mild depressive symptoms not meeting criteria for major depressive disorder to 12 weeks of saffron extract (Affron 28 mg/day) or placebo. Saffron beat placebo on the primary endpoint: greater reduction in depression on the Depression Anxiety Stress Scales (beta −2.92 points, effect size 0.39). Clinically meaningful response (at least 7 points) occurred in 72% with saffron vs 54% with placebo. Sleep and anxiety measures were unchanged, except in a subgroup analysis where patients with baseline sleep trouble showed modest improvement.
Schuster et al studied a different proprietary saffron extract (Safr’Inside 20 or 30 mg/day) vs placebo in 165 adults with moderate insomnia. Insomnia severity dropped about 1 point more with saffron than placebo on the 24-point Athens Insomnia Scale, their primary endpoint, with an effect size of 0.45. Benefits emerged after three weeks and persisted through the fourth week.
Side effects—mainly mild GI upset or headache—were uncommon across both studies, with no serious events. In Lopresti et al, one patient in the placebo group and three in the saffron group reported side effects. For Schuster et al, side effects were reported by 10 patients taking 30 mg of saffron, 6 patients taking 20 mg, and 4 patients on placebo.
CARLAT TAKE Saffron nudged mood and sleep in the right direction, with small to moderate effect sizes for both. The mood study’s 54% placebo response is significant, suggesting substantial improvement may occur without active treatment in this population. For patients with subclinical depression or sleep problems requesting a supplement recommendation, you might consider saffron alongside lifestyle interventions. The formulations studied here are available over the counter for about $30/month. For major depression or chronic insomnia, stick to treatments with more evidence.
