Efficacy of combined Eschscholtzia californica Cham. and Valeriana officinalis L. extracts in alleviating insomnia associated with anxiety: A randomized, double-blind, placebo-controlled trial

• Randomized, double-blind study in adults (≤ 65 years) presenting insomnia and anxiety • Four-week combined eschscholzia and valerian extract supplementation versus placebo • Insomnia and anxiety significantly improved by supplementation versus placebo • Observed changes in gut microbiota may have contributed to these beneficial effects • Supplementation safe and well tolerated with no signs of addiction To evaluate the efficacy of a supplement comprising eschscholtzia and valerian extracts in alleviating insomnia associated with anxiety. Double-blind, randomized, placebo-controlled study conducted in young adults with an Insomnia Severity Index (ISI) score ≥ 15 and a Hamilton Anxiety Rating Scale (HAM-A) score > 8 and < 25 at inclusion. Participants received three tablets per day of either the supplement (providing 847 mg of eschscholtzia extract and 353 mg of valerian extract) or a placebo from day (D) 7 to D35, with follow-up until D57. Sleep habits were assessed daily using an actimeter and an electronic sleep diary, ISI and HAM-A scores being determined on days 7, 36 and 57. On D36, reductions in ISI scores were significantly greater in the supplemented group versus the placebo group (6.21 ± 4.91 [ 95% CI -7.82; -4.60] vs 3.89 ± 4.45 [ 95% CI -5.21; -2.57], p=0.030), as were reductions in HAM-A scores (6.24 ± 6.45 [ 95% CI -8.36; -4.12] vs 3.57 ± 5 [ 95% CI -5.28; -1.85], p=0.049). No significant between-group difference was evident on D57. No severe adverse events or supplement-related adverse events were reported. Few participants reported either difficulty in discontinuing the supplement or withdrawal symptoms, with no significant between-group difference. Exploratory analyses indicated changes in intestinal microbiota composition with the supplement, suggesting possible involvement of the gut-brain axis in its beneficial effects on sleep. The results show that the supplement tested could be beneficial in patients with insomnia, in particular those with underlying conditions that preclude the use of conventional pharmaceutical treatments.