A standardised saffron extract improves subjective and objective sleep quality in healthy older adults with sleep complaints: results from the gut-sleep-brain axis randomised, double-blind, placebo-controlled pilot study

Sleep disturbances are associated with an increased risk of neurodegenerative diseases and alterations in gut microbiota composition. Saffron (<i>Crocus sativus</i>) has been shown to improve sleep and modulate the gut microbiome, but its effect on sleep quality <i>via</i> the gut microbiota-brain axis remains largely unexplored. This randomised, placebo-controlled pilot study investigated the impact of four weeks of saffron supplementation (30 mg day^-1) on sleep quality and gut microbiota in older adults (ages 55-85) with self-reported sleep complaints (<i>N</i> = 52). Subjective sleep quality was assessed using validated questionnaires, while objective measures were captured <i>via</i> an electroencephalography-based sleep tracker. Gut microbiota composition was analysed in a subgroup (<i>N</i> = 26). Saffron supplementation significantly improved subjective sleep quality (<i>p</i> = 0.02) and sleep efficiency (<i>p</i> = 0.04). Objective outcomes included reduced latency to persistent sleep (<i>p</i> = 0.003) and shorter sleep onset latency (<i>p</i> = 0.03). Microbiome analysis using linear discriminant analysis effect size (LEfSe) revealed significant increases in <i>Faecalibacterium</i> (<i>q</i> = 0.013), <i>Lachnoclostridium</i> (<i>q</i> = 0.045), <i>Prevotella</i> (<i>q</i> = 0.022), <i>UBA1819</i> (<i>q</i> = 0.020) and <i>Oscillibacter</i> (<i>q</i> = 0.045), alongside a decrease in <i>Dialister</i> (<i>q</i> = 0.028). Univariate analysis further identified increases in <i>Lachnospiraceae-UGC-001</i> (<i>p</i> = 0.020) and <i>Roseburia</i> (<i>p</i> = 0.03), with a reduction in <i>Turicibacter</i> (<i>p</i> = 0.045) in the saffron group. Correlational analyses revealed that <i>Oscillibacter</i> and <i>UBA1819</i> were positively associated with subjective sleep efficiency (<i>r</i> = 0.63, <i>p</i> = 0.0007) and inversely associated with sleep latency (<i>r</i> = -0.39, <i>p</i> = 0.04). Alterations in in <i>Dialister</i>, <i>Turicibacter</i> and <i>UBA1819</i> correlated with objective sleep quality parameters including wake duration, latency to persistent sleep and wake-after-sleep-onset. In summary, four-weeks saffron supplementation improved both subjective and objective sleep quality in older adults with sleep complaints, and modulated gut microbiota composition, particularly increasing short-chain fatty acids producing bacteria. These findings pave the way for further randomised controlled trials exploring the links between sleep quality and gut health and may help in devising new preventative strategies for age-related brain disorders.