2.1. Study Design
ICH
The study was a randomized, double-blinded, placebo-controlled, and parallel-designed study, carried out at a single site at Atlantia Clinical Trials, Cork, Ireland, between June 2021 and March 2022. It consisted of a screening visit, followed by a 2 week run-in phase and four assessment visits during a 12 week supplementation phase. Eligible subjects were randomized into the study at visit 2, baseline (week 0). Study assessments carried out during the visits included saliva awakening cortisol, analysis of biomarkers in blood samples, cognitive assessment, perceived stress, quality of sleep, and mood assessment. Subjects also answered questions regarding their lifestyle such as diet, exercise, and job on all occasions to determine if there had been some changes during the study time. Apart from the cognition tests that were conducted at baseline and at week 12, all other study assessments as well as safety assessments were carried out at baseline, visit 3 (week 4), visit 4 (week 8), and visit 5 (week 12). Before any study-related procedures, all subjects gave written informed consent, which specifically indicated that participation was voluntary and could be terminated at any time without giving any reason. The study was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals, Cork (ECM 4 (ll) 9 March 2021) and registered at Clinical Trials (NCT04931082) before the first participant was included. The study was conducted in accordance with the ethical principles in the Declaration of Helsinki, the International Council for Harmonization, and E6 R2 Guideline for Good Clinical Practice (ICH GCP). 