Effects of Oral Ingestion of L-Ornithine on Mental Stress and Fatigue Based on the Trier Social Stress Test in Healthy Humans: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

<b>Background:</b> With changes in the social environment typified by COVID-19, an increasing number of people are suffering from mental stress in interpersonal relationships and the resulting fatigue in recent years. L-ornithine oral ingestion reportedly suppresses the secretion of cortisol, a stress marker, through the hypothalamic-pituitary-adrenal (HPA) axis. However, there is insufficient research to determine whether L-ornithine exerts an ameliorative effect on social stress. Therefore, in this study, we investigated how L-ornithine affects mental stress and fatigue after social stress in healthy participants. <b>Methods:</b> We randomly assigned 65 participants into two groups, ingesting orally either 1600 mg of L-ornithine or a placebo for 7 days. On the day of the Trier Social Stress Test (TSST), participants took test products one hour before the testing. We evaluated the effects on saliva cortisol and mood states, including fatigue. <b>Results:</b> While L-ornithine did not affect saliva cortisol levels, it significantly improved the fatigue-inertia and anger-hostility scales of the Profile of Mood States on the morning after the TSST in the L-ornithine group compared to the placebo group. <b>Conclusions:</b> In conclusion, L-ornithine could potentially improve interpersonal social-stress-associated fatigue without involving the HPA axis. Trial registration: UMIN Clinical Trials Registry: UMIN000048949.