We evaluated the effects of ornithine on the alcohol-induced deterioration of mood states and on salivary stress markers the morning after alcohol intake in experiment 1 and on acute ethanol metabolism in experiment 2. Although flushers only constitute approximately 35% of the Japanese population [16, 17], we chose to only use flushers as our study subjects. In a previous study we showed that ornithine-aspartate supplementation ameliorated alcohol-derived feelings of fatigue in flushers but not in non-flushers using almost the same study design as in the present study . To be able to observe the effects of ethanol to the same degree, we decided to only screen flushers in this study. Previous studies by other groups generally used larger amounts of alcohol (0.7 to 1.6 g/kg body weight) [18–20], but the amount of alcohol consumed by flushers in our previous study (0.4 g/kg body weight) was considered appropriate to evoke the negative effects of alcohol the next morning.
In experiment 1, the subjective VAS factors “awareness”, “feeling of fatigue”, and “lassitude”, the OSA-MA factor “sleep length”, and the POMS factors “anger-hostility” and “confusion” the morning after drinking were significantly improved by ornithine intake. As all subjective factors tended to be improved by ornithine intake; alcohol-derived negative feelings seemed to be improved. Considering the fact that the OSA-MA factor “sleep length” was improved but substantive sleep time was not, ornithine made the subjects feel subjectively that they slept longer, even though the actual duration was the same.
Furthermore, the salivary stress marker cortisol was significantly reduced by ornithine intake. These results suggest that taking 400 mg of ornithine after alcohol consumption improves the mood on awakening, which is confirmed by the decrease in an objective stress marker.
In experiment 2 we aimed to clarify the influence of ornithine on acute alcohol metabolism. The feeling of drunkenness and other subjective and physiological symptoms of alcohol consumption were not significantly altered by ornithine intake. Thus, ornithine has little influence on acute alcohol metabolism at this dosage and the effect of ornithine on the alcohol-derived mood state the next morning was not caused by increased alcohol metabolism. Ornithine must therefore affect mood and physical state the next morning through other mechanisms. One of the possibilities may be through ammonia metabolism. Ammonia metabolism is disturbed by alcohol consumption , but is stimulated by ornithine administration [5, 6]. Furthermore, there is a correlation between decreased ammonia metabolism and fatigue [21, 22]. Thus, we speculate that ornithine may improve subjective feelings like “feeling of fatigue” by correcting the imbalance in ammonia metabolism caused by alcohol consumption. Further extensive studies are needed to clarify these associations.
Another mechanism behind the effects of ornithine on mood states after alcohol consumption may be through the improvement in sleep quality. Low amounts of alcohol can aid falling asleep, whereas higher amounts of alcohol cause sleep disturbances including frequent awakening and impaired normal sleep patterns. Omori et al. reported that oral administration of ornithine increased the amount of non-rapid eye movement (NREM) sleep in mice without changing the amount of rapid eye movement (REM) sleep . In addition, intracerebroventricular injection of ornithine has a sedative effect on neonatal chicks, and ornithine can serve as a precursor for glutamate and proline, which have also been reported to have sedative or hypnotic effects [24–26]. Thus, the effect of ornithine on sleep length may be partially mediated by improvements in the disturbed sleep patterns caused by alcohol consumption.
Along with the subjective parameters, ornithine also improved salivary concentrations of cortisol. Cortisol is used in many studies as an indicator of the stress response of the hypothalamic-pituitary-adrenal (HPA) axis [27–30], which is activated by exposure to an acute stressor. A previous report has shown that oral administration of ornithine in mice reduced the stress-induced corticosterone levels . Thus, ornithine may improve stress on awakening through suppression of the HPA axis.
There were some limitations with respect to the analysis, which may affect the accuracy of the results. The sample size was not sufficient to lead to a firm conclusion (experiment 1; n = 11, experiment 2; n = 16), and the proportion of female subjects was notably low in experiment 1. More extensive studies are needed to confirm our findings.
We investigated the effects of ornithine on the alcohol-derived adverse effects on subjective feelings and salivary markers the morning after alcohol consumption and on acute alcohol metabolism. Ornithine improved various negative feelings and decreased the salivary stress marker cortisol, but did not affect acute alcohol metabolism. Our results show that intake of 400 mg ornithine after alcohol consumption improved feelings of stress and fatigue upon awakening the next morning. Ornithine may be a potential dietary supplement for attenuating the morning after adverse psychological and physiological effects of alcohol.