Ryptophan and kynurenine levels in patients with obstructive sleep apnea syndrome and their relationship with excessive daytime sleepiness

This study aimed to investigate the levels of tryptophan (TRP), kynurenine (KYN), and other kynurenine pathway metabolites in patients with obstructive sleep apnea syndrome (OSAS), and to evaluate the associations of these biomarkers with disease severity, excessive daytime sleepiness, and polysomnographic parameters. The study was conducted with the approval of the Ethics Committee of Selçuk University Faculty of Medicine and included 77 adult OSAS patients who underwent polysomnography and 70 healthy controls without OSAS. Clinical, demographic, and polysomnographic data of the participants were recorded. Patients were categorized as mild, moderate, and severe OSAS groups according to apnea-hypopnea index (AHI) and they were grouped as normal, increased, and severely increased groups according to Epworth Sleepiness Scale (ESS) scores. Serum TRP, KYN, and other metabolite levels were measured using high-performance liquid chromatography (HPLC), and the KYN/TRP ratio was calculated. Based on the findings, TRP levels were not different in groups. In contrast, KYN levels were higher in OSAS patients compared to controls, with a particularly notable increase in the mild OSAS group. The KYN/TRP ratio was not detected significant differences among groups. Kynurenic acid (KYNA) levels were higher in the severely increased ESS group compared to the increased group. The levels of other metabolites were not different between the groups. KYN and KYNA levels showed a positive correlation with the oxygen desaturation index (ODI), and negative correlations with minimum oxygen saturation as well as mean oxygen saturation during both sleep and wakefulness. The results demonstrate significant associations between KYN levels and the presence of OSAS, as well as between hypoxemia parameters and both KYN and KYNA levels. In this context, KYN and KYNA may be considered candidate biomarkers reflecting disease burden and may hold potential value in the risk stratification and treatment monitoring of OSAS. Notably, the elevated KYN levels observed in the mild OSAS group suggest that this metabolite could provide an opportunity for earlier detection of the disease. Furthermore, the relationship observed between KYNA levels and ESS scores may reflect the multifactorial nature of excessive daytime sleepiness. This study addresses an underexplored area in the literature, and through comprehensive evaluation combining polysomnography, biochemical analyses, and clinical data, provides one of the most technically detailed investigations into this topic. Taken together, these findings deepen our understanding of the pathophysiological significance of the kynurenine pathway in OSAS, highlight its potential clinical implications, and indicate the need for further confirmatory and large-scale studies to validate these observations and strengthen their translational relevance. Overall, this work contributes to positioning the kynurenine pathway as a promising avenue for future research in OSAS.