It is well appreciated that dysregulation of the kynurenine pathway (KP) has been linked to many disorders and diseases, for example depression (see 2023 September highlight), Parkinson’s, Alzheimer’s (see 2024 August highlight), various cancers (see 2023 March and 2022 July highlights), among others. Most studies investigating KP alterations rely on blood (serum or plasma) or cerebral spinal fluid (CSF) samples. While this is insightful, obtaining these samples is invasive and can often be difficult, prompting interest in less invasive alternatives like sweat. Detection and quantitation of tryptophan (TRP) and its metabolites frequently use chromatography techniques such as high-performance liquid chromatography (HPLC) methods optimized for a specific sample type, e.g., blood or CSF. Recently, HPLC methods were optimized to measure TRP , kynurenine (KYN), and kynurenic acid in sweat (T. Saran et al, 2021). While promising, these methods require further optimization to detect additional KP metabolites, a goal pursued by Dr. Kanlaya Prapainop Katewongsa and colleagues.
In a recently published study, Dr. Katewongsa focused on optimizing a HPLC method to detect 3-hydroxyanthranillic acid (3HAA), TRP, and KYN in sweat samples. 3HAA has been shown to be protective and its accumulation has been shown to extend the lifespan of C. elegans (see December 2023 highlight), making it a potential biomarker for neurodegenerative diseases and monitoring disease progression.
In this study, sweat samples were collected from healthy middle aged and older adults and analyzed for TRP, KYN, and 3HAA. First the authors demonstrated that TRP, KYN, and 3HAA were accurately measured in sweat using their HPLC method, with recovery rates between 86 and 103%, suggesting efficient detection of TRP, KYN, and 3HAA in sweat. Furthermore, repeat analysis showed good reproducibility of this method across these analytes. Next, they applied this method to determine any age-related differences in TRP, KYN, and 3HAA. Levels of KYN and 3HAA were significantly elevated in the sweat of older individuals (70-79 years old) vs middle aged (50-59 years old), suggesting that 3HAA levels in sweat increase with age. While this method offers potential, there are many questions that remain unanswered. Specifically, how does 3HAA levels in sweat relate to disease/disease progression and how does it compare to plasma/CSF levels. Addressing these questions could enhance the potential of sweat as a valuable biofluid for monitoring KP alterations in health and disease.