Association of B-Vitamin–Related Tryptophan–Kynurenine Pathway Metabolites with Fatty Liver Index in Older Adults: Findings from the Bushehr Elderly Health Study

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent hepatic disorders among older adults and is closely linked to chronic inflammation, oxidative stress, and disturbances in B-vitamin metabolism. The tryptophan–kynurenine pathway, a key metabolic and inflammatory axis regulated by B-vitamins, may contribute to NAFLD pathogenesis. Methods: This cross-sectional study utilized data from 396 participants aged ≥60 years enrolled in the second phase of the Bushehr Elderly Health (BEH) cohort study. Participants were categorized into two groups based on the Fatty Liver Index (FLI): FLI < 60 and FLI ≥ 60. Plasma metabolites of the kynurenine pathway were quantified using GC-MS/MS and LC-MS/MS. Statistical analyses included independent t-tests, Mann–Whitney U tests, and logistic regression models. Results: Among the participants, 173 (43.7%) had FLI ≥ 60 and exhibited a significantly more adverse metabolic profile. Plasma levels of kynurenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, and nicotinamide were significantly elevated in the FLI ≥ 60 group. In the fully adjusted logistic regression model, higher levels of these metabolites remained independently associated with an increased risk of elevated FLI. Conclusion: Activation of the tryptophan–kynurenine pathway and alterations in B-vitamin–related metabolites are independently and significantly associated with fatty liver in older adults. These findings suggest that profiling this metabolic pathway may serve as a non-invasive biomarker strategy for early identification of individuals at risk of NAFLD. Furthermore, nutritional interventions aimed at optimizing B-vitamin status may hold promise for the prevention and management of NAFLD in the elderly.