Associations between circulating amino acids and hepatic steatosis indices in Iranian adults aged over 50: findings from the Bushehr elderly health (BEH) program.

Background: Emerging evidence highlights the role of amino acid metabolism in non-alcoholic fatty liver disease (NAFLD) pathogenesis; however, data remain limited in Middle Eastern population. This study aimed to investigate the association between circulating amino acid profiles and NAFLD screened by the Fatty Liver Index (FLI) and Framingham Steatosis Index (FSI) among Iranian population 50years and over. Methods: This cross-sectional study included 1642 participants aged ≥ 50years from Bushehr Elderly Health Program. Amino acid levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). FLI and FSI were calculated as surrogate markers for NAFLD. Logistic regression and principal component analysis (PCA) were employed to assess associations between individual and clustered amino acid patterns and NAFLD indices, adjusting for confounders such as age, sex, BMI, diabetes, lipid profile, and inflammation markers. Results: The study included 1642 people (mean age62.24 ± 8.18 years). Higher levels of branched-chain, amino acids leucine (FSI: OR = 1.0083;FLI: OR = 1.0102) and valine (FSI: OR = 1.0064) and aromatic amino acids, tyrosine (FSI: OR = 1.0101;FLI: OR = 1.0211), phenylalanine (FLI: OR = 1.0131), tryptophan (FLI: OR = 1.0072), along with alanine (FSI: OR = 1.0039;FLI: OR = 1.0034) and glutamic acid (FSI: OR = 1.0032;FLI: OR = 1.0085), were positively associated with increased FLI and FSI scores (FDR < 0.05). PCA revealed component1 (rich in alanine, glutamic acid, leucine, valine, and proline) was positively associated with increased FLI(OR = 1.073,p = 0.019). Conversely, component4 (threonine, serine) was inversely associated with FSI(OR = 0.860,p = 0.024). Conclusions: Elevated levels of branched-chain and aromatic amino acids, are associated with increased FLI and FSI, while glycine, serine, threonine, and citrulline may exert protective effects. These findings underscore the potential role of amino acid metabolism in NAFLD pathogenesis and opportunities for dietary or metabolic interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-025-01733-2.