The relationship between homoarginine and liver biomarkers: a combination of epidemiological and clinical studies

Homoarginine (hArg) is a non-essential cationic amino acid which inhibits hepatic alkaline phosphatases to exert inhibitory effects on bile secretion by targeting intrahepatic biliary epithelium. We analyzed (1) the relationship between hArg and liver biomarkers in two large population-based studies and (2) the impact of hArg supplementation on liver biomarkers. We assessed the relationship between alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatases (AP), albumin, total bilirubin, cholinesterase, Quick's value, liver fat, and Model for End-stage Liver Disease (MELD) and hArg in appropriately adjusted linear regression models. We analyzed the effect of L-hArg supplemention (125 mg L-hArg daily for 4 weeks) on these liver biomarkers. We included 7638 individuals (men: 3705; premenopausal women: 1866, postmenopausal women: 2067). We found positive associations for hArg and ALT (beta 0.38 mu katal/L 95% confidence interval (CI): 0.29; 0.48), AST (beta 0.29 mu katal/L 95% CI 0.17; 0.41), GGT (beta 0.033 mu katal/L 95% CI 0.014; 0.053), Fib-4 score (beta 0.08 95% CI 0.03; 0.13), liver fat content (beta 0.016% 95% CI 0.006; 0.026), albumin (beta 0.030 g/L 95% CI 0.019; 0.040), and cholinesterase (beta 0.003 mu katal/L 95% CI 0.002; 0.004) in males. In premenopausal women hArg was positively related with liver fat content (beta 0.047% 95%CI 0.013; 0.080) and inversely with albumin (beta - 0.057 g/L 95% CI - 0.073; - 0.041). In postmenopausal women hARG was positively associated with AST (beta 0.26 mu katal/L 95% CI 0.11; 0.42). hArg supplementation did not affect liver biomarkers. We summarize that hArg may be a marker of liver dysfunction and should be explored further.

Automated summary

Homoarginine (hArg), a non-essential amino acid, inhibits hepatic alkaline phosphatases and affects bile secretion. In this study, we investigated the relationship between hArg and liver biomarkers and evaluated the impact of hArg supplementation. Our results showed that hArg was positively associated with ALT, AST, GGT, AP, albumin, total bilirubin, cholinesterase, Quick's value, liver fat, and MELD score. However, hArg supplementation did not affect liver biomarkers. These findings suggest that hArg may serve as a marker of liver dysfunction and warrant further exploration.