Glycine Insufficiency as a Metabolic Vulnerability in MASLD: Implications for Precision Nutrition

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, but effective nutritional interventions remain limited. Low glycine availability is among the most reproducible metabolomic findings in MASLD, and lower glycine levels correlate with greater steatosis, inflammatory activity, and fibrosis severity. This review examines the evidence linking glycine metabolism to MASLD and discusses whether glycine insufficiency may contribute to disease progression beyond its role as a metabolic biomarker. Proposed mechanisms linking altered glycine metabolism to MASLD include changes in SHMT2-related metabolic flux and glycine utilization for glutathione synthesis under oxidative stress. Altered glycine metabolism may be linked to disturbances in one-carbon metabolism, inflammatory signaling, gut-liver axis function, and fibrotic signaling. However, evidence regarding the causal relationships among these processes and the contribution of dietary glycine supply remains limited. Preclinical studies suggest that glycine or glycine-based compounds restore metabolic balance and reduce liver injury, but human trial data remain scarce. Glycine metabolism is therefore a candidate target for precision nutrition. Randomized controlled trials are still needed to determine efficacy, optimal dosing, and which patients are most likely to benefit.