Polyamine Dysregulation in Metabolic Dysfunction-associated Steatotic Liver Disease: a Systematic Review of Human Observational Evidence.

Authors

Alicia González-González, Lucía Aránega-Martín, Kamar Ouahbi-Chadli, Miguel Jiménez-Pérez, Bruno Ramos-Molina, Gabriel Olveira, José Carlos Fernández-García

Published in

Current obesity reports. Volume 15. Issue 1. Nov 11, 2026. Epub Nov 11, 2026.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is closely associated with obesity, insulin resistance, and increased cardiovascular risk. Polyamines have emerged as potential regulators of metabolic and inflammatory pathways implicated in MASLD. We aimed to systematically evaluate the association between polyamines and MASLD severity and related hepatic and metabolic outcomes in human observational studies.
A systematic review was conducted in accordance with PRISMA 2020. PubMed, Embase, Web of Science and Scopus were searched from inception to April 2026 (PROSPERO registration CRD420261540945). Observational studies assessing polyamine levels or polyamine-related pathways in relation to MASLD and related hepatic or metabolic outcomes were included. Study selection, data extraction, and risk of bias assessment (Newcastle-Ottawa Scale, NOS) were performed independently. A qualitative synthesis was undertaken. Nine studies were included, comprising more than 1,400 participants across clinical cohorts, together with transcriptomic analyses based on publicly available datasets; NOS scores ranged from 6 to 9. Increased hepatic putrescine, together with upregulation of ornithine decarboxylase, was associated with greater histological disease severity and hepatocellular injury in one study. In contrast, lower spermidine levels in circulating and fecal samples were associated with greater disease severity in some studies. Alterations in polyamine-related molecular pathways, including the eukaryotic initiation factor 5​A hypusination pathway, and changes in microbially derived polyamines were also associated with disease severity. Findings varied across studies, with differences in biological matrices, analytical approaches, and disease assessment methods potentially contributing to the observed heterogeneity.
Distinct alterations in polyamine profiles, particularly increased putrescine and reduced spermidine in specific biological matrices, were associated with MASLD-related disease severity in some observational studies. However, none of the included studies established diagnostic performance using measures such as area under the receiver operating characteristic curve (AUC), sensitivity, specificity, predefined cut-offs, or external validation. Therefore, polyamines should currently be considered promising candidate molecular biomarkers requiring prospective validation rather than established biomarkers of MASLD severity. The available evidence remains observational and heterogeneous, precluding definitive causal inferences and limiting conclusions regarding clinical utility. Prospective, longitudinal, and multicenter studies using standardized analytical methods, predefined thresholds, and appropriate internal and external validation are required to determine whether polyamine measurements provide incremental value beyond established non-invasive tools.

PMID:
43013151
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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