A metabolomic signatures in hyperuricemia: a systematic review

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not reported in abstract; meta-analysis (n=2 studies) identified elevated Alanine, Leucine, Phenylalanine, and Tyrosine and decreased Histidine in HUA versus controls — no standardised mean differences or odds ratios provided

• Primary Outcome: Identification of consistently dysregulated blood metabolites in hyperuricemia: 54 consistently elevated and 20 consistently decreased metabolites across 27 studies (1,187 total metabolites identified)

• Nnt Or Sensitivity: Not applicable — no diagnostic accuracy metrics, NNT, or hazard ratios reported; study is biomarker discovery/hypothesis-generating in design

• Confidence Interval: Not reported

Clinical Application

Routine clinical metabolomic profiling for HUA is not currently feasible in standard practice. Identified amino acid dysregulations (branched-chain amino acids, aromatic amino acids) are measurable via targeted assays but lack validated clinical thresholds for HUA diagnosis or risk stratification. Pathway findings (folate, glutathione, arginine metabolism) suggest potential dietary and supplementation intervention targets requiring RCT validation. In Australia, hyperuricemia affects approximately 15-20% of adults, with gout being the most common inflammatory arthritis. Current RACGP and Therapeutic Guidelines recommend urate-lowering therapy (allopurinol, PBS-listed) as first-line for recurrent gout. Febuxostat is TGA-approved but not PBS-listed for all indications. The metabolomic findings suggesting broader amino acid and energy metabolism dysregulation are consistent with HUA's recognised association with metabolic syndrome, which is highly prevalent in Australian Indigenous populations. However, this review does not provide evidence sufficient to alter current RACGP gout management guidelines. Metabolomic biomarker panels are not currently reimbursed under Medicare for HUA assessment. The findings may inform future research priorities within Australian metabolomics consortia and NHMRC-funded longitudinal cohort studies. Adults with established or suspected hyperuricemia, particularly those with concurrent metabolic comorbidities (obesity, metabolic syndrome, type 2 diabetes, chronic kidney disease). Findings are most relevant to populations with high HUA prevalence. Direct clinical application is premature pending prospective validation studies with standardised metabolomic platforms.

Abstract

BACKGROUND: Hyperuricemia (HUA) is traditionally viewed as a disorder of purine metabolism. However, its broader metabolic alterations remain incompletely understood. Metabolomics provides a useful approach for exploring metabolite changes associated with HUA, but a comprehensive synthesis of existing findings is still lacking. AIM OF REVIEW: This systematic review and meta-analysis aimed to characterize the systemic metabolic signature of HUA beyond purine pathways. By synthesizing data from 27 metabolomics studies involving 12,335 participants, the study sought to identify consistent metabolite biomarkers and key dysregulated pathways to provide new insights for diagnosis and therapeutic targeting. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review included 27 metabolomics studies involving 12,335 participants and identified 1,187 metabolites reported in association with HUA. Qualitative synthesis showed 54 consistently elevated and 20 consistently decreased blood metabolites, mainly involving amino acids, lipid-related metabolites, energy-related compounds, vitamins and their derivatives, and purine nucleoside metabolites. The meta-analysis was limited to two eligible studies, with one study contributing most of the statistical weight; it suggested higher levels of Alanine, Leucine, Phenylalanine, and Tyrosine and lower Histidine levels in HUA. Pathway enrichment analysis highlighted "One carbon pool by folate," "Arginine biosynthesis," "Glutathione metabolism," and related amino acid and energy metabolism pathways. Overall, these findings suggest that HUA may be associated with metabolic perturbations beyond purine metabolism alone, but the candidate metabolites and pathways require further validation in longitudinal, standardized, and mechanistic studies.

References

1. 1.Wu, Y., Han, X., Jin, J., Chen, Y., Cui, D., Ma, X., Guo, H., & Jiang, M. (2026). A metabolomic signatures in hyperuricemia: a systematic review. Metabolomics: Official Journal of the Metabolomic Society. https://doi.org/10.3390/ijms22179221