Influence of Sex on Urinary Organic Acids: A Cross-Sectional Study in Children

Marianna Caterino1,2, Margherita Ruoppolo1,2, Guglielmo Rosario Domenico Villani1,2

  • 1Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', 80131 Napoli, Italy.

Insights

Urinary organic acid levels differ significantly between males and females, with these sex differences varying by age and impacting metabolic pathways. Personalized medicine may require sex- and age-specific reference values.

Area of Science:

  • Metabolomics
  • Pediatric Research
  • Personalized Medicine

Background:

  • Urinary metabolome analysis is crucial for personalized medicine, reflecting individual physiological states.
  • Factors like sex and age significantly influence urinary metabolite profiles.
  • Understanding these influences is key to interpreting metabolic data accurately.

Purpose of the Study:

  • To investigate sex-based differences in 72 urinary organic acids in children aged 1-36 months.
  • To determine how these sex differences vary across different age groups.
  • To identify specific metabolic pathways affected by sex and age.

Main Methods:

  • Gas chromatography-mass spectrometry (GC-MS) analysis of urine samples.
  • Study cohort: 291 children (152 males, 139 females) aged 1-36 months.
  • Data stratified by age into four groups to analyze sex-specific trends.

Main Results:

  • Specific organic acids were exclusively found in males (e.g., 4-hydroxy-butyrate) or females (e.g., phenylacetate).
  • Sex differences were more pronounced in infants under 6 months old.
  • Key affected pathways included mitochondrial homeostasis, citrate cycle, and amino acid metabolism, with distinct patterns in males and females.
  • Age influenced metabolic pathways differently between sexes, notably phenylalanine metabolism in males.

Conclusions:

  • Sex profoundly impacts both the quantity and type of urinary organic acids, with age-dependent variations.
  • Sex-specific and age-stratified reference values for urinary organic acids may be necessary for accurate clinical interpretation.
  • These findings underscore the importance of considering sex and age in metabolomic studies for personalized health approaches.

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