Urinary metabolites and fatigue in a population-based metabolomics study: an exploratory analysis

Area of Science:

• Metabolomics
• Biochemistry
• Human Health

Background:

• Chronic fatigue is prevalent, affecting nearly 20% of adults.
• The etiology and underlying mechanisms of chronic fatigue remain poorly understood.
• Metabolomics offers novel approaches to identify disease-related metabolites.

Purpose of the Study:

• To investigate the association between urinary metabolites and fatigue in the general population.
• To explore potential biochemical markers and mechanisms related to fatigue.

Main Methods:

• Utilized the Fatigue Assessment Scale (FAS) to measure fatigue severity.
• Quantified 51 urinary metabolites using ¹H nuclear magnetic resonance (¹H-NMR).
• Employed multivariable linear regression models with adjustment for confounders in 570 participants from the MEIA study.

Main Results:

• Four urinary metabolites (hypoxanthine, 3-hydroxyhippurate, dimethylamine, trimethylamine-N-oxide) initially showed significant associations with fatigue.
• Hypoxanthine's association was particularly noted in individuals with obesity (BMI ≥ 30 kg/m²).
• After adjusting for multiple testing (false discovery rate), no associations remained statistically significant.

Conclusions:

• Urinary metabolites linked to purine degradation and gut microbial metabolism may indicate fatigue-related biological processes.
• Urinary metabolomics shows promise for identifying biochemical alterations and potential pathophysiological mechanisms of fatigue.
• Further research is needed to validate these findings and elucidate the role of specific metabolites in fatigue.