Circadian Modulation of Protein Catabolism: Insight from a Population Study

Background/Objectives: Urinary urea excretion is a marker of protein catabolism and follows circadian biological rhythms. Although small-scale studies have suggested a diurnal pattern, its population-level characterisation and determinants remain poorly defined. Methods: This cross-sectional study was conducted within the Ticino Epidemiological Stiffness Study (TEST-study), a population-based cross-sectional analysis of 1202 adults (≥18 years) recruited in the Italian-speaking region of Switzerland in 2017–2018. A final analytical sample of 859 participants provided 24 h urine collections divided into diurnal and nocturnal fractions, from which a day-to-night (Day/Night) urea excretion ratio was calculated as the primary outcome. Multivariable linear regression was used to identify independent determinants. Results: Across the cohort, a predominant nocturnal pattern of urinary urea excretion was observed, with a mean Day/Night ratio below 1. In younger women (<40 years), the ratio approached 1, indicating an attenuated Day/Night pattern, whereas older women (>65 years) displayed a significantly more pronounced nocturnal predominance. No comparable age-related trend was observed in men. In multivariable analysis, advancing age, greater nocturnal blood pressure dipping, and higher sodium excretion were independently associated with the Day/Night urea ratio. Conclusions: Urinary urea excretion, a surrogate marker of protein catabolism, exhibits a measurable Day/Night variation, associated with age, sex, and hemodynamic factors. These findings provide insights for chrononutritional strategies aimed at preserving muscle health across lifespan.