Evening chronotype is associated with higher circulating pyruvate levels in adults

Chronotype reflects interindividual differences in the circadian timing system. Animal studies suggest reduced mitochondrial oxidative metabolism and tricarboxylic acid (TCA) cycle activity in individuals with an evening chronotype; however, human evidence linking chronotype to mitochondrial metabolic alterations remains limited. This cross-sectional study examined whether chronotype is associated with differences in circulating TCA-related metabolites, including pyruvate, lactate, and citrate.

A total of 272 adults from the 2022 Gangwon Obesity and Metabolic Syndrome Cohort were classified as having morning (≥18), intermediate (12-17), or evening (≤11) chronotype using the reduced Morningness-Eveningness Questionnaire. Fasting serum concentrations of pyruvate, lactate, and citrate were measured. Associations were examined using general linear models adjusted for fasting status; demographic, socioeconomic, and lifestyle factors; as well as body mass index. Sensitivity analyses excluded participants taking metabolic disease-related medications.

Major clinical and metabolic indicators did not differ across chronotypes. Serum pyruvate concentrations were higher in the evening chronotype group than in the morning chronotype group across all adjusted models (p < 0.048), whereas lactate and citrate concentrations did not differ. These findings remained consistent in sensitivity analyses excluding participants with metabolic diseases (p = 0.006-0.010).

Across analyses that included and excluded participants using metabolic disease-related medications, evening chronotype was consistently associated with higher circulating pyruvate concentrations, a key metabolic branch point downstream of glycolysis. These findings suggest chronotype-related differences in pyruvate metabolism, with potential implications for metabolic regulation.