Long-Term Leisure-Time Physical Activity and Serum Metabolome

Study Questions:

Does a long-term pattern of routine physical activity lead to changes in the serum metabolome?


Sixteen same-sex twin pairs were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in three population-based cohorts were also studied (1,037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance.


Persistent physical activity was associated with a characteristic metabolic profile in the twins (p = 0.003), and in all three population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (p < 0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very low-density lipoprotein (p < 0.001) and higher large and very large high-density lipoprotein (p < 0.001) particle concentrations. The findings persisted after adjustment for body mass index (BMI).


The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals.


Habitual physical activity is widely considered to be beneficial toward a variety of health measures. The magnitude of the benefit and the underlying mechanisms involved are unclear, as studying the effect of long-term exercise in a randomized, controlled trial is difficult. These cohort studies demonstrate that even after controlling for BMI, regular physical activity produces differences in circulating factors that are associated with improved outcomes. The differences observed in the metabolome implicate pathways that might be targeted pharmacologically—for those who do not exercise.

Clinical Topics: Dyslipidemia, Sports and Exercise Cardiology, Hypertriglyceridemia, Lipid Metabolism

Keywords: Physical Fitness, Lipoproteins, VLDL, Lipoproteins, Orosomucoid, Glucose, Lipoproteins, LDL, Body Mass Index, Cardiology, Leisure Activities, Motor Activity, Isoleucine, Lipoproteins, HDL, Metabolome, Gender Identity

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