Abstract
Introduction: Cardiorespiratory fitness (CRF) is a powerful predictor of health outcomes, but its determinants are incompletely understood at the population level. Prior studies have suggested associations between dietary components and CRF, but they have generally been limited by small sample sizes, reliance on estimated CRF, variable dietary instruments, and lack of molecular interrogation to support shared biology. Hypothesis: Shared metabolite associations across dietary quality and CRF will prioritize metabolites potentially responsible for linking dietary quality with improved CRF in the community. Methods: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for quantification of CRF by peak oxygen uptake (VO 2 ) and completed food frequency questionnaires at a routine study visit. Dietary quality was assessed by the Mediterranean-style Diet Score (MDS), and fasting levels of 201 metabolites were quantified. Results: In 2380 FHS participants (age 54 ± 9 years, 54% women, BMI 28 ± 5 kg/m 2 ), a 1-SD higher MDS was associated with 4.4% (3.5% - 5.3%, p < 0.0001) greater peak VO 2 in linear models adjusted for age, sex, cardiovascular risk factors, and physical activity. In a representative subsample that had metabolite profiling (N = 1154), 80 metabolites were statistically significantly associated with MDS, 57 with peak VO 2 , and 27 with both MDS and peak VO 2 in multivariable linear models (FDR < 5% for all, Figure). These metabolites included dimethylguanidino valeric acid, medium chain acylcarnitines, and C16 ceramide, which are markers of insulin resistance and increased risk for cardiovascular disease. Metabolites with less established functions include C38:7 plasmalogens, which correlate with fish intake and may have anti-inflammatory effects. Conclusions: Healthy diet is associated with greater CRF in the community and may be partially explained by favorable metabolic health.
Published Version
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