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Background  Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of people at risk is continuously growing. New methods for early risk prediction are therefore needed to actuate prevention strategies  before  the individuals are diagnosed with CVD. Several studies report that aerobic fitness level, measured as maximal oxygen uptake (VO 2max ), is the single best predictor of future CVD mortality in healthy people. Based on this, we wanted to study differences between healthy individuals with a large difference in VO 2max -level to identify new biomarkers of low aerobic fitness that may also have potential as early biomarkers of CVD risk.    Methodology/Principal Findings  Serum samples from 218 healthy individuals with a low VO 2max  (n = 108, 63 women) or high VO 2max  (n = 110, 64 women) were analysed with MR metabolomics. In addition, standard clinical-chemical analyses for glucose, lipids, liver enzymes, micro-CRP, and colorimetric analysis on circulating choline were performed. Individuals in the low VO 2max -group had increased serum levels of free choline, decreased phosphatidylcholine, increased glucosę and decreased unsaturated fatty acids compared to the individuals in the high VO 2max –group.    Conclusions/Significance  Aerobic fitness dependent differences in serum levels of free choline and phosphatidylcholine are observed. They should be further studied as potential early markers of CVD risk.

Serum Levels of Choline-Containing Compounds Are Associated with Aerobic Fitness Level: The HUNT-Study