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The purpose of this trial was to determine whether exercise without weight loss would reduce F2-isoprostanes in previously sedentary young women. Participants (N=319) were randomized to four months of 150min/week aerobic exercise or a control group. Plasma free F2-isoprostanes were measured by gas chromatography-mass spectrometry. Other assessments included fitness and % body fat. Intervention groups were compared with stratification by quartiles of baseline plasma F2-isoprostane. This stratified comparison was linearly adjusted for baseline plasma F2-isoprostane and we also used baseline plasma F2-isoprostane as a propensity score to balance the intervention. Training resulted in significant improvements in aerobic fitness (0.88 METs) and body fat percent (1%) in exercisers compared to controls (p<0.001). The exercise group had significantly higher mean baseline plasma F2-isoprostanes (79.1 vs 67.9pg/mL) than the control group in the highest quartile of baseline plasma F2-isoprostanes. Within this highest quartile, exercise led to a greater decline in plasma F2-isoprostanes (-20.2±2.5pg/mL) than control (-7.4±2.5pg/mL); with adjustment for baseline plasma F2-isoprostanes and in the balanced groups, this difference was reduced but remained significant. Four months of exercise training resulted in significant reductions of systemic oxidative stress only among previously sedentary young women who were in the highest quartile of plasma F2-isoprostanes at baseline (≥57pg/mL). Our findings indicate that the benefits of aerobic exercise in reducing systemic oxidative stress may be limited to those who present higher baseline levels of plasma F2-isoprostanes., (Copyright © 2012 Elsevier Inc. All rights reserved.)