We examined the effect of a yearlong aerobic exercise intervention compared to a stretching control program on urinary F2-isoprostane, a marker of systemic oxidative stress, among previously sedentary, overweight/obese, postmenopausal women. Overall, exercisers decreased F2-isoprostane concentrations, as predicted by our primary hypothesis, but the effect was not statistically significant, except in planned analyses by strata of gain in aerobic fitness.
Few previous studies have examined the effects of exercise alone on F2
-isoprostane concentrations (6
), and no earlier studies, to our knowledge, were conducted exclusively among postmenopausal women. These studies suggest that exercise may reduce quite strongly F2
-isoprostanes among relatively younger women (6
), whereas this beneficial effect may be attenuated among older study subjects, as observed currently, and previously (15
). The three earlier studies, and the current study, noted similarly decreased body mass and increased aerobic fitness after exercise intervention, despite the wide range of intervention periods and age groups studied. Thus, these data suggest a potential age effect for the capacity of exercise to reduce oxidative stress. The mechanisms to explain such an effect are discussed in detail elsewhere (2
), and are largely based on experiments with lab animals: essentially, older animals have been observed to experience damage to cardiac and skeletal muscle after short-term exercise training if it is not initiated prior to a certain age, indicative of a physiologic age threshold. Alternatively, if exercise is initiated prior to this age, older animals experience the same health benefits as younger exercising animals. However, it is important to note that the older adults in the current study, and the participants in the previous study (15
), marginally decreased oxidative stress levels, although the effects were not statistically significant, suggesting the lab animal data are not entirely generalizable to humans.
We observed an inverse linear association between aerobic fitness and oxidative stress, suggesting a hormetic effect of exercise training (10
). This finding for aerobic fitness and oxidative stress compliments recent results from a subset of participants in this trial (n = 115) where we reported that the effect of exercise on inflammation (C-reactive protein and serum amyloid A) was restricted to participants who were obese (BMI ≥ 30 kg·m−2
or WC > 88 cm) at baseline (4
). In contrast, baseline obesity status did not modify the influence of exercise on F2
-isoprostane in the current study (data not shown). For our study participants in particular, these results suggest that gains in aerobic fitness improve oxidative stress levels, probably because of exercise-induced adaptations of the antioxidant-defense system (3
), and this effect occurs independent of general- or abdominal-obesity status. While our subgroup analyses among exercisers by strata of weight/fat loss were largely not statistically significant, it is worth noting that this trial was not designed to elicit large amounts of weight loss, and our exercise participants only reduced body weight by about 1.3 kg, on average. Therefore, we could not assess the effects of large amounts of weight/fat loss on oxidative stress, a limitation that future studies should address.
Particular strengths of this study include: the selection of a sensitive and stable biomarker for oxidative stress (9
); the long period of exercise intervention, with high participant retention; the good participant adherence to the exercise protocol; the bona fide effects of the aerobic exercise intervention, quantified by direct measures of maximal O2
uptake; and the gold-standard randomized, controlled trial design. Limitations of this study include the highly homogeneous study sample which limits comparisons to other groups, and that we studied only one biomarker of oxidative stress, F2
-isoprostane; future studies should consider other measures of lipid peroxidation, such as TBARS, and biomarkers that additionally reflect oxidative damage to protein and DNA.
In conclusion, in a randomized, controlled trial with excellent retention and good adherence to the aerobic exercise intervention, conducted among 173 previously sedentary, overweight/obese, postmenopausal women, we observed a modest reduction in F2-isoprostane overall that was not statistically significant. When exercisers were stratified by gain in aerobic fitness, as measured by maximal O2 uptake, an inverse and linear association was observed between aerobic fitness and F2-isoprostane, suggesting a training-effect on oxidative stress.