Abstract
We aimed to study whether lifestyle intervention could reduce systemic oxidative stress (OS) and the association between OS and cardiometabolic outcomes in women with obesity and infertility. From 2009 to 2012, infertile women with a BMI ≥ 29 kg/m2 were randomly assigned to a six-month lifestyle intervention followed by infertility treatment (N = 289) or to prompt infertility treatment (N = 285). Fasting serum free thiols (FT) concentrations were determined by colorimetry at baseline, at three and six months after randomization. Generalized estimating equations and restricted cubic spline regressions were used to estimate mean differences in serum FT levels between groups and to explore associations between serum FT levels and cardiometabolic outcomes. Baseline serum FT levels did not differ between the two groups (N = 203 in the intervention group vs N = 226 in the control group, 222.1 ± 48.0 µM vs 229.9 ± 47.8 µM, p = 0.09). Body weight decreased by 3.70 kg in the intervention group compared with the control group at six months (95% confidence interval [CI]: −7.61 to 0.21, p = 0.06). No differences in serum FT levels were observed between groups at either three months (N = 142 vs N = 150, mean differences: −1.03 µM, 95% CI: −8.37 to 6.32, p = 0.78) or six months (N = 104 vs N = 96, mean differences: 2.19 µM, 95% CI: −5.90 to 10.28, p = 0.60). In a pooled analysis of all available measurements, triglycerides (crude B: 5.29, 95% CI: 1.08 to 9.50, p = 0.01), insulin (crude B: 0.62, 95% CI: 0.26 to 0.98, p = 0.001), and homeostasis model assessment of insulin resistance (crude B: 2.50, 95% CI: 1.16 to 3.38, p < 0.001) were positively associated with serum FT levels. High-sensitivity C-reactive protein (hs-CRP) was negatively associated with serum FT levels (crude B: −0.60, 95% CI: −1.11 to −0.10, p = 0.02). The change in hs-CRP during the lifestyle intervention was strongly and inversely associated with serum FT levels (crude B: −0.41, 95% CI: −0.70 to −0.13, p = 0.005). No significant deviations from linear associations were observed between serum FT and hs-CRP. We do not observe an improvement in systemic OS in women with obesity and infertility with modest weight loss. There were potential associations between OS and biomarkers of cardiometabolic health. Trial registration: This trial was registered on 16 November 2008 at the Dutch trial register (NTR1530).
Highlights
Oxidative stress (OS) refers to the imbalance between reactive oxygen species (ROS) production and the ability to scavenge these reactive metabolites [1]
A total of 577 women with obesity and infertility and a BMI ≥ 29 kg/m2 (29 was chosen because in a subfertile obese cohort, the chance of becoming pregnant in one year decreases with 4% with every BMI increase above a BMI of 29 [28]) who were between 18–39 years old were included and randomly assigned to a six-month lifestyle intervention followed by infertility treatment or to prompt infertility treatment without lifestyle intervention in the period of June 2009 to June 2012
From the 289 subjects who were allocated to the intervention group, there were 228 (78.9%) subjects who had at least one serum Free thiols (FT) measurement, versus 242 (84.9%) subjects in the control group
Summary
Oxidative stress (OS) refers to the imbalance between reactive oxygen species (ROS) production and the ability to scavenge these reactive metabolites [1]. ROS are implicated in a myriad of physiological processes [2], pathological overproduction of ROS, as occurs in the case of OS, is considered to be associated with the development of various chronic OS-related diseases, such as obesity, diabetes, chronic obstructive pulmonary diseases, chronic kidney diseases, and cardiovascular diseases (CVD) [3,4]. The exact mechanisms leading to an increased obesity-associated cardiovascular risk profiles and the role played by OS in this process remains not fully understood. Previous study confirmed that serum FT levels are lower in patients with Crohn’s disease compared to healthy controls [12]. Kundi et al [16] were the first to demonstrate that FT can be measured as a relatively cheap and robust OS marker in subjects with acute myocardial infarction, showing that serum FT levels were statistically significantly decreased in patients with acute myocardial infarction as compared to healthy controls
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