Structured lifestyle intervention in patients with the metabolic syndrome mitigates oxidative stress but fails to improve measures of cardiovascular autonomic neuropathy

Aims: To assess the role of oxidative stress in mediating adverse outcomes in metabolic syndrome (MetS) and resultant cardiovascular autonomic neuropathy (CAN), and to evaluate the effects of lifestyle interventions on measures of oxidative stress and CAN in subjects with MetS. Methods: Pilot study in 25 non-diabetic subjects with MetS (age 49 +/- 10 years, 76% females) participating in a 24-week lifestyle intervention (supervised aerobic exercise/Mediterranean diet), and 25 age-matched healthy controls. CAN was assessed by cardiovascular reflex tests, heart rate variability (HRV) and PET imaging with sympathetic analog [C-11] meta-hydroxyephedrine ([C-11]HED). Specific oxidative fingerprints were measured by liquid-chromatography/mass-spectrometry (LC/MS). Results: At baseline, MetS subjects had significantly higher oxidative stress markers [3-nitrotyrosine (234 +/- 158 vs. 54 +/- 47 mu mol/mol tyrosine), ortho-tyrosine (59 +/- 38 vs. 18 +/- 10 mu mol/molphenylalanine, all P < 0.0001], and impaired HRV at rest and during deep breathing (P = 0.039 and P = 0.021 respectively) compared to controls. Twenty-four-week lifestyle intervention significantly reduced all oxidative stress markers (all P < 0.01) but did not change any of the CAN measures. Conclusions: Subjects with MetS present with signs of CAN and increased oxidative stress in the absence of diabetes. The 24-week lifestyle intervention was effective in ameliorating oxidative stress, but did not improve measures of CAN. Larger clinical trials with longer duration are required to confirm these findings. (C) 2017 Elsevier Inc. All rights reserved.