Obese subjects with impaired glucose tolerance (IGT) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease. This randomised controlled investigation was designed to test the hypothesis that alpha-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT. All data were collected from 24 obese (BMI >= 30 kg/m2) IGT patients. Following participant randomisation into two groups, fasting venous blood samples were obtained at baseline, and before and following intervention. The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65% HRmax for 30 minutes a day, 5 days per week, while ingesting 1 gram per day of alpha-lipoic acid for 12 weeks. The second group consisted of 12 participants who completed the same 12 week control phase, but this was followed by 12 weeks of 1 gram per day of alpha-lipoic acid supplementation only (no exercise). The main findings show a comparatively greater rate of low density lipoprotein (LDL) oxidation in the group consisting of alpha-lipoic acid only (p < 0.05 versus pre intervention), although total oxidant status was lower post intervention (p < 0.05 versus baseline) in this group. However, exercise and alpha-lipoic acid in combination attenuates LDL oxidation. Furthermore, in the alpha-lipoic acid supplement plus exercise training group, total antioxidant capacity was significantly increased (p < 0.05 versus baseline and pre intervention). Body fat percentage and waist and hip circumference decreased following exercise training (p < 0.05 versus post intervention). There were no selective treatment differences for a range of other clinical outcomes including glycaemic regulation (p > 0.05). These findings report that alpha-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise, suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances, but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD. However, when alpha-lipoic acid is combined with exercise, this atherogenic effect is abolished.

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