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Background. The improvement of insulin sensitivity by exercise has been shown to be inhibited by supplementation of vitamins acting as antioxidants. Objective. To examine effects of exercise with or without blueberries, containing natural antioxidants, on cardio-metabolic risk factors. Methods. Fifteen healthy men and 17 women, 27.6 ± 6.5 years old, were recruited, and 26 completed a randomized cross-over trial with 4 weeks of exercise by running/jogging 5 km five times/week and 4 weeks of minimal physical activity. Participants were also randomized to consume 150 g of blueberries, or not, on exercise days. Laboratory variables were measured before and after a 5 km running-race at maximal speed at the beginning and end of each period, i.e. there were four maximal running-races and eight samplings in total for each participant. Results. Insulin and triglyceride levels were reduced while HDL-cholesterol increased by exercise compared with minimal physical activity. Participants randomized to consume blueberries showed an increase in fasting glucose levels compared with controls, during the exercise period (blueberries: from 5.12 ± 0.49 mmol/l to 5.32 ± 0.29 mmol/l; controls: from 5.24 ± 0.27 mmol/l to 5.17 ± 0.23 mmol/l, P = 0.04 for difference in change). Triglyceride levels fell in the control group (from 1.1 ± 0.49 mmol/l to 0.93 ± 0.31 mmol/l, P = 0.02), while HDL-cholesterol increased in the blueberry group (from 1.51 ± 0.29 mmol/l to 1.64 ± 0.33 mmol/l, P = 0.006). Conclusions. Ingestion of blueberries induced differential effects on cardio-metabolic risk factors, including increased levels of both fasting glucose and HDL-cholesterol. However, since it is possible that indirect effects on food intake were induced, other than consumption of blueberries, further studies are needed to confirm the findings. Funding Agencies|University Hospital of Linkoping, Linkoping University||County Council of Ostergotland