Brain activation provokes nonoxidative carbohydrate consumption and during exercise it is dominated by the cerebral uptake of lactate resulting in that up to approximately 1 mmol/ 100 g of glucose equivalents cannot be accounted for by cerebral oxygen uptake. The fate of this 'extra' carbohydrate uptake is unknown, but it may be that brain metabolism is balanced by a yet-unidentified substance(s). This study used a nuclear magnetic resonance-based metabolomics approach to plasma samples obtained from the brachial artery and the right internal jugular vein in 16 healthy young males to identify carbon species going to and from the brain. We observed a carbohydrate accumulation of 255+/-37 mumol/100 g glucose equivalents at exhaustion not accounted for by the oxygen uptake. Although the cumulated uptake was lower than earlier observed, the results show that glucose and lactate are responsible for the majority of the carbon exchange across the brain. Even during intense exercise associated with the largest nonoxidative carbohydrate consumption, the brain did not show significant release of any other metabolite. We conclude that during exercise, the surplus carbohydrate uptake by the brain cannot be accounted for by changes in the NMR-derived plasma metabolome across the brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 24 February 2010; doi:10.1038/jcbfm.2010.25.