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Background Recent studies have shown that ingestion of glucose water lowers blood pressure (BP) in patients with perturbed autonomic control and more modestly lowers BP in elderly normal subjects. Whether glucose water affects cardiovascular control during orthostatic stress in normal young healthy subjects is unknown. We hypothesized that glucose water ingestion will reduce orthostatic tolerance in young healthy volunteers. Methods In a randomized, controlled, within-subject study, 15 healthy male subjects (21-28 years of age) ingested water or 10% glucose water 5 min before tilt-table testing. We measured finger BP, brachial BP, heart rate, and peripheral vascular resistance. Orthostatic tolerance was measured as the time to presyncope during a 70° head-up tilt, in which the head was tilted for 45 min or until presyncopal symptoms were observed. Results During the first 45 min of tilt, 8 of 15 subjects who ingested 10% glucose water experienced presyncope, but only 2 of 15 who ingested water (P = 0.029) experienced presyncope. Ingestion of 10% glucose water increased the heart rate significantly more than pure water during head-up tilt (P = 0.026). Ingestion of water increased the peripheral vascular resistance significantly >10% glucose water during the head-up tilt test (P = 0.013). Conclusions Ingestion of 10% glucose water impairs head-up tilt tolerance relative to water ingestion. The contrasting effect of 10% glucose water vs. pure water on orthostatic tolerance is associated with increased heart rate and attenuation of the increase in peripheral vascular resistance in head-up tilt testing. [ABSTRACT FROM AUTHOR]