Objective Because elevated copeptin, a marker of vasopressin, is linked to low water intake and high diabetes risk, we tested the effect of water supplementation on copeptin and fasting glucose. Design, Setting, and Participants Thirty-one healthy adults with high copeptin (>10.7 pmol · L −1 in men and >6.1 pmol·L −1 in women) identified in a population-based survey from 2013 to 2015 and with a current 24-hour urine osmolality of >600 mOsm · kg −1 were included. Intervention Addition of 1.5 L water daily on top of habitual fluid intake for 6 weeks. Main outcome measure Pre- and postintervention fasting plasma copeptin concentrations. Results Reported mean water intake increased from 0.43 to 1.35 L · d −1 ( P < 0.001), with no other observed changes in diet. Median (interquartile range) urine osmolality was reduced from 879 (705, 996) to 384 (319, 502) mOsm · kg −1 ( P < 0.001); urine volume increased from 1.06 (0.90, 1.20) to 2.27 (1.52, 2.67) L · d −1 ( P < 0.001); and baseline copeptin decreased from 12.9 (7.4, 21.9) pmol · L −1 to 7.8 (4.6;11.3) pmol · L −1 ( P < 0.001). Water supplementation reduced fasting plasma glucose from a mean (SD) of 5.94 (0.44) to 5.74 (0.51) ( P = 0.04). The water-associated reduction of both fasting copeptin and glucose concentration in plasma was most pronounced in participants in the top tertile of baseline copeptin. Conclusions Water supplementation in persons with habitually low water consumption and high copeptin levels is effective in lowering copeptin. It appears a safe and promising intervention with the potential of lowering fasting plasma glucose and thus reducing diabetes risk. Further investigations are warranted to support these findings.

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