Water Supplementation Reduces Copeptin and Plasma Glucose in Adults With High Copeptin: The H2O Metabolism Pilot Study

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.