Hydration, arginine vasopressin, and gluco-regulatory health in humans: A critical perspective

Gluco-regulatory diseases, such as type 2 diabetes are currently a key public health priority. Public health messages have started to include the addition of water in their dietary guidelines. Such guidelines however are not based on causal evidence pertaining to the health effects of increased water intake, but rather more heavily based upon non-causal or mechanistic data. One line of thinking linking fluid intake and health is that hypohydration induces elevated blood concentrations of arginine vasopressin (AVP). Research in the 1970s and 1980s implicated AVP in gluco-regulation, supported by observational evidence. This important area of research subsequently appeared to stop until this century during which interest in hypertonic saline infusion studies, animal AVP receptor knockout models, dietary and genetic associations, and human interventions manipulating hydration status have resurged. This narrative review briefly describes and critically evaluates the usefulness of the current AVP-gluco-regulatory research. We offer suggestions on how to test the independent gluco-regulatory effects of body mass reductions versus elevated circulating AVP concentrations, such as investigating hydration manipulations using 3,4-Methylenedioxymethamphetamine. Whilst much research is still needed before making firm conclusions, the current evidence suggests that although AVP may only be partially implicated in gluco-regulation; more ecologically valid models using human participants suggests this effect is independent of hydration status. The key implication of this hypothesis if confirmed in future research is that manipulating hydration status to reduce circulating AVP concentrations may not be an effective method to improve gluco-regulatory health.