A Journey through the Early Evidence Linking Hydration to Metabolic Health.

The idea that water intake or hydration may play an intrinsic, independent role in modulating metabolic disease risk is relatively recent. Here, we outline the journey from early experimental works to more recent evidence linking water and hydration to metabolic health. It has been known for decades that individuals with existing metabolic dysfunction experience challenges to body water balance and have elevated arginine vasopressin (AVP), <underline>a key</underline> hormone regulating body fluid homeostasis. Later, intervention studies demonstrated that altering fluid balance in these individuals could worsen their condition, suggesting that hydration played a role in modulating glycemic control. More recently, observational and interventional studies in healthy individuals have implicated the hydration-vasopressin axis in the pathophysiology of metabolic diseases. Individuals with higher AVP (or its surrogate, copeptin) are at higher risk for developing type 2 diabetes and components of the metabolic syndrome, an association that remains even when controlling for known risk factors. Supporting preclinical work also suggests a causal role for AVP in metabolic dysfunction. It is known that individuals who habitually drink less fluids tend to have higher circulating AVP, which may be lowered by increasing water intake. In the short term, water supplementation in habitual low drinkers with high copeptin may reduce fasting glucose or glucagon, generating a proof of concept for the role of water supplementation in reducing incident metabolic disease. A large randomized trial is ongoing to determine whether water supplementation for 1 year in subjects with low water intake can meaningfully reduce fasting glucose, risk of new-onset diabetes, and other cardiometabolic risk factors.