A Journey through the Early Evidence Linking Hydration to Metabolic Health

Abstract

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.

Current Hydration Habits: The Disregarded Factor for the Development of Renal and Cardiometabolic Diseases

“…Experimentally, the chronic administration of desmopressin (a vasopressin V2 receptor agonist) induced albuminuria and kidney damage in rodents and humans [ 79 , 80 ]. Similarly, stimulation of the V1a receptor may cause renal vasoconstriction [ 81 ] as well as gluconeogenesis and glycogenolysis [ 5 ]; and coronary artery vasoconstriction [ 81 ].…”

“…However, the intake of drinking water is critical to the maintaining of the osmolarity and concentrations of electrolytes needed to allow critical biochemical reactions to take place in both the intracellular and extracellular environment [ 3 ]. While it is well-recognized that the host can reduce water losses and accommodate in the setting of mild dehydration to maintain serum osmolarity, only recently has it been recognized that the chronic stimulation of biological responses to maintain osmolarity can have deleterious consequences on health [ 4 , 5 ]. This suggests that ‘underhydration’, in which the activation of these biological processes results in normal serum osmolarity, may represent an unrecognized but significant risk factor for disease.…”

Osmoadaptive GLP-1R signalling in hypothalamic neurones inhibits antidiuretic hormone synthesis and release

“…Interestingly, translational human studies are showing strong therapeutic potential for OXT as a treatment for diabetes and obesity in its own right [ 4 ]. There is also increasing experimental, pharmacological, and epidemiological evidence that supports a causative role for sustained increases in circulating AVP in the development of diseases, suggesting the AVP system as a prognostic marker and thus a potential therapeutic target [ [5] , [6] , [7] , [8] , [9] , [10] , [11] ].…”

The improvement of insulin level after hydrogen-rich water therapy in streptozotocin-induced diabetic rats

“…Alteration of the fluid balance elevates arginine vasopressin as a key hormone regulating body fluid homeostasis. These conditions lead to the development of type 2 diabetes mellitus (T2DM) [4].…”