Efficacy of a Water Intervention in the Improvement of Anabolic Resistance and Some Physiologic Adaptive Water Conservation Mechanisms in Institutionalized Aged Population. A Randomized Controlled Trial.

Population ageing, frailty and sarcopenia:

Population aging is one of the main challenges faced by Western societies. The lengthening of life expectancy has led to an increase in the need for medical and social care. Frailty is one of the most relevant consequences of the population ageing. Frailty is a well established geriatric syndrome characterized by a decrease in the body's reserves and its ability to respond against external stressors. It results in a decline in the function of several organs and systems that leads to greater vulnerability to suffer diseases, adverse health outcomes, functional decline, falls, disability or dependency. Frail subjects are in an increased risk of hospitalization, nursing home admission and mortality. Prevalence of frailty increases with age and can reach 50% in the population over 80 years old. Frailty evolves but is also potentially reversible (and treatable), especially in its initial stages. For all these reasons, frailty is considered today a real public health problem and a social threat that needs urgent attention. However, the ultimate causes of frailty is still unknown. Frailty is related with reduced muscle mass and function and with sarcopenia, which is defined as the loss of muscle function (strength or performance) accompanied by loss of muscle quantity or quality (EWGSOP2). Sarcopenia is a main determinant of functional decline, disability and dependency in aged population. Functional dependency has a prevalence of 20% in ≥65 year old population and of 30% in ≥75 years old population, with clear predominance in women. Different related factors contribute to sarcopenia, including changes in protein kinetics, hormonal regulation, grow factors, vascularization, inflammation, mitochondrial function, nutrition or physical exercise, but its pathophysiology is not completely understood. Currently, there is no effective drug to treat sarcopenia, but resistance exercises and nutritional measures are effective anabolic stimuli to maintain or ameliorate muscle function.

Dehydration in aged population:

Water is a main component in the human body and an essential nutrient for life and health. Water represents approximately 50-60% of total body weight in adults and has fundamental structural, metabolic, transport and thermo regulation functions. Water in the body is distributed in the extracellular and intracellular compartments and flows from one compartment to the other through a group of transmembrane proteins called aquaporines (AQP) by diffusion process guided by osmotic pressure. Water balance in human body is tightly regulated by the kidneys, which can concentrate or dilute urine depending on the metabolic waste and water intake. Water losses occur mainly in urine and sweat, but also through feces and breathing. Vasopressin (AVP) plays a fundamental role in water homeostasis by, in response to osmotic and pressure stimuli, increasing renal water reabsorption. From adulthood, there is a progressive decline in the water content of the body. Muscle is the main water reservoir in the organism. Loss of muscle mass is related with loss of total body water, especially when there is an increase in fat mass. Nonetheless, there are reasonable doubts about whether loss of muscle mass is responsible for loss of body 5 water or, by contrary, loss of body water is responsible for loss of muscle mass. Causes of the progressive chronic dehydration process in aged population are not well known, but may include a decreased water intake, decreased water absorption, decreased capacity to concentrate urine because of peripheral resistance to AVP or increased water losses due to medications or other circumstances such as situations of high heat or physical exercise. The renal solutes load (RSL) is the amount of metabolic waste by-products that must be eliminated by the kidney, while the obligatory urine water volume (OUV) is the minimum amount of water eliminated by the kidneys that is required to eliminate the RSL. OUV depends on the RSL and the renal capacity to concentrate urine. If the ability to concentrate urine is reduced, then the amount of urine should be increased to ensure elimination of waste products, but water intake should also be increased to avoid dehydration. It is difficult for aged population to increase water intake (because of anorexia, decreased thirst, urine incontinence, prostatic symptoms, etc.) so they are at increased risk of dehydration. Prevalence of dehydration in the elderly is usually under-recognised and has been estimated at 20%- 30% and is associated with greater disability, morbidity and mortality. There are no clear and objective clinical signs of early dehydration in the elderly, but plasma and urinary osmolaritiescan be considered the gold standard for a diagnosis of dehydration. In a population-based observational study (PI19/00500) with 237 subjects aged 70 years or over our group showed that: a) urine osmolarity was lower in women and decreases with age; b) plasma hyperosmolarity (>295 mOsm/L) was present in no women but in 4.5% of men, and was significantly 14 times greater in the older group; c) prevalence of resistance to AVP was 12.3%, 10.4% in subjects aged 70-79 vs 20.7% in subjects aged ≥80; and d) subjects with resistance to AVP presented higher plasma osmolarity and a prevalence of plasma hyperosmolarity of 10.0% (compared to 0.7%; p=0.004, in subjects with no resistance to AVP). Thus, the investigators concluded that urine concentration capacity decreases and plasma hyperosmolarity increases after the age of 80 years, and that peripheral resistance to AVP, with an overall prevalence of 12.3% in ≥70 years old population, greatly increases the risk of plasma hyperosmolarity (intracellular dehydration). Dehydration represents a heterogeneous group of conditions and its assessment is a major clinical challenge due to a complex, varying pathophysiology, non-specific clinical presentations and the lack of international consensus on its definition and diagnosis. Dehydration should mainly refer to hypertonic or isotonic dehydration. Hypertonic dehydration is due to a pure water deficit (without deficit of solutes) because insufficient dinking, excessive sweating or inability to concentrate urine (typical in aged population). It results in an increase in plasmatic osmolarity and a movement of water from intracellular to extracellular spaces (fluid loss is primarily from within cell). In contrast, isotonic dehydration with water and solute loss due to acute blood loss, vomiting or secretory diarrhea and no osmotic gradient between fluid compartments, is characterized by extracellular volume loss and intravascular fluid depletion (hipovolemia), which requires volume resuscitation with salt-containing fluid.

Hyperosmotic stress and its consequences: