Osmoadaptation clinical trials at University of California Health

Social relevance: For 30 years, people have been confused about how much plain water to drink. Over 30 years, health professionals have criticized media advice to drink 8 glasses of water per day, citing lack of evidence (Valtin et al, 2002; Yamada et al, 2022). Health authorities have not set drinking water-specific recommendations, assuming 1) that any or all types of drinks hydrate equivalently, i.e. that people do not need to drink plain water to replace lost body water, and 2) the average healthy person can rely on thirst as guide for water intake. The lack of drinking water-specific recommendations significantly impacts daily lives because it translates into limited or no support for drinking water in public health services, laws, and retail options. Scientific relevance: Thirst is considered the primary driver of water intake and main defense against body water deficit in healthy young adults (IOM, 2005). Health authorities set total water intake recommendations for the average healthy man and woman (e.g. 2.5 L/d for men and 2.0 L/d for women in Europe) but, additionally, advise people to use thirst as a guide for water intake, recognizing that individual water requirements vary widely (EFSA, 2010; IOM, 2005). Although thirst can be satiated by water intake, it can also be ignored per custom (Greenleaf, 1992) or suppressed by an upward-shifted thirst threshold. The thirst threshold, the set-point where osmoreceptor cells shrink and release their neural or hormonal signal, is a function of the solute concentration or osmolality inside and outside the osmoreceptor cells (Nose et al, 1988a,b). Cells with higher intracellular solute content require a higher external osmolality to shrink. Specific Aims The ultimate goal of this study is to address gaps in the literature about drinking water and check assumptions that limit the development of drinking water-specific recommendations. The study will examine if osmoadaptation to chronic hypertonicity, due to daily intake of hypertonic fluid sources, can explain suppressed thirst in healthy individuals under conditions of daily life. To facilitate causal inference about drinking water effects for long-term health, this study was designed to link experimental data about osmoadaptation at the cellular level with clinical data relevant for conditions of daily life in Salzburg Austria with population-based data about water intake and chronic disease risk in Salzburg Austria. This study will test effects of drinking enough plain water to dilute urine everyday for 4 weeks (about 500 mL 4 times per day in summer). The study will include healthy, normal weight, young, men and women, who all usually meet European adequate intake recommendations for total water intake (TWI), but usually consume less than 1L/d PWI, and have biomarkers of chronic hypertonic stress (concentrated urine and saliva) for 4 consecutive weeks before starting the randomized study.