Effects of Habitual Water Intake on Thirst in Healthy Young Adults Explained by Osmoadaptive Metabolism, Brain and Kidney Function (Adapt-Thirst)

NCT07464002 | Not Yet Recruiting

• 1 other identifier: PMU-EK-2025-0043
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Chronic Underhydration; Thirst; Due to Deprivation of Water; Aestivation Metabolism; Warburg Effect; Osmoadaptation; Dysglycemia; Protein Breakdown; Brain Function; Healthy

Keywords

Randomized clinical trial; Drinking water; Metabolomics; Zinc isotope; Amino acid tracing (13C,15N-glycine); Deuterium elimination; Oura ring

Outcome Measures

Primary Outcomes (1)

• Increase in thirst rating after overnight food and water restriction

  Thirst rating on a visual analog scale ranging from 0 to 100 is expected to be significantly higher in Week 9, by +10 or more (out of 100) units, compared to a baseline rating below 70 (ensured by screening criteria). Participants will be asked to rate their thirst at the same time in the morning, each week, after food and water restriction at the weekly in-person study site visit.

  For each study participant, change in thirst rating will be calculated as rating in Week 9 minus rating in Week 4. The mean absolute change in ratings and % of participants who increase ratings >70 will be described for intervention and control groups.

Secondary Outcomes (4)

• Change in serum, urine, saliva metabolomic profile

  Week 4 vs. Week 9

• Change in brain functional MRI (fMRI)

  Week 10 compared to Week 5.

• Change in zinc excretion

  Week 9 vs. Week 4

• Change in total body protein breakdown

  Week 9 vs. Week 4

Study Arms (2)

Control

NO INTERVENTION

After completing 4 weeks of baseline data collection and random assignment in week 5, the control group will continue to maintain their same usual conditions for the remainder of the study.

Intervention

EXPERIMENTAL

After completing 4 weeks of baseline data collection and random assignment in week 5, the intervention group will be instructed to increase intake of drinking water everyday in weeks 6-9 by a volume adequate to dilute urine specific gravity below 1.013 everyday, approximately 500 mL 4x/day.

Other: Drinking water to dilute urine

Interventions

Drinking water to dilute urine OTHER

After Weeks 1-4 baseline data collection, people randomized in Week 5 will be instructed to increase drinking water to approx. 4 times 500 mL/d in Weeks 6-9 to reach a volume that is enough to dilute urine specific gravity below 1.013 everyday. The PWI exposure is approx. 20 mL/kg PWI for men, 25 mL/kg PWI for women. Addition of PWI to the diet may increase TWI and minimally displace some other beverage intake. Based on Adapt Study data, the hypo-osmotic share of TWI is expected to increase from below 50% to 50% or higher. The intervention dose is also aligned with observational data from the Paracelsus 10000 study in Salzburg, which found that healthy adults who met hydration criteria reported at least 1L/d PWI. The intervention will be communicated to participants in terms of L/d instead of mL/kg, because L/d are easier to translate into portion size and drinking behavior.

Intervention

Eligibility Criteria

• Age: 19 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• weeks of 3-day mean total water intake of 35 ml/kg body weight
• weeks of \<1L/d drinking water
• weeks of \<1 hr/d moderate or vigorous physical activity given daily life conditions in Salzburg, Austria
• No history of chronic disease
• Normal blood pressure,
• Normal blood chemistry and complete blood count (CBC) test results
• Normal overnight urine concentration, and normal acute urine dilution after 500mL drinking water
• Normal weight and height between 160-170 cm for women and 175-185 cm for men)
• After overnight food and water restriction urine osmolality above 800 mmol/kg, salivary osmolality above 100 mmol/kg, and a thirst score below 70 mm on a 100 mm visual analog scale.

You may not qualify if:

• Individuals will be excluded from participation if the gender-specific target numbers have already been reached
• Perceived stress score of \> 20 at any time during Weeks 1-4
• Schedule that does not allow continuous study participation
• Intention to spend more than a day outside the Salzburg area during the study period (to reduce exposure to ground water with different background D2O as potential source of error)
• Headache within the last six months
• Pregnant, planning a pregnancy, or irregular or unknown menstrual cycle
• Active use of tobacco or e-cigarettes
• Daily consumption of alcohol
• Regular use of medication
• Agoraphobia or claustrophobia that would prevent brain fMRI testing
• Metal-containing intrauterine device (IUD) that would prevent fMRI testing
• Doubtful or unwilling to complete all study procedures (including drinking alcohol; drinking plain tap water, blood tests, 24-hour urine collection, fMRI scans, and stable isotope tests)
• Unwilling to be randomly assigned to intervention or control
• Incomplete baseline data in Weeks 1-4 (including blood tests, 24-hour urine collection, and MRI scans).

Sponsors & Collaborators

• Jodi Stookey: lead
• Paracelsus Medical University: collaborator
• University of Salzburg: collaborator
• University of California, Davis: collaborator

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Study Officials

• Jodi D Stookey, PhD

  Water and Hydration Translational Epidemiological Research, LLC

  PRINCIPAL INVESTIGATOR

• Markus Ritter

  Paracelsus Medical University

  PRINCIPAL INVESTIGATOR

• Hubert Kerschbaum, PhD

  Paris Lodron University of Salzburg

  PRINCIPAL INVESTIGATOR

• Andrew Hall, PhD

  University of California, Davis

  STUDY DIRECTOR

Central Study Contacts

Jodi D Stookey, PhD

CONTACT

1-415-312-0237; jodidstookey@gmail.com

Markus Ritter, MD

CONTACT

43-662-2420-80500; markus.ritter@pmu.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Individuals processing diet and activity data and lab samples.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Founder and sole proprietor of Water and Hydration Translational Epidemiological Research, LLC

Model Details: Sex-stratified 2-arm parallel group randomized controlled trial with 4-week baseline period and brain fMRI scans before randomization and 5 week follow-up period after randomization

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 11, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share