Adequate Hydration and Health Outcomes

NCT ID: NCT07179107

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-29
• Study Completion Date: 2028-12-31

Brief Summary

Cardiovascular diseases (CVD) are the leading cause of death in middle- and high-income countries, according to data from the World Health Organization (WHO). Epidemiological studies have associated low water intake and underhydration with diabetes, chronic kidney disease, and an increased risk of CVD. Similarly, the prevalence of chronic metabolic dysfunction is increasing dramatically worldwide, becoming both a significant public health concern and a global economic burden. Reports from the WHO indicate that the number of people with diabetes worldwide has risen from 108 million in 1980 to 422 million in 2014, representing 8.5% of adults. Therefore, there is an urgent need to identify modifiable risk factors that could help prevent metabolic dysfunction and mitigate the epidemic of type 2 diabetes (T2D). Evidence suggests that the hormone arginine vasopressin (AVP) may play a key role. AVP is the primary hormone responsible for regulating body fluid balance; however, increased AVP secretion, such as under conditions of low water intake, appears to be a risk factor for developing diabetes.

Increasing water intake may represent a simple and cost-effective way to improve glucose regulation and cardiovascular health. However, many individuals do not prefer drinking plain water, and although beverages with high sugar content may promote greater fluid intake, they also contribute additional calories that can negatively impact body weight and overall health. Thus, the central research question of this study is whether improving hydration with non-sugar-sweetened beverages can provide equivalent benefits for hydration and health outcomes in adults.

Aim 1: To explore the association between habitual fluid intake and fluid preferences (water and non-sugar-sweetened beverages), hydration biomarkers, and health outcomes in normal-weight and obese adults.

Aim 2: To compare the impact of increased total water intake, provided as plain water or non-sugar-sweetened beverages, on hydration, cardiovascular health, and glucose regulation in normal-weight and obese adults.

Detailed Description

Protocol

Subjects will first come into the lab for a screening visit (approximately 1 hour). In this visit, they will learn more about the study, provide written informed consent (if they choose to participate), fill out a medical history form, have their weight, height, and body composition measured, and have a finger stick blood test to measure glycosylated hemoglobin (HbA1c). Those with A1c values >7% at screening will not be included in the study. We will provide them with information about HbA1c levels that meet the diagnostic criterion for diabetes immediately. Those with A1c values from 6.5 to ≤7% will be provided with information about HbA1c levels that meet the diagnostic criterion for diabetes at the end of the trial. We will suggest they share this information with their doctor. We will answer any questions they may have.

Two groups of 72 volunteers each will be grouped as having normal weight or obesity based on their BMI. The subjects who enroll in the study will undergo an 8-week cross-ver study with two separate arms based on BMI category. Subjects in each BMI category will be evaluated weekly as described below and depicted in Figure 1:

Week 1: Baseline. During this week, the subjects will maintain their habitual fluid intake without any intervention.

Weeks 2-4 & Weeks 6-8: All subjects will follow 3 weeks of consuming only plain water and a 3-week of non-sugar sweetened beverages, in a random order.

Weeks 2 and 6: The subject will consume very-low fluid intake, of 1.2 and 1.5 L/day for females and males, respectively.

Week 3 & week 7: Subjects will consume low fluid intake, of 1.6 and 2.0 L/day for females and males, respectively.

Week 4 & week 8: Subjects will consume adequate fluid intake according to the US dietary guidelines (2.2 and 3.0 L/day L/day for females and males, respectively).

Week 5: Wash-out period, where subjects can return to their habitual fluid and dietary intake.

Fluid intake:

Fluid intake will be controlled by providing drinks and programmable smart water bottles to record fluid intake and provide periodic reminders.

Plain Water:

During the 3 weeks, subjects will be instructed to consume fluids only in the form of plain water (tap, bottle, sparkling), coffee up to 1 cup a day, and alcohol, up to 2 servings per week only during week 5 but not anywhere else during the study.

Non-Sugar-Sweetened beverages:

During the 3-week period, of the NSSB portion of the study 1.0 L of fluids per day will be coming from non-sugar-sweetened beverages, with the rest coming from water.

Procedures:

During this study, beverages will be provided for participants. Programmable smart water bottles will be used to record fluid intake and provide periodic reminders.

Participants will be instructed to keep their diet as usual, without making any changes during the study. The ASA24 will be administered at the end of weeks 1, 2, 3, 4, 5, 6, 7, and 8. The volunteers will be asked to fill out 24-hour recalls (ASA24) three times each one of the weeks 1, 2 and 3. We will collect 2 weekdays and 1 weekend day. ASA24 is an online nutritional assessment tool developed by the NCI.

1 Week before data collection begins: Subjects will visit the lab to place the CGM for baseline data collection, distribute frozen meals, watches, urine containers, and water bottles.

Day Before each Testing:

During the 24 hours prior to each testing day, subjects will be provided with verbal and written instructions on the 24-h urine collection protocol and two 3L urine collection containers, which will include the preservative. They will be asked to collect all their urine beginning with the second void of the day. The first morning urine sample will not be collected; the second void on the day before testing will begin the 24-hour collection. The last urine sample to be collected will be the first morning urine sample of the testing day in a separate container. To measure compliance with the 24-h urine collection protocol, subjects will be asked to complete a 24-h urine collection log. They will record the time when they collect the urine samples, and if they missed any voids. Urine will be analyzed for hydration measures, urine creatinine, and non-nutritive sweeteners. Also participants will have to consume the same dinner before each one of the 8 lab visits, that will be provided in the form of frozen meal from the research team.

TESTING DAYS Each subject will visit the lab once a week for 8 consecutive weeks after at least 10 h of fasting. Upon arrival in the lab, subjects will provide a urine sample measured for hydration biomarkers and their body weight and body composition will be assessed on a bioelectrical impedance scale. We will acess seated blood pressure. Next, participants will fill out cognitive and perceptual questionaires. After this we will access resting metabolic rate, endothelial function by flow mediated dilation (FMD). After the completion of the FMD test, we will proceed to the oral glucose tolerance test (OGTT).

Glycemic Test:

Three separate glycemic tests will be performed depending on the stage of the protocol:

1. Insulin Resistance on Matthews's homeostatic model assessment of insulin resistance (HOMA-IR) is based on fasting glucose and insulin.

2. Oral Glucose Tolerance Test (OGTT). This 120-minute test consists of a fasted blood sample followed by 75 grams of glucose solution ingestion. Four more blood samples will be collected 30, 60, 90, and 120 minutes after the ingestion.

3. Ambulatory 24-hour glucose responses will be assessed via continuous glucose monitor (CGM) during the 7-week intervention. Each CGM lasts for 14 days, thus 4 monitors will be used for each volunteer. The Abbott libre pro will be used to asses interstitial blood glucose every 15 min.

Blood Analysis:

Fasting blood samples will analyzed for :

• Glucose and insulin to assess insulin resistance based on Matthews's homeostatic model assessment of insulin resistance (HOMA-IR).
• Osmolality, sodium, and copeptin for hydration assessment.
• Glucagon and cortisol, since both are stimulated by vasopressin, and impacting glucose regulation.

Blood Samples during the Oral Glucose Tolerance Test (OGTT) will be analyzed:

• Glucose, insulin, glucagon, and cortisol. The primary outcome of the OGTT will be the area under the curve for glucose, insulin, glucagon, and cortisol during the 120-minute test.

Cognitive Data:

A neuropsychological test measuring such aspects of cognition as attention, executive function and memory will be administered to each subject. We will ask participants to complete a cognitive task designed to examine mostly their Executive function (inhibition) abilities, named the Flanker's test. The task will be administered on a laptop computer, lasts 5 minutes and will be given at each visit.

Perceptual Data:

Perceptual data on hunger, cravings, thirst, and mouth dryness will be collected in a pen and paper format.

Mood Assessment:

Mood will be assessed by the validated thirty-five-question Adult Short Profile of Mood States (POMS) questionnaire (POMS 2®-A Short, Multi-Health Systems Inc.). It will be administed on a laptop computer and it lasts 5 min

Sleep Quality Assessment:

This will be assessed via the Pittsburgh Sleep Quality Index. This is a short questionnaire that takes about 2-3 minutes to fill out. The sleep quality assessment will be completed on paper.

Resting Blood pressure:

After the cognitive/ perceptual test, a resting blood pressure in seated position will be taken with and automated blood pressure cuff in duplicate.

Resting Metabolic Rate:

Resting metabolic rate via indirect calorimetry for 30 minutes. This will take place while subjects are resting prior to the flow mediated dilation test.

Flow Mediated Dilation Test:

Endothelium-dependent, FMD of the brachial artery is assessed at baseline (pre-condition) and at the end of each visit (post-condition), at the end of weeks 1, 2, 3, 4, 5, 6, 7, and 8. Measurement procedures are done in accordance with established guidelines and performed by a registered sonographer using B-mode ultrasound (Philips Epic Elite™,Bothell WA). FMD analyses are conducted in a dim, quiet, temperature-controlled environment (22-25 oC) with the participants lying down on an ultrasound bed. Participants will be sized for appropriate blood pressure cuff (Hokanson Instruments, Bellevue, WA) and cuff will be placed around the right arm, 2-3 cm below the elbow/forearm area. Simultaneous ultrasound images (B-mode) and doppler waveforms of the brachial artery are captured for baseline before the blood pressure cuff is inflated to a suprasystolic pressure of 250 mmHg for 5 minutes. After 5 minutes, the cuff will be rapidly deflated, and arterial images will be obtained for 6 minutes post-inflation. Subjects may experience mild discomfort as the cuff is inflated on the upper arm. The images are obtained and analyzed by a trained, blinded researcher using an automated, previously validated FMD software.

Oral Glucose Tolerance Test (OGTT):

Before this test, an indwelling catheter will be placed in an antecubital vein by a trained and experienced phlebotomist using sterile techniques. After a couple of minutes of rest, a baseline blood sample will be taken and the subject will ingest a drink containing 75 g glucose. Four more blocatheterd samples will be taken at 30, 60, 90, and 120 minutes after the drink ingestion. Blood samples will be analyzed for glucose, insulin, glucagon, cortisol, and copeptin. Extra plasma and serum aliquots will be stoford in the deep freezer to -nalysis of other health related biomarkers. The first blood sample will be 15 mL and the remaining four samples will be 10 mL. The total volume for each test will be 55 mL.The total blood volume for all samples during the eight testing sessions will be 440 mL, which is equivalent to a blood donation.

Continuous Glucose Monitor (CGM):

Ambulatory glucose measurements will be obtained using CGM sensors during the entire 8-week period. Since the sensors work for 14 days, a new sensor will be used every two weeks and placed on an alternate arm. The Abbot FreeStyle Libre Pro sensor will be used and it will be applied at the back of the upper arm. A protective round band-aid will also be used to ensure the sensor will not fall off.

Physical Activity:

Physical activity will be assessed via the validated International Physical Activity Questionnaire (IPAQ). This questionnaire will take approximately 2 minutes to complete. Participants will take the questionnaire on paper. The questionnaire will be administered at the end of weeks 1, 2, 3, 4, 5, 6, 7, and 8. IPAQ data will be expressed as a continuous variable of MET-min per week and a three-level categorical variable of physical activity level.

Also, participants will wear a Garmin smart watch that provides heart rate, sleep quality, and time spent on different levels of physical activity. Participants will wear this watch for the entire duration of the intervention. Researchers will provide the watch, and participants will be required to return the watch upon completion of the study.

Conditions

Dehydration; Dehydration (Physiology); Glucose Abnormalities; Cardiovascular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Baseline - week 1

Habitual fluid intake during week 1 of the study

Group Type: OTHER

Baseline - week 1

Intervention Type: OTHER

Habitual fluid intake during week 1

Low Water intake - week 2

Low water intake as described by the protocol

Group Type: EXPERIMENTAL

Low Water Intake - week 2

Intervention Type: OTHER

Low water intake as described by the protocol

Moderate water intake - week 3

Moderate water intake as described by the protocol

Group Type: EXPERIMENTAL

Moderate Water Intake - week 3

Intervention Type: OTHER

Moderate Water Intake - Week 3

Adequate Water intake - Week 4

Adequate water intake as described by the protocol

Group Type: EXPERIMENTAL

Adequate Water Intake - week 4

Intervention Type: OTHER

Adequate Water Intake - week 4

Washout period - week 5

Habitual fluid intake week

Group Type: OTHER

Washout - week 5

Intervention Type: OTHER

Washout - week 5

Low fluid intake with non caloric sweeteners - Week 6

Low fluid intake with non-caloric sweeteners - Week 6

Group Type: EXPERIMENTAL

Low fluid intake with non caloric sweeteners - Week 6

Intervention Type: OTHER

Low fluid intake with non caloric sweeteners - Week 6

Moderate fluid intake with non caloric sweeteners - Week 7

Moderate fluid intake with non caloric sweeteners - Week 7

Group Type: EXPERIMENTAL

Moderate fluid intake with non caloric sweeteners - Week 7

Intervention Type: OTHER

Moderate fluid intake with non caloric sweeteners - Week 7

Adequate fluid intake with non caloric sweeteners - Week 8

Adequate fluid intake with non caloric sweeteners - Week 8

Group Type: EXPERIMENTAL

Adequate fluid intake with non caloric sweeteners - Week 8

Intervention Type: OTHER

Adequate fluid intake with non caloric sweeteners - Week 8

Interventions

Baseline - week 1

Habitual fluid intake during week 1

Intervention Type: OTHER

Low Water Intake - week 2

Low water intake as described by the protocol

Intervention Type: OTHER

Moderate Water Intake - week 3

Moderate Water Intake - Week 3

Intervention Type: OTHER

Adequate Water Intake - week 4

Adequate Water Intake - week 4

Intervention Type: OTHER

Washout - week 5

Washout - week 5

Intervention Type: OTHER

Low fluid intake with non caloric sweeteners - Week 6

Low fluid intake with non caloric sweeteners - Week 6

Intervention Type: OTHER

Moderate fluid intake with non caloric sweeteners - Week 7

Moderate fluid intake with non caloric sweeteners - Week 7

Intervention Type: OTHER

Adequate fluid intake with non caloric sweeteners - Week 8

Adequate fluid intake with non caloric sweeteners - Week 8

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• BMI 18.5-24.9 or 30.0-39.9 kg/m2
• HbA1c ≤7%
• Age 20-65 y
• available for 8 consecutive weeks same day and time

Exclusion Criteria

• Diabetes
• HbA1c >7% BMI ≤18.5, BMI of 25 to <30, or ≥ 40 kg/m2
• night shifting work
• losing or gaining weight during the last 2 months (>5 lbs. fluctuation)
• thyroid medication
• bariatric surgery
• Habitual strenuous exercise (>120 min/week) Strenuous exercise is defined as activities that take hard physical effort and make you breathe much harder than normal.
• Construction and other workers that spend signifant portion of their work day outdoors
• Commuting by bicycle
• Eating disorders
• Use of aspirin during the duration of the study
• Cancer
• Renal disease (including kidney stones or recurrent urinary track infections
• Hepatic disease
• Cardiac conditions
• Current infection requiring medication
• Chronic, contagious, infectious diseases such as tuberculosis, Hepatitis A, B, C, or HIV
• Medication that could affect appetite or body weight regulation
• GLP1-RA medication
• Anti-depressent SSRI medication
• Testosterone replacement therapy
• Participating in another study at the same time
• Unable to abstain from alcohol during the study
• Unable to limit caffeinated beverage intake to 1 cup per day
• Donated blood during the past two months
• Uneasibly acessable veins
• Does not have smart phone

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Arizona State University

OTHER

Sponsor Role: lead

Responsible Party

Stavros Kavouras

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

850 PBC

Phoenix, Arizona, United States

Site Status: RECRUITING

850 Phoenix Bioscience Core

Phoenix, Arizona, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Holly Emmanuel

Role: CONTACT

hydrate.study@gmail.com

602-935-7138

Facility Contacts

Holly Emmanuel, MA

Role: primary

hydrate.study@gmail.com

602-935-7138

Veronica Martinez, MBA

Role: primary

veronica.m.martinez@asu.edu

480-487-7734

Other Identifiers

FP00043890

Identifier Type: -

Identifier Source: org_study_id