Recruiting

Ketone Ester

Sponsor:

Indiana University

Code:

NCT06868719

Conditions

Salt; Excess

Hypertension

Aging

Inflammation

Blood Pressure

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Accepted

Interventions

No Salt, No β-OHB

High Salt, No β-OHB

High Salt, High β-OHB

Study Details

Brief summary:

Most Americans consume excess dietary salt based on the recommendations set by the American Heart Association and Dietary Guidelines for Americans. High dietary salt impairs blood pressure control by affecting systemic blood vessels and the kidneys. These changes contribute to excess salt consumption being associated with increased risk for chronic kidney disease and cardiovascular disease, the leading cause of death in America. Salt is particularly deleterious in older adults who are more likely to exhibit salt-sensitive hypertension. However, salt consumption remains high in the United States. Thus, there is a critical need for strategies to counteract the effects of high dietary salt as consumption is likely not going to decrease. One promising option is ketones, metabolites that are produced in the liver during prolonged exercise and very low-calorie diets. While exercise and low-calorie diets are beneficial, not many people engage in these activities. Limited evidence indicates that ketone supplements improve cardiovascular health in humans. Additionally, published rodent data indicates that ketone supplements prevent high salt-induced increases in blood pressure, blood vessel dysfunction, and kidney injury. Our human pilot data also indicates that high dietary salt reduces intrinsic ketone production, but it is unclear whether ketone supplementation confers humans' protection against high salt similar to rodents. Therefore, the investigators seek to conduct a short-term high-dietary salt study to determine whether ketone supplementation prevents high dietary salt from eliciting increased blood pressure, blood vessel dysfunction, and kidney injury/impaired blood flow. The investigators will also measure inflammatory markers in blood samples and isolate immune cells that control inflammation. Lastly, the investigators will also measure blood ketone concentration and other circulating metabolites that may be altered by high salt, which could facilitate novel therapeutic targets to combat high salt.

Conditions

Salt; Excess

Hypertension

Aging

Inflammation

Blood Pressure

Study ID

NCT06868719

Start date

Mar 6, 2025

Status verified date

Aug, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Between the ages of 60-85
  • Resting blood pressure no higher than 150/90
  • BMI below 35 kg/m2 (or otherwise healthy)
  • Free of any metabolic disease (diabetes or renal), pulmonary disorders (COPD, severe asthma, or cystic fibrosis), cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular)
  • Do not have any precluding medical conditions that prevent participants from exercising (i.e., cardiovascular issues, or muscle/joint issues including painful arthritis) or giving blood (e.g., blood thinners)

Exclusion Criteria:

  • High blood pressure - greater than150/90 mmHg
  • Obesity (BMI > 30 kg/m2)
  • History of metabolic disease (diabetes or renal disease), pulmonary disorders (e.g., COPD, severe asthma, \& cystic fibrosis), and cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular).
  • Medical issues that prevent safe exercise (i.e., cardiovascular issues, or muscle/joint issues including painful arthritis)
  • Medical issues that prevent giving blood (e.g., blood thinners).
  • Current smoking, using smokeless tobacco, or vaping (within past 12 months)
  • Current pregnancy

Study Design

Enrollment

35 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

active comparator: Placebo/Placebo, then Salt/Placebo, then Salt/Ketone

Participants will consume each of the supplemental interventions for 10 days (in this assigned order). On Day 10 of each interventional condition, participants will arrive at the laboratory where the investigators will assess resting blood pressure, arterial stiffness, endothelial function, renal blood flow, and submaximal exercise blood pressure reactivity. Blood will be collected to investigate inflammatory and immune responses to the dietary conditions. After a washout period, participants will consume the next assigned supplemental intervention for 10 days, and repeat the Day 10 assessments. After another washout period, participants will consume the final assigned supplemental intervention for 10 days, and again repeat the Day 10 assessments.

active comparator: Salt/Placebo, then Salt/Ketone, then Placebo/Placebo

Participants will consume each of the supplemental interventions for 10 days (in this assigned order). On day 10 of each interventional condition, participants will arrive at the laboratory where the investigators will assess resting blood pressure, arterial stiffness, endothelial function, renal blood flow, and submaximal exercise blood pressure reactivity. Blood will be collected to investigate inflammatory and immune responses to the dietary conditions. After a washout period, participants will consume the next assigned supplemental intervention for 10 days, and repeat the Day 10 assessments. After another washout period, participants will consume the final assigned supplemental intervention for 10 days, and again repeat the Day 10 assessments.

active comparator: Salt/Ketone, then Placebo/Placebo, then Salt/Placebo

Participants will consume each of the supplemental interventions for 10 days (in this assigned order). On day 10 of each interventional condition, participants will arrive at the laboratory where the investigators will assess resting blood pressure, arterial stiffness, endothelial function, renal blood flow, and submaximal exercise blood pressure reactivity. Blood will be collected to investigate inflammatory and immune responses to the dietary conditions. After a washout period, participants will consume the next assigned supplemental intervention for 10 days, and repeat the Day 10 assessments. After another washout period, participants will consume the final assigned supplemental intervention for 10 days, and again repeat the Day 10 assessments.

Interventions

No Salt, No β-OHB

Participants will consume the following for ten days. Enteric capsules will be filled with a dextrose placebo. The placebo supplement will be a β-OHB-free, taste and viscosity-matched, beverage produced by KetoneAid.

High Salt, No β-OHB

Participants will consume the following for ten days. Enteric capsules will be filled with Morton's table salt. Sodium consumption will be normalized to caloric intake (2 mg Sodium/Calorie). The placebo supplement will be a β-OHB-free, taste and viscosity-matched, beverage produced by KetoneAid.

High Salt, High β-OHB

Participants will consume the following for ten days. Enteric capsules will be filled with Morton's table salt. Sodium consumption will be normalized to caloric intake (2 mg Sodium/Calorie). Ketone beverage will be the β-OHB supplement produced by KetoneAid. Participants will consume 24 mL (12 grams β-OHB) of the ketone beverage three times a day (total 36 grams β-OHB).

Primary outcome measure

  • Resting blood pressure [ Time Frame: This measure is completed on day 10 of each 10-day intervention (low salt, high salt, high salt+ ketone) over 3-4 months and values will be compared across interventions. ]
  • Blood pressure reactivity responses [ Time Frame: This measure is completed on day 10 of each 10-day intervention (low salt, high salt, high salt + ketone) over 3-4 months and values will be compared across interventions. ]

Central Contacts and Locations

Central contacts

Austin T Robinson, PhD

5745141034ausrobin@iu.edu

Kallie E Dawkins, MS

8505566251kaldawki@iu.edu

Locations

School of Public Health

Recruiting

Bloomington, Indiana, United States, 47405

Contacts

Austin T Robinson, PhD

574-514-1034ausrobin@iu.edu

More Information

Sponsor

Indiana University

Last update posted

Aug 19, 2026

Last verified

Aug, 2026

Keywords

  • Blood Pressure
  • Salt
  • Aging
  • Inflammation
  • Cardiovascular Disease

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Indiana University on 2026-08-19.