Daily ketone ester drink to lower liver fat and improve metabolism

Effect of Ketone Esters on Liver Fat and Metabolic Function in Adolescents With Obesity and MASLD

This trial tests whether a daily ketone ester drink for 6 weeks can reduce liver fat and improve blood sugar control in 18–25-year-olds with MASLD who are overweight or have obesity.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 25 Years
• Sex: All
• Sponsor: Washington University School of Medicine (Academic / other)
• Locations: 1 site (St Louis, Missouri)
• Trial ID: NCT07097506 on ClinicalTrials.gov

What this trial studies

Young adults with MASLD and BMI 25.0–44.9 will be randomly assigned to drink either a ketone ester beverage or a matched placebo each day for six weeks. Liver fat will be measured by MRI-PDFF before and after the intervention, and metabolic outcomes such as blood glucose and insulin sensitivity will be monitored. Key eligibility criteria include age 18–25, intrahepatic triglyceride content >5%, and exclusion of diabetes (HbA1c ≥6.5%), very-low-carbohydrate diets, or medications that affect study outcomes. The trial tests whether raising circulating ketone levels with an exogenous ketone di-ester produces short-term improvements in hepatic steatosis and related metabolic measures.

Who should consider this trial

Good fit: Ideal candidates are 18–25-year-olds with BMI 25.0–44.9 and MRI-confirmed liver fat >5% who do not have diabetes and are not using medications, supplements, or diets that affect ketone or liver metabolism.

Not a fit: People with diagnosed diabetes (HbA1c ≥6.5%), current very-low-carbohydrate diets, active eating disorders, recent significant gastrointestinal symptoms, or excessive alcohol or tobacco use are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could offer a short-term, non-dietary way to reduce liver fat and improve blood sugar control in young adults with MASLD.

How similar studies have performed: Animal models and some human studies of exogenous ketones have shown improvements in glucose control and hepatic steatosis with ketogenic diets, but direct evidence that ketone esters reduce liver fat in young adults is limited.

Eligibility criteria

Inclusion Criteria:

* Age: ≥18 and ≤25 years;
* BMI 25.0 - 44.9 kg/m2;
* Intrahepatic triglyceride content \>5% assessed by using magnetic resonance imaging-proton density fat fraction (MRI-PDFF).

Exclusion Criteria:

* HbA1C ≥6.5%;
* taking dietary supplements or medications known to affect our study outcomes including corticosteroids and other drugs associated with steatosis (metformin use will be allowable if participants have taken a stable dose for at least 3 months without any gastrointestinal-related symptoms);
* active eating disorder, any anaphylactic food allergy and/or consuming a very-low-carbohydrate (\<50 g/day) diet;
* Fibroscan controlled attenuation parameter (CAP) score \<240 dB/m assessed within last 2 months before entering the study;
* recent (\<2 months) history of moderate-severe nausea, vomiting, diarrhea, or other significant gastrointestinal symptoms;
* consume tobacco products, excessive alcohol (females: \>14 drinks/week; males: \>21 drinks/week), or illegal drugs determined by medical history;
* evidence of significant active organ system dysfunction, liver disease other than MASLD (e.g., Wilson disease, viral hepatitis, inborn errors of metabolism, or alpha-1 antitrypsin deficiency) or cirrhosis as a results of any condition or disease;
* have had bariatric surgery or plan to have endoscopic or bariatric surgery therapy for obesity;
* have undergone organ transplantation;
* have HIV and any other type of congenital or acquired lipodystrophy;
* unwilling or unable to provide informed consent;
* major psychiatric illness;
* metal implants that are not MRI-compatible;
* pregnancy, as determined by a urine HCG screening test assessed performed at all screening, baseline testing, and follow-up visits. In addition, male and female participants of reproductive and childbearing age who wish to enroll will be required to agree to use contraception throughout the study period, and for 30 days after the last dose of C8 ketone di-ester;
* female participants who are currently lactating;
* Structured exercise: ≥75 min/wk of vigorous exercise (e.g., jogging, activity that causes heavy breathing and sweating) or ≥200 min/wk of low intensity physical activity (e.g., brisk walking);
* Unstable weight (\>3% change during the last 2 months before entering the study);
* Anemia (hemoglobin \<10.5 g/dL in females and \<11.0 g/dL in males);
* Unable or unwilling to follow the study protocol or who, for any reason, is considered an inappropriate candidate for the study by the research team.

Where this trial is running

St Louis, Missouri

• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)

Study contacts

• Principal investigator: Samuel Klein, MD — Washington University School of Medicine
• Study coordinator: Nikki Plassmeyer, RDN, LD

Conditions MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; Obesity; Overweight