Effect of Ketone Esters on Liver Fat Content and Metabolic Function

Prior treatment

• 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);
• Fibroscan controlled attenuation parameter (CAP) score \<240 dB/m assessed within last 2 months before entering the study;
• consume tobacco products, excessive alcohol (females: \>14 drinks/week; males: \>21 drinks/week), or illegal drugs determined by medical history;
• have had bariatric surgery or plan to have endoscopic or bariatric surgery therapy for obesity;
• have undergone organ transplantation;
• metal implants that are not MRI-compatible;
• Unstable weight (\>3% change during the last 2 months before entering the study);

Other illness

• active eating disorder, any anaphylactic food allergy and/or consuming a very-low-carbohydrate (\<50 g/day) diet;
• recent (\<2 months) history of moderate-severe nausea, vomiting, diarrhea, or other significant gastrointestinal symptoms;
• 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 HIV and any other type of congenital or acquired lipodystrophy;
• major psychiatric illness;

Lab values

• HbA1C ≥6.5%;
• Anemia (hemoglobin \<10.5 g/dL in females and \<11.0 g/dL in males);

Age

• 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;

Other

• unwilling or unable to provide informed consent;
• 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);
• 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.

• Age: ≥18 and ≤40 years;
• BMI 25.0 - 49.9 kg/m2;
• Intrahepatic triglyceride content \>5% assessed by using magnetic resonance imaging-proton density fat fraction (MRI-PDFF).