A randomized clinical trial published August 27, 2026, in Cell Metabolism reveals that a ketogenic diet reduced liver fat by 67% in adults with obesity, prediabetes, and fatty liver disease, outperforming Mediterranean and low-fat diets despite participants achieving identical 10% weight loss across all three plans.
Weight loss is frequently prescribed as a cure-all for metabolic disease, but a clinical trial led by WashU Medicine researchers suggests that the specific composition of a diet plays a critical role independent of shedding pounds. While shedding roughly 10% of body weight improved muscle insulin sensitivity across the board, carbohydrate restriction delivered uniquely potent benefits for the liver and blood sugar control.
Washington University Clinical Trial Design and Participant Demographics
To isolate the effects of dietary macronutrients from simple weight loss, researchers at Washington University School of Medicine in St. Louis, Missouri, enrolled adults with metabolically unhealthy obesity. The trial initially randomized 55 participants who faced prediabetes and fatty liver disease. Ultimately, 42 participants completed the intervention, boasting an average age of roughly 43 and an average starting body mass index of about 39.
The study protocol removed adherence variables by supplying 100% of the food and snacks consumed during the trial. Participants met weekly with a study dietitian, logging their intake through a secure app with reported adherence exceeding 95% across every dietary group. Calorie intake was adjusted individually so participants in all three arms reached the targeted 10% weight loss threshold, which took approximately four to five months depending on the regimen.
Contrasting Macronutrient Splits Across the Three Diet Groups
The trial compared three popular eating plans with sharply differing ratios of carbohydrates, fats, and proteins. The very-low-carbohydrate ketogenic diet restricted carbohydrates to just 4% of total calories, devoting 73% of energy to fat and 23% to protein. By contrast, the Mediterranean diet derived 50% of its calories from carbohydrates, 35% from fat, and 15% from protein. The very-low-fat, plant-forward diet skewed even higher in carbohydrates, sourcing 70% of energy from carbs, 15% from fat, and 15% from protein.
| Dietary Plan | Carbohydrate Share | Fat Share | Protein Share |
|---|---|---|---|
| Ketogenic Diet | 4% | 73% | 23% |
| Mediterranean Diet | 50% | 35% | 15% |
| Plant-Forward Low-Fat | 70% | 15% | 15% |
Dramatic Reductions in Liver Fat and Prediabetes Criteria
While all three diets successfully reduced body fat and boosted whole-body muscle insulin sensitivity by roughly 50%—proving that weight loss alone repairs muscle metabolism—the liver responded differently. Intrahepatic triglyceride content fell by an average of 67% among participants following the ketogenic diet. Participants on the Mediterranean and plant-forward low-fat diets saw an average liver fat reduction of 45%.
Blood sugar control followed a similar divergence. After completing the weight-loss intervention, approximately half of the participants in the keto group no longer met diagnostic criteria for prediabetes. That outcome contrasted sharply with the Mediterranean group, where 29% cleared the threshold, and the low-fat plant-forward group, where only 7% did so.
“Our data suggest that if you have high liver fat content and prediabetes, reducing carbohydrate intake can have important therapeutic effects on metabolism beyond just weight loss alone.”
Samuel Klein, Danforth Professor of Medicine and Nutritional Science at WashU Medicine
Hormonal Shifts and Implications for Metabolic Disease
Participants on the ketogenic diet showed the largest drop in circulating insulin and blood glucose alongside a distinct rise in glucagon, a hormone that encourages the breakdown and clearance of stored liver fat. These hormonal shifts suppressed the liver’s internal production of new fat.