A new clinical trial published in the peer-reviewed journal Cell Metabolism indicates that a very low-carbohydrate, high-fat ketogenic diet provides stronger metabolic and liver health benefits for people with obesity than either a Mediterranean diet or a low-fat diet. Researchers at Washington University School of Medicine enrolled participants with obesity, prediabetes, and fatty liver disease to evaluate whether different macronutrient makeups alter cardiometabolic risks beyond weight loss alone.
Clinical Trial Compares Three Diets for Obesity and Liver Health
Obesity affects approximately four in 10 Americans, and many face associated risks such as insulin resistance, prediabetes, and fat buildup in the liver. Left untreated, these conditions can progress to Type 2 diabetes, chronic liver disease, and cardiovascular events. While weight loss remains a standard approach for reducing these health risks, the relative efficacy of specific diets has remained unclear.
Dietary Study Design and Macronutrient Distribution
To compare the effects of different nutritional approaches, the research team randomly assigned participants to follow one of three eating plans: a ketogenic diet, a Mediterranean diet, or a low-fat, plant-forward diet. The research team supplied all food, and participants met with a dietitian weekly to maintain adherence. Calorie intake was adjusted so that participants across all groups lost about 10% of their body weight, a target that took roughly four to five months to reach.
The diets featured distinct macronutrient breakdowns:
- Ketogenic Diet: Supplied 4% of calories from carbohydrates and 73% from fat, including foods rich in saturated fat and animal products.
- Mediterranean Diet: Emphasized plant-based foods such as vegetables, olive oil, and nuts, along with moderate amounts of fish and dairy, with 50% of calories from carbohydrates and 35% from fat.
- Plant-Forward Diet: Provided 70% of calories from carbohydrates and 15% from fat.
By the end of the intervention, participants in all three groups significantly reduced body fat and boosted insulin sensitivity in muscle cells by roughly 50% from baseline, demonstrating that weight loss itself improved muscle insulin sensitivity regardless of the specific combination of fat and carbohydrates.
Ketogenic Diet Delivers Greater Reductions in Liver Fat
Despite equivalent weight loss across all groups, the ketogenic diet produced the strongest changes in measures of liver and metabolic health. Liver fat fell by an average of 67% among individuals following the keto diet, compared with an average reduction of 45% in both the Mediterranean and plant-forward groups.
Researchers tracking participant metabolism over a 24-hour period observed that individuals in the ketogenic group showed the largest rise in glucagon, a hormone that helps reduce fat stored in the liver. They also experienced the greatest decline in blood insulin levels. Max C. Petersen, an assistant professor of medicine at WashU Medicine and the study’s first author, noted that participants following the ketogenic diet did not experience an increase in blood fat or cholesterol levels despite consuming the highest amount of fat.
Prediabetes Reversal and Broader Implications
The intervention also affected prediabetes status differently across the groups. After the weight loss period, about 50% of participants following the ketogenic diet no longer met the criteria for prediabetes. By comparison, prediabetes was resolved in 29% of participants on the Mediterranean diet and 7% of those on the plant-forward diet.
While GLP-1-based medications have provided effective pharmacotherapy for weight loss, researchers emphasize that dietary composition offers targeted benefits for specific health outcomes beyond weight loss alone. The research was supported by the National Institutes of Health and the Foundation for Barnes-Jewish Hospital.
