Ketogenic Diet Offers Liver Benefits Beyond Weight Loss Alone

A randomized clinical trial comparing 3 popular weight-loss diets found that although all 3 improved metabolic health in adults with obesity, prediabetes, and hepatic steatosis, a very-low-carbohydrate ketogenic diet produced greater improvements in liver fat, hepatic insulin sensitivity, and glycemic control than a Mediterranean or very-low-fat plant-forward diet, even when weight loss was matched across groups.^1,2

The findings, published August 27, 2026, in Cell Metabolism, come from investigators at Washington University School of Medicine in St. Louis who set out to determine whether diet macronutrient composition affects cardiometabolic outcomes independent of weight loss itself.²

“For patients with obesity, prediabetes and fatty liver disease, weight loss induced by a very low-carbohydrate diet provides additional therapeutic effects on glucose and lipid metabolism that should further help prevent the progression to more severe metabolic diseases than weight loss alone,” said Samuel Klein, MD, the study’s senior author.¹

What the Trial Compared and Found in Liver and Glycemic Outcomes

Investigators randomly assigned 55 adults with metabolically unhealthy obesity—defined as obesity accompanied by prediabetes and hepatic steatosis—to a ketogenic, Mediterranean, or plant-forward diet for approximately 5 months.^1,2 All food was provided to participants throughout the study, and participants met weekly with a dietitian; dietary adherence exceeded 95% in all 3 groups.2 Forty-two participants completed testing before and after approximately 10% weight loss, which did not differ significantly among the 3 diet groups.²

Skeletal muscle insulin sensitivity increased by roughly 50% after weight loss regardless of diet assignment, indicating that weight loss itself, rather than macronutrient composition, drove this outcome.^1,2 Hepatic insulin sensitivity told a different story: the increase was 2- to 3-fold greater in the ketogenic diet group than in the other 2 groups.2 Intrahepatic triglyceride content fell by 67% with the ketogenic diet compared with 45% in both the Mediterranean and plant-forward groups.^1,2

Glycemic measures followed a similar pattern. Twenty-four-hour plasma glucose concentrations decreased by 20% in the ketogenic group versus 8% in the other 2 groups, and 24-hour insulin concentrations fell by 74% with the ketogenic diet compared with 44% and 27% with the Mediterranean and plant-forward diets, respectively.^1,2 Half of participants in the ketogenic group had remission of prediabetes, compared with 29% in the Mediterranean group and 7% in the plant-forward group.^1,2

Clinical Context for Metabolic Dysfunction–Associated Steatotic Liver Disease

Hepatic steatosis, now classified as metabolic dysfunction–associated steatotic liver disease (MASLD), affects a large proportion of adults with obesity and is a recognized risk factor for progression to type 2 diabetes and cardiovascular disease.^1,2 Weight loss remains the standard approach for improving obesity-related metabolic risk, but the trial authors noted that prior diet studies have been limited by inconsistent adherence and unequal weight loss across comparison groups, making it difficult to isolate the effect of macronutrient composition itself.² By providing all study food and matching weight loss across arms, the investigators aimed to isolate diet-specific effects from those attributable to weight loss alone.²

No serious adverse events were reported in any diet group during the trial.2 The ketogenic diet was not associated with adverse changes in LDL cholesterol, apolipoprotein B, or 24-hour plasma triglyceride concentrations relative to the other diets, despite its higher saturated fat content.²

Unanswered Questions

The investigators said future work will explore the mechanisms underlying the metabolic benefits of weight loss, including in combination with GLP-1 receptor agonist therapy.¹

References

1. Wegorzewska M. Low-carb diet delivers added liver benefits beyond weight loss. WashU Medicine. August 27, 2026.

2. Petersen MC, Smith GI, Farabi SS, et al. Effect of diet macronutrient content on the cardiometabolic response to weight loss: a randomized clinical trial. Cell Metab. Published online August 27, 2026. doi:10.1016/j.cmet.2026.07.020