High-Fat Diets May Harm Liver More Than High-Carb Diets, Mouse Study Finds - Video

In recent years, carbohydrates have often been blamed for weight gain and poor health. However, a new study from researchers at Penn State suggests that diets high in fat — including the popular ketogenic (keto) diet — may cause greater harm, at least in mice.

The study, published in the Journal of Nutrition, examined how different ratios of fats and carbohydrates affect metabolic health and liver function over 16 weeks. Mice were fed one of four diets: high-carbohydrate, high-fat, ketogenic (very high fat and almost no carbs), or a standard whole-grain-rich chow used as a control diet.

All mice consumed similar amounts of calories, and protein levels were kept consistent. The main difference was the balance between fats and carbohydrates.

Researchers found that mice on the high-fat and keto diets gained significant weight — nearly doubling their body weight over the study period. These mice also developed impaired glucose tolerance, higher blood sugar levels, liver damage, fat buildup in the liver, and increased inflammation. Harmful changes were seen as early as two weeks into the diets. Mice on the keto diet also showed elevated triglycerides, a risk factor for heart disease.

In contrast, mice on the high-carbohydrate diet did not show the same level of weight gain or liver damage. The healthiest outcomes were observed in mice that ate the standard whole-grain-rich chow diet.

In a separate experiment involving mice that were already obese, adding fiber to the keto diet helped reduce some harmful effects without interfering with ketosis. This suggests fiber may offer protective benefits in certain situations.

While researchers caution that mice and humans have different metabolisms, the findings highlight potential risks of very high-fat diets. Experts emphasize that balanced, whole-grain-based diets remain the safest and most beneficial approach for long-term metabolic health.

REFERENCE: Umesh K Goand, Devendra Paudel, Anthony M Koehle, et al.; Invited: Longitudinal Assessment of Diets with Varying Carbohydrate-to-Fat Ratios and Fiber Supplementation on Immunometabolic Markers, Liver Function, and Gut Microbiome; The Journal of Nutrition; https://doi.org/10.1016/j.tjnut.2025.101285