Prolonged adherence to a ketogenic diet, which is based on high fat intake and minimal carbohydrates, can lead to serious health issues. This conclusion was reached by scientists who observed laboratory mice that were fed exclusively a ketogenic diet for a year.

Ketogenic Diet: History and Effects

The ketogenic diet was originally developed as a treatment for epilepsy. It suppresses appetite, helps reduce body weight, and lowers blood sugar levels. These effects are attributed both to calorie restriction and to the specific action of ketone bodies produced in the liver. Despite its proven effectiveness for epilepsy, the long-term safety of the ketogenic diet for managing type 2 diabetes and obesity remains uncertain.

The Experiment: Long-Term Consequences

To investigate the long-term effects of the ketogenic diet, a research team led by Molly R. Gallop from the University of Utah (USA) conducted an experiment on rodents. For a year, the mice were fed a diet consisting of 90% fat and almost no carbohydrates. As expected, at the beginning of the experiment, the animals’ body weight increased more slowly and even decreased. However, by the end of the study, the rodents developed fatty liver disease (accumulation of fat in liver cells), pronounced hyperlipidemia (elevated levels of triglycerides, free fatty acids, and cholesterol), and glucose intolerance, especially in males.

Changes in Metabolism and Organ Function

Within just a few weeks, mice on a strict ketogenic diet showed significant changes in lipid metabolism: their blood levels of triglycerides and free fatty acids were twice as high as those of animals on other diets. Male mice developed fatty liver and signs of inflammation. While females were more resistant to liver damage, both sexes eventually experienced impaired pancreatic function.

Although short-term adherence to the ketogenic diet helped control blood glucose levels, after several months the situation changed. During stress tests, the animals’ blood sugar spiked sharply: by week 33, male mice had blood glucose levels reaching 539 mg/dl—significantly higher than those on a standard “high-fat” diet. Despite maintaining insulin sensitivity, the beta cells of the pancreas stopped releasing the hormone in a timely manner.

Causes of the Disorders

Under an electron microscope, scientists discovered that the normal “packaging” and release of insulin granules was disrupted by an enlarged Golgi apparatus—a membrane structure in the cell responsible for transporting synthesized substances. As a result, insulin was secreted with delays and in insufficient amounts, leading to severe glucose intolerance.

Conclusions and Recommendations

Since 12 months represent a significant portion of a rodent’s lifespan, the observed processes are characteristic of older animals. In humans, similar effects might only appear after decades.

Therefore, long-term use of the ketogenic diet for the prevention of metabolic disorders should be approached with caution. Although the results of the study, published in the journal Science Advances, do not mean that the ketogenic diet is equally harmful for everyone, its long-term impact on health may be associated with the risk of developing serious problems.