Study finds long-term ketogenic diet accumulates aged cells in tissues

A recent study led by researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has revealed potential drawbacks of adhering to a continuous, long-term ketogenic diet. The research indicates that such a diet may induce cellular senescence, or aging cells, in normal tissues, which particularly affects heart and kidney functions. However, integrating planned breaks from the ketogenic regimen can help mitigate these adverse effects.

The ketogenic diet, often adopted for weight loss and diabetes management, involves a high-fat, low-carbohydrate intake that leads the liver to produce ketones by breaking down fats. While this diet has shown benefits for certain health conditions, it also has been associated with pro-inflammatory outcomes.

The UT Health San Antonio study highlights that continuous, long-term adherence to a ketogenic diet can lead to the accumulation of aged cells in multiple organs, including the heart and kidneys. These findings suggest that aging cells contribute to inflammation and potential organ dysfunction over time. Conversely, an intermittent ketogenic diet, which includes planned breaks or "keto vacations," did not exhibit the same pro-inflammatory effects.

David Gius, MD, PhD, assistant dean of research and professor in the Department of Radiation Oncology at UT Health San Antonio, and associate cancer director for translational research at the institution's Mays Cancer Center, emphasized the importance of these findings for the millions of Americans who follow a ketogenic diet. Gius, the lead author of the study titled "Ketogenic diet induces p53-dependent cellular senescence in multiple organs," published in the journal Science Advances, noted that planned breaks from the diet are crucial to avoid long-term negative consequences.

The research team included members from various departments at UT Health San Antonio, as well as collaborators from the Houston Methodist Cancer Center and Houston Methodist Research Institute. They conducted experiments on mice subjected to different ketogenic diet regimens and at varying ages. The results revealed that continuous ketogenic diets induced cellular senescence in multiple organs, but these effects could be counteracted by senolytics—molecules that target and destroy aged cells—and prevented by an intermittent ketogenic diet schedule.

"As cellular senescence has been implicated in the pathology of organ disease, our results have important clinical implications for understanding the use of a ketogenic diet," Gius stated. He pointed out that the key to harnessing the benefits of a ketogenic diet while minimizing its risks lies in taking regular breaks from the regimen.

The study's findings are particularly relevant given the popularity of the ketogenic diet, with approximately 13 million Americans currently following this dietary approach. The research underscores the necessity for these individuals to consider intermittent dietary patterns to prevent potential long-term health issues associated with continuous ketogenic dieting.

In conclusion, while the ketogenic diet can offer significant health benefits, it is essential to approach it with caution. Continuous, long-term adherence to the diet can lead to the development of aged cells in vital organs, contributing to inflammation and possible dysfunction. However, incorporating planned breaks into the diet can help mitigate these adverse effects and enhance the overall benefits, making the ketogenic diet a safer and more effective long-term dietary strategy.