Long-term ketogenic diet accumulates old cells in normal tissues

A strict “keto-friendly” diet, popular for weight loss and diabetes management, may not be so harmless depending on the diet itself and the individual’s individual characteristics.

A new study conducted by scientists at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) found that long-term adherence to the ketogenic diet may cause senescence, or cellular aging, in normal tissues, with particularly pronounced effects on cardiac and renal function. However, an intermittent ketogenic diet, with scheduled breaks, did not show the pro-inflammatory effects caused by senescent cells, according to the study.

The findings have significant clinical implications, suggesting that the beneficial effects of the ketogenic diet may be enhanced by scheduled breaks.

"To put this into perspective, 13 million Americans are on the ketogenic diet, and we say you need to take breaks from this diet or there may be long-term consequences," said David Gius.

Jius is the lead author of a new study entitled "Ketogenic diet induces p53-dependent cellular senescence in multiple organs," published in Science Advances.

The study's authors also represent the Department of Radiation Oncology and the Mays Cancer Center, as well as the Institute for Longevity and Aging. Sam and Anne Barshop, Center for Precision Medicine, School of Nursing and Division of Nephrology, Department of Medicine at UT Health San Antonio; and Houston Methodist Cancer Center and Research Institute.

Too Much of a Good Thing The ketogenic diet, popularly known as the keto-friendly diet, is a high-fat, low-carb diet that results in the formation of ketones, a type of chemical the liver produces when it breaks down fats. While the ketogenic diet improves certain health conditions and is popular for weight loss, pro-inflammatory effects have also been documented.

Two Different Ketogenic Diets Cause Cellular Senescence. Source: Science Advances (2024). DOI: 10.1126/sciadv.ado1463

A new study shows that mice on two different ketogenic diets and at different ages develop cellular senescence in multiple organs, including the heart and kidneys. However, this cellular senescence was reversed by senolytics, or a class of small molecules that can kill senescent cells, and prevented by the introduction of an intermittent ketogenic diet regimen.

"Because cellular senescence has been implicated in the pathology of organ diseases, our findings have important clinical implications for understanding the use of the ketogenic diet," Gius said. "As with other nutritional interventions, you need to take a 'keto break.'"