Keto Diet May Age Organs

A ketogenic diet increases the number of aged and damaged cells in mice, particularly in the rodents’ hearts and kidneys, a new study suggests. These abnormalities could raise the risk of heart disease and cancer, according to the researchers behind the study.

Given their findings, the researchers have encouraged humans following the ketogenic diet to take intermittent breaks.

The results were published in Science Advances.

Keto costs

Millions around the world use the ketogenic diet to help lose weight and regulate health conditions.

The regimen excludes common high-carbohydrate foods like bread, pasta and cereals and promotes high-fat foods like cheese. In the world of medicine, it is sometimes recommended for people with epilepsy, as brain neurons fueled by ketones (a by-product of fat) appear to misfire less than neurons fueled by glucose (a by-product of carbohydrates).

But over a long period of time, adherence to the diet can lead to complications such as kidney stones and, according to the new study, accelerated tissue aging.

Researchers at the University of Texas Health Science Center at San Antonio put mice of different ages (16, 24 and 52 weeks old) on a ketogenic diet for 3 weeks.

The caloric content of the mice’s keto-pellets consisted of 90.5% calories from fat, 9.2% from protein and 0.3% from carbohydrates. The mice fed on the control diet consumed 17% of their calories from fat, 25% from protein and 58% from carbohydrates.

After the rodents were euthanized, the researchers studied tissue samples taken from their hearts, kidneys, livers and brains. Notable levels of cellular senescence were observed in the samples taken from mice fed the ketogenic diet.

Prolonged cellular senescence, however, can be detrimental and actually contribute to cancer development and age-related diseases.

By injecting the mice with different enzyme inhibitors, the researchers determined that this cellular senescence process is mediated through the enzyme adenosine monophosphate–activated protein kinase (AMPK) and the inactivation of the protein mouse double minute 2 (MDM2) by the enzyme caspase-2, leading to accumulation of the protein p53.

The researchers were able to reverse this increase in p53, however, by returning the mice to their regular diet for a week.

The team therefore posit that humans living off the ketogenic diet could also benefit from intermittent breaks in their routine.

“To put this in perspective, 13 million Americans use a ketogenic diet, and we are saying that you need to take breaks from this diet or there could be long-term consequences,” said David Gius, an assistant dean of research and professor at UT Health San Antonio’s Department of Radiation Oncology.

“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 added. “As with other nutrient interventions, you need to ‘take a keto break.’”

This article is a rework of a press release issued by UT Health San Antonio. Material has been edited for length and content.

Reference: Wei SJ, Schell JR, Chocron ES, et al. Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Sci Adv. 2024. doi:10.1126/sciadv.ado1463