Long-term Keto Diet May Damage Our Organs

Ketogenic Diet and Its Effects

In recent years, so-called ketogenic diets have become increasingly popular. A diet with very low carbohydrate content forces the body to tap into fat stores. Liver cells produce ketone bodies, which serve as an alternative energy source. On this diet, typically 70–80% of energy intake comes from fats, and only 5–10% from carbohydrates. For comparison, in a "normal" diet, about half of the energy intake comes from carbohydrates.

The keto diet first emerged approximately 100 years ago at the Mayo Clinic in the United States as a therapeutic regimen for childhood epilepsy. Ketogenic nutrition proved to be an effective treatment for refractory epilepsy. It likely also has beneficial effects in cancer or neurodegenerative diseases.

Controversial Mouse Data

In studies conducted on mouse models, anti-inflammatory effects, extended lifespan, and positive impacts on neurological and metabolic processes and obesity were observed. On the other hand, some studies noted a pro-inflammatory effect, increased risk of cardiac fibrosis, and kidney damage.

Scientists from the University of Texas in San Antonio did not initially intend to study the negative effects of the keto diet. They were interested in how this eating regimen affects the protein p53, a powerful tumor suppressor.

Cellular Aging and Protein p53

One of the roles of protein p53 is ensuring cellular senescence, which halts the division of worn-out cells before they start causing problems. Senescent cells are subsequently removed by the immune system. However, if their removal does not occur, issues arise. For example, when stem cells enter senescence, tissue repair capabilities can become impaired. Moreover, senescent cells secrete pro-inflammatory agents.

Effects of the Keto Diet

The research team encountered the connection between the keto diet and senescence during experiments with a “super keto diet,” where mice received 90% of their daily energy intake in the form of plant fat, while the control group consumed only 17% fats. After 7 or 21 days on this diet, scientists examined tissue samples from the mice’s hearts, kidneys, livers, and brains.

An increase in the number of senescent cells was observed in several organs, including the heart and brain. Levels of protein p53 in animals on the keto diet significantly increased, as did the levels of other molecular markers of senescence. After a 3-week break from the ketogenic diet, the levels of senescent cells almost returned to normal.

The researchers therefore examined the effect of an intermittent keto diet, where mice were fed a high-fat diet for 4 days and then fed regular food for 7 days. After three cycles of this regimen, no accumulation of senescent cells was observed in the mice’s organs.

Does It Harm or Help?

The results of this study confirm that the effects of the keto diet are complex. It may have both potential benefits and possible side effects, depending on many variables, including timing and the exact composition of the diet. The health status of the individual, their genetic factors, and endocrine parameters also play a role. Ketogenic nutrition should therefore always be considered in the context of the individual patient.

“Given that cellular senescence contributes to the pathology of organ diseases, our findings have important clinical significance. As with other nutritional interventions, it is probably necessary to take a keto break,” summarizes lead researcher David Gius.

Editorial Team, Medscope.pro

Sources:

1. Wei S. J., Schell J. R., Chocron E. S. et al. Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Sci Adv 2024 May 17; 10 (20): eado1463, doi: 10.1126/sciadv.ado1463.

2. Lee S. A long-term ketogenic diet accumulates aged cells in normal tissues, a UT Health San Antonio-led study shows. The University of Texas Health Science Center at San Antonio, 2024 May 17. Available at: https://news.uthscsa.edu/a-long-term-ketogenic-diet-accumulates-aged-cells-in-normal-tissues-a-ut-health-san-antonio-led-study-shows

3. Leslie M. Keto diet may cause organ damage, mouse study finds. News from Science, 2024 May 17. Available at: www.science.org/content/article/keto-diet-may-cause-organ-damage-mouse-study-finds