Ketogenic diets, high in fats and almost without carbohydrates, have become very popular in recent years. Keto diets are used for weight loss and treating various diseases. When we consume a few carbohydrates, the liver produces ketones, an alternative energy source. Research has shown that keto diets are effective in treating epilepsy and can also help with cancer and neurodegenerative diseases. Experiments on mice have shown that ketogenic diets reduce inflammation and can improve health with age. However, there is also data indicating that low-carb diets can cause inflammation and increase the risk of cardiac fibrosis and kidney damage.
The effects of the ketogenic diet depend on factors such as a person’s age and diet duration. Studies on mice have shown that the ketogenic diet improved memory and muscle condition in middle-aged mice but caused developmental disorders in young mice. Children with epilepsy who adhered to the keto diet continuously for more than 6 years had an increased risk of kidney stones, bone fractures, and growth disorders.
Scientists from the Institute for Research on Aging (USA) found that the ketogenic diet can accumulate aging cells in various organs. This effect was observed in mice that followed two different ketogenic diets with varying ratios of fatty acids for 21 days. Regardless of age and fatty acid ratio, mice on the keto diet had increased levels of cell aging markers, which was associated with the risk of organ diseases.
A human study showed that following a ketogenic diet for six months also increases aging markers. However, breaks in the keto diet may help avoid the accumulation of aging cells.
The Keto Diet Contributes to Heart, Kidney, Liver, and Brain Cell Aging
For the experiment, mice were divided into two groups:
- One group received a regular diet with a standard content of fats, proteins, and carbohydrates;
- The other group received a keto diet, where 90% of calories came from fats, 9% from proteins, and only 0.3% from carbohydrates.
The effects of different diets were assessed after 7 and 21 days.
The keto diet caused a significant increase in aging markers in heart, kidney, liver, and brain cells. These changes were independent of the mice’s age. Additionally, mice on the keto diet showed decreased glucose tolerance, although insulin sensitivity remained unchanged. Blood tests revealed increased free fatty acids, triglycerides, low-density lipoproteins, and high-density lipoproteins.
Keto Diet Increases p53 Protein Level, Implicated in Cellular Aging
The p53 protein plays a pivotal role in cellular stress response, including growth arrest, DNA repair, apoptosis, and cellular aging. The ketogenic diet significantly elevated p53 levels in all examined tissues: heart, kidneys, liver, and brain at 7 and 21 days. Besides p53, the keto diet raised the level of the p21 protein, which is also associated with cellular aging, but did not alter the level of p16. p53 interacts with p21, initiating cellular aging during the keto diet.
Prolonged Keto Diet Promotes Inflammation
Aging cells can negatively impact surrounding tissues by releasing pro-inflammatory cytokines. An experiment on mice showed that after 21 days of the ketogenic diet, serum levels of pro-inflammatory cytokines TNFα, IL-1β, IL-6, and the aging marker CCL5 significantly increased.
Similar increases in pro-inflammatory cytokine levels were observed in humans after 6 months of the keto diet. Both men and women experienced significant increases in TNFα and IL-1β levels, with women also showing elevated IL-6 levels.
These data confirm that prolonged keto diets contribute to cellular aging in humans. The cause of cellular aging lies in the elevation of lipids or lipoproteins, not ketones, and is not associated with reduced protein intake. The effect was independent of the type of fat in the diet and age.
Cellular Aging Depends on Keto Diet Duration and Reversibility
The ketogenic diet minimally increased aging markers after 4 days compared to 7 and 21 days.
Do aging cells disappear after discontinuing the keto diet? To answer this question, scientists experimented: mice were kept on a ketogenic diet for 7 days and then switched to a regular diet for 1, 2, or 3 weeks. Aging markers began to decline after just one week of returning to a regular diet and continued to decrease to control levels within 2-3 weeks. These results indicate that cellular aging induced by the keto diet may be reversible upon returning to a regular diet.
Breaks in the Keto Diet Prevent Cellular Aging
Aging cells may disappear after discontinuing the ketogenic diet, leading scientists to seek methods that either improve the removal of aging cells or prevent their accumulation during the keto diet.
The senolytic Navitoclax effectively removed aging cells. Mice were given this drug at 50 mg/kg per day for seven days after completing a 21-day keto diet. Navitoclax successfully eliminated most aging cells, confirming the reduction of aging markers.
Breaks in the keto diet prevented cellular aging. Intermittent keto dieting daily improved cardiac function in mice with heart failure, while weekly intervals reduced mortality in middle-aged males, age-related memory loss, and other health issues in male mice. Alternating 4-day and 7-day keto diets over three cycles did not increase p53 levels or cellular aging markers.
Conclusion
The effect of the ketogenic diet depends on its duration. Prolonged keto diets may exacerbate inflammation and contribute to the aging of the heart, kidneys, liver, and brain. However, short-term keto diets improve metabolism.
Breaks in the keto diet prevent the accumulation of aging cells. Intermittent keto dieting has fewer side effects than continuous dieting but still positively impacts health.
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Reference
Ketogenic diet induces p53-dependent cellular senescence in multiple organs