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Keto Diet May Accelerate Organ Aging

A long-term ketogenic diet may induce aged cells in normal tissues, particularly affecting heart and kidney function, a new study in mice suggests.

A ketogenic (keto) diet has boomed in popularity in recent years due to its potential benefits for weight loss and diabetes. An estimated 13 million Americans eat keto diets, where most of the calories come from fat.

However, the diet has been criticized for its restrictive nature and side effects ranging from constipation to elevated risk of heart disease.

A new study led by researchers at The University of Texas Health Science Center at San Antonio and published in Science Advances reveals that accelerated aging may be another side effect of a ketogenic diet when it is followed long-term.

In the study, six mice of different ages were fed either a control diet, with most calories coming from carbohydrates, or a keto diet, with over 90% of caloric intake coming from fat. The primary fat source in the ketogenic diet was hydrogenated vegetable shortening Crisco.

The keto diet induced cellular senescence (aging) in multiple organs, including the heart and kidney, regardless of the mice's age. These findings contradict previous studies suggesting that the age at which one undergoes a keto diet plays a role in determining its effects.

To ensure that a ketogenic diet, not a specific ingredient, caused cell aging, the researchers repeated the experiment, replacing Crisco with cocoa butter.

After 21 days, mice fed on ketogenic diets did not experience a significant change in insulin sensitivity but saw increased triglycerides and cholesterol levels, raising the risk of heart disease.

A senolytic, a class of small molecules that can destroy senescent cells, eliminated the cellular aging caused by a long-term keto diet and prevented it by administering an intermittent ketogenic diet regimen.

"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. As with other nutrient interventions, you need to 'take a keto break,'" said David Gius, M.D., Ph.D., assistant dean of research and professor with the Department of Radiation Oncology in the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio.

It is noteworthy that the trial was conducted in mice, meaning that the findings may not necessarily apply to humans. Moreover, previous research on animals has suggested that the keto diet may extend longevity and health span.

Keto diet, food on blue background. Selective focus.
Image by Milena Khosroshvili via Shutterstock

Is the keto diet good for you?

In the typical keto diet, about 70-80% of calories come from fat, 20-25% from protein, and 5-10% from carbohydrates. Sources of healthy fat in the keto diet include avocados, nuts, seeds, oily fish, olives, and cuts of fresh meat, especially white meat.

The goal of the diet is to induce ketosis, a process when the body doesn't have enough carbohydrates to burn for energy and burns fat instead.

The potential benefits of a keto diet include weight loss, often up to 10 pounds in 2 weeks, and improved gut microbiome. Some studies have associated the diet with a lower risk of heart disease due to LDL cholesterol and inflammation levels, lower blood pressure, and improved glucose control.

There is evidence suggesting that the keto diet may improve metabolic and ovulatory dysfunction in women with polycystic ovary syndrome. Moreover, the diet may improve the management of neurodegenerative disorders like Alzheimer's or Parkinson's disease.

However, the evidence of the keto diet's benefits and risks is inconclusive, and it may have some serious side effects.

Two to seven days after initiation of the diet, people may experience the so-called "keto flu," characterized by nausea, vomiting, headache, fatigue, dizziness, and constipation, among other mild symptoms.

Following the diet long-term may cause a deficiency of essential vitamins, minerals, and phytochemicals. As this eating pattern lacks fiber, people may experience digestive issues like constipation, bloating, and diarrhea.

Additionally, some studies have associated the ketogenic diet with a higher risk of kidney stones, heart disease, and cognitive decline. The diet leads to rapid weight loss and can cause muscle loss.

The ketogenic diet is not suitable for individuals with pancreatitis, liver failure, and disorders of fat metabolism. Patients with diabetes taking insulin or oral hypoglycemic agents are at risk of experiencing severe hypoglycemia if their medications are not appropriately adjusted before initiating the diet.

The authors of a new study emphasize that the ketogenic diet is not necessarily harmful but recommend taking "keto breaks" while following this eating pattern.


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