BREAKING: Keto diets can cause premature ageing of the organs

The ketogenic diet, commonly known as the keto diet, has gained immense popularity due to its efficacy in rapid weight loss. Originally developed as a treatment for epilepsy, the diet involves a high intake of fats and a significant reduction in carbohydrates. While many people achieve their desired weight loss outcomes through this diet, recent research suggests that the long-term effects may not be as beneficial as previously thought. In particular, a study by researchers from the University of Texas Health San Antonio-USA has shed light on the potential for the keto diet to accelerate the ageing of vital organs such as the heart and kidneys.

Understanding the keto diet

The keto diet primarily focuses on a macronutrient distribution that heavily favours fats, with a typical intake comprising 55 to 60% of calories from fats, 30 to 35% from protein, and a mere 5 to 10% from carbohydrates. This starkly contrasts with the FDA’s recommendations, which advise limiting saturated fats and maintaining a higher carbohydrate intake. The dramatic shift in macronutrient consumption forces the body into a state of ketosis, where it burns fat for energy instead of carbohydrates. While this metabolic state can lead to significant weight loss, it also prompts several physiological changes that may not be entirely benign.

In ketosis, the liver converts fat into ketones, which become the primary energy source for the body. This process mimics starvation, which can be beneficial for short-term weight loss. However, long-term adherence to the keto diet raises concerns about its impact on overall health. The diet’s high-fat content, particularly saturated fats from sources like butter, beef, and pork, can increase the risk of heart disease if not carefully managed. Moreover, the reduced carbohydrate intake can lead to nutrient deficiencies, particularly in fibre, vitamins, and minerals essential for health.

Research findings: Accelerated cellular ageing

The study conducted on mice provided critical insights into how the keto diet impacts cellular ageing. The researchers divided the mice into two groups: a control group with a standard diet and a test group fed a high-fat, low-carbohydrate diet similar to the keto diet. The test group’s diet mainly consisted of Crisco, a fat source with 84% unsaturated fat and 14% saturated fat. The results were alarming. Mice on the keto diet exhibited higher rates of cellular ageing in their major organs, particularly the heart and kidneys. This was evidenced by an accumulation of senescent cells, which are damaged cells that no longer divide but do not die off, leading to inflammation and potential organ damage.

Senescence is a natural part of ageing, but its acceleration can result in premature organ failure and increase the risk of chronic diseases. The researchers noted that this cellular ageing was linked to proteins such as AMPK and p53. Blocking these pathways in the mice halted the accelerated ageing process, suggesting potential avenues for mitigating the diet’s adverse effects.

Specifically, the study found that mice on the keto diet had increased levels of senescent cells in their heart, liver, and kidneys. These cells, characterised by the presence of senescence-associated β-galactosidase (SA-β-gal), are markers of cellular ageing. The buildup of these cells can lead to chronic inflammation, which is a known risk factor for various diseases, including cancer and cardiovascular disease.

Further investigation revealed that the keto diet’s high-fat content, particularly saturated fats, played a significant role in inducing cellular senescence. When researchers tested a different high-fat diet using cocoa butter, which has a higher saturated fat content than Crisco, they observed similar results. This suggests that the type of fat consumed on the keto diet can influence the extent of cellular ageing.

Mechanisms of cellular ageing on the keto diet

The researchers delved deeper into the mechanisms behind the observed cellular ageing. They discovered that the process was likely tied to the activation of specific proteins, such as AMPK and p53. AMPK, or adenosine monophosphate-activated protein kinase, is an enzyme that plays a crucial role in cellular energy homeostasis. It is activated in response to low energy levels, such as those induced by a keto diet.

The study showed that the activation of AMPK, combined with the inactivation of MDM2 (mouse double minute 2 homolog) by caspase-2, led to the accumulation of p53, a protein that regulates the cell cycle and promotes cellular senescence. When the researchers blocked the pathways of these proteins, the mice did not exhibit the same levels of cellular senescence, suggesting that targeting these pathways could mitigate the adverse effects of the keto diet.

Moreover, the study explored whether the process of cellular senescence was reversible. By switching the mice from a keto diet back to a standard diet, researchers found that the markers of cellular ageing decreased over time. This finding indicates that the negative effects of the keto diet may be managed by intermittent dieting or through pharmacological interventions that target the proteins involved in cellular ageing.

Broader implications and human relevance

The implications of these findings extend beyond mice. Although the study was conducted on animal models, the potential for similar effects in humans cannot be ignored. Medical experts like Scott Keatley, a registered dietician, emphasise the need for long-term studies in humans to understand fully the keto diet’s impact on cellular ageing. These studies should span years rather than weeks or months to capture the diet’s long-term consequences accurately.

The accelerated ageing observed in the study raises significant concerns, especially for individuals with pre-existing health conditions or those at risk of chronic diseases. The keto diet’s popularity among these groups, driven by its short-term benefits, might inadvertently expose them to severe long-term health risks.

For example, individuals with kidney disease or a predisposition to cardiovascular issues may find that the high-fat content of the keto diet exacerbates their conditions. The increased levels of low-density lipoproteins (LDL) observed in the study highlight a potential risk factor for heart disease. Additionally, the diet’s low carbohydrate intake can impact glucose metabolism and insulin sensitivity, potentially leading to complications for people with diabetes.

Managing the risks

While the findings highlight potential dangers, they also offer insights into managing these risks. The research indicated that the negative effects of the keto diet could be mitigated through intermittent dieting or medications that block specific proteins involved in cellular ageing. For instance, an intermittent keto diet (IKD), where individuals alternate between keto and regular diets, showed promise in preventing cellular senescence. This approach could help people enjoy the benefits of the keto diet without the associated long-term risks.

Moreover, senolytic drugs that target and eliminate senescent cells could play a role in managing the side effects of a sustained keto diet. These drugs could potentially clear the buildup of damaged cells, reducing inflammation and preventing organ damage. One such senolytic, navitoclax (ABT-263), has shown effectiveness in removing senescent cells induced by the keto diet in mice. Administering this drug post-diet helped clear most of the senescent cells, suggesting a potential therapeutic strategy for managing the adverse effects of the keto diet.

The research continues

The keto diet’s popularity as a weight loss solution is undeniable, but its long-term effects on health require careful consideration. The recent study from UTHealth San Antonio underscores the need for a balanced approach to dieting, especially when it involves significant changes to macronutrient intake. For individuals considering or currently following a keto diet, it is crucial to do so under medical supervision and be aware of the potential risks.

As research continues to unfold, it is becoming increasingly clear that the keto diet’s impact on cellular ageing and organ health is complex and multifaceted. While it offers short-term benefits, the long-term implications highlight the importance of personalised dietary plans that consider an individual’s unique health profile and needs. The future of dieting may lie in finding a balance that maximises benefits while minimizing risks, ensuring that weight loss does not come at the expense of overall health

In light of these findings, it is essential for healthcare providers to consider both the short-term and long-term effects of the keto diet when advising patients. Personalised nutrition, which takes into account individual health conditions, genetic factors, and lifestyle, may be the key to optimizing the benefits of the keto diet while mitigating its risks. Additionally, further research in humans is necessary to confirm these findings and develop effective strategies for managing the diet’s potential adverse effects.

By understanding the complex interactions between diet, cellular ageing, and overall health, we can better navigate the benefits and risks of the keto diet, ensuring that it remains a safe and effective tool for weight management and disease prevention.

The study findings were recently published in this peer-reviewed journal.