Ketogenic Diet, Alternated Weekly With a Normal Diet, Can Increase Healthspan and Memory

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The ketogenic diet has been making waves in both the general population and the scientific community in recent years, thanks to its potential benefits for various aspects of health. This dietary approach, commonly called the keto diet, has gained popularity primarily for its association with weight loss and the potential prevention of chronic diseases.

However, the diet also faces its fair share of controversy, with critics arguing that increasing fat intake and losing body weight can be achieved simultaneously, casting doubt on the validity of the ketogenic diet as a sustainable and evidence-based eating pattern.

Amidst the ongoing debate, it becomes crucial to delve into the latest research surrounding the keto diet and its impact on health to separate fact from fiction. This article provides a comprehensive review of the current scientific knowledge on the ketogenic diet, addressing its pros and cons and shedding light on its possible health outcomes.

The article primarily refers to the 2017 Cell Metabolism publication by John C. Newman et al.: Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.


Cyclic Ketogenic Diet Reduces Midlife Mortality and Preserves Memory in Mice

Ketogenic Diet: Definition, Mechanisms, and Benefits

What Is a Ketogenic Diet?

A ketogenic diet is a dietary approach that focuses on triggering a metabolic state called ketosis. In this state, the body shifts from using glucose (derived from carbohydrates) as its primary energy source to burning fat for fuel.

A high-fat, low-carbohydrate, and moderate-protein intake characterizes the keto diet. The macronutrient composition of a keto diet consists of 70% fat, 10% carbohydrates, and 20% protein. As a result, the body is prompted to enter ketosis by significantly reducing carbohydrate intake, leading to a shift in metabolic processes.


How Does Ketogenic Diet Work?

The low carbohydrate intake in a ketogenic diet restricts the availability of glucose, the preferred energy source for the body. As a result, the body starts breaking down stored fats into molecules called ketones through ketogenesis.

Ketones, such as beta-hydroxybutyrate (BHB), serve as an alternative fuel source for various tissues, including the brain. This metabolic adaptation allows the body to utilize stored fat for energy production, leading to weight loss and other health benefits.

The controversy is, does increasing fat intake in the ketogenic diet (70%) increase body fat before causing the body to burn stored fat as energy?

No, increasing fat intake does not inherently lead to increased body fat. Instead, on a well-formulated ketogenic diet, implemented every other week and not continuously, high fat intake provides satiety, promotes stable blood sugar levels, and helps sustain energy levels. At the same time, the body efficiently burns stored fat for fuel.


Ketogenic Diet Benefits


  • Weight loss: The ketogenic diet has been associated with significant weight loss, primarily due to increased fat-burning and reduced appetite.
  • Improved insulin sensitivity: By limiting carbohydrate intake, the ketogenic diet can help stabilize blood sugar levels and improve insulin sensitivity, benefiting people with diabetes or metabolic syndrome.
  • Enhanced mental clarity and focus: Ketones are an efficient energy source for the brain, which may result in improved cognitive function and mental clarity.
  • Reduced inflammation: Some research suggests that the ketogenic diet may reduce inflammation in the body, which is associated with various chronic diseases.
  • Potential seizure control: The ketogenic diet has been a therapeutic approach for reducing seizures in individuals with epilepsy, particularly children.
  • Potential cardiovascular benefits: A ketogenic diet may improve cardiovascular factors, such as triglyceride levels, blood pressure, and cholesterol.
  • Potential benefits for neurological conditions: The ketogenic diet is under investigation for its potential benefits in various conditions such as Alzheimer’s disease, Parkinson’s disease, and neuronal injury.


Ketogenic Diet: Why Alternate-week and Not Continuous

The Continuous Ketogenic Diet Is Obesogenic

Research by John C. Newman et al. has shed light on the obesogenic effects of a continuous ketogenic diet and, in turn, discovered the most optimal pattern.

Their study involving mice showed that mice fed a ketogenic diet continuously from 12 to 36 months of age experienced a significant increase in body weight, reaching up to 70% higher compared to those fed a standard diet before reaching the 24-month mark.

While these continuously ketogenic diet-fed mice eventually reduced their weight to a greater extent than their counterparts on a standard diet before reaching the end of their lifespan at 36 months, they exhibited a greater tendency towards obesity during midlife.


Body weight in lifespan study. Source: Cell Metabolism.
Body weight in lifespan study. Source: Cell Metabolism.


The Continuous Ketogenic Diet Affects Healthspan


The study highlighted that mice continuously fed a ketogenic diet displayed a slightly shorter lifespan. Survival rate analysis also revealed a notable decline in health span, with the most significant drop occurring before the mice reached three-quarters of their maximum age.

These findings suggest prolonged adherence to a ketogenic diet may adversely affect overall health and longevity.

Survival rate trajectories between continuous ketogenic diet and control. Source: Cell Metabolism.
Survival rate trajectories between continuous ketogenic diet and control. Source: Cell Metabolism.


The Cyclic Ketogenic Diet: A Non-obesogenic Diet

In contrast to the continuous ketogenic diet, a cyclic ketogenic diet offers distinct advantages, alternating between periods of ketogenic and standard diet.

Mice following a cyclic ketogenic diet maintained similar health characteristics to those on a standard diet, including body weight and lifespan. Moreover, this diet demonstrated additional benefits, such as improved metabolic flexibility and cognitive function.

Notably, the cyclic ketogenic diet was non-obesogenic, as it allowed sufficient time for metabolic adaptation and prevented the development of obesity in the mice.


Ketogenic Diet Improves Midlife Survival But Not Lifespan

The research findings by John C. Newman et al. suggest that a cyclic ketogenic diet (Cyclic KD; 10% protein and 90% fat; fat content: 24% saturated, 39% monounsaturated, and 37% polyunsaturated) improves midlife survival. However, it does not extend the overall lifespan compared to a control (10% protein, 13% fat, and 77% carbohydrates) diet.

Mice on Cyclic KD showed similar body weight to the control group, while mice on a cyclic high-fat diet (Cyclic HF; 10% protein, 75% fat, 15% carbohydrates) were slightly heavier.

Caloric intake was higher during KD or HF diet weeks and lower during control diet weeks for both groups. Cyclic KD and Cyclic HF reduced early mortality and modestly increased median lifespan compared to the control group.

However, there was no difference in maximum lifespan, and the overall survival curves were not significantly different. Cyclic KD had a pattern of reduced early mortality compared to HF, similar to Cyclic KD versus the control group.

Necropsy data showed that the causes of earlier deaths were not distinct from later deaths, with lower tumor prevalence in the Cyclic KD group. These findings suggest that cyclic KD positively impacts midlife survival, but its effects on lifespan are less pronounced.

Survival rate trajectories between cyclic ketogenic diet and control. Source: Cell Metabolism.
Survival rate trajectories between cyclic ketogenic diet and control. Source: Cell Metabolism.


Ketogenic Diet Preserves Memory and Physical Performance


When assessing the impact on aging, a composite score compiled from multiple health span tests showed that Cyclic KD modestly ameliorated the age-related decline in overall performance, with improvements observed across various parameters.

Specifically, Cyclic KD positively affects memory and physical performance, preserving cognitive function with aging. Mice in the Cyclic KD group showed improved memory compared to the control group in the place avoidance and object recognition tests.

They also demonstrated better physical performance, as indicated by the maximum velocity achieved during the place avoidance test. However, there were fewer differences in physical function and spontaneous activity, with only slight improvements in the Cyclic KD group.

Anxiety-related behaviors were not affected by the diet. However, the Cyclic KD group maintained a more youthful cardiac phenotype, as seen in the composite cardiac score incorporating various cardiac parameters.

These findings suggest that the Cyclic KD diet benefits memory, physical performance, and overall healthspan, contributing to improved aging outcomes.

Effect of Cyclic KD on memory and other healthspan measures with aging. Source: Cell Metabolism.
Effect of Cyclic KD on memory and other healthspan measures with aging. Source: Cell Metabolism.


Ketogenic Diet Activates Fasting-like Gene Expression

The study suggests that the altered gene expression in the liver of the Cyclic KD-fed mice may contribute to the health benefits observed in the regimen. Cyclic KD increased protein acetylation and activated a fasting-like gene expression pattern, similar to during fasting. Also, key genes involved in lipid synthesis were repressed by Cyclic KD.

Also, RNA sequencing was performed to investigate the transcriptional changes. The results showed that KD and HF shared similarities in downregulating specific genes related to glucose metabolism, insulin, and fatty acid synthesis.

However, Cyclic KD exhibited unique upregulation of genes associated with fatty acid oxidation, mitochondrial proteins, and activation of PPARα, a key transcription factor involved in metabolic regulation. Also, this pattern was consistent across various tissues.

The long-term effects of KD were even examined in older mice, and it was observed that the fasting-like gene expression pattern, particularly the upregulation of PPARα target genes and genes involved in fatty acid oxidation, persisted into old age.


Bottom Line: Ketogenic Diet Pros and Cons for Longevity

The findings by John C. Newman et al. emphasize the importance of considering the duration and pattern of ketogenic diet consumption, as continuous adherence may lead to weight fluctuations and potential adverse health outcomes.

On the other hand, the cyclic approach presents a promising alternative that warrants further exploration to understand its applicability and potential benefits in humans.



The ketogenic diet stands out among other dietary patterns due to its remarkable potential for rapid weight loss. Research has demonstrated that individuals following ketogenic diets can lose about 2.2 kg more weight than those on low-fat diets after one year, with the peak of weight loss occurring at around five months.

In addition to its efficacy in weight management, the ketogenic diet offers other notable advantages. For example, the low carbohydrate intake in this diet can improve insulin sensitivity, making it beneficial for individuals with insulin resistance or type 2 diabetes.

Moreover, the high-fat content of the ketogenic diet promotes enhanced satiety, reducing appetite and fostering feelings of fullness, ultimately resulting in lower calorie intake compared to other dietary approaches.



  • Initial adaptation phase: Switching to a ketogenic diet can cause initial side effects such as fatigue, brain fog, and gastrointestinal issues as the body adapts to using ketones as its primary fuel source.
  • Nutrient deficiencies: The restrictive nature of the diet may lead to deficiencies in specific nutrients, including fiber, vitamins, and minerals, if not carefully planned.
  • Limited food choices: The cyclic ketogenic diet restricts carbohydrate intake, which means certain food groups like grains, fruits, and legumes are limited or eliminated, leading to a monotonous diet and difficulty in meeting dietary preferences.
  • Sustainability: The strict nature of the cyclic ketogenic diet can make it challenging to follow in the long term, leading to difficulty consistently adhering to the diet.
  • Potential health risks: While research on the long-term effects of the cyclic ketogenic diet is limited, there are concerns about potential adverse effects such as increased cholesterol levels, liver problems, and micronutrient imbalances.



Newman J. (2017). Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice. Journal of Cell Metabolism.

Kosinski C. et al. (2017). Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. Nutrients by MDPI.

Meira I. et al. (2019). Ketogenic Diet and Epilepsy. What We Know So Far. Frontiers in Neuroscience.

Kovács Z. et al. (2021). Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases. Nutrients by MDPI.


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