Chances are, you or someone you know has tried the keto diet at some point in time. This high-fat, very low-carbohydrate eating plan appeals to many due to its promise of rapid weight loss. In this blog, Dr. Sears explores some of the latest scientific findings on ketogenic diets and provides caution before hopping on this trend.

What is a Ketogenic Diet?

The ketogenic diet is a high-fat, very low-carbohydrate eating plan. This significant reduction in carbohydrates to induce a metabolic state is called ketosis. This only occurs when there is not enough carbohydrates in your liver to completely convert fatty acids to carbon dioxide and water. The normal conversion generates the chemical energy (ATP) that keeps us alive. In the absence of ketosis, each fatty acid generates 108 molecules of ATP when oxidized in the mitochondria. Ketone bodies make less ATP when they are metabolized by mitochondria. How much less? About five times less. This is like switching the gasoline in your car from high-octane fuel to low octane fuel as ketone bodies increase in the blood.

Furthermore, contrary to popular belief, ketones are not an ideal energy source for the brain, as glucose remains the preferred fuel for ATP production in brain cells. Lack of blood glucose is a highly stressful situation for the brain. This is why the body secretes the stress hormone cortisol from the adrenal glands during ketosis to breakdown protein and convert the amino acids into glucose for the brain. This explains why even under complete starvation for 38 days, the blood glucose levels never dropped below 68 mg/dL. This is still considered as a normal blood sugar level. Where did this blood glucose come from if there was none in the diet for 38 days? The answer is neo-glucogenesis primarily using lean body mass.

Ketogenic Diets Pros and Cons

Interest in ketogenic diets rises and falls about every 20 years. They’re very low-carbohydrate diets that claim that carbohydrates make you fat and keep you fat. This is simply not true. It is not carbohydrates per se but a disrupted metabolism that makes you fat. To be more specific, it is the inhibition of AMPK, the master regulator of your metabolism that makes you fat. Why? As AMPK activity increases, you burn stored fat faster.

Frankly, I’ve always been amazed by the re-emergence of ketogenic diets. Eighteen years ago, I published the premier clinical study demonstrating that, under equal calorie intake in which all the food was provided to the subjects for six weeks, the Zone Diet was better than a ketogenic diet in reducing total weight, excess body fat, and inflammation.

Now, a recent study revealed some more very concerning findings about the long-term effects of ketogenic diets. This new study indicated that following a keto diet causes a rise in senescent cells, popularly known as “zombie cells.”

Zombie Cells are damaged cells that no longer divide but don't die. That’s bad enough, but zombie cells continue spreading inflammation throughout the body. As the number of zombie cells increases in your body, they become a living nightmare. Why? Zombie cells accelerate aging because they cause the earlier development of many chronic diseases.

In this study they found that zombie cells in the animals began to appear while they were on a ketogenic diet. The zombie cells then disappeared when researchers changed the diet to a “non-ketogenic diet” (i.e., the Zone diet). And when the animals were given a Keto diet again, the zombie cells reappeared. Notice a trend? If you want to hear more about this study you can listen to our recent podcast at Dr.Sears.com.

Based on earlier blogs, this adds to the list of downsides for following a ketogenic diet versus the Zone Diet.

PROS

• Rapid initial weight loss: This is primarily due to the loss of retained water from the glycogen stores in the liver, which is rapidly used up to maintain blood sugar levels. Since these glycogen stores in the liver contain significant levels of retained water, much of the initial weight loss is water rather than stored body fat. If your main goal is loss retained water, this can be seen as a benefit. Of course, going to a sauna would also work.
• Reduced hunger: Ketogenic diets are rich in protein. Any increase in protein intake can help reduce hunger.

CONS

• Production of acetone: One of the ketone bodies produced during ketosis is acetone, which is also the main chemical in nail polish.
• Increased calcium loss: A ketogenic diet can lead to higher calcium loss from bones.
• Limited fat utilization: High levels of dietary fat reduce the likelihood of using stored body fat for energy unless you also significantly restrict calories. Reduced energy levels: The lack of ATP production on a ketogenic diet can lead to easier fatigue during mild exercise.
• Damage from cheat meals: After seven days on a keto diet, a single high-carb cheat meal can damage blood vessels. Lack of polyphenols: This makes it difficult to activate genes that optimize metabolism by improving mitochondrial efficiency in converting fat into ATP.
• No long-term weight loss advantage: Long-term studies show no difference in weight loss between a ketogenic diet and a low-fat, high-carb diet.
• No short-term metabolic advantage: Careful studies demonstrate that fat loss on a ketogenic diet is the same as on a low-fat, high-carb diet with the same caloric intake.
• Compromised gut health: A lack of fermentable fiber from carbohydrates can lead to poor gut health and an increased risk of developing a leaky gut, which can cause significant inflammation. Furthermore, short-chain fatty acids (SCFA) are the metabolic product of fermentable fiber. These SCFA are powerful epigenetic signaling agents that enhance gene transcription. Ketosis generates a different type of hydroxylated short fatty acid (3-hydroxyl butyrate, that has no effect on gene transcription. In addition, the lack of SCFA has significant negative consequences on the gut-brain axis.
• Cortisol build-up: To produce glucose for the brain, cortisol levels increase to breakdown protein to make sufficient glucose via neoglucogenesis. Excess cortisol can lead to insulin resistance that cause regain of some of initially loss body fat. In addition, increased cortisol levels cause a depressed immune system as well as destruction of memory cells in the hippocampus.

The initial benefits of following the ketogenic diet result in some initial weight loss (primarily water weight rather than fat loss), long-term studies show no significant differences in overall weight loss. Now new findings show a ketogenic diet may lead to significant adverse health consequences by accelerating the formation of zombie cells.

Call me crazy, but I feel the key to longevity and wellness comes down to better metabolic control instead of living in a constant state of ketosis. Following Metabolic Engineering® for a lifetime provides that pathway of losing body fat without ketosis.

References

1. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 2006 83:1055-61.

2. White AM, Johnston CS, Swan PD, Tjonn SL, and Sears B. “Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: a pilot study.” J Am Diet Assoc. 2007 107:1792-1796.

3. Sung-Jen Wei, Joseph R Schell, E Sandra Chocron, Mahboubeh Varmazyad, Guogang Xu, Wan Hsi Chen, Gloria M Martinez, Felix F Dong, Prethish Sreenivas, Rolando Trevino Jr , Haiyan Jiang, Yan Du, Afaf Saliba, Wei Qian, Brandon Lorenzana, Alia Nazarullah, Jenny Chang, Kumar Sharma, Erin Munkácsy, Nobuo Horikoshi, David Gius. Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Sci Adv. 2024 May 17;10(20):eado1463. doi: 10.1126/sciadv.ado1463.

4. Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574-83. doi: 10.1172/JCI106016.

5. Chriett, S., Dąbek, A., Wojtala, M. et al. Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. Sci Rep 9, 742 (2019). https://doi.org/10.1038/s41598-018-36941-9.

6. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020 Jan 31;11:25. doi: 10.3389/fendo.2020.00025.