What are Ketones: Your Brain’s Best Friend or Worst Enemy?

Article written and reviewed by Cyrus Khambatta, PhD
Published January 30, 2018

Without doubt, the human brain is the most sophisticated biological machine in existence.

In fact, the human brain is so sophisticated that it can’t even understand itself.

Modern science has discovered many interesting facts about how your brain functions, including the location of your memory center, the location of your speech center, where long-term memories are formed, and how sleep restores neurological function.

Yet despite a deep understanding of this organ, scientists routinely debate the answer to an incredibly basic question:

What Is Your Brain's Optimal Fuel Source?

It’s a simple question with a simple answer, but unfortunately the answer has become overly complicated due to conflicting dietary philosophies.

Attempting to understand how to fuel your brain optimally is a challenging task indeed. Read 10 articles on the internet and you’ll likely get 10 different answers. Read 10 more articles and you’re bound to get utterly confused.

In the quest for understanding what to eat to fuel your brain optimally, the two most prominent arguments are:

  • Argument #1: Your brain runs best when fueled by glucose.
  • Argument #2: Your brain runs best when fueled by ketones.

In order to get to the bottom of this debate, let’s dig into basic brain physiology and understand the logic behind both arguments.

Argument #1: Your Brain Runs Best When Fueled by Glucose

Make no mistake, your brain is the most selfish organ in your body. Think of your brain as a metabolic pig – constantly taking energy from the bloodstream and storing none of it for itself.

It’s no wonder that your brain is one of the hungriest organs in your body – more than 80 billion neurons are sending and receiving electrical signals 24 hours a day, creating complex thoughts and emotions.

Even when you are asleep, neurons in your brain are busy sending a flurry of electrical signals from one region to the next, consolidating memories and information from the previous day. To put things in perspective:

Your brain occupies only 2% of your body weight but consumes about 20% of your body’s oxygen and up to 50% of your body’s glucose.

Unlike your muscle and liver, your brain cannot store fuel, it simply oxidizes (or burns) fuel on demand.

In addition, your muscle and liver are capable of oxidizing glucose, amino acids, and fatty acids for energy, whereas your brain oxidizes glucose easily, and cannot oxidize either amino acids or fatty acids for energy.

Your brain lacks the biological mechanisms necessary to burn amino acids and fatty acids, and therefore must rely on glucose for the bulk of its energy demands.

Think of your brain as a picky child, burning glucose almost exclusively, incapable of burning amino acids and fatty acids at any cost.

Your brain is so picky in fact, it is specifically designed to operate on glucose for 99.9999% of your waking life, and only switches to oxidizing ketones when carbohydrates are in short supply in your diet.

Hypoglycemia is Brain Starvation

Given what you now know about your brain’s ability to use only glucose as fuel, when the concentration of glucose in your blood falls, your brain is one of the first organs to recognize the problem.

When threatened by low blood glucose, your brain is actually starved for fuel, resulting in confusion, lightheadedness, a loss of balance, slurred speech, and impaired vision. This state is called hypoglycemia, or low blood glucose.

Hypoglycemia can be very dangerous and sometimes fatal – when your brain is starved for glucose, your cognitive abilities rapidly decline, resulting in a system-wide panic.

That’s why it’s very important to ensure that you recognize the symptoms of hypoglycemia immediately, and consume carbohydrate-rich food to restore your brain function back to normal once again.

Your Brain Despises Refined Sugars

Since glucose is the most important brain fuel, it stands to reason that a diet high in whole carbohydrate energy can make a significant positive impact on your cognitive ability.

Studies have shown that eating carbohydrate-rich whole foods can improve memory within an hour after ingestion, and that glucose from refined sources actually impairs brain function (1).

In a 2007 study entitled Dietary Influences on Cognitive Function with Aging, the authors describe how diet can affect brain function, and reason that “…[diets] high in fruits, vegetables, cereals, and fish are associated with better cognitive function and lower risk of dementia (1).”

That being said, refined sugars can have detrimental effects on brain function, especially for those living with any form of diabetes. Consume whole carbohydrate energy from plants rather than refined sweeteners from packages and bottles in order to maximize cognitive function.

Researchers have investigated the effects of refined sugars on cognitive function, and conclude that “Special care in food selection at meals should be exercised by those with type 2 diabetes since ingestion of rapidly absorbed, high–glycemic index carbohydrate foods further impairs medial temporal lobe function, with food-induced increases in oxidative stress and cytokine release likely explaining the association between food ingestion and reduction in cognitive function in those with type 2 diabetes (1).”

What are Ketones?

Ketones or ketone bodies are a collection of fuels that your liver is capable of manufacturing when your brain is deprived of glucose.

If you eat a ketogenic diet and restrict your carbohydrate intake to approximately 30 grams per day, your selfish brain says, “Hey, I need some more glucose! If you don’t have any left, then provide me with another fuel that I can use to stay alive.”

Your liver then responds by converting stored fatty acids (from meats, eggs, dairy, and fatty vegetables) into ketone bodies, to be used as an emergency backup fuel to keep your brain happy. Your liver makes 3 primary ketones, named acetone, acetoacetate, and 2-hydroxybutyric acid (or beta-hydroxybutyric acid).

These ketones are shuttled to your brain to be used as backup fuels, to keep your brain operating at full capacity. Because your brain is a finely tuned organ, it may take a few days to adapt from oxidizing glucose to oxidizing ketones.

In the same way that your laptop computer has a backup battery when a wall outlet is unavailable, ketone bodies are the backup power source for your brain when carbohydrates are out of reach.

Side Effects of Ketogenic Diets

Originally developed as a treatment for epilepsy, ketogenic diets result in flatline blood glucose profiles and reduced A1c values, both of which are positive indicators that your diabetes health is improving.

In the short term, restricting carbohydrate intake can dampen overall cognitive function (2). In a study conducted in 2008, women placed on a low-carbohydrate diet for 28 days suffered from impaired reaction time and reduced spatial memory compared to women placed on a high-carbohydrate diet.

The researchers concluded that, “The brain needs glucose for energy and diets low in carbohydrates can be detrimental to learning, memory, and thinking (3).”

It’s also important to understand that just because a diet flatlines your blood glucose does NOT mean that it is a safe diet in the long-term. Ample scientific evidence shows that ketogenic diets come with a laundry list of unwanted side effects that simply cannot be overlooked (4), shown here:

  • Diarrhea
  • Nausea
  • Constipation
  • Vomiting
  • Acid reflux
  • Hair loss
  • Kidney stones
  • Muscle cramps or weakness
  • Hypoglycemia
  • Low platelet count
  • Impaired cognition
  • Inability to concentrate
  • Impaired mood
  • Renal tubular acidosis
  • Disordered mineral metabolism
  • Stunted growth in children
  • Increased risk for bone fractures
  • Osteopenia and osteoporosis
  • Increased bruising
  • Sepsis
  • Pneumonia
  • Acute pancreatitis
  • Beta cell death
  • Hyperlipidemia
  • High cholesterol
  • Elevated cortisol
  • Increased risk for heart disease
  • Increased risk for atherosclerosis
  • Cardiomyopathy
  • Heart arrythmia
  • Myocardial infarction
  • Menstrual irregularities
  • Amenorrhea
  • Increased risk of all-cause mortality

These side effects are chronic health conditions that are fueled by a diet low in carbohydrates, high in fat, high in protein, and low in water, antioxidants, vitamins, fiber and water.

Most importantly, low-carbohydrate diets increase your risk for all-cause mortality, premature death from any cause (5–13).

And independent of any other positive or negative outcome – if your diet increases your risk for premature death, it’s time to seriously reconsider your options.

Take Home Messages

To answer the question: What are ketones? – remember the following things:

  • Ketones are manufactured by your liver as a backup fuel source for your brain to protect against brain starvation on a low-carbohydrate diet.
  • Your brain is biologically designed to oxidize glucose for the majority of your life, and can adapt to burning ketones when glucose is limited.
  • Low-carbohydrate diets (including the ketogenic diet) increase your risk for heart disease, high cholesterol, insulin resistance, prediabetes, type 2 diabetes, atherosclerosis, heart attacks, and stroke.
  • Even though a ketogenic diet can flatline your blood glucose, low-carbohydrate diets (including the ketogenic diet) significantly increase your risk for premature death.

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About the author 

Cyrus Khambatta, PhD

Cyrus Khambatta, PhD is a New York Times bestselling co-author of Mastering Diabetes: The Revolutionary Method to Reverse Insulin Resistance Permanently in Type 1, Type 1.5, Type 2, Prediabetes, and Gestational Diabetes.

He is the co-founder of Mastering Diabetes and Amla Green, and is an internationally recognized nutrition and fitness coach who has been living with type 1 diabetes since 2002. He co-created the Mastering Diabetes Method to reverse insulin resistance in all forms of diabetes, and has helped more than 10,000 people improve their metabolic health using low-fat, plant-based, whole-food nutrition, intermittent fasting, and exercise.

Cyrus earned a Bachelor of Science in Mechanical Engineering from Stanford University in 2003, then earned a PhD in Nutritional Biochemistry from the University of California at Berkeley in 2012. He is the co-author of many peer-reviewed scientific publications.

He is the co-host of the annual Mastering Diabetes Online Summit, a featured speaker at the Plant-Based Nutrition and Healthcare Conference (PBNHC), the American College of Lifestyle Medicine Conference (ACLM), Plant Stock, the Torrance Memorial Medical Center, and has been featured on The Doctors, NPR, KQED, Forks Over Knives, Healthline, Fast Company, Diet Fiction, and the wildly popular podcasts the Rich Roll Podcast, Plant Proof, MindBodyGreen, and Nutrition Rounds.

Scientific Publications:

Sarver, Jordan, Cyrus Khambatta, Robby Barbaro, Bhakti Chavan, and David Drozek. “Retrospective Evaluation of an Online Diabetes Health Coaching Program: A Pilot Study.” American Journal of Lifestyle Medicine, October 15, 2019, 1559827619879106. https://doi.org/10.1177/1559827619879106

Shrivastav, Maneesh, William Gibson, Rajendra Shrivastav, Katie Elzea, Cyrus Khambatta, Rohan Sonawane, Joseph A. Sierra, and Robert Vigersky. “Type 2 Diabetes Management in Primary Care: The Role of Retrospective, Professional Continuous Glucose Monitoring.” Diabetes Spectrum: A Publication of the American Diabetes Association 31, no. 3 (August 2018): 279–87. https://doi.org/10.2337/ds17-0024

Thompson, Airlia C. S., Matthew D. Bruss, John C. Price, Cyrus F. Khambatta, William E. Holmes, Marc Colangelo, Marcy Dalidd, et al. “Reduced in Vivo Hepatic Proteome Replacement Rates but Not Cell Proliferation Rates Predict Maximum Lifespan Extension in Mice.” Aging Cell 15, no. 1 (February 2016): 118–27. https://doi.org/10.1111/acel.12414

Roohk, Donald J., Smita Mascharak, Cyrus Khambatta, Ho Leung, Marc Hellerstein, and Charles Harris. “Dexamethasone-Mediated Changes in Adipose Triacylglycerol Metabolism Are Exaggerated, Not Diminished, in the Absence of a Functional GR Dimerization Domain.” Endocrinology 154, no. 4 (April 2013): 1528–39. https://doi.org/10.1210/en.2011-1047

Price, John C., Cyrus F. Khambatta, Kelvin W. Li, Matthew D. Bruss, Mahalakshmi Shankaran, Marcy Dalidd, Nicholas A. Floreani, et al. “The Effect of Long Term Calorie Restriction on in Vivo Hepatic Proteostatis: A Novel Combination of Dynamic and Quantitative Proteomics.” Molecular & Cellular Proteomics: MCP 11, no. 12 (December 2012): 1801–14.

Bruss, Matthew D., Airlia C. S. Thompson, Ishita Aggarwal, Cyrus F. Khambatta, and Marc K. Hellerstein. “The Effects of Physiological Adaptations to Calorie Restriction on Global Cell Proliferation Rates.” American Journal of Physiology. Endocrinology and Metabolism 300, no. 4 (April 2011): E735-745. https://doi.org/10.1152/ajpendo.00661.2010

Bruss, Matthew D., Cyrus F. Khambatta, Maxwell A. Ruby, Ishita Aggarwal, and Marc K. Hellerstein. “Calorie Restriction Increases Fatty Acid Synthesis and Whole Body Fat Oxidation Rates.” American Journal of Physiology. Endocrinology and Metabolism 298, no. 1 (January 2010): E108-116.