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Glucose vs Ketones: The Best Fuel Source for the Brain

Article written and reviewed by Cyrus Khambatta, PhD
Published September 5, 2021

Can the Brain Use Ketones? Choosing the Optimal Brain Fuel

With the rise of the ketogenic diet, there has been a significant debate over which form of biological “fuel” helps your brain run optimally.

For the vast majority of your life, your brain oxidizes glucose for energy. When you eat a low-carbohydrate diet or fast for extended periods of time, your liver can convert stored fatty acids into ketone bodies to be used as a secondary fuel.

In short periods, like those found in intermittent fasting, the evidence suggests that these ketone bodies can actually have a strong, beneficial effect on certain tissues.

However, in the ketogenic diet, which is designed to put your body in a state where your brain oxidizes primarily ketone bodies, there can be some unwanted long-term side effects.

In this article, we’ll discuss some of the science behind these different “fuel” sources, as well as the benefits of ketosis in small instances, like intermittent fasting.

Then, we’ll explain why the ketogenic diet — though it may have some immediate health results — is actually not ideal for your health in the long term.

Brain Function on the Ketogenic Diet

Your body naturally functions by primarily converting glucose into ATP, the cellular form of energy. Cells in your liver can create ATP from fatty acids through a process called de novo lipogenesis, but your brain cannot

Your brain accounts for 25-40% of your energy expenditure, and glucose is the preferred fuel of choice.

However, when glucose is not available, your liver produces a family of ketone bodies which include acetoacetate, beta-hydroxybutyrate, and acetone. Acetoacetate and beta-hydroxybutyrate are metabolized by multiple tissues including your brain as an alternate fuel source when glucose is limited.

The keto diet is an intentionally low-carbohydrate diet designed to put your body in a continuous state of ketogenesis.

Ketosis vs Ketoacidosis

Ketosis and ketoacidosis both cause the levels of ketones in your blood to increase.

Ketosis occurs when glucose is limited, while ketoacidosis is a life-threatening condition.

Like we mentioned above, ketosis occurs when glucose is limited – resulting in the production of ketone bodies by your liver as an alternate fuel source for your brain, muscle, and other peripheral tissues.

Diabetic ketoacidosis on the other hand occurs in an insulin deficient state, which results in an extremely high blood glucose value, liver ketone production, extreme thirst, fatigue, and unexplained weight loss.

Brain Health Benefits of Keto

The evidence has shown that your brain can function for extended periods of time in ketosis, and may actually have some positive benefits, which we’ll touch on below. However, there are two things to be aware of as we explore the benefits of ketosis.

The first is that many of the metabolic benefits of ketosis often coincide with rapid weight loss, reduced blood glucose, reduced triglycerides, and reduced blood pressure. 

The second is that the ketogenic diet, despite its immediate benefits, can actually have some very negative side effects in the long term, including a significantly increased level of liver and muscle insulin resistance in addition to increased LDL cholesterol.

Ketosis and Alzheimer's Disease

There has been quite a bit of research done recently on the effect of the ketogenic on the advancement and incidence of Alzheimer’s disease.

We wrote a comprehensive article on the presence of brain insulin resistance and type 3 diabetes which gives you a detailed overview of the research in this field.

However, the research isn’t decisive as to how ketone bodies affect these conditions directly, or if other factors are at play.

Some research implies that the ketone bodies themselves benefit the brain, while others imply that the short-term improved cardiovascular health provided by a ketogenic diet is the main factor.

Ketosis and Parkinson's Disease

The cardiovascular benefits of ketosis come into play here as well, suggesting that the ketone bodies of a high-fat ketogenic diet may be a valuable asset in fighting Parkinson’s disease.

However, the key here again is that ketone bodies may help fight this disease, or may simply provide an alternative that improves cardiovascular health in the short term, and in turn helps fight this neurodegenerative disease.

The two studies were either focused on small group sizes or pilot studies judging feasibility, so there’s a need for more research here.

Ketosis and Congenital Hyperinsulinism

Another area where a ketogenic diet has shown some short term benefits is through the prevention of seizures in a patient with congenital hyperinsulinism. This diet, in addition to medication, helped control the insulin levels in the patient, and had a beneficial effect.

It’s important to note that this was a case study done on a single patient, so the effects are still unclear, and require more investigation.

Ketosis and Traumatic Brain Injuries

The cognitive benefits of ketosis show some promise in other areas as well, though many projects are still in early phases and have not reached clinical trials.

Animal studies of the ketogenic diet have shown that ketones present a possibly favorable alternative to blood glucose after traumatic brain injury, and it is theorized that in these particular cases ketones can be ‘easier’ on the brain as it recovers.

Ketosis and Memory Loss

Other studies have shown ketogenic diets to slightly improve cognitive function in those with memory loss, though it’s theorized that this connection may be a result of improved blood and cardiovascular activity, rather than ketones’ favorability as a brain fuel.

Ketosis and Brain Function

And finally, ketosis has been linked to slightly improved brain function in those at a higher risk for Alzheimer’s or mild cognitive brain impairment.

This is another area where further human research is needed, with existing research limited to both healthy rats and aged rats.

Are Ketone Bodies the Best Brain Fuel?

In essence, the research has shown that ketosis itself is not an unnatural or even an unhealthy process, and the research shows that ketosis may actually have some benefits for your brain.

However, there’s little research that compares ketones to glucose head to head in terms of brain performance, so it’s hard to categorize either fuel source as “the best” specifically for your brain.

Taking a broader perspective though, a ketogenic diet can actually present long-term metabolic complications. Though ketosis has short term benefits including rapid weight loss, reduced blood glucose, reduced triglycerides, and reduced blood pressure, ultimately it impairs insulin action in your liver and muscle, which can set the stage for an increase in the risk of prediabetes and type 2 diabetes in the long-term.

One alternative to more safely and sustainably produce ketone bodies, while also adding the benefits of weight loss and reduced insulin resistance, is intermittent fasting, strategic periods of fasting that can put your body into ketosis without requiring a high-fat diet.

And when intermittent fasting is combined with a low-fat, plant-based, whole-food diet, you can add the health benefits of eating fruits and vegetables, you can multiply the mental and physical benefits of ketosis, without any of the negative side effects.

To learn more about other ways to get these brain, body, and blood glucose benefits, and put together a dietary plan that sets you up for long term success, you can explore our coaching program, which includes expert guidance, a lively community, and a vast library of online resources.

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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. https://doi.org/10.1074/mcp.M112.021204 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. https://doi.org/10.1152/ajpendo.00524.2009