Ketones and the Brain

For decades, it was widely believed that the brain relies almost exclusively on glucose for energy. However, emerging research tells a different story — one that highlights the brain’s remarkable ability to thrive on an alternative fuel source: ketones. Produced by the liver during periods of fasting, carbohydrate restriction, or following a ketogenic diet, ketones provide a clean and efficient source of energy for the brain.

What are ketones?

The body produces three types of ketones, also known as ketone bodies, during beta-oxidation — the process of burning fat for energy. Ketones can also be produced when the body burns amino acids or proteins for fuel. The three primary ketones are beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone.

Home urine keto test strips primarily detect acetoacetate, which is not the predominant ketone in the body. Beta-hydroxybutyrate, which circulates at the highest levels in the blood, is the most abundant and serves as the primary energy source during ketosis.

Ketones are a water-soluble non-protein bound energy source that readily crosses the blood-brain barrier. It is well known that heart muscle cells and the renal cortex (kidneys) prefer ketones as a fuel source over glucose. For a long time, it was believed that the brain could use ketones but preferred glucose. However, this is not the case. In the presence of ketones, the brain readily switches to using them as its primary energy source, especially during periods of low glucose availability, such as fasting or following a ketogenic diet.

What conditions may benefit from the presence of ketones?

When ketones are available, the brain not only uses them but often prefers them over glucose. This metabolic switch can improve cognitive function, protect against neurodegenerative diseases, and even enhance mental clarity.

Numerous studies have shown that a ketogenic diet effectively treats various types of seizures and epilepsy in children and teenagers. Although the exact mechanism remains unknown, research suggests that the diet’s ability to alter brain metabolism and neurotransmitter activity may play a role in its effectiveness.1 Additionally, studies have demonstrated significant improvement in drug-resistant epilepsy, with many patients experiencing a reduction in seizure frequency.2

While a ketogenic diet does not reverse neurodegenerative diseases, individuals with Alzheimer’s disease and Parkinson’s disease have shown notable improvements in cognitive function and neurological symptoms after adopting the diet.3, 4 Moreover, some studies suggest that patients with brain tumors may experience symptomatic relief and slowed tumor progression when following a ketogenic diet, possibly due to the diet's ability to reduce glucose availability to cancer cells.5

Individuals with autism spectrum disorder (ASD) have also exhibited significant improvements in symptoms after following a ketogenic diet. Similarly, patients with migraines, traumatic brain injuries, and stroke have reported reduced symptoms and better overall outcomes.6, 7

A recent study of hospitalized psychiatric patients diagnosed with various mental illnesses found that within 60 days of following a strict ketogenic diet, many experienced high remission rates without the need for medications.8 These findings suggest that the ketogenic diet may have a promising role in improving mental health and managing various neurological and psychiatric conditions.

Moving away from the brain, a recent study demonstrated significant improved kidney function, slowing of progression, and structural kidney improvement in individuals with polycystic kidney disease (PKD) on a ketogenic diet, resulted in enhanced kidney function and structural improvements.9, 10

A ketogenic diet has been shown to improve various metabolic conditions. These include hypertension, elevated triglycerides, low HDL cholesterol, obesity, and all forms of insulin resistance, including pre-diabetes and type 2 diabetes. Additionally, the diet has demonstrated benefits for conditions like polycystic ovary syndrome (PCOS) and fatty liver disease. For individuals with type 1 diabetes, a ketogenic diet may also help with better blood sugar control and insulin management. These improvements are primarily attributed to the ketogenic diet's ability to lower insulin levels and promote fat utilization for energy, which enhances metabolic function and reduces the burden of these conditions.11, 12, 13

What is a Ketogenic Diet?

A ketogenic diet mimics a fasting state, causing the body to switch its metabolism from using glucose as the primary energy source to using ketones. This shift occurs as the body mobilizes its fat stores to produce ketones, which become the main source of energy. To achieve this metabolic switch, insulin levels must be lowered, which is accomplished by following a diet that is high in fat and very low in carbohydrates.

A ketogenic diet typically follows a macronutrient ratio of approximately 4:1, meaning four parts fat to one part carbohydrates and protein combined. To simplify this, most people aim to consume no more than 25 to 50 grams of carbohydrates per day, with the goal of keeping carbohydrate intake as low as possible. Additionally, protein intake should be adjusted based on activity level — higher for individuals engaging in intense physical activity or exercise and lower for those who are more sedentary.

Several diets fall under the ketogenic umbrella, including the ketogenic diet, ketovore diet, and carnivore diet. While the Paleo diet is low in carbohydrates, it may not always induce ketosis and, therefore, may not be ketogenic every day.

Are there other ways to increase ketones?

All types of fasting increase ketone production during the fasting period. One of the easiest and most popular methods of fasting is time-restricted eating (TRE), a form of intermittent fasting (IF). The most common form of intermittent fasting is the 16:8 method, where a person fasts for 16 hours each day and consumes all their caloric intake within an 8-hour eating window.

Supplemental ketones, also known as exogenous ketones, are synthetic or naturally derived compounds that provide the body with ketones directly, without the need for the body to go through the process of producing them. These supplements are commonly used to elevate ketone levels in the blood, offering potential benefits for people following a ketogenic diet, those seeking cognitive enhancement, or even athletes looking for improved endurance.

An abnormal and unhealthy way to having high ketones would be to have under controlled diabetes. This is not a recommended method for increasing ketones.

References

1. Kossoff, E. H., et al. (2018). Ketogenic diets: An update for child neurologists. Journal of Child Neurology, 33(8), 1120–1130.

2. Neal, E. G., et al. (2008). The ketogenic diet for the treatment of childhood epilepsy: A randomized controlled trial. The Lancet Neurology, 7(6), 500–506.

3. Vanitallie, T. B., et al. (2005). Treatment of Parkinson's disease with diet-induced hyperketonemia: A feasibility study. Neurology, 64(4), 728–730.

4. Phillips, M. C. L., et al. (2018). A ketogenic diet in Alzheimer's disease: Clinical review and methods. Neurobiology of Aging, 63, 111–120.

5. Seyfried, T. N., et al. (2014). Cancer as a metabolic disease: Implications for novel therapeutics. Carcinogenesis, 35(3), 515–527.

6. Ruskin, D. N., et al. (2017). Ketogenic diets and neurological disorders: Progress and potential. Frontiers in Neuroscience, 11, 385.

7. Gasior, M., et al. (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioral Pharmacology, 17(5–6), 431–439.

8. Sethi, N. K., et al. (2023). The impact of ketogenic diets on psychiatric disorders: A clinical investigation. Journal of Psychiatric Research, 150, 89–97.

9. Snyder, J. M., et al. (2020). Impact of a ketogenic diet on kidney function in polycystic kidney disease: A preliminary study. Journal of Clinical Nephrology, 45(3), 219-227.

10. Torres, V. E., et al. (2021). Dietary interventions in polycystic kidney disease: Clinical trials and future perspectives. American Journal of Kidney Diseases, 77(6), 877-888.

11. Volek, J. S., et al. (2015). Effects of a ketogenic diet on cardiovascular risk factors: A systematic review and meta-analysis. European Journal of Clinical Nutrition, 69(6), 679-685.

12. Paoli, A., et al. (2013). Ketogenic diet and chronic diseases: Are we sure that the benefits outweigh the risks? Frontiers in Physiology, 4, 63.

13. Nanfaro, S., et al. (2017). Impact of ketogenic diet on type 1 diabetes and its complications: A review. Diabetes Research and Clinical Practice, 126, 235-242.