Ketones
Why Are They a Better Brain Fuel?

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By KetoDiet Team, updated November 22 20236
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Quick Summary tl;dr

The brain can use two fuels: glucose and ketones. As compared to glucose, ketones are a more efficient and cleaner energy source.

Ketones are more efficient because they expand the mitochondrial "electron transport chain redox span," a fancy way of saying cells get more energy bang for their buck.

Ketones are cleaner because they produce fewer toxic byproducts of metabolism ("reactive oxygen species").

It is quickly becoming common knowledge that ketone bodies are a better fuel for the brain than glucose. But it's one thing to believe and another thing to understand. If you're reading this, we figure you want to understand. Be warned, the rest of this piece gets a little bit technical. But we at KetoDiet credit your intelligence and have confidence you're up the challenge.

The brain can use two fuels: glucose and ketones. As compared to glucose, ketones are a more efficient and cleaner energy source.

Big Picture: Analogy #1 - Hummers (Glucose) and Teslas (Ketones)

Let's start with the big picture. Imagine your brain cells are like cars. Brain cells running on glucose are like a gas-guzzling Hummers. They are clunky, inefficient, and produce a lot of pollution. By contrast, brain cells running on ketones are like new Tesla. They are faster, more efficient, and produce very little population.

So, brain cells on glucose are slow and dirty Hummers, whereas brain cells on ketones are fast and clean Teslas. This analogy is meant to ground you, but it still doesn't offer true understanding. Dig your trends into the asphalt and rev your engine because we are about to drive deep into your brain cells and talk biochemistry!

Ketones are cleaner because they produce fewer toxic byproducts of metabolism ("reactive oxygen species").

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Deeper Dive: Analogy #2 - Bowling Balls Rolling Down Stairs

Your brain cells' car engine is called its "mitochondria." Mitochondria are what turn glucose and ketones into energy. How they do so is complicated but involves converting the energy stored in glucose and ketone molecules' chemical bonds into "high-energy electron particles."

Let's imagine these high-energy electron particles like bowling balls sitting at the top of a flight of stairs. To produce energy, your mitochondria roll the electron (bowling ball) down the stairs. Each bump releases energy that your brain cells can use to do work. You can think of the accumulated amount of noise produced with each "crash, crash, crash" as the amount of energy your brain gets from each electron particle.

In our bowling ball stair analogy, when your brain is using glucose, the staircase is short and the stairs are made of wood. Therefore, there are fewer "crashes," less energy is produced, and the wooden stairs are damaged in the process. (In brain cells, these processes are respectively referred to as a short "electron transport chain redox span" and elevated "reactive oxygen species" production.)

However, when your brain is using ketones, the staircase gets longer and the stairs turn into stainless steel. Therefore, more energy is produced as the high-energy electron bowling balls made from ketones crash down more stairs. What's more, the stairs are now stronger and resistant to damage. (In brain cells, these processes are respectively referred to as an expanded "electron transport chain redox span" and decreased "reactive oxygen species" production.)

Ketones are more efficient because they expand the mitochondrial "electron transport chain redox span," a fancy way of saying cells get more energy bang for their buck.

Ketones as a Brain Fuel In a Nutshell

At the big picture level, brain cells on glucose are like inefficient and dirty Hummers and brain cells on ketones are like efficient and clean Teslas. This is because, at the molecular level, glucose produces electron bowling balls that bounce down short wooden mitochondria staircases, creating less energy and more damage. By contrast, ketones produce electron bowling balls that bounce down long steel mitochondria staircases, creating more energy and less damage.

Phew! I know that was a lot! If you didn't follow, perhaps try trading your Hummer for a Tesla? And, if you need a keto charging port for your brain Tesla brain, Martina's blog and books are a great place to start.

Resources If You Want to Read More

Sato K, et al., Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. (1995)
Norwitz NG, et al., The Mechanisms by Which the Ketone Body D-β-Hydroxybutyrate May Improve the Multiple Cellular Pathologies of Parkinson's Disease. Front Nutr. (2019)

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Joey 5 years ago # Reply

     While both glucose and ketones serve as fuel sources I suspect that there is a nuanced difference in the purpose between the two.
     For those who do HIIT exercises, the high intensity utilizes glucose through the aerobic glycolysis pathway. From an evolutionary POV we can get quick ATP(without O2) so that we can get high bursts of energy which allowed us/animals to either runaway or fight for our lives. We can all walk forever(ketone use) but no one can sprint forever(glucose use). Yes at the biochemical level, the energy payoff comes when you run the downstream products of glycolysis through the mitochondria(2 ATP vs 36ATP per glucose). But with glycolysis you get the energy instantly.
     Which organ is our body is the biggest energy hog? The heart? Your muscles? No, your brain. This 3-4 pound of fat and cholesterol consumes 30% of all our energy. No doubt, ketones can provide all the necessary energy for the brain. The baseline energy for the brain is already enormous: cell metabolism, movement of neurotransmitters, deployment of membrane NA gated ion channel, maintenance of neuronal microtubules, and autophagy. However, I believe that glucose is important for the role of learning.  Learning is the physiologic HIIT of our brain. When we learn something we need a high quick energy burst to enable increased interneural signaling and subsequent physical remodeling at the intracellular microtubule and extracellular synpatic/dendritic level in the hippocampus.  I suspect this is insulin mediated. There is a high correlation with dementia and insulin resistance. Brains that can't uptake glucose can't learn very well. Sure give them some ketones, and they improve but their inability to use glucose is gone as is their new memory formation.
     Does this mean we need to eat carbs? No. While our liver has many many vital functions, it's MOST important job imo is gluconeogenesis. It makes glucose: for our red cells which has no mitochondria(isn't that ironic that the cells that bring us the O2 can't utilize it, talk about the ultimate team player or slave depending on how you look at it), for our muscles so we can run away, for our brains so we can learn.

Nicholas Norwitz 5 years ago # Reply

Very true Joey. You're very knowledgeable. My lay articles are written for those with less background than yourself. You might enjoy more spending some time on pubmed or writing content of your own. The challenge is to translate the information you have a good grasp over into language that is attractive to the general public. We can talk all day in our labs and offices and find satisfaction in tossing terminology at one another, but what's the use for public health if it ends up being an echo chamber and broader society isn't educated and inspired to change it behavior? That's not to say I don't very much appreciate your replies. Feel free to keep dropping elaborations as you please. Just forgive me if I decide not to reply on a point-by-point basis. (I did think your point about the irony of erythrocytes lacking mitochondria and being an oxygen slave was funny.)

Thank you for your kind response. Yes, please don't think I'm expecting a point for point response. And I apologize if it looks like I'm flexing. I use these venues as a way to digest and consolidate my own thoughts. It's medicine for my brain. But a lot of times my interpretations do not originate spontaneously; they need the prompting of intelligent content such as yours. But you are right, it does feel good to be in the echo chamber.

Joey, nothing negative comes from your posts, only positive. I simply meant to imply that your intelligence might be more effectively partitioned more judiciously. However, if these venues are a place for you to digest your own thoughts, please continue to do so. Your comments only add to the content and elevate the discussion for those with the background. Don't be offended if I don't reply to everything, but feel free to comment freely. Best wishes.

Peter 5 years ago # Reply

I love the bowling balls! That makes so much sense. Finally!

Martina @ KetoDiet 5 years ago # Reply

I agree, a great analogy with bowling balls!

Ketones
Why Are They a Better Brain Fuel?

Quick Summary tl;dr

Big Picture: Analogy #1 - Hummers (Glucose) and Teslas (Ketones)

Deeper Dive: Analogy #2 - Bowling Balls Rolling Down Stairs

Ketones as a Brain Fuel In a Nutshell

Resources If You Want to Read More

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