Ketones are a brain fuel that can readily pass the blood brain barrier and be used by brain cells. It's no surprise that many people in ketosis feel a boost of mental clarity and focus.
How and why?
Watch Geoffrey Woo walk through the current scientific evidence and muse over the potential (but promising) mechanisms of action.
At a Glance
Potential Mechanisms of Action:
- Efficient ATP production via mitochondrial biogenesis
- Support & grow brain neurons via BDNF upregulation
- Glutamate / GABA regulation
- Reducing free radicals in the brain
Formal Studies Mentioned:
- Intermittent Running and Cognitive Performance after Ketone Ester Ingestion
- Novel Ketone Diet Enhances Physical and Cognitive Performance
Overview & Context
Ketones are a brain fuel. They cross the blood brain barrier and can be used by brain cells. Not only do many people report they can "feel" ketosis, but also that they gain a boost of mental clarity and focus. How...and why?
Let's set the stage here.
Glucose, or sugar, is the standard, primary fuel for the brain. Like ketones, glucose readily crosses the blood brain barrier and provides efficient fuel for brain cells. However, the human body has a limited store of glucose - about 2000 calories or 24 hours worth. This storage form is called glycogen. And our big brains require a massive amount of energy. In fact, the brain, which is only 2% of our body weight, requires 20% of the oxygen and 25% of the glucose we have in our body.
What happens when that glucose runs out? We don't just go brain dead and die. We all know that we can fast for more than 24 hours...I've done a 7 day fast and felt insanely mentally sharp. What happens is that the body converts its fat stores into ketones, and the brain uses ketones as a fuel source. When carbs are eliminated or minimized, ketones can provide up to 70% of the brain's energy needs.
Okay, we've now established that ketones can be brain fuel. The question is, are they superior? In this video, we'll go over the potential mechanisms of action & formal studies behind ketones for cognition.
Potential Mechanisms of Action
First, let's start off with the potential mechanisms at work here.
This mechanism may allow the brain to use energy more efficiently. Mitochondria are the power plants of cells. They take fuel like glucose or ketones and use it to make ATP, which is energy. Mitochondrial biogenesis is the creation of new mitochondria. On a standard diet with ample consumption of carbohydrates, glucose is the default fuel for the brain. As we established, ketones can replace glucose, and a rule of thumb is that every ~1mM of BHB (the main ketone body) can account for 10% of brain metabolism. Again, glucose and/or ketones are used by the mitochondria within brain cells to generate ATP.
A growing corpus of research suggests that ketosis upregulates mitochondrial biogenesis in the brain. Two ways upregulation happens includes:
- BHB as a signaling molecule for mitogenesis.
- The increased reliance on BHB and fat oxidation and less reliance of carbohydrate metabolism inducing the adaptation of *mitochondrial biogenesis.
An Emory University research group proposed that mitochondrial biogenesis is actually responsible for the anticonvulsant benefits of the ketogenic diet for people suffering from epilepsy.Thus, if this mechanism continues to pan out, ketone-induced mitochondrial biogenesis in the brain will improve its function because of the increased ability of brain cells to utilize fuel and create ATP.
Upregulation of BDNF - brain derived neurotrophic factor.
You often hear that fasting or exercise is good for the brain. People say that because fasting and exercise have been shown to upregulate BDNF. BDNF supports the health of existing neurons and helps grow new ones, as well as increasing the number of connections between cells and synapses. This promotes long-term cognitive health and function. Especially as our BDNF production tends to decline as we age. Recent work suggests that this effect is mediated through ketones. Therefore it may be possible that ketones themselves are the main driver of the BDNF upregulation effect from fasting or exercise.
Glutamate and GABA regulation.
The brain is balanced between excitation and inhibition through two main neurotransmitters, the excitatory glutamate and the inhibitory GABA. Anytime you are talking, thinking, or processing information, glutamate is involved. But more is not always better. Too much glutamate and not enough turnover of glutamate into GABA is hypothesized to be one mechanism that contributes to brain fog and increased anxiety. Neurons in a ketone metabolism state turnover extra glutamate and generate GABA more efficiently. This also may have an anxiolytic effect that we discuss in more detail on our previous Ketones for Anxiety video.
Reducing free radicals.
Increasing evidence demonstrates that accumulation of oxidation of DNA, proteins, and lipids by free radicals are responsible for the functional decline in aged brains. A theoretical mechanism is that ketone metabolism is more efficient than glucose metabolism. This is overly technical for this format, but relates to the the 'electron span' of the electron transport chain for ATP production. The larger electron span implies that less free radicals are generated while cells are ketotic. Less free radicals imply less cellular damage and wasted energy for repair.
In summary, ketones impact and potentially enhance cognition via these 4 mechanisms. Now, theoretical mechanisms are one thing. What do the experiments directly testing cognition show?
This area is actively being studied with some recent results teasing at the potential cognitive applications.
This first study is titled: "Intermittent Running and Cognitive Performance after Ketone Ester Ingestion". This was published in 2018 from a University of Dublin research group.
Early human models suggest ketones improve decision making. This study asked subjects to take a multitasking test both before and after exercise. 4 Participants drinking a placebo had more incorrect responses from pre- to post-exercise; those drinking ketone ester performed the same both before and after exercise. This shows the ability of ketones to maintain cognitive function (better than placebo) during stressful situations. Imagine a time when you were in a highly stressful situation at work, your mind was likely scattered and sprinting in every direction. Focusing and thinking clearly with logic during these situations is paramount as a business owner. Ketone esters being helpful for maintaining cognitive performance during stressful moments is quite promising.
There's also strong data on improved decision making in rats. Obviously, rats aren't people but the following study is a solid supplement to the existing human data.
This study is titled: "Novel ketone diet enhances physical and cognitive performance".
The researchers studied how long rats took to complete a maze. Before changes to their diets, all rats completed the maze with the same time. After diet alterations, rats fed a ketone ester were 38% faster in completing an eight-arm radial maze compared to rates fed a carbohydrate-heavy diet. Decision-making ability (as measured by the number of correct maze arm choices) was also studied. Before diet changes, all rats made the same number of correct choices. Ketone ester fed rats made more correct decisions before making a mistake, compared to rats fed other diets, which showed no significant performance difference.
So, the experiments with ketones esters on humans and animals are promising, and we have reasonable mechanisms on how ketones could impact and improve cognitive performance.
We didn't even touch on the many, many, many anecdotes out there. Many H.V.M.N. customers use ketone ester for cognitive performance in the office. They use it to power through an important session or their most creative part of the day. Speaking even more broadly, the entire butter/coconut oil coffee movement is predicated on ketone production, which fans claim to improve mental clarity, focus, and performance. While we lack many formal studies on this subject in healthy people, the fact that it’s a “movement" suggests there's definitely some signal here. Now with H.V.M.N. Ketone, perhaps you can skip the fat bomb and go directly for the ketones themselves.
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