The Story Of Ketones And How They Might Be Able To Prevent Alzheimer’s Disease

Your brain is a very "expensive" organ to maintain, in terms of its energy needs. This remarkable structure, weighing about 3 pounds in the average adult, is about 60 percent fat, with the rest of its tissues made up of a combination of water, carbohydrates, protein, and salts. Your brain, without which arguably you would not be you, is expensive because it consumes a whopping 20 percent of the daily energy needed to keep your whole body running. This is despite its relatively small size when compared to the entirety of your whole body.

So what’s going on here? Why is your brain such an energy hog and what does this have to do with ketones and Alzheimer’s disease? Let’s get a closer look at how your brain uses energy.

First, let’s examine glucose, which is the main fuel source for both body and brain. Glucose, from the Greek word glykys meaning "sweet", is what is known as a simple sugar, and is made of carbon, hydrogen and oxygen. This sugar is used throughout the body to provide fuel for the body’s multiple energy needs. Your body can get glucose by breaking down sugars such as fructose and lactose found in foods, and it can break down starchy foods to also produce glucose.

Your body can also produce glucose from the glycogen that is stored in your liver and muscles, into a usable form. This is known as glycogenolysis (say "GLY-co-gen-OLL-eh-sis") from “lysis” meaning “to cut.”

Another way your body produces glucose is a process called gluconeogenesis (say "GLUE-co-neo-GEN-eh-sis") which you can probably guess means the creation of new glucose. This process occurs mainly in your liver and kidneys where your body uses non-carbohydrate precursors such as lactate to produce glucose. This form of glucose production is especially active when you are recovering from intense exercise.

Your body uses glucose to produce ATP (adenosine triphosphate) which is a molecule that can carry energy. You can think of ATP as the currency of your cells, as it stores energy, and when it’s broken down, it releases energy that powers all of the vital processes necessary for life. Now back to the brain.

Your brain, because it consumes most of your body’s energy, has to have a reliable and steady source of energy, otherwise cell death and likely permanent damage will be the result. This energy from glucose is critical for the processing of information by your brain, including the formation of long-term memories. One of the good things about glucose is that it is a good source of energy, as each glucose molecule produces a notable amount of ATP. Even so, the process of producing the glucose is not very efficient, but it does represent a very significant source of energy for your body, as it’s usually readily available.

But what does the brain do when glucose levels are low, as happens in long periods of intense exercise, going for a long time without eating, or even in disease states like diabetes? For an organ that is critical to life, it makes sense that your brain has an alternate source of fuel, and that fuel is fat. Not fat in the normal sense, but fat that has been broken down in the liver into something called ketone bodies.

Ketones are the clear winner when it comes to an energy source for the brain because they are made by a much more efficient pathway than glucose, meaning much more ATP is produced per molecule. Ketones are also a "cleaner" fuel, in that they produce much less in the way of "dirty" metabolic by-products than does the metabolism of glucose.

Newer research is also pointing to the idea that ketones serve other roles besides simply fuel, such as serving as regulators of the activity of neurons, having effects on gene expression and acting as signalling molecules in your brain cells.

You don’t have to run a marathon or go days without eating to produce ketones, as many people use the so-called "keto diet" which is a low carbohydrate, high fat program, to help them switch into ketosis. Many people report that when they are in ketosis, their ability to focus and concentrate is markedly increased. People who regularly practice intermittent fasting reach what is known as metabolic flexibility, and can easily switch from burning carbs when eating, to burning fat (and producing ketones) while fasting. Intermittent fasters also report the same feelings of increased focus, concentration and wellbeing as people on a keto diet.

 So what does all this have to do with Alzheimer’s disease?

In 2016, there was an intriguing research article published in Frontiers In Molecular Neuroscience titled “Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease.” The authors propose that in people who go on to develop Alzheimer’s, there is a deficit in brain energy pertaining to glucose that shows up well before they start exhibiting symptoms of the disease.

They base their reasoning on four findings:

One - In people who are older than 64 and who are cognitively normal on testing, the uptake of glucose in the frontal cortex of their brain is lower than those who are younger.

Two - In people who are less than 40 years of age but who have either genetic or lifestyle risk factors for Alzheimer’s disease, but who are also cognitively normal, the uptake of glucose in the frontal cortex is also low, compared to healthy people in the same age group without the genetic or lifestyle risk factors.

Three - People who have been diagnosed both with Alzheimer’s disease (AD) or with mild cognitive impairment (MCI) have the same impaired glucose uptake as the groups in one and two above, but their brain’s uptake of ketones is the same as in age-matched controls who are cognitively healthy.

Here’s where the author’s reasoning is so far: the first three research findings clearly suggest a deficit in brain glucose that precedes the decline in cognitive ability and becomes even more severe as mild cognitive impairment proceeds towards Alzheimer’s disease. But take a look at the fourth research finding:

Four - When interventions are made that raise the availability of ketones to the brains of people who have both MCI and AD, their cognitive ability improves.  

From this, the authors conclude that in order to develop a successful therapeutic approach for mild cognitive decline as well as Alzheimer’s, this exhaustion of the brain’s energy supply needs to be overcome. Because the brain’s uptake of ketones still appears to be normal in people with MCI and Alzheimer’s disease, an intervention that supplies ketones to the brain looks promising to at least delay the development of, or the progression of Alzheimer’s. Some of these interventions are supplementation with MCT oil (medium chain triglycerides) which has been shown to have benefit in people with Alzheimer’s disease, and other methods such as fasting, a high fat ketogenic diet or a regular diet to which ketone esters or MCT oil is added.

Of course there is much more research to be done, but increasing the brain’s available ketone supply appears to be a safe, research supported, and well-tolerated way to bypass the energy deficit in people whose brains are prone to Alzheimer’s disease. 

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