I’ve previously written about some experiments I’ve conducted involving ketosis, from intermittent fasting to longer five-day fasts and caloric restriction, to help my body kick-start production of ketones. However, in these cases getting into ketosis involved a lot of work so I was looking for ways to shortcut/“hack” the process.
Exogenous Ketone Esters and Ketone Salts – A Shortcut to Mimicking Ketosis
In recent years, exogenous ketone supplements have become very popular. They elevate blood-ketone levels without having to eat large amounts of fats, follow (excessively carbohydrate-restrictive) ketogenic diets, or fast constantly. These ketones (beta-hydroxybutyrate) come in two forms, ketone salts and ketone esters:
- Ketone Salts: While the body uses and makes BHB ketones salts naturally, in supplement form ketone salts are synthetically (lab) made compounds that combine sodium (and/or potassium, calcium, or magnesium) with BHB. The salt is used to raise the pH and make things less acidic. Currently, all ketone supplements on the market are made from ketone salts. While they raise ketone levels, most people will only experience mild nutritional ketosis (~0.6-1.0 mmol/L).
- Ketone Esters: These are not normally found in the body, but exogenous ketone esters convert into BHB once it is in the body. They are also synthetically (lab) made compounds that link an alcohol to a ketone body, which can then be metabolized by the liver into a ketone. They are like ketone salts on steroids as they have 5-10 time more BHB per serving/maximum daily intake than ketone salts. To date, pure ketone esters have been very expensive to produce and have only been available to researchers, elite athletes (Tour de France cyclists), and the US Department of Defense (people have spent more than $20,000 to have an independent lab produce a single serving!).
Ketone Esters and Longevity
A recent study, Ketone Bodies Mimic the Life Span Extending Properties of Caloric Restriction, showed the effects of exogenous ketones on longevity (ketone esters, specifically) and concluded that ketones should be labeled as an “anti-aging” compound (suggesting that the real reason caloric restriction has been shown to extend life span is actually due to resulting ketosis).
Ketone Esters – Like “110 Octane Racing Fuel!”
I came across a new company called KetoneAid that has begun producing small batches of ketone monoesters (KMEs). The main molecule in their product (D-β-hydroxybutyrate / D 1,3-butanediol) is based on a five-year, $10M study commissioned by the Defense Advanced Research Projects Agency (DARPA), looking to create the most powerful source of energy for special operations soldiers such as Navy SEALs, when undertaking very physically and cognitively challenging missions. In fact, the main researcher of the DARPA study is Dr. Richard Veech, the same person that authored the longevity study I just mentioned. Very cool.
After reaching out and speaking to KetoneAid’s founders to learn more about their ketone esters, I was sent a bottle of their product to try out and use in some self-experiments.
Reaching Therapeutic Ketone Levels and Lowering Glucose with Exogenous Ketone Esters
For the first part of my experiment, I would simply record my blood ketone and glucose levels over a period of two hours after taking the ketone esters. While I am already fairly keto-adapted and can attain nutritional ketosis fairly easily (> 0.5 mmol/L), it wasn’t until the end of my Five-day Fasting Mimicking Diet that I was even close to reaching therapeutic ketosis levels (>5.0 mmol/L).
The chart below shows my ketone and glucose response to consuming 40g of KetoneAid’s ketone esters, which had been calculated to be my optimal serving size based on my weight (170lbs) and type of activity (I am moderately active/athletic, but cognitive experiments are a “low” physical activity). Normally, for increased physical performance ketone esters are consumed along with some glucose, but since I was only focusing on cognitive performance I did not consume any glucose.
I had heard horror stories about how bad ketone esters tasted (like “rocket fuel”!) so was prepared for the worst. I followed their instructions and drank the contents of the bottle in one gulp, then chased it with a sip of sparkling mineral water. While not the most pleasant aftertaste, the flavor wasn’t any worse than after a shot of well tequila. Within 15 minutes I was already well into therapeutic ketosis, and after 30 minutes my ketone meter displayed a “HI” error message (meaning my level was greater than 8.0 mmol/L)!
It was like getting the benefits of a five-day fast in just 15 minutes! As my body and brain began sucking up the ketones, I felt a rush of energy and my mind became very sharp and focused in ways beyond what I attain doing an extended fast. But in this case it was the 40g of ketones I had just consumed. Even at the two-hour mark, when I took my last reading, I was still in deep ketosis.
My blood glucose levels also went down significantly, from mid 90s to low 70s mg/dL, where levels remained even after two hours (to convert glucose from mmol/L to mg/dL, just multiply values by 18).
Ketones and Cholesterol (Lowered Triglycerides?)
I also tested my lipids (total cholesterol, LDL, HDL, triglycerides) just before and two hours after drinking the ketones. All of my cholesterol numbers remained fairly constant, with the exception of triglycerides, which went from 68 down to below 45 (which is the lowest value my testing device can measure).
It was explained to me that exogenous ketones inhibit lipolysis (breaking down of fat cells), therefore triglycerides should be expected to go down. They theorize that ketones may promote transfer of triglycerides from blood into cells, which primes the pump for fat burning, but to verify would require conducting biopsies to measure blood versus tissue.
Increasing Cognitive Performance with Exogenous Ketone Esters
While the KetoneAid folks have been seeing tremendous success working with elite athletes to improve athletic performance, I thought it would be interesting to quantify the effects of ketone esters on cognitive performance. For the week prior to taking the ketones, I re-established baseline scores in a number of cognitive testing areas using Lumosity*:
- Memory: working memory, spatial recall
- Attention: selective attention, divided attention
- Problem Solving: quantitative reasoning, logical reasoning
- Flexibility: task switching, response inhibition
- Speed: information processing, spatial orientation
I began by simply playing all of the games over and over again (each game many dozens of times over the period of a week) to remove any “learning effect.” I then selected two games from each category (for a total of 10 games) and for a period of five days prior to “ketone-day” played each game five times each day. My “before ketones” baseline scores put me in the top 4% of all Lumosity users, so I was already in a good place. But could I improve even more, just one hour after consuming the ketones?
In a nutshell… WOW! The chart above shows each of the games/categories I played, showing my prior 5-day averages compared to the day I took the ketone esters. Compared to my baselines, my scores increased across the board, with the biggest improvements in spatial orientation (+32.2%), working memory (+23.7%), quantitative reasoning (21.5%), task switching (+14.9%), and information processing (+14.9%). Below are more detailed comparisons:
Memory (Working Memory +23.7%, Spatial Recall +1.6%)
Working memory involves temporarily storing and manipulating information. The game involves seeing three cards – a top card with a symbol that then moves along a track and is flipped over, exposing a new card above. The goal is to remember the symbol of the cards two cards back and indicate whether it matches the visible card or not. If you have ever played dual n-back games, this is very similar.
Spatial recall involves tracking location and position of items within an environment. The game involves seeing a grid of tiles that will briefly light up a random pattern, then turn off. The goal is to recreate the pattern that was shown.
Attention (Selective Attention +8.9%, Divided Attention +6.7%)
Selective attention involves focusing only on relevant information while suppressing the impulse to pay attention to irrelevant distractions. A v-shaped flock of birds are displayed. The center (target) bird points in one direction and is surrounded by birds that either match the target’s direction or do not. The task is to rapidly identify which direction the target bird is pointing.
Divided attention involves processing multiple streams of information. The game involves observing a pond full of koi fish swimming around, and tapping each fish only once to feed it a pellet without feeding any fish previously fed. Each level adds more fish with increasing speed and redirection. It’s similar to pretending to be an air-traffic controller who must keep track of every plane on their radar.
Problem Solving (Quantitative Reasoning +21.5%, Logical Reasoning +6.1%)
Quantitative reasoning involves understanding numerical concepts and relationships to solve problems. Two cards are shown with an equation on each card. The card with the greater solution must be selected as quickly as possible (or indicate they are equal) before being shown the next card.
Logical reasoning combines multiple cognitive processes to recognize patterns, draw conclusions, and make decisions. Groups of fruits and vegetables are shown, which must be arranged in the correct order based on a series of rules/logic. In some cases the solution is impossible based on the constraints.
Flexibility (Task Switching +14.9%, Response Inhibition +12.6%)
Task switching is the process of adapting to changing circumstances (switching from one goal to another). Two cards are shown one above the other, and a combination of letter and a number (i.e., “A4”) will appear on one of the two cards. If it appears on top, the task is to indicate whether the number is an even number, and if on the bottom the task is to indicate whether the letter is a vowel.
Response inhibition is the ability to suppress inappropriate responses that interfere with goal-directed actions. Two cards are shown, one above the other, each containing the name of a color in a certain color. The goal is to rapidly indicate if the meaning of the color on top (i.e. “yellow”) matches the color of the color on the bottom (i.e., card says “red” but is colored yellow).
Speed (Information Processing +14.9%, Spatial Orientation +32.2%)
Information processing involves the initial identification and analysis of incoming sensory input. A card is shown with symbol containing three circles, one of which is solid while the other two are not. The task is to indicate if the symbol on the next card matches the previous card.
Spatial orientation (also known as sense of direction) involves being aware of the surrounding environment. The game involves navigating a penguin through a two-dimensional maze (up, down, left, right) to get to a fish. As the penguin moves through the maze, the entire screen periodically rotates to another orientation, so “up” for the penguin then becomes, say, “left” to the player, who must quickly adapt to the navigation controls.
Ketone Esters Versus Ketone Salts
Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.
Whereas ketone esters are 100% D- form, most ketone salts are a 50/50 mix of left and right-handed beta hydroxybutyrate, which is known as a racemic mixture. These beta hydroxybutyrate molecules are linked to a mineral, such sodium (Na), calcium (Ca), potassium (K), or magnesium (Mg). This kind of ketone supplement gets broken down to left and right-handed version of beta hydroxybutyrate along with the mineral.
A typical serving of racemic ketone salts contains around 12g of beta hydroxybutyrate, of which only half is the D- form (6g). Compared to the 40g ketone esters I consumed (which are 100% D- form), I would need to consume somewhere around seven to nine packets of ketone salts to get the same amount of D-β-hydroxybutyrate (some D- form is wasted burning of the L- form), along with the huge amount of salts contained and more than a gallon of water (since the powders must be mixed). Even if one could consume that amount of ketone salts, they will probably suffer from what people often refer as “disaster pants” (aka diarrhea) due to the amount of salt consumed.
In the longevity study I mentioned earlier, they found that only the D- form of βHB extended lifespan (the L- form did nothing).
So, if the D- form is superior, why would ketone salts be produced as a 50/50 racemic mixture? Simple – it is MUCH, MUCH more expensive to produce D-β-hydroxybutyrate!
Ketones Versus Nootropics
I’ve experimented with a number of nootropics (piracetam, aniracetam, choline, various “stacks,” etc.), but for some reason I have never experienced huge cognitive effects. That doesn’t mean they don’t work – my body’s chemistry just doesn’t respond much. I often joke that caffeine (coffee) is my favorite nootropic.
However, with the ketone esters, the effects are nearly immediate, and my entire body was humming throughout the entire day, but not in a jittery way. I was full of mental and physical energy that lasted without any sort of crash (it was a gradual taper). During my cognitive tests, things felt almost effortless as I played the various games. After my experiment was complete I continued writing code for several hours, then went to the gym to work out. I did forget to each lunch though, so there must be some suppressive effect on appetite.
But that’s just my N of 1 observation. Your mileage may vary.
KetoneAid’s ketone esters are the real deal, and I think everyone should experience some form of exogenous ketones. My N of 1 experience showed a huge uptick in cognition and physical energy.
While ketone salts are widely available, unfortunately in the near-term ketone esters are in short supply and the only people who will be able to afford taking them several times per day will be elite athletes, the military, corporate CEO-types, and professional poker players. Even with economies of scale and ramping up production, the cost of raw materials to produce pure ketone esters will keep their price tag prohibitively high for most people, but could realistically get down to a few dollars per gram.
That being said, if you are interested in trying ketone esters for yourself, you should visit KetoneAid’s website for updates on product availability.
I am hoping to get my hands on a bottle of KetoneAid’s next batch so I can do some physical experiments with ketones. Stay tuned!
Tools and Resources:
Ketone Bodies Mimic the Life Span Extending Properties of Caloric Restriction – study published in IUMBM Life
Story about DARPA funding for Dr. Veech’s Ketone Esters (YouTube)
Articles and Scientific Papers on Ketone Esters and Dr. Veech
KetoneAid – pure ketone monoesters
Ketone and Glucose Testing:
Brain Games and Brain Training Apps:
(see full list in my Resources section)
* I’m not going to debate whether or not Lumosity “works” to make you smarter (they were recently fined by the FTC), as I simply used their games/tests as an assessment tool.