Mastering Ketones: A Deep Dive into Exogenous vs. Endogenous Sources

Mastering Ketones: A Deep Dive into Exogenous vs. Endogenous Sources

When it comes to “energy” supplements, we tend to gravitate toward things like caffeine, or sugars, and while these things can certain work, there are other options out there that may be more sustainable and even more beneficial over time.

When I say energy here, I am talking very literally about energy in the context of what the body uses to generate adenosine triphosphate (ATP), the energy currency of a cell. Now a lot of us are probably familiar that carbohydrates are a very common source of energy for our cells. Carbohydrates are broken down into sugars, when enter glycolysis, the Krebs cycle, and then the electron transport chain where they generate ATP. This is called cellular respiration. However, fats can also be broken down and turned into energy for the body to generate ATP derived from ketone bodies. This process is different than cellular respiration and requires an adaptation phase for most individuals depending on their current metabolic status, and lifestyle habits, but ketones are a more efficient source of fuel than glucose, while providing some interesting benefits. Here we will dive into what ketones are, briefly discuss what exogenous and endogenous mean in this context and check out a few exogenous ketone supplements.

What Are Ketones?

Ketones, in the context of human physiology, play a role as an alternative energy source to glucose. Ketones are produced in the liver from fatty acids during periods of low carbohydrate intake, prolonged intense exercise, or during starvation in extreme cases. The primary ketones that are produced are acetoacetate, beta-hydroxybutyrate (BHB), and their spontaneous breakdown product, acetone.

The ketogenic diet is a diet that primarily consists of fats, with low carb intake, and moderate protein intake. This diet prompts the body to shift from using carbohydrates as its primary source of energy to ketones produced from fats. The state of using ketones as a primary source of energy is called ketosis. Ketones serve as a major source of energy for the brain and various other tissues. Normally the brain uses glucose, but in this context the brain will primarily use ketones, and glucose from the small amount of carbohydrate consumed, and protein derived glucose from gluconeogenesis.

The production and utilization of ketones not only help sustain energy levels, but also have a plethora of therapeutic effects on various neurological and metabolic disorders and conditions, such as epilepsy, Alzheimer’s disease, type 2 diabetes, and much more. This shift to ketone metabolism can also lead to reduced hunger, increased weight loss, and improved cognition.

Endogenous Versus Exogenous

This will be quick, but you may see these words floating around there in a variety of different contexts.

  • Endogenous: This refers to substances or processes that originate from within an organism, cell, or system. These are typically naturally produced by the body. For example, endogenous hormones like insulin are produced by the pancreas. Similarly, endogenous ketones are produced by the liver while in ketosis.
  • Exogenous: This term refers to substances or processes that originate from outside an organism and introduced from external sources. For instance, exogenous insulin can be administered to a diabetic patient to help manage blood sugar levels. In the context of ketones, exogenous ketones are introduced by the body via supplementation, to boost the body’s ketone levels without requiring the body to be in a state of ketosis through diet alone.

Endogenous Ketones

Endogenous ketones are produced by the liver during states of reduced carbohydrate intake or increased fatty acid oxidation, such as during fasting, prolonged exercise, or a ketogenic diet. Here's a quick breakdown of the three primary types of ketone bodies: acetone, beta-hydroxybutyrate (BHB), and acetoacetate, along with their functions:

Acetoacetate (AcAc):

  • Production: Generated first in the ketogenesis process from the breakdown of fatty acids.
  • Function: Can be converted into beta-hydroxybutyrate or acetone. It's used by peripheral tissues (like muscle) for energy when converted back to acetyl-CoA.

Beta-Hydroxybutyrate (BHB):

  • Production: Formed from acetoacetate in the mitochondria of liver cells.
  • Function: Not technically a ketone by structure, but considered one due to its role in the ketone metabolism. It travels through the bloodstream and can be converted back into acetoacetate to be used as energy in various tissues, including the brain. BHB is often the major ketone found in the blood and is a more stable ketone that can be used as a direct indicator of a ketogenic state.

Acetone:

  • Production: Comes from the spontaneous decarboxylation of acetoacetate.
  • Function: It’s the least utilized ketone body and is primarily exhaled through the lungs or excreted in the urine. Acetone is often responsible for the "keto breath" noticed in individuals who are in a deep state of ketosis.

Types of Exogenous Ketone Supplements

When talking about exogenous ketone supplements, there are a couple of types, ketone salts, and ketone esters.

  • Ketone salts are formed when ketones (typically beta-hydroxybutyrate) are bound to minerals such as sodium and potassium. The process of binding makes the supplement more stable and palatable when compared to ketone esters. Ketone salts are absorbed more slowly than ketone esters and tend to raise blood ketone levels to a lesser extent but are still valuable and effective. Because they include electrolytes, they can help mitigate electrolyte imbalances that can occur while on a ketogenic diet.
  • Ketone esters are raw forms of ketones (usually BHB), bound to an ester compound. Ketone esters are quickly metabolized by the liver, rapidly releasing ketones into the blood stream. This rapid release can provide immediate energy to the brain and muscles. While ketone esters are effective at delivering ketones quickly to the body, they tend to have an unpleasant taste.

There are pros and some cons to each of these (mostly pros in my honest opinion), and really, we love them all for different reasons. You really can’t make a bad decision here. We are just presenting some of the options out there for you to try, so that you can determine which works best for you. If you are looking for quick ketones, ketone esters are probably going to be your choice, but if you are looking for a sustained boost in ketones, then ketone salts may be a better option for you.

Our Favorite Exogenous Ketone Supplements

So, we are comparing some of our favorite exogenous ketone supplements here, however, I must state, we love each of these for their own reasons. We will start with Ketostart® by Audacious Nutrition®, then cover deltaG®, and end with Cognitive Switch ™ by Juvenescence ™.

Ketostart® by Audacious Nutrition®

Ketostart® is a ketones salt based exogenous ketone, which offers a form of beta-hydroxybutyrate and electrolytes, as well as caffeine in one of their formulations if you are looking for an extra kick. Ketostart® uses a 1 to 1 ratio of D- and L-BHB (often called racemic), instead of just D-BHB, and while some may claim that D-BHB itself is better, there are many benefits to the L- form as well. For example, the L- form is important for signaling, provides anti-inflammatory effects, and is an epigenetic regulator. Each of these forms of BHB are metabolized at different speeds, with L-BHB being metabolized more slowly than D-BHB, which may result in a higher and more sustained blood levels of BHB compared to consuming just D-BHB. So essentially, the D- form will kick in more quickly, and the L- form will sustain the effects of ketosis for longer. Moreover, this formulation has been found to be more GI tolerable. It is important to note that current blood ketone meters do not detect L-BHB, so if you are taking ketone supplements with L-BHB, your ketone reading will likely be lower than what is actually the case.

Audacious Nutrition® currently has four products on the market:

  • Ketostart
    • 6g Clacium-BHB
    • 6g Sodium-BHB
    • Plus Electrolytes
  • Ketostart+
    • 6g Clacium-BHB
    • 6g Sodium-BHB
    • 100mg caffeine
    • Plus Electrolytes
  • Ketospike Instant Coffee with BHB
    • 1800mg Clacium-BHB
    • 1800mg Sodium-BHB
    • 2mg caffeine
    • Plus electrolytes
  • Ketospike Instant Tea with BHB
    • 1800mg Clacium-BHB
    • 1800mg Sodium-BHB
    • 2mg caffeine
    • Plus electrolytes

Additionally, because the state of ketosis suppresses insulin, (much more so on dietary ketosis), the kidneys retain less water and excrete more sodium. Because of this, Ketostart adds the electrolytes magnesium, sodium, and potassium to regulate electrolyte levels.

deltaG® Ketone Ester

deltaG® is a ketone monoester developed by scientists in collaboration with the University of Oxford and the National Institutes of Health, with funding from DARPA’s “Metabolic Dominance” program. Research conducted by Dr. Kieran Clarke and Dr Richard Veech dating back to 2000 led to the creation of deltaG®, also know as the Oxford Ketone Ester. deltaG® uses an ester bond to deliver high amounts of D-BHB, which is the bio-identical ketone body that our body produces naturally.

deltaG® is about twenty times stronger than MCT oil, three times stronger than ketone salts, and three times stronger than 1, 3-butanediol (BDO), another form of exogenous ketone.

deltaG® has four products out currently, some intended for “Clinical Ketosis” and some intended for “Performance Ketosis” based on research by deltaG®:

  • ΔG Ketone Performance
    • 27g Ketone Ester per bottle
    • 1-2 servings
    • Bitter Blueberry Flavor
    • For “Performance Ketosis”
  • ΔG Tactical
    • 32g Ketone Ester per bottle
    • 1-2 servings
    • Pure Ester
    • For “Performance Ketosis”
  • ΔH Ketone Health
    • 10g Ketone Ester
    • 1-2 Servings
    • Lemon Zest Flavor
    • 3-5 hours of Clinical Ketosis
  • ΔGold Ketone Booster
    • 32g Ketone Ester
    • Pure Ester
    • 2-4 hours of Clinical Ketosis

Now, there is something to note here if I am being fair. While ketone esters are absolutely effective at rapidly raising blood ketone levels in a significant manner, the taste is…well…really something. Ketone esters are commonly described as tasting like “rocket fuel,” and therefore may be more difficult to get down. Aside from the flavored versions of deltaG®, the pure ester forms can be mixed in with other beverages like coffee, and from personal experience, I would recommend this. They work, but my goodness, the taste is VERY potent, with the exception of a different product which we will talk about below.

Cognitive Switch ™ by Juvenescence™

Cognitive Switch ™ is a ketone di-ester, using C8 medium chain triglyceride (MCT) esterified to one part 1,3-butadiol (BDO). When Cognitive Switch ™ is consumed, the ester bonds are hydrolyzed (broken down) which produces C8 MCT and butanediol, which are absorbed and transported to the liver, the site of ketogenesis. C8 in itself is not a ketone but is a type of triglyceride that is quickly turned over into ketones (like BHB) in the liver. BDO is converted into ketones through an alternate pathway.

Now, I know what I said about ketone esters when talking about deltaG®, and that is what makes Cognitive Switch™ really neat. Somehow, cognitive switch was able to formulate a ketone ester powder that tastes pleasant. When adding it to coffee, it seamlessly dissolves and does not really add much of a flavor. The other bonus is that is adds a creamy consistency to the beverage you add it to.

Cognitive Switch™ has two products out currently which are: Cognitive Switch™ flavorless mix-in, which gives you 12.g grams of their exclusive C8 ketone di-ester, and a tropical ketone di-ester drink.

Putting These To The Test

This month I will be doing my own n=1 experiment to determine how each of these make me feel, and how they affect my blood glucose and ketones with the use of a Keto Mojo. Something to note here however is that I will not be doing this on a ketogenic diet. I will be doing this as an omnivore that has been fully ketogenic in the past and is athletic and lean.

The experiment will consist of remaining omnivorous, tracking and being consistent with my macros so as not to affect the blood readings when switching between the products. I will use each product for 5 days consecutive each, checking my blood glucose and blood ketones two hours after waking up, then an hour after consuming the ketone supplement, and two hours after my meal following the ketone supplementation. I will also state the days I exercise as these things tend to affect both blood ketones and glucose.

I very much look forward to testing these products and sharing my experience here! Stay tuned for my final results on the final blog this month!

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