Chances are you’ve been seeing more advertisements and posts on social media about the wonders of exogenous ketones.
But why are these supplements growing in popularity so rapidly? More pertinently, what the heck are exogenous ketones and why should be using them? This article will guide you to these answers and much more!
What is an Exogenous Ketone?
Quite simply, exogenous ketones are ketone bodies that come from a source outside of the body (e.g. dietary supplement). The term ‘exogenous’ is generally used in science and medicine to refer to a substance that originates from outside the body.
For example, the vitamin C you ingest from a multi-vitamin supplement would be considered exogenous vitamin C. Nutrients you obtain from food are also considered exogenous.
Remember that the ketones you produce as part of the ketogenic diet are a form of energy that your body uses instead of glucose (carbohydrates). In this sense, exogenous ketones are a supplemental form of the ketones your body produces naturally (and thus, they have a variety of benefits).
The benefits of using exogenous ketones are quite similar to benefits of ketosis, such as:
- Improved cognitive function
- Reduced appetite
- Lasting energy
- Enhanced cardiovascular function
- Health and longevity benefits
Don’t worry if you’re not quite sure what a ketone is, we will cover that in the next section.
The Science Behind Ketones
Not sure what a ketone is? Physiologically speaking, ketones are organic /carbon-based molecules that contain an inner carbon atom bonded to oxygen and two carbon-based chemical groups, designated by an “R” symbol (see the skeleton structures below).
Ketones are ‘simple’ molecules because they don’t contain any chemical groups that readily react.
The human body naturally produces three different ketone bodies in the liver mitochondrial, including acetone, acetoacetic acid (AcAc), and beta-hydroxybutyric acid (BHB).
However, be careful to note that BHB is technically not a ketone as it has a reactive hydroxyl (OH) group where an oxygen atom would usually be. Even so, BHB functions as a ketone in humans (we will discuss this more later).
Ketones Serve as An Alternative Energy Source to Sugar
Ketones serve as an alternative energy source for the human body, specifically our mitochondria – the ‘powerhouse’ of cells.
Some dietitians and nutritional scientist argue that glucose (sugar) is the main source of energy for humans, but sugar is not an essential macronutrient.
In other words, humans can theoretically (and practically) subsist without consuming carbohydrates in the diet.
Contrarily, ketones are byproducts of fatty acid metabolism in humans when carbohydrate intake is exceptionally low; thus, dietary fats (and ketones) are essential nutrients for our existence.
Difference Between Ketone Bodies in Humans
As aforementioned, BHB functions like a ketone in humans and is converted to energy in the form of acetyl-CoA, a key molecule in the citric acid cycle that produces ATP (the energy ‘currency’ of cells).
AcAc and acetone may also be converted to acetyl-CoA; however, the conversion of acetone to acetyl-CoA is inefficient and won’t do much for energy or performance-enhancing purposes.
Ultimately, BHB is oxidized (converted) into AcAc via BHB dehydrogenase. A large portion of the resulting AcAc is then decarboxylated via acetoacetate decarboxylase into acetone.
Basically, BHB has the most potential as an exogenous ketone compared to AcAc and acetone.
Why Use Exogenous Ketones?
In short, using an exogenous ketone supplement provides your body with an immediate source of BHB to utilize.
In turn, even if you’re not on a ketogenic/low-carb diet, exogenous ketones will help mimic the effects of your body being in nutritional ketosis very rapidly (typically within 30 minutes or less after ingestion). Pretty neat, isn’t it?
a Shortcut to Ketosis
If you’ve ever followed a ketogenic diet yourself, you may well know it typically takes a solid two weeks for your body to become ‘fat-adapted’ and produce a nominal amount of ketones endogenously.
Hence, if you are to use exogenous ketones along with a ketogenic diet, your body will become fat-adapted quicker.
However, this does not preclude people who consume carbohydrates regularly from benefiting from exogenous ketones.
The Benefits of Ketosis
Again, whether or not you have a modest amount of glucose floating through your blood, exogenous ketones will essentially ‘switch on’ ketosis and provide benefits such as enhancing cognitive function, reducing inflammation, controlling blood sugar, mitigating food cravings, and increasing energy levels.
Moving on, let’s take a look at the research and science behind the many benefits of exogenous ketone use.
Benefits of Exogenous Ketone Use and How They Work
We will dive more into how exogenous ketones can help you reach your fitness and performance goals later in this book.
For now, let’s take a look at the wide range of benefits exogenous ketones (particularly BHB salts) impart, according to scientific research.
Exogenous Ketones Beneficial Effects on Weight (Fat) Loss
- Helps reduce food cravings: A recent four-week animal study demonstrates that exogenous ketones are efficacious for decreasing weight/fat gain on a high-calorie diet. The lessening of weight gain appears to come from the appetite-suppressing effects of exogenous ketones.
- Excess ketones are excreted: When you consume too much protein, fat and/or carbohydrates, they can be converted to adipose tissue. Exogenous ketones, on the other hand, will rarely ever be stored as body fat, since your kidneys work rapidly to filter them out through urine.
- Furthermore, you would have to take exceptionally large amounts of BHB to reach a point where you have ‘too much’ in the body. Don’t misconstrue this to mean that it’s impossible for excessive ketones to be converted to body fat, but when used practically, it’s not a concern.
Exogenous Ketone Nootropic (Brain Enhancing) Properties and Physical Performance Benefits
- Athletic performance benefits: The use of exogenous ketone supplements for bettering physical/athletic performance is promising for several reasons. Firstly, taking exogenous ketones (particularly BHB salts) induces acute nutritional ketosis for upwards of eight hours, mimicking fasting physiology (e.g. increases fat burning, insulin sensitivity, etc.).
- Next, BHB salts are the only supplement that elevates BHB levels while muscle glycogen remains at capacity (low muscle glycogen can drastically impede long-duration athletic performance). In short, athletes who consume carb-based diets, and those on low-carb diets, stand to benefit from exogenous ketone supplements taken prior to training/exercise.
- Cognitive/Nootropic benefits: For centuries, it was thought that the brain needs glucose to operate optimally. Lo and behold, data shows that increases in plasma ketone concentrations actually drives the brain to utilize ketone bodies for the synthesis of phospholipids, which encourage neuronal myelination.
- Usually, glucose is the brain’s preferred substrate, despite being less efficient metabolically. As such, using exogenous ketones can enhance cognitive function and the speed at which nerve impulses are conducted.
Exogenous Ketone Longevity Benefits
- Anti-cancer potential: Recent research suggests that ketogenic diets can blunt malignant tumor growth. This is due to the fact cancer cells can’t metabolize ketones effectively to nourish their growth and replication. Astonishingly, one study found that supplementing with BHB salts increases odds of survival in mice with systemic cancer by up to 70% in comparison to mice who didn’t receive exogenous ketones.
- Neuroprotective benefits: A natural part of the aging process is neurodegeneration, which is largely responsible for cognitive defects like Alzheimer’s disease. Recent research suggests that exogenous ketone supplementation can drastically slow neurodegeneration and the resulting decrease in mental function. However, the mechanism behind this finding remains to be elucidated; though, researchers suggest exogenous ketones act to reduce brain inflammation. Glucose, on the contrary, may actually accelerate inflammatory response in the brain.
- Anti-Inflammatory benefits: Exogenous ketones have anti-inflammatory properties in many bodily tissues by blocking the actions of inflammasomes – a subset of proteins that induce an inflammatory response.
Physiology of Exogenous Ketones: How they Work & How to Use Them
Shortly after consuming BHB, various metabolic adaptations occur:
- As noted earlier, research demonstrates that consuming BHB rapidly increases blood values of BHB in the body for as long as eight hours. In so doing, your body can enter nutritional ketosis rather quickly.
- BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells. With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.
- Animal research findings report that BHB supplementation also enhances oxygen utilization, especially in the central nervous system (CNS). While molecular oxygen is a crucial molecule for health and longevity, too much of it can be potentially toxic and speed the effects of aging in tissues throughout the body.Therefore, using a BHB supplement can effectively mitigate the toxic buildup of molecular oxygen, particularly in the CNS/brain.
In summary, exogenous ketones are surely going to be a hot niche of dietary supplements in the near future, and research will grow in order to verify their usefulness.
The extant data is somewhat compelling, but lacking human trials (which are best for testing dietary supplement claims).
Nevertheless, exogenous ketones hold promise as a cancer-preventing, overall longevity supplement.
They also seem potent for promoting cognitive function, managing blood sugar, and possibly enhancing weight loss and physical performance.
If you liked this article, we highly recommend reading more content on the benefits and practices of ketogenic dieting here:
- 5 Tips to Get You Into Ketosis Quickly
- Ketogenic Diet Myths You Have Always Believed Were True Debunked
- Everything You Need to Know about Ketosis
 Shannon L. Kesl, corresponding author Angela M. Poff, Nathan P. Ward, Tina N. Fiorelli, Csilla Ari, Ashley J. Van Putten, Jacob W. Sherwood, Patrick Arnold, and Dominic P. D’Agostino (2016). Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutrition & Metabolism, 13(9)
 Clark, V. L., & Kruse, J. A. (1990). Clinical methods: the history, physical, and laboratory examinations. JAMA, 264(21), 2808-2809.
 Cox, P. J., & Clarke, K. (2014). Acute nutritional ketosis: implications for exercise performance and metabolism. Extreme Physiology & Medicine, 3, 17.
 Yeh, Y. Y., & Sheehan, P. M. (1985, April). Preferential utilization of ketone bodies in the brain and lung of newborn rats. In Federation proceedings (Vol. 44, No. 7, pp. 2352-2358).
 Zhou, W., Mukherjee, P., Kiebish, M. A., Markis, W. T., Mantis, J. G., & Seyfried, T. N. (2007). The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition & metabolism, 4(1), 5.
 Poff, A. M., Ari, C., Arnold, P., Seyfried, T. N., & D’Agostino, D. P. (2014). Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. International journal of cancer, 135(7), 1711-1720.
 Hertz, L., Chen, Y., & Waagepetersen, H. S. (2015). Effects of ketone bodies in Alzheimer’s disease in relation to neural hypometabolism, β‐amyloid toxicity, and astrocyte function. Journal of neurochemistry, 134(1), 7-20.
 Hashim, S. A., & VanItallie, T. B. (2014). Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. Journal of lipid research, 55(9), 1818-1826.
 Youm, Y. H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., … & Kang, S. (2015). The ketone metabolite [beta]-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature medicine, 21(3), 263-269.
 Balasse, E. O., & Neef, M. A. (1975). Inhibition of ketogenesis by ketone bodies in fasting humans. Metabolism, 24(9), 999-1007.
 D’Agostino, D. P., Pilla, R., Held, H. E., Landon, C. S., Puchowicz, M., Brunengraber, H., … & Dean, J. B. (2013). Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 304(10), R829-R836.