Exogenous Ketones: The 10 Things You Must Know!

At their most basic, exogenous ketones are ketones that occur outside the body (e.g. supplement, food, etc.). Chemically speaking, ketones comprise a class of organic molecules that contain a central carbon atom bonded to oxygen and two carbon-containing chemical groups.

As a byproduct of lipolysis (fat breakdown), the liver creates several different ketones, including beta-hydroxybutyric acid (BHB), acetone, and acetoacetic acid. In terms of chemical structure, BHB isn’t a ketone body as it has a reactive -OH (hydroxyl) group where an oxygen atom normally would be present; nevertheless, BHB works like a ketone throughout the body.

Ketones provide your body with an alternative fuel source, and also work as a signaling molecule, particularly in mitochondria - cellular “power generators”. Fats (and ketones) are necessary nutrients for our survival (especially if carbohydrate consumption is limited).

How Exogenous Ketones Work

Exogenous ketones are naturally-derived compounds that combine a salt, such as sodium, calcium, or magnesium with BHB to improve intestinal absorption. This grants users additional benefits by providing the necessary electrolytes to keep you hydrated and performing at max capacity.


Promptly after ingesting BHB salts, a variety of metabolic adaptations take place:

  • Research shows that ingesting BHB salts is an efficient way to rapidly increase plasma levels of BHB (up to 3 mMol) for 7-8 hours. This means your body will enter a state of ketosis relatively quickly.
  • Consuming BHB salts can boost insulin sensitivity and promote utilization of oxygen throughout the body. For gym-goers, bodybuilders, and fitness aficionados alike, enhancing insulin sensitivity with exogenous ketones is an exceptional benefit. This puts your body in prime position to use carbohydrates for assisting muscle repair and energetic purposes rather than converting them to fat.

Why Use Exogenous Ketones?

Taking exogenous ketones gives your body an instant supply of BHB. As long as you're following a low-carbohydrate diet, the consumption of exogenous ketones causes your body to “switch on” ketosis rapidly (in as little as 15 minutes) and lasts upwards of eight hours. This translates to a multitude of benefits, which we will be detailed in the following sections.

Exogenous Ketones: Benefits and Health Applications

Easier, More Efficient Fat Loss

  • Decreases food cravings: In a 4-week trial, rats who consumed exogenous ketones exhibited significantly less weight/body fat gain than rats receiving no supplement.[3] It is postulated that the reduced weight gain is a result of exogenous ketones reducing overall food intake/energy consumption.
  • Boost mitochondrial content and function: Mitochondria are basically the engine that converts fat into ATP for fuel. Ketones increase the number and function of these engines so you can burn more fat for fuel, faster.

Performance Enhancement and Nootropic Properties

  • Athletic performance enhancement: Taking BHB salts can create a state of ketosis lasting 7-8 hours, enacting the physiology of fasting (i.e. increased fatty acid oxidation, elevated growth hormone secretion, etc.).[4] Moreover, BHB salts are a unique sports supplement that can elevate ketone values in the blood while muscle glycogen remains substantial (decreased muscle glycogen is well known to impair sustained physical performance). Essentially, athletes can benefit from BHB salts before training or competing.
  • Nootropic properties: Research shows that exogenous ketones can support cognitive function and enhance mental processing by encouraging the manufacture of phospholipids in the brain.[5]  Phospholipids are key substrates that regulate hypertrophy and integrity of neurons.

Health and Longevity Benefits

  • Anti-carcinogenic: Cancer cells appear to lack the capacity to appropriately use ketone bodies for replication and growth. In fact, one study shows that exogenous ketone use increased the survival rates of mice with cancer upwards of 70% in contrast to mice taking no supplemental ketones.[6]
  • Neuroprotection: Recent demonstrates that supplemental ketone intervention can significantly slow the neurodegenerative process and ensuing decline in cognitive capacity.[7] While the mechanism underlying this phenomenon is yet to be elucidated, researchers surmise that ketones work to decrease inflammatory response in the brain. Contrarily, glucose/sugar has been shown to increase inflammation throughout the brain.[8]
  • Anti-Inflammatory: BHB salts may reduce inflammation by effectively inhibiting the activity of inflammasomes - special proteins that mediate inflammatory response.[9]

Wrap-Up

Exogenous ketones are going to be a hot topic of research in the coming years. While there is good evidence of the performance-enhancing and health benefits of BHB salts, you can expect to see more studies surfacing that investigate the potential benefits of this revolutionary class of sports supplements.

References

  1. Balasse, E. O., & Neef, M. A. (1975). Inhibition of ketogenesis by ketone bodies in fasting humans. Metabolism, 24(9), 999-1007.
  2.  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.
  3.  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)
  4.  Cox, P. J., & Clarke, K. (2014). Acute nutritional ketosis: implications for exercise performance and metabolism. Extreme Physiology & Medicine, 3, 17.
  5.  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).
  6.  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.
  7.  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.
  8.  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.
  9.  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.
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