WHAT ARE EXOGENOUS KETONES?

You may have read our previous article about a Ketogenic Diet explaining what ketosis is and how ketones are produced naturally inside the body. Well, this article focusses on Exogenous Ketones, ketones which are produced outside the body.

Endogenous – Originates from a source internal to the body

Exogenous – Originates from a source external to the body

Ketones, aka ketone bodies, are a result of the body burning fat instead of glucose as its major fuel source. The body goes into a state of natural ketosis when carbohydrates are limited to no more than 20g per day. Exogenous ketones are lab-made supplements which provide an instant supply of ketones to the body (peaks at ~1-2 hours), without the prior depletion of carbohydrate reserves (Cox 2014, Pinckaers 2017).

Ketones are a result of increased glycogen breakdown, gluconeogenesis (generation of glucose), lipolysis (the breakdown of fats), fatty acid oxidation and ketogenesis (Comstock 1990). When exogenous ketones are ingested, they undergo many biological processes with the end result of Acetyl-CoA molecules. Acetyl-CoA then enters the Krebs Cycle and generates a source of energy known as adenosine triphosphate (ATP), as can be seen in the image below.

Acetoacetate (AcAc) and Beta-Hydroxybutyrate (BHB) are formed endogenously by the liver in response to low blood glucose and insulin levels (Cox 2014). BHB is the ketone used in most commercial supplements.  

Ketone Esters: Synthetically made compounds which link an alcohol to a ketone and is metabolised in the liver. These are unpleasant in taste and mostly used in research environments.

Ketone Salts: Naturally derived compounds which mix ~1g sodium (most common), calcium or potassium with ~8-12g BHB to improve its absorption (Pinckaers 2017).

• Endurance athletes – Elevate ketone levels without the prior depletion of muscle carbohydrates (Cox 2014).
• Cognition – Studies have shown that the brain (which normally utilises glucose for energy) can readily utilise ketones as an alternative fuel (Hashim 2014).
• Epilepsy, Parkinson’s Disease, Alzheimer’s Disease – Exogenous ketones, in relatively low doses, have an ameliorating effect on cognitive function (Hashim 2014, Hertz 2015, Pinckaers 2017).
• Oxidative Stress – Exogenous ketones have been shown to be protective against oxidative stress in rodent studies (Kim 2007). Further research on humans is required.
• Cancer – Inhibit the growth and viability of tumour cells, even in the presence of high glucose. Ketone administration showed anti-cancer effects in vitro (test tube) and in vivo (living organism – rodents) independent of glucose levels or calorie restriction (Poff 2014).
• Cardiovascular – Data obtained from rodents demonstrated a 28% increase in cardiac efficiency in response to combined glucose and ketones, as opposed to glucose alone (Pinckaers 2017).

Not only have exogenous ketones been linked with abdominal distention and headaches, but they have also been shown to reduce lipolysis (fat burning) in both active and sedentary individuals (Pinckaers 2017, Fery 1988). This action is hypothesised to be due to reduced circulatory free fatty acid (FFA) availability and/or the stimulation of excessive insulin release (Pinckaers 2017, Fery 1988).  While there are only limited studies suggesting reduced lipolysis, as exogenous ketones are frequently marketed as a weight loss strategy, this is important for individuals to know, and for researchers to study further.

While there is an abundance of research identifying all the benefits of exogenous ketones, it is important to remember that the body is in an unnatural state of ketosis which is extremely different to the metabolic conditions of naturally going into ketosis through dietary means (Cox 2014). Whether exogenous ketones ‘spare’ carbohydrate reserves or impair carbohydrate utilisation is unclear (Pinckaers 2017). Most research papers suggest further research to study the long-term effects of exogenous ketone supplementation. It is recommended that consumers of exogenous ketones remain up to date with scientific evidence and seek advice from a healthcare professional for their individual needs.

• Exogenous ketones are lab-made supplements which provide an instant supply of ketones to the body without the prior depletion of carbohydrate reserves.
• BHB is the ketone used in most commercial supplements.
• Ketone Salts are naturally derived compounds which mix ~1g sodium (most common), calcium or potassium with ~8-12g BHB to improve its absorption.
• Exogenous ketones can benefit individuals with epilepsy, Alzheimer’s Disease, Parkinson’s’ Disease as well as endurance athletes. Rodent studies show promising results with cancer, cardiovascular health and oxidative stress.
• Side effects of exogenous ketones may include headaches, abdominal distention and reduced lipolysis.
• Further research is required to study the long-term effects of exogenous ketone supplementation.

Comstock, J., Garber, A. 1990. ‘Ketonuria’. Clinical Methods: The History, Physical and Laboratory Examinations. 3rd Edn. Chapter 140. Source:  http://www.ncbi.nlm.nih.gov/books/NBK247/

Cox, P., Clarke, K. 2014. ‘Acute nutritional ketosis: implications for exercise performance and metabolism.’ Extreme Physiology and Medicine, vol 3, no. 17. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212585/

Ferry, F., Balasse, E. 1988. ‘Effect of Exercise on the Disposal of Infused Ketone Bodies in Humans.’ The Journal of Clinical Endocrinology and Metabolism, vol 67, no. 2, pp. 245-50. Source: http://academic.oup.com/jcem/article-abstract/67/2/245/2651771/Effect-of-Exercise-on-the-Disposal-of-Infused?redirectedFrom=fulltext

Hashim, S., Vanltallie, T. 2014. ‘Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.’ Journal of Lipid Research, vol 55, no. 9, pp. 1816-26. Source:  http://www.ncbi.nlm.nih.gov/pubmed/24598140

Holdsworth, D., Cox, P., Clarke, K. 1967. ‘Oral ketone body supplementation accelerates and enhances glycogen synthesis in human skeletal muscle following exhaustive exercise.’ Department of Physiology, Anatomy and Genetics, pp. 32-56. Source:

http://www.physoc.org/sites/default/files/BBEP2016_abstracts_oralcomms.pdf

Kim, D., Davis, L., Sullivan, P., Maalouf, M., et al. 2007. ‘Ketone bodies are protective against oxidative stress in neocortical neurons.’ Journal of Neurochemistry, vol 101, no. 5, pp. 1316-26. Source: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2007.04483.x/full

Pinckaers, P., Churchward-Venne, T., Bailey, D., van Loon, L. 2017. ‘Ketone Bodies and Exercise Performance: The Next magic Bullet or Merely Hype?’, Sports Medicine, vol 47, no. 3, pp. 383-91. Source: http://link.springer.com/article/10.1007/s40279-016-0577-y

Poff, A., Ari, C., Arnold, P., Seyfried, T., et al. 2014. ‘Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer’, International Journal of Cancer, vol 135, no. 7, pp. 1711-20. Source: http://www.ncbi.nlm.nih.gov/pubmed/24615175

Kelly Hodges, BNutrDiet – Accredited Practicing Dietitian