Exogenous Ketone Supplements

Intro

Work on exogenous ketone supplements began in the early 2000's and have recently garnered a large amount of attention when their use was rumoured in the Tour de France by several professional cycling teams. Since then, there has been a lot of claims made about the benefits and use of these supplements (improved cognition/weight loss/clinical benefits) with very little published research to back them up, but this is now changing as more groups are applying for and gaining access to funding for projects. Their main purpose is to increase the levels of circulating ketones in the blood without being in a carbohydrate depleted state such as starvation or a ketogenic diet. Through the modulation of carbohydrate/fat/protein metabolism and intracellular signalling that they are theorised to improve athletic performance/recovery/adaptation.

Ketone bodies (KB) are short chain, four carbon organic acids and are now readily available in a number of commercial supplements. Beta-hydroxybutyrate (BHB) is the most abundant KB in the blood and the one used (for the most part) in these products. Supplementation of KB in their free acid form is both expensive and ineffective at producing nutritional ketosis, so they are combined with other molecules to improve absorption. 

Types of Ketone Supplements:

(i) Ketone Salts: The most common KB supplements available to the general public, which is simply a BHB molecule attached to a sodium/magnesium/pottasium/calcium salt. One typical serving of BHB salts delivers 12-13g of BHB and 1.5g sodium and has the ability to increase circulating KB to 0.5-1.0mM. They can be in either liquid or powder form and are considered equally as effective. 

Data from KetoSports KetoForce 

(ii) Ketone Esters: Primarily used in research, a BHB/AcAc molecule attached to an alcohol unit. There are two prominent ketone esters: the R,S-1,3-butanediol acetoacetate diester currently used in Dominic D'agostino's lab and the Veech (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester. Acute ingestion of either ester can result in short-term (0.5 to 6 h) nutritional ketosis indicated by BHB concentrations >1 mM. For the Veech ketone monoester, ingestion at a dose of 573 mg/kg body weight resulted in BHB concentrations of 3.0 mM after 10 min and rising to 3.0 mM 30 min after ingestion

From Cox et al. (2016) in Cell Metabolism

(iii) Added Ingredients: A lot of KB products you'll see contain extra ingredients such as MCT oils and amino acids. These ingredients are added to further enhance their ketogenic properties, with some being more efficacious than others. MCT oils may be worth adding in (make sure it's C8) for it's ability to stimulate ketogenesis in the liver as there is a linear relationship between dose of MCT ingested and blood BHB concentrations. Some amino acids (leucine, lycine) are ketogenic but their contribution to a ketogenesis is very small.

From Cunnane (2016) from Annals of the New York Academy of Sciences

Below is a list (click to visit spreadsheet) of the current exogenous ketone products available on the market 

Problems With Ketone Supplementation:

(i) Taste: There have been progress made in this area but people tend to find the supplements hard to swallow after repeat bouts.

(ii) Cost: More expensive than your average sport supplement with the ketone esters currently going in the thousands/litre.

(iii) Gastro-intestinal problems: Nausea/diarrhoea/vomiting etc. can occur when ingesting large volumes all at once. 

Key Points:

1. Research on KB supplementation and its applications is still in the early stages (both clinically and in sporting applications) so its use must be considered on a case by case basis (if at all until more research presents itself)

2. Consider the type of supplement you use as ketone esters are more efficacious at raising blood levels. Mixing ketone salts with other ingredients such as MCT oils may further enhance their ketogenic capacity. 

3. When first using products like these, titrate yourself on to them, as large doses can cause stomach problems. 

References

Abraham R. Ketones: controversial new energy drink could be next big thing in cycling. 2015. http://www.cyclingweekly.co.uk/news/latest-news/ketones-controversial-new-energy-drink-next-big-thing-cycling-151877

Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB & Veech RL (2012). Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol 63, 401–408. 

Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL & Clarke K (2016). Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab 24, 256–268. 

Cunnane SC, Courchesne-Loyer A, St-Pierre V, et al. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease. Ann N Y Acad Sci 2016; 1367: 12–20.

Evans, M., Cogan, K. E. and Egan, B. (2016), Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol. doi:10.1113/JP273185

https://ketosource.co.uk/exogenous-ketones-how-they-work/

Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P & D’Agostino DP (2016). Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond) 13, 9. 

Pinckaers PJ, Churchward-Venne TA, Bailey D & van Loon LJ (2016). Ketone bodies and exercise performance: the next magic bullet or merely hype? Sports Med. (in press; DOI: 10.1007/s40279-016-0577-y).