Overview

Exogenous ketones (also known as ketone supplements) raise beta-hydroxybutyrate levels in the blood (BOHB). The idea is to assist the body in burning fat as its major source of energy rather than carbohydrates.

Key Benefits

• It suppresses hunger and lowers cravings by causing the body to burn fat for fuel.
• Supports in post-exercise recuperation
• Aids in endurance performance
• Helps in brain energy metabolism
• Aids in the reduction of glucose
• Helps in the reduction of blood lipids
• Improves insulin sensitivity

History of Usage

Ketones are chemicals made in the liver. The body produces them when it doesn’t have enough insulin to turn glucose into energy. Ketone monoesters, which were very recently created, are a dietary source of ketones that boost d-β-hydroxybutyrate (βHB) – a compound used by the brain as an energy source when blood glucose levels are low.

Historically, the only way to raise blood ketone levels was to fast for several days or to follow a strict low-carb, high-fat diet. Ketone drinks and supplements, which have just been available on the market for a couple of years, are currently very interesting. Since they are so new, there has been very little research on how to affect metabolism.

What we do know is that ketone supplements raise βHB to comparable quantities in minutes, with βHB remaining elevated for several hours.

Ketone supplements facilitate acute ingestion of βHB that results in nutritional ketosis without practicing a restrictive diet. According to preliminary findings, this method modifies the metabolic response to exercise and enhances exercise performance. Other studies suggest roles in recovery from exercise, and many other possible health benefits. The research into how these function in the body and what benefits they offer is still evolving.

There are already a number of such products available for sale – chemical compounds – that help your body make better use of your own ketones.

Biochemistry

There are two general formulations for dietary exogenous (EK) ketone supplements: salts derived from the keto-acid or an ester formed between the keto-acid and alcohol.

Ketone salts are made by adding artificial ketones to electrolytes such as calcium, magnesium, potassium, and sodium to improve the absorption of the ketones already existing in your body. They are available in drinks, pills, and powders. This metabolic state doesn’t last as long as it does with ketone esters.

The most active type of exogenous ketones is ketone esters. They are synthetically made compounds that link alcohol to a ketone body with the hopes of increasing one’s own ketone levels for the sake of increased weight loss or increased ketone-fueled performance. They can cause longer ketosis periods than other EK supplements. But these are more expensive and usually have a strong, unpleasant taste.

Ketone supplementation elevates blood levels of the ketone bodies: HB, acetoacetate (AcAc), and acetone. These compounds have a positive effect on mitochondria, glycolysis, neurotransmitter levels, free fatty acid receptor 3 (FFAR3), hydroxycarboxylic acid receptor 2 (HCAR2), and histone deacetylase activity, as well as the NOD-like receptor pyrin domain 3 (NLRP3) inflammasome and mitochondrial uncoupling protein (UCP) expression.

When glucose availability is low, the liver produces ketone bodies, which serve as an alternate fuel source for peripheral tissues such as the brain, heart, and skeletal muscle. Nutritional ketosis caused by the supplement leads to metabolic alterations and improvements in mitochondrial function and inflammatory processes.

Typical doses on the market are 11.7g of βHB. It is advised that consumers start at 5g of βHB per day to avoid Gi distress and gradually increase the dose every 3 days to achieve the desired energy performance and tolerability.

Recent Trends

Intermittent fasting and the keto diet trends have boosted the market for ketone supplements. As a result, exogenous ketones are now included in morning beverages to help consumers maintain their fast, in “clean energy drinks” and “shots,” in meal replacements, coffee creamers, and endurance formulas.

The global market size of the ketones is estimated at a growth rate of $6.3 percent between $443 million in 2021 and $640 million by 2026. The use of ketone supplements among athletes is believed to be the main factor that’s driving the market.

Precautions

• Pregnant and breastfeeding women should not take ketones.
• Diabetics should not take ketones without consulting their health care provider.
• Gastrointestinal upset may result after taking ketones.
• Consuming adequate amounts of water is important.

References

1. Stubbs, Brianna J, Cox, Pete J, Clarke, Kieran. ON the Metabolism of Exogenous Ketones in Humans. Frontiers in Physiology, 2017; 8; 849.
2. Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol. 2017 May 1;595(9):2857-2871. doi: 10.1113/JP273185. Epub 2016 Dec 7. PMID: 27861911; PMCID: PMC5407977.
3. Kovács Z, D’Agostino DP, Diamond D, Kindy MS, Rogers C, Ari C. Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature. Front Psychiatry. 2019 May 23;10:363. doi: 10.3389/fpsyt.2019.00363. PMID: 31178772; PMCID: PMC6543248.
4. Soto-Mota A, Vansant H, Evans RD, Clarke K. Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regul Toxicol Pharmacol. 2019 Dec;109:104506. doi: 10.1016/j.yrtph.2019.104506. Epub 2019 Oct 23. PMID: 31655093.
5. Deemer SE, Plaisance EP, Martins C. Impact of ketosis on appetite regulation-a review. Nutr Res. 2020 May;77:1-11. doi: 10.1016/j.nutres.2020.02.010. Epub 2020 Feb 20. PMID: 32193016.
6. Jensen NJ, Wodschow HZ, Nilsson M, Rungby J. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Int J Mol Sci. 2020 Nov 20;21(22):8767. doi: 10.3390/ijms21228767. PMID: 33233502; PMCID: PMC7699472.
7. Myette-Côté É, Neudorf H, Rafiei H, Clarke K, Little JP. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. J Physiol. 2018 Apr 15;596(8):1385-1395. doi: 10.1113/JP275709. Epub 2018 Mar 2. Erratum in: J Physiol. 2019 Nov;597(22):5515. Abstract corrected. PMID: 29446830; PMCID: PMC5899975.