Ketone Salts Supplementation

Ketone Salts Supplementation

Let’s analyze the properties of ketone salts and their potential ergogenic effects. Is it possible to take exogenous ketones?

The ketosis is a physiological state caused by a nutritional component.

When we considerably restrict the intake of carbohydrates, the body starts to empty its glycogen deposits (glycogenolysis). In other words, if we do not take this nutrient, it will use what is available in our body…

What happens when our glycogen reserves are low?

However, the glycogen that the body is capable of storing is limited (see figure I). So, depending on the:

  1. energy requirements of the subject
  2. the previous state of said deposits

These reserves can be completely emptied in a matter of days.

Glycogen content in liver and muscle

Figure I. Glycogen content in the liver and muscle. (Hargreaves, 2012; in Murray & Rosenbloom, 2018)

When this happens, the body needs to give up the main energy supply of the CNS and it uses it to resynthesize ATP.

Consequently, the body starts oxidizing fatty acids as practically the only source of energy

Said oxidation of the fatty acids can result in the accumulation of Acetyl-CoA in the mitochondria.

Moreover, its transformation into pyruvate stops when there is no glycolysis in the cytoplasm. This element is a precursor (through carboxylation) of oxalacetate, an intermediary that can limit the production of ATP (energy) in the Krebs cycle.

The Acetyl-CoA produced through the oxidation of fatty acids starts to gather in the mitochondrial matrix. There, it starts to undergo a series of processes that transform its excess in:

  • Acetoacetate
  • Acetone
  • Beta-Hydroxybutyrate

These ketone bodies will be used as energy by those organs that do not have glucose to synthesize ATP (specially the brain).


Figure II. Ketogenesis metabolism and its impact on the energy metabolism. Taken from:

What is BHB or Beta-Hydroxybutyrate?

The Acetyl-CoA that starts to accumulate in the mitochondria due to an excess or a lack of intermediary metabolites cannot just stay there. Therefore, the body starts using it to obtain Beta-Hydroxybutyrate.

It is the most abundant ketone body in the organism because it is the most reduced of them all. In other words, this means that Beta-Hydroxybutyrate works as an energy reserve. In fact, it is available in the organism until a cell needs energy.

This ketone body enters the cell mitochondria where it undergoes an inverse process:

Beta-Hydroxybutyrate -> Acetoacetate -> Acetoacetyl-CoA -> Acetyl-CoA

After obtaining Acetyl-CoA, we will be able to use it to produce ATP (energy) once again. However, this time there will not be an excess, just enough to complete the Krebs cycle.

According to this physiological evidence, there are a group of supplements known as “ketone salts”. These are basically made up of Beta-Hydroxybutyrate bound to an ion (BHB). But, what are ketone salts use for?

Ketone salts, why use them

First of all, we need to understand that an excess of ketone bodies will be excreted through the urine. Otherwise, their accumulation in the blood plasma can alter the pH and trigger acidosis (ketoacidosis).

Therefore, ketone salts are used to trigger a state of ketosis faster. But when we are already in ketosis, it will provide energy gradually.

Most of the studies that have tried to prove that taking exogenous ketone salts enhances the sport performance have failed. For example, O’Malley et al. (2017) compared an experimental group with a control group that was not in ketosis. In fact, its intake without a carbohydrate restriction is pointless.

Although some of the readers may reject this idea… The ketosis is a physiological state with clinical purposes, but not for the sport performance. This is due to the fact that the time until we become exhausted is directly conditioned by the amount of carbohydrates from the diet. Therefore, it will directly affect the energy availability through the glycolysis (See figure II).

Glucose oxidation

Figure III. Relation between the oxidation of glucose, fat and exercise duration until exhaustion with different diets.(Guyton & Hall, 2016)

However, taking ketone salts has actually improved the fat and carbohydrate metabolism markers. Apart from triggering a state of ketosis in human beings

Taking Ketone Salts before the workout

First of all, increasing the serum ketone bodies by taking 0.3g/kg of body weight of pre-workout B-Hydroxybutyrate will: increase the oxidation of fatty acids in a 23% and reduce the glucose oxidation in an 8%.

Carbohydrate total oxidation

Figure IV. Carbohydrate total oxidation (CHO) and fat (FAT) in the control group (placebo) vs experimental group (ketone). (O’Malley et al. 2017)

What does this mean?

  • Taking the previous dose of ketone salts before the workout can produce ergogenic effects. These are interesting when it comes to enhancing the oxidation of fatty acids and, consequently, to burn fat.
  • Moreover, it can be an interesting strategy if we want to save organic glycogen during competitions. In fact, its integrity is determinant for the performance, since it reduces its oxidation.

Ketone Salts vs Esters

Up until now, we have talked about taking ketone salts. Above all, this is the most accessible way of getting B-Hydroxybutyrate (BHB)

However, a study by Stubss et al. (2017) that used both ketone salts and esters showed how the ketone concentrations were higher with the ester and not the salt.

D-Beta-Hydroxybutyrate Concentration

Figure V. Serum concentration (measured in mMoles) of D-Beta-Hydroxybutyrate from its intake until 4 hours later. (Stubbs et al. 2017)

The urinary excretion of ketones is significantly higher with esters than with the salts. Consequently, taking ketone esters seems to increase the D-Beta-Hydroxybutyrate serum concentrations more than the salts. In addition, it also produces a higher breakdown of said substance, so the final result is quite similar in the end.

Concentrations of free fatty acids, triacylglycerol and glucose

Figure VI. Serum concentrations (measured in mMoles) of free fatty acids (A), Triacylglycerol (B) and Glucose (C) from its intake until 4 hours later with different doses (Stubbs et al. 2017)


Despite the superiority of ketone esters over ketone salts, both have similar effects without significant differences

Taking a ketone salt drink considerably reduced the plasma concentrations of fatty acids (from 0.7 to 0.4mM), triacylglycerides (1.1 to 0.9mM) and glucose (from 5.7 to 4.8mM) after an hour. In the end, these levels went back to normal after 4 hours of its intake.

All in all, this proves that the ergogenic effects of exogenous ketones are acute and not chronic

However, these results show how taking exogenous ketones can have clinical benefits in people who suffer metabolic disorders.


  1. Hall, J. E., & Guyton, A. C. (2016). Guyton & Hall Compendio de fisiología médica (12a. ed.). Barcelona [etc.]: Elsevier.
  2. Murray, B., & Rosenbloom, C. (2018). Fundamentals of glycogen metabolism for coaches and athletes. Nutrition Reviews, 76(4), 243–259
  3. O’Malley, T., Myette-Cote, E., Durrer, C., & Little, J. P. (2017). Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Applied
  4. Trevor O’Malley, Etienne Myette-Cote, Cody Durrer, Jonathan P. Little. Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males.
  5. Stubbs, B. J., Cox, P. J., Evans, R. D., Santer, P., Miller, J. J., Faull, O. K., … Clarke, K. (2017). On the Metabolism of Exogenous Ketones in Humans. Frontiers in Physiology, 8, 848.

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About Alfredo Valdés
Alfredo Valdés
He is a specialist in metabolic physiopathology training and in the biomolecular effects of food and physical exercise.
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