Ketone Salts: Benefits for Health and Sports Performance

Alfredo Valdés 11 min. of reading Energy and Endurance Leave a comment

We analyse supplementation with ketone salts and its potential ergogenic effects, both for sports performance and health. Is it possible to take exogenous ketones?

How our body obtains energy

Our body has a highly refined bioenergetic system, which predominantly uses the oxidative energy production system (in the presence of oxygen); around 95% of our energy comes from this mechanism.

When energy demands increase significantly, for example during intense physical exercise, such as performing a HIIT session, the system prefers to break down glucose in the absence of oxygen in the cytoplasm of muscle cells (sarcoplasm).

Because it is faster and more effective.

Simplified graphic representation of human metabolism (catabolism above, anabolism below).

Although this process allows a greater amount of energy to be obtained, it quickly produces waste substances, protons, which alter the pH balance of the medium and produce acidosis.

That is why there is now so much talk about “metabolic flexibility”, that is, the ability to continue using aerobic metabolism even in situations of high energy demand.

Keto diet and energy

One of the most common questions is:

“If I follow a keto diet, I do not have glycogen available to obtain energy extensively and blood glucose has to remain stable… Where do I get energy from to train intensely?“

This is the question that has sparked debate regarding the possible negative effects of the ketogenic diet on sports performance, something I have already discussed in this article.

In fact, energy in a keto diet is obtained predominantly from free fatty acids and ketone bodies, which are the topic at hand, as they are responsible for providing most of the energy to muscles and the nervous system in keto diets.

What are ketone bodies?

Ketone bodies are organic acids produced predominantly in the liver, in cases where the capacity of the tricarboxylic acid cycle (formerly called the Krebs cycle) to produce the elements from which we obtain energy is exceeded.

Metabolism of β-Hydroxybutyrate (synthesis from fatty acids), transport into the blood, transport to the muscle cell and use as an energy source.

At that point, Acetyl-CoA (Ac-CoA in the previous image) is transformed into Acetoacetate, and this in turn into Beta-hydroxybutyrate, which is the most reduced ketone body, highly hydrophilic, that our body handles and uses easily.

It is a simple way to handle large volumes of energy intermediates that are produced by ceasing to use glucose predominantly.

Graphic representation of blood ketone concentrations and metabolic state, as well as their energy potential.

The amount of ketones produced in the body depends on the nutritional state we are in; normally, someone is considered to be in ketosis when their blood BHB concentrations are at 0.5mmol/L.

What is the role of exogenous ketones?

The exogenous administration of ketones has been proposed as a potentially useful strategy to increase energy availability in keto diets, even as an alternative mechanism for providing high amounts of energy nutrients in people who do not follow a keto diet.

What do ketones do? They put you into a state of nutritional ketosis, even if your carbohydrate intake is completely normal.

Ketone concentrations under different conditions. In red, the range normally achieved through supplementation with ketone salts.

The consumption of ketone salts can make it possible to reach concentrations of 1-5mmol/L of blood depending on the amount consumed, whether or not a ketogenic diet is followed, and genetic factors.

The effect is transient and lasts between half an hour and approximately 6 hours.

Benefits of Exogenous Ketones

Ketone salts as an energy source

We have already mentioned that the main virtue of ketone bodies, especially BHB, is to provide energy to muscle tissues, especially the heart, kidneys and muscles.

One study (a very interesting one, by the way) showed that the body uses exogenous ketones efficiently when they are administered.

Graph showing the % of the administered dose per gram of tissue in different organic structures.

Muscle tissue (of the musculoskeletal organ) is part of this group of systems capable of using ketones as an energy source, allowing amounts to be obtained that are not limited by the beta-oxidation of fatty acids and perhaps…

Facilitating the famous metabolic flexibility?

Metabolism of BHB (3-OH Butyrate).

Not only do our skeletal muscles (biceps, latissimus dorsi or vastus lateralis) use exogenous ketones, but our heart also uses them.

They can become an energy source with an important contribution to cardiac function during physical exercise, especially during a keto diet.

PET/CT with heat scale showing the activity of the tracer used (a ketone body). Notice the greater presence in the heart, which implies high utilisation in this organ.

If I do not follow a Keto Diet, can I use ketone salts?

It is true that, normally, for this energy-related purpose, ketone salts make sense when used by people who follow keto diets.

However, in people following diets for athletes with traditional nutrient distributions (>4g/kg CHOs), ketone salts may be useful by sparing glycogen.

In other words, they are used as energy that we already have in the blood, allowing us to “save fuel” that we have stored for when we need it.

Total oxidation of carbohydrates (CHO) and fats (FAT) in the control group (placebo) vs experimental group (ketone). (O’Malley et al. 2017).

Although the effects of this have not been directly evaluated, it may be presumed that ketone salts can increase athletes’ energy availability, a key aspect in ultra-endurance, for example.

Recovery and adaptations

The ketogenic diet is famous for its influence on the AMPK protein and its effect on autophagy.

Although this is true from a physiological point of view, it is not the only aspect of interest in the field of physical exercise.

The presence of sufficient amounts of BHB in the blood, achieved by following a keto diet or consuming ketone salts, has potential for the epigenetic regulation of genes such as NLRP3, linked to the inflammatory activity of the inflammasome, reducing it and potentially improving post-training recovery.

Ketogenesis and metabolic and genomic effects in skeletal muscle.

They have protective mechanisms for muscle tissue, reducing proteolysis and promoting positive protein turnover.

They can improve insulin sensitivity by increasing the utilisation of intramuscular triglycerides.

They can increase the transcriptomic activity of DNA by reducing the expression of the HDAC enzyme (histone deacetylase), increasing histone acetylation.

This may have antioxidant and cytoprotective effects (protecting cells from aggressions) and therefore, perhaps, help adaptation to training.

The proposed mechanisms are summarised in this image. Not bad when we are talking about a supplement, right?

Proteomic and metabolic effects of BHB.

Exogenous ketones and health improvement

BHB salts emulate the positive effects of the ketogenic diet on health.

At least in part, those of calorie restriction, a strategy that is strongly supported in animal models for its effectiveness in extending life expectancy.

One of the proposed mechanisms is through histone hypermethylation (via HDAC inhibition) and other genomic and non-genomic mediators.

Consequences of histone deacetylase inhibition on genomic methylation (blue), the modulation of different regulatory mechanisms (pink) and functional consequences (yellow).

A fascinating topic:

Could supplementation with BHB salts really have any positive effect on cell survival, protection of the DNA replication process and increased life expectancy?

Proposed biomolecular models for the regulation of life expectancy and the influence of BHB on them.

Of course, we are still a long way from being able to establish this, even in animals, which are the first step of in vivo evidence; but without doubt, the proposed models of action shed light and hope on a very promising strategy.

Metabolic modulations and cellular signalling mechanisms of BHB.

Especially regarding neurological protection, on which several trials have already been carried out with positive results, showing that the presence of ketone bodies in the blood has a positive effect on the regulation of neuronal survival and the neuroendocrinometabolic maintenance of these cells.

Effects of BHB in the body and those derived from activation of the GRP109A receptor (HCAR2).

Its possible effects on neurodegenerative diseases such as dementia, Parkinson’s, Huntington’s disease or Alzheimer’s are currently being investigated.

Potential therapeutic effects of ketone bodies in hypoxic-ischaemic encephalopathy (neurological disorder).

Conclusions

Could we emulate the potential positive health effects of ketogenic diets without following a keto diet, simply by taking a supplement?

Time will tell; for now, everything shines and looks very promising.

It is possible that exogenous ketones are here to stay as a strategy for increasing sports performance and, in my opinion, where they have the greatest potential: for improving cellular health.