What Are Exogenous Ketone Supplements?

While ketones are produced naturally by the body (and have been around as supplements for decades), the exogenous ketone debate is bubbling up in pro cycling and triathlon. What do you need to know?

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As competitive athletes, we’re often looking for a performance edge. This increase in performance can come in the form of the newest super-bike, carbon fiber wheels, more scientific training, or better recovery. Recently, exogenous ketones have entered the realm—prompting bans and debate in pro cycling. As a potential fuel source, ketones have been around for many years. This topic has long had strong supporters and strong opponents. Now, the ketone debate is back!

Exogenous ketone supplements show great potential for improving aerobic endurance and recovery; however, the long-term effects are still relatively unknown. We’re not here to convince you whether or not exogenous ketones are good or bad, but to inform you about the current research on this nutritional supplement.

Ketone supplements: What are they, and what do they do?

Ketones are a potential fuel source to assist endurance athletes in going further. Typically, the body produces ketones in the liver when there is low carbohydrate (CHO) availability. To understand ketone’s place in energy production, let’s discuss how the body uses energy.

We ingest three macronutrients when we eat: CHO, fats, and proteins. Protein is not an energy source; however, CHO and fats are used to create energy. These two macronutrients are used to create a molecule called adenosine triphosphate (ATP). ATP is the “currency” for all processes in the body. For example, when a muscle contracts, it utilizes ATP. The human body produces ATP via aerobic (with oxygen) and anaerobic (without oxygen) pathways. The rate at which ATP is needed (i.e., the exercise intensity) determines the primary pathway for ATP production. For example, you will need ATP at a faster rate when performing a 400m sprint vs. running a 5K. Each of these events is performed at different exercise intensities.

RELATED: What’s the Difference Between Aerobic and Anaerobic?

Fats are initially the primary fuel source. As intensity increases toward the lactate threshold, CHO makes up more of the fuel percentage to create ATP. Once the exercise intensity exceeds the threshold up to VO2 max, CHO is the only fuel source. Fats are not a fuel source when exercise intensity exceeds the threshold.

VO2 Max and lactate threshold with the traditional six training zones, showing fuel source spectrum.

Ketones come into play as a fuel source once the body has little to no CHO available. Ketosis is the process when the body burns fats and produces endogenous ketones to create ATP. The liver, where ketones are produced, creates two main types of ketones, acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB). To utilize these sources as energy, an athlete must follow a stringent low CHO diet; these diets are generally called ketogenic diets. These diets do not work for everyone and can have unpleasant side effects such as fatigue, confusion, lightheadedness, etc. When an athlete reaches ketosis, the endogenous ketones (i.e., the ones created within your body naturally) play a role as a fuel source. The attractiveness of exogenous ketones (i.e., external ketones taken as supplements) is that they increase blood ketone levels without following a strict ketogenic diet.

RELATED: Can the Keto Diet Work for Endurance Athletes?

What are exogenous ketone supplements—and how do they produce energy?

Exogenous ketones are any type of ketone you ingest from an external source. They come in two forms, ketone esters and ketone salts. Each version costs about $40-$80 per dose. As of the article’s writing, DeltaG is the only ketone ester to be shown to work via peer-reviewed research. The attractiveness of exogenous ketones is the ability to tap into their potential benefits without following a low CHO or restrictive caloric diet. As with endogenous ketones, exogenous ketone esters come in two forms: 3HB and AcAc.

Exogenous and endogenous ketones are used to create ATP via the aerobic pathway. (Ketones are not a fuel source for ATP production via anaerobic pathways.) They enter the cell and the aerobic pathway at the point where the cycle is in the mitochondria. Once the ketones enter this cycle, the process for creating ATP is the same as if glucose was the fuel source. No matter the fuel source for the aerobic pathway, 36 ATP are produced versus the two ATP produced via anaerobic glycolysis. Based on this information, you might be asking yourself, “What is the benefit of taking exogenous ketones?” Well, we’ll get to that next.

ATP is produced via aerobic and anaerobic pathways. Endogenous ketones are made in the liver while exogenous ketones are ingested. Both types of ketones enter the cell and enter the aerobic pathway at the Tricarboxylic (TCA) Cycle in the mitochondria to produce ATP. However, endogenous and exogenous ketones are not a fuel source for ATP production via anaerobic processes. Note. The human body has two anaerobic pathways: the phosphagen pathway and glycolysis. This figure only depicts glycolysis for ATP production. The phosphagen pathway is not shown or discussed.

What are the benefits of taking ketone supplements?

By taking exogenous ketones, you artificially increase the ketone levels in your blood. You would need to go into ketosis via a deficient CHO diet to do this naturally. However, a body of research shows performance benefits to increasing blood ketone levels via exogenous means.

A series of studies conducted by Dr. Kieran Clarke shows exogenous ketones have a “CHO sparing effect.” The authors hypothesize that exogenous ketone usage reduces the body’s reliance on CHO as a fuel source to produce ATP, but increases fats as the fuel source in trained athletes. In the study, the trained athletes who drank a ketone-CHO mix went 2% further during a cycling time trial than those who drank a CHO-only mix. While this is not large for the majority of age-group athletes and was not seen in untrained athletes, the 2% improvement is significant for high-performing age-group athletes and elites. At the highest levels of endurance sports, winning could be a difference of less than a second.

Another potential enhancement from exogenous ketones is an improved recovery. A series of studies (Holdsworth et al., 2017, Vandoorne et al., 2017, Poffe et al., 2019) showed that if a trained athlete takes the proper amount of CHO and protein post-workout with a ketone monoester (as recommended by the manufacturer), recovery time was improved. The hypothesis behind this phenomenon is two-fold. The first aspect of the hypothesis is that ketones have an anti-oxidant effect by scavenging free radicals caused by exercise. As a result, muscle repair will occur more rapidly by eliminating the free radicals, and ATP production pathways are less likely to be blunted. The second aspect of the hypothesis is that the “glucose sparing” effect means the glucose stores do not need to be replenished as much. In short, less fuel and less time must be filled to repeat workouts.

The performance enhancements of exogenous ketones sound impressive. However, they are not for everyone. The performance improvement and recovery only appear to be seen in well-trained athletes, not untrained athletes. This means that a novice triathlete will not see these performance improvements. Additionally, the performance enhancements are only seen in certain well-trained athletes. Like with any nutritional supplement, performance enhancement does not occur in everyone.

Exogenous ketones also have a number of acute side effects. These side effects include the following: flatulence, nausea, diarrhea, dizziness, heartburn, and metabolic acidosis. Metabolic acidosis is a drop in blood pH below 7.0 (the blood becomes more acidic). While this phenomenon does occur naturally during exercise, the body can compensate for it, but the body has difficulty maintaining pH caused by external sources. A study by Poffe et al. demonstrated bicarbonate could mitigate metabolic acidosis in some athletes. However, sodium bicarbonate also has many side effects, such as flatulence, vomiting, and diarrhea.

Even with these known performance enhancements, ketone supplementation also has significant performance degradation. The ketone “CHO sparing” effect appears to limit high-end efforts. This limiting of CHO means sprinting capacity and higher intensity workloads are more likely to be diminished. This is caused by limiting the fuel source for ATP production. (Remember, CHO is the only fuel source used to produce ATP via anaerobic pathways, and exercise intensity determines the energy pathway that primarily produces ATP.) Exercise efforts above the lactate threshold up to VO2 Max require CHO as the fuel source. If the body cannot utilize CHO for anaerobic efforts, this aspect limits the athlete’s ability to perform high-intensity efforts. Remember, ketones cannot be a fuel source for efforts above the lactate threshold; they are only used via the aerobic pathway.

Finally, no research shows the long-term effects of exogenous ketone usage on human physiology. Researchers do not know if this supplement causes any long-term negative changes. The research has not evolved enough yet.

Exogenous ketones are shown to have performance-enhancing properties with increases in aerobic endurance and improved recovery time. However, not everyone sees these benefits and exogenous ketones have acute side effects. The Australian Institute of Sports has a series of easy-to-read handouts and pamphlets on ketone supplementation. By knowing the benefits and limitations of exogenous ketone supplementation, you can decide whether it’s right for you.

RELATED: Triathlete’s Complete Guide to Nutrition and Fueling

Chris Myers has a PhD in exercise physiology and is a USAT and Ironman-certified coach who works with triathletes of all abilities. 

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