Exogenous Ketones: What Health and Exercise Professionals Need to Know

The ketogenic diet is a hot topic in nutrition today. Keto recipes are everywhere and everyone knows someone who has at least tried the keto diet. But what exactly are “exogenous ketones,” where are they found, and how do they impact health and performance?

What are Ketones?

Ketones (also referred to as ketone bodies) are metabolites of fat oxidation and are produced in the liver. The foremost circulating ketones in the blood are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB). Their primary function is providing brain fuel because the brain can only utilize glucose and ketone bodies for energy. Additionally, ketones can function as hormone signalers and be oxidized in muscles during exercise.

Nutritional Ketosis

Nutritional ketosis (i.e., increased ketone levels in the body) can be achieved in multiple ways, including fasting, following a carbohydrate-restricted diet (<50 grams/day), prolonged exercise without carbohydrate intake, or by consuming exogenous ketones. Exogenous means consuming a product (produced outside of the body), whereas endogenous describes breaking down stored fuels in the body (typically carbohydrate, fat and protein).

The terms ketosis and ketogenic have slightly different meanings. Ketosis describes elevated blood ketone levels from either endogenous or exogenous ketones (i.e., produced from the liver or taken as a supplement). Ketogenic describes a state of elevated ketone bodies from following a low-carbohydrate, high-fat diet (such as the ketogenic diet).

Forms of Exogenous Ketones

Exogenous ketones are available in two forms: salts and esters (both mono- and di-esters). Ketone salts are commercially available, relatively affordable (~$4/serving) and palatable (taste similar to sports drinks). They have only a mild impact on ketone levels, usually raising blood ketone levels to around 1 mmol, and carry a high salt load (as the ketone body chemically needs to be attached to sodium, potassium or magnesium).

Ketone esters, conversely, significantly impact blood ketones, potentially raising levels to 3-4 mmol within 20 to 30 minutes of ingestion. However, they are not widely available. At the time of this publication, one product is commercially available and is extraordinarily expensive at ~$30/serving. At this time, ketone esters are largely only accessible for research purposes, which is in its infancy.

Application and Research on Exogenous Ketones

To date, limited human-subject research has examined the effects of exogenous ketones for endurance performance. Interestingly, the two most substantial studies have conflicting results.  Cox et al. (2016) and Leckey et al. (2017) demonstrate positive and negative results, respectively. However, it is worth noting that these two studies had significant differences in the testing protocols employed by the researchers.

Proponents believe that the potential benefits of exogenous ketones stem from an improvement in overall substrate metabolism. Exogenous ketones may preserve endogenous fuel; that is, limit (or possibly suppress) the breakdown of carbohydrate for energy during exercise. Unlike the conventional model of fat utilization during exercise, ketones are oxidized at high intensities. Additionally, ketones do not impact insulin as carbohydrate and amino acids do; thus, they may be a preferential supplement for individuals with insulin resistance.

The possible disadvantages of exogenous ketones are their palatability and tolerance. Supplemental ketone esters are very bitter and cause significant gastric upset in some subjects.

Ketone salts and esters likely have no effect on body composition, because they still provide calories. They may be mis-marketed as fat-burning supplements (which is technically correct as ketones are derived from fat), but exogenous ketones will likely not produce the same body composition-improving results as an energy-restricted or ketogenic diet.

Exogenous ketones may have an application in the medical field as well, with some suggesting that they have the potential to improve symptoms of Alzheimer’s, traumatic brain injury, oxygen toxicity and certain cancers. Brain trauma (either acute or chronic) and vascular disease reduce the brain’s ability to utilize glucose. Thus, circulating ketones may provide a fuel source to an energy-deprived brain.

Summary

During exercise, exogenous ketones may essentially function as a fourth fuel source. Based on limited research, they do not necessarily provide an advantage over other exogenous fuels (carbohydrate, fat or protein). If you can afford and tolerate them, exogenous ketones likely do not decrease performance (as the only side effects thus far are high cost and gastrointestinal upset) and may preserve endogenous fuels.