Are Exogenous Ketone Supplements Worth the Hype?

In the 1920s, scientists discovered that the state of ketosis—when the body switches from using glucose to ketone bodies for fuel—effectively reduced the number of seizures in children with epilepsy. [1]  Why and how this works remains unknown. Nevertheless, the ketogenic (AKA keto) diet is often used to reach ketosis and is still prescribed as a pediatric anti-seizure treatment. Scientists are even considering it as a potential treatment for other neurological disorders like Alzheimer's and Parkinson’s disease. And because a common side effect of ketosis is weight loss, the keto diet has recently skyrocketed in popularity. Now, supplement companies are trying to capitalize on this trending diet by selling exogenous ketones—ketones produced synthetically, outside the body.  



What are (exogenous) ketones? A quick review on energy metabolism 

For a typical diet, 45-60% of calories come from carbohydrates. The digestive system breaks these carbs down into glucose to provide fuel or energy (in the form of ATP) for cells. All three macronutrients—carbohydrates, fats, and protein—can be converted to ATP through distinct, complex processes. Carbs, however, are most easily and efficiently converted to ATP, making it the body’s preferred energy source. 

During fasting or low-carb diets like keto, the body first uses up blood glucose for energy. As blood glucose runs low, the body breaks down the supply of stored glucose (glycogen) found in muscles and the liver. Once depleted of both blood glucose and glycogen, the body adjusts to relying on a different energy source—fat. A process known as ketogenesis breaks down fat into ketone bodies, which are then delivered from liver to peripheral tissues like the brain and muscle to generate ATP.

There are three different ketone bodies found in the body: acetoacetate, beta-hydroxybutyrate, and acetone. Of the three ketones, beta-hydroxybutyrate (BHB) is the only stable ketone available in supplemental form. You can find it as a ketone salt (bound to a salt, usually sodium, potassium, calcium, or magnesium) or as a ketone ester (combined with an ester in liquid form). The former is more readily available in supplements, while the latter is often used in research settings. 

Ketone supplements are marketed as a quick solution to reach ketosis and achieve weight loss. And the increasing demand for these supplements is projected to continue to drive market growth. But do these supplements and their purported benefits live up to the hype? 

Claim 1: Exogenous ketones induce ketosis faster

Ketosis refers to an increase in ketones throughout the blood as a result of the beta-oxidation (breakdown) of fatty acids. Multiple studies show that taking exogenous ketones raises blood ketone levels safely and effectively. [2-5] One study showed that supplementing with 11 grams of BHB increased blood BHB by over 300%. But while these supplements may successfully increase blood ketone levels, it often only lasts a few hours. Multiple doses of exogenous ketones may be needed per day to maintain a desired threshold of blood ketones. 

Claim 2: Exogenous ketones cause your body to utilize fat for fuel 

As mentioned above, ketosis occurs during a fast or low-carb diet—both of which force the body to catabolize fat stores for fuel. But ingesting exogenous ketones immediately provides our body with a source it can utilize for energy, which theoretically attenuates the process of ketogenesis. In a six-week, highly controlled study, researchers examined the effects of a keto diet versus a keto diet + ketone supplements on body composition. Both of these groups experienced decreases in body mass, body fat, and lean muscle mass. But there were no significant differences between the groups—so taking ketone supplements in addition to the keto diet did not provide any additional benefits. The authors also hypothesized that ketone supplementation may reduce the loss of muscle mass often experienced during the keto diet, but reported no such findings. 



Claim 3: Supplemental ketones boost athletic performance 

The research on this is quite mixed. In one study, exogenous ketones actually impaired athletic performance. Cyclists also cited gut discomfort and a higher perception of effort after consuming ketones prior to a time trial. A handful of studies indicate exogenous ketones have no impact on athletic performance. [6-7] But some studies do show they may improve athletic performance. [8-9] In one such study, cyclists who were given a carbohydrate + ketone drink (versus just a carbohydrate drink) experienced a 2% improvement in performance during a time trial. More conclusive evidence is needed on this topic. 



Claim 4: Ketones support a healthy metabolism 

In simplest terms, metabolism is the way we utilize calories from our food to produce the energy needed to keep our body running seamlessly. A healthy metabolism functions best when all three macronutrients are present in our diet. Furthermore, because two of the keto bodies are organic acids (acetoacetate and BHB), maintaining a state of ketosis—either through diet and/or exogenous ketones—can be dangerous as it changes our body’s acid-base balance. ​[10]​

Claim 5: Exogenous ketones manage cravings

No studies have specifically looked at the link between exogenous ketones and cravings. However, in this 2018 randomized control trial, researchers examined exogenous ketone levels and appetite. After an overnight fast, 15 participants consumed either a ketone-rich drink or a control beverage. Following the consumption of the ketone drink, participants experienced a 50% decrease in “perception of hunger” and “desire to eat” for up to four hours. The hunger hormone, ghrelin, declined after the ingestion of both drinks and remained significantly lower for longer (up to 4 hours) in participants who had the ketone drink. This aligns with other research that indicates ketones produced by ketogenesis reduces appetite. [11] It is important to also note that exogenous ketones contain calories and their effects are short-lived, meaning multiple doses are often necessary to reach this potential benefit as well. 



Are exogenous ketone supplements worth the hype? 

Based on the preliminary available information, it may be best to save your money and skip that $5 per serving of ketone supplements. It’s also important to remember that the Food and Drug Administration doesn't regulate dietary supplement claims as rigorously as pharmaceutical drugs. This means that supplements aren't subject to the same strict processes to prove their effectiveness, purity, or marketing claims before entering the market. And some claims around exogenous ketones overstate the benefits. 

A recap of the science behind exogenous ketones

• Endogenous ketones can raise blood ketone levels safely and effectively. However, the effects only last a few hours. 
• Taking exogenous ketones does not guarantee weight loss or fat burn—a claim made by many supplement companies.  
• The research of the impact of exogenous ketones on athletic performance is mixed—ranging from having no effect, to impairing performance, to improving performance.
• Ketones  have been shown to reduce appetite. However, exogenous ketones do contain calories and are costly.

References:

[1] https://onlinelibrary.wiley.com/doi/full/10.1111/eci.12591

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810007/

[3] https://pubmed.ncbi.nlm.nih.gov/29953297/

[4] https://pubmed.ncbi.nlm.nih.gov/24598140/

[5] https://pubmed.ncbi.nlm.nih.gov/29446830/

[6] https://pubmed.ncbi.nlm.nih.gov/29953297/

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311686/

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886359/

[9] ​​https://pubmed.ncbi.nlm.nih.gov/27475046/

[10] Smith, J., Carr, T., & Gropper, S. (2016). Advanced nutrition and human metabolism (7th ed.). CENGAGE Learning Custom Publishing.

[11] https://pubmed.ncbi.nlm.nih.gov/25402637/