Do Exogenous Ketones Work? And Are They Really Safe?

Exogenous ketones have gained recent popularity due to their promising effects of quickly bringing the body into ketosis. If you’re new to the keto diet and wonder whether exogenous ketones are worth the try, then you’re on the right page.

We will discuss the types, benefits, downsides, and more recommendations on exogenous ketones to help you decide.

Key Takeaways:

• Exogenous ketones are a supplemental source of ketone bodies.
• They induce ketosis but do not enhance performance.
• Studies show no significant side effects of exogenous ketones.

Table of Contents:

• What Are Exogenous Ketones?
• Types of Exogenous Ketones
• Do Exogenous Ketones Work?
• Are Exogenous Ketones Safe?
• Downsides of Exogenous Ketones
• Best Exogenous Ketones Supplement
• When to Take Them
• The Bottom Line

What Are Exogenous Ketones?

Exogenous ketones are compounds external to the body, elevating blood ketone levels¹ and mimicking the physiological state of ketosis.

Ketosis is a metabolic state where the body predominantly utilizes fat for energy production, leading to the generation of ketone bodies. Exogenous ketones provide an alternative fuel source to carbohydrates, facilitating a body’s energy metabolism shift.

Types of Exogenous Ketones

Ketone Esters

Ketone esters are chemical compounds containing raw, unbound ketone molecules, such as beta-hydroxybutyrate (BHB) or acetoacetate.

Ketone esters are known for their rapid and efficient elevation of blood ketone levels,² surpassing the effects of other exogenous ketones. Ketone esters elevate blood ketone levels in as early as 15 minutes of taking.

Due to their unaltered chemical structure, ketone esters are readily absorbed into the bloodstream, making them a potent and direct source of ketones. This reason makes ketone esters the standard option for research use.

Ketone esters often have a strong, unpalatable taste, which can be a drawback for some individuals.

Ketone Salts

Ketone salts are compounds formed by combining ketones, typically BHB, with mineral salts such as sodium, potassium, or magnesium.

Studies show that ketone salts are also effective in inducing ketosis.³

Ketone salts are generally more palatable than ketone esters, making them a more favorable option for those sensitive to taste. Ketone salts take about an hour to increase blood ketone levels.

Moreover, they contribute additional electrolytes, which can benefit individuals following ketogenic diets prone to electrolyte imbalances, making them a more common option for athletes and those doing workouts, as the electrolytes aid in maintaining proper hydration.

However, adding electrolytes also poses a consideration for electrolyte imbalance, especially when taken in higher doses.

Other Supplements

These supplements may include ingredients like medium-chain triglycerides (MCTs),⁴ amino acids, or herbs to enhance the overall effects or address specific health objectives.

This category includes various formulations that combine ketones with other compounds to achieve specific goals, such as improved cognitive function, mental clarity, or targeted energy release.

Do Exogenous Ketones Work?

Ketosis

Studies suggest that exogenous ketones, both esters and salts, provide an immediate source of ketone bodies,¹ bypassing the need for the body to produce them through the breakdown of fats.

Ketones, especially beta-hydroxybutyrate (BHB), serve as an alternative fuel source for cells, particularly the brain and muscles, during low carbohydrate availability.

Numerous studies confirm the ability of exogenous ketones to induce ketosis,⁵ as evidenced by an increase in blood ketone levels and its ability to provide the same benefits as ketosis from endogenous sources.

However, there are debates on whether relying on exogenous sources suits a holistic ketosis approach. Some scientific reviews report⁶ concerns about the difference between the usage and metabolism of endogenous and exogenous ketones and the lack of long-term studies.

Athletic Performance

Some athletes using exogenous ketones claim to experience improvements in endurance and stamina, attributed to the sustained release of energy from ketones.

However, the impact on athletic performance can vary among individuals, and factors such as training status, metabolic adaptability, and the nature of the exercise play a role.

In a study, while exogenous ketones did elevate the blood ketone levels, there were no noted improvements in exercise⁷ completion compared to placebo. Moreover, current studies do not support the benefits⁸ of acute ketone supplementation on sports performance, cognition, or muscle recovery.

Psychiatric Disorders and Epilepsy

Ketones, exogenously obtained, have been studied for their potential neuroprotective effects. This has led to investigations into their role in managing psychiatric disorders and epilepsy.

While there is a lack of human clinical trials, animal studies conclude that exogenous ketones can serve as a therapeutic agent for epilepsy.⁹ A more recent review also suggests that exogenous ketone supplementation-induced ketosis may be an effective therapeutic tool against psychiatric diseases.⁵

Are Exogenous Ketones Safe?

While considered generally safe for healthy adults, the safety of exogenous ketones depends on various factors, including individual health status, dosage, and the specific form of exogenous ketones consumed.

A 28-day study among healthy adults¹⁰ supplemented with 25 ml ketone esters showed no concerning changes in fasting blood glucose, cholesterol, triglyceride or electrolyte concentrations, blood gases, or kidney function.

However, mild nausea was observed among its participants.

Downsides of Exogenous Ketones

Cost

High-quality exogenous ketone supplements can be relatively expensive compared to other dietary supplements. Online reviews reveal that the cost could go up to $50/week of daily exogenous ketone use.

Possible Gastrointestinal Issues

Gastrointestinal issues are one of the most common side effects of acute exogenous ketone use. Some individuals may experience gastrointestinal discomfort, such as nausea, stomach cramps, or diarrhea.

A study suggests these symptoms were noticed in participants taking ketone esters and salts.¹¹ However, these symptoms were fully resolved by the end of the study.

Electrolyte Imbalances

Ketone salts, in particular, contribute additional minerals (sodium, potassium, magnesium), possibly leading to electrolyte imbalances if not appropriately managed.

Those with pre-existing kidney or cardiovascular conditions should be cautious with increased mineral intake since current studies on exogenous ketone supplementation only cater to healthy adults.

Best Exogenous Ketones Supplement

Ketone esters provide a faster and higher spike of ketones in the blood than ketone salts. However, ketone salts are more palatable.

Choosing the correct brand is crucial when taking any supplement. Always purchase from a reputable brand with transparent ingredient lists and third-party testing for quality assurance.

Consider your personal goals, as brands offer different approaches and purposes.

When to Take Them

For those aiming to enhance athletic performance, taking exogenous ketones before workouts can provide an additional energy source, potentially improving endurance and stamina.

Individuals seeking cognitive benefits may consider consuming exogenous ketones during mentally demanding tasks.

You could experiment with different timing and doses and observe personal responses, especially during the first few days of using them.

The Bottom Line

While exogenous ketones show promise in various applications, their effectiveness and safety can vary. Before incorporating these supplements into a routine, individual response, health status, and specific goals must be considered.

Those with existing health conditions should seek professional guidance before deciding on getting into exogenous ketones.

Frequently Asked Questions (FAQ)

References

¹Stubbs, B. J., Cox, P. J., Evans, R. D., Santer, P., Miller, J. J., Faull, O. K., Magor-Elliott, S., Hiyama, S., Stirling, M., & Clarke, K. (2017). On the Metabolism of Exogenous Ketones in Humans. Frontiers in physiology, 8, 848. https://doi.org/10.3389/fphys.2017.00848

²Veech RL. Ketone ester effects on metabolism and transcription. J Lipid Res. 2014 Oct;55(10):2004-6. doi: 10.1194/jlr.R046292. Epub 2014 Apr 8. PMID: 24714648; PMCID: PMC4173993.

³Holland-Winkler A, Moore A, Ansley J. Exogenous Beta-Hydroxybutyrate Ketone Salts Elevate Circulating Acetoacetate Levels. Curr Dev Nutr. 2021 Jun 7;5(Suppl 2):502. doi: 10.1093/cdn/nzab041_017. PMCID: PMC8180788.

⁴D C Harvey CJ, Schofield GM, Williden M, McQuillan JA. The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and Symptoms of Keto-Induction in Healthy Adults: A Randomised Controlled Clinical Trial. J Nutr Metab. 2018 May 22;2018:2630565. doi: 10.1155/2018/2630565. PMID: 29951312; PMCID: PMC5987302.

⁵Kovács Z, D’Agostino DP, Diamond D, Kindy MS, Rogers C, Ari C. Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature. Front Psychiatry. 2019 May 23;10:363. doi: 10.3389/fpsyt.2019.00363. PMID: 31178772; PMCID: PMC6543248.

⁶Shaw, D. M., Merien, F., Braakhuis, A., Maunder, E., & Dulson, D. K. (2020). Exogenous Ketone Supplementation and Keto-Adaptation for Endurance Performance: Disentangling the Effects of Two Distinct Metabolic States. Sports medicine (Auckland, N.Z.), 50(4), 641–656. https://doi.org/10.1007/s40279-019-01246-y

⁷Prins PJ, Koutnik AP, D’Agostino DP, Rogers CQ, Seibert JF, Breckenridge JA, Jackson DS, Ryan EJ, Buxton JD, Ault DL. Effects of an Exogenous Ketone Supplement on Five-Kilometer Running Performance. J Hum Kinet. 2020 Mar 31;72:115-127. doi: 10.2478/hukin-2019-0114. PMID: 32269653; PMCID: PMC7126257.

⁸Valenzuela PL, Castillo-García A, Morales JS, Lucia A. Perspective: Ketone Supplementation in Sports-Does It Work? Adv Nutr. 2021 Mar 31;12(2):305-315. doi: 10.1093/advances/nmaa130. PMID: 33094332; PMCID: PMC8243601.

⁹Si J, Wang Y, Xu J, Wang J. Antiepileptic effects of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy. Exp Ther Med. 2020 Dec;20(6):177. doi: 10.3892/etm.2020.9307. Epub 2020 Oct 9. PMID: 33101467; PMCID: PMC7579833.

¹⁰Soto-Mota, A., Vansant, H., Evans, R. D., & Clarke, K. (2019). Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regulatory toxicology and pharmacology : RTP, 109, 104506. https://doi.org/10.1016/j.yrtph.2019.104506

¹¹Stubbs, B. J., Cox, P. J., Kirk, T., Evans, R. D., & Clarke, K. (2019). Gastrointestinal Effects of Exogenous Ketone Drinks are Infrequent, Mild, and Vary According to Ketone Compound and Dose. International journal of sport nutrition and exercise metabolism, 29(6), 596–603. https://doi.org/10.1123/ijsnem.2019-0014