What to Combine Exogenous Ketones With — and What to Avoid
Ketone drinks moved from military research labs to the pockets of professional cyclists within a decade. Yet their effects depend heavily on what they are taken with: the same ketone ester can help, do nothing or even hinder performance depending on the context. Our editorial team reviews which combinations have actually been studied and where caution is needed.
Ketone esters, salts and how they work
Ketone bodies, chiefly beta-hydroxybutyrate (βHB) and acetoacetate, are fuels the liver produces during fasting or very low-carbohydrate eating. Exogenous ketones allow blood ketone levels to rise within 30–60 minutes without the weeks of dietary adaptation that a ketogenic diet requires.
Two main product types exist. Ketone esters, such as the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate monoester, raise blood βHB substantially but are expensive and notoriously bitter. Ketone salts bind βHB to sodium, potassium, calcium or magnesium; they are cheaper but produce smaller rises in blood ketones and deliver a considerable mineral load.
Stubbs and colleagues showed that esters achieve markedly higher blood βHB than equivalent amounts of salts, and that taking them with a meal blunts the peak. This explains why studies using salts often report weaker effects.
The theoretical appeal for athletes lies in an additional fuel source, potential glycogen sparing and possible effects on recovery. In practice, results have been mixed, which makes the choice of combinations crucial.
Combinations with supporting evidence
Carbohydrate. The influential study by Cox and colleagues in 2016 gave trained cyclists a ketone ester together with carbohydrate and found improved distance covered in a subsequent time trial compared with carbohydrate alone. Ketones were not used to replace carbohydrate but to add to it. Most researchers now consider carbohydrate co-ingestion the default context.
Sodium bicarbonate. Ketone esters cause a mild drop in blood pH. Poffé and co-workers tested adding bicarbonate to neutralise this acidosis and reported that the combination improved performance in a late-race sprint, whereas ketones alone did not. This is an intriguing but still narrow body of evidence.
Protein after training. In a training-overload study, Poffé's group gave a ketone ester after sessions and before sleep alongside protein and carbohydrate, and observed fewer signs of overreaching. This supports a recovery role rather than an acute performance boost.
Caffeine. Caffeine is often paired with ketones in commercial products. Each is studied separately, but robust trials of the combination are scarce; the rationale is plausible rather than proven.
Combinations that are unhelpful or risky
Using ketones instead of carbohydrate in high-intensity events appears counterproductive. Leckey and colleagues found that professional cyclists performed worse in a 31 km time trial after a ketone diester, and reported gastrointestinal discomfort. High-intensity efforts rely heavily on glycogen, and ketones may even reduce its use when it is most needed.
Combining several ketone salt servings with salty sports drinks or electrolyte tablets can push sodium intake surprisingly high. A single serving of some salts provides around a gram of sodium or more, a relevant figure for people with high blood pressure.
Alcohol is another poor partner. The ketone monoester releases 1,3-butanediol, which the liver converts to βHB partly via the same enzyme that handles ethanol, so alcohol may compete with that pathway; the combination has not been properly studied and offers no benefit.
Medicines deserve special mention. SGLT2 inhibitors used for type 2 diabetes and heart failure (such as dapagliflozin and empagliflozin) carry a recognised risk of diabetic ketoacidosis with near-normal blood glucose. Adding exogenous ketones in this setting could complicate monitoring, so anyone on these drugs, insulin or other diabetes treatment should speak to their diabetes team first.
| Combination | Verdict | Reason |
|---|---|---|
| With carbohydrate | Most studied | Adds fuel rather than replacing it |
| With sodium bicarbonate | Promising, limited data | Offsets mild acidosis |
| With protein post-training | Possible recovery role | Overreaching markers reduced in one study |
| Replacing carbohydrate | Avoid for high intensity | Performance decline in elite cyclists |
| With SGLT2 inhibitors or insulin | Medical advice needed | Ketoacidosis risk and monitoring confusion |
Practical points for UK athletes
Ketone esters are sold in the UK as food products and are not prohibited under the World Anti-Doping Code. They are, however, costly, and their benefits are most plausible in long endurance events or heavy training blocks rather than in strength sports.
If you decide to experiment, a few practical rules apply:
- test them in training, never for the first time on race day;
- take them with your usual carbohydrate plan, not instead of it;
- start with a small serving to gauge gut tolerance;
- avoid stacking multiple salt-based products on the same day.
Meta-analytic work by Valenzuela and colleagues found no overall performance benefit from acute ketone supplementation across studies, which is a useful reality check against marketing.
Finally, ketone drinks produce a measurable rise in blood ketones that may show up on home meters. This is expected and differs from ketosis caused by fasting or illness, but it is worth knowing if you monitor ketones for medical reasons.
Conclusions of the editorial team
Exogenous ketones are best thought of as a supplement to carbohydrate, not a replacement. The most consistent findings involve combining them with carbohydrate during endurance work and, possibly, with protein and carbohydrate during recovery.
Pairing with bicarbonate is an interesting avenue, while caffeine combinations remain largely untested. Replacing carbohydrate with ketones before intense efforts is a recipe for worse performance.
People with diabetes, kidney disease or high blood pressure, and anyone on SGLT2 inhibitors, should seek medical advice before using ketone products.
For further reading, see our articles on carbohydrate periodisation, sodium bicarbonate for high-intensity sport and caffeine timing before competition.
References
- Cox PJ, Kirk T, Ashmore T, et al. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab. 2016;24(2):256–268.
- Stubbs BJ, Cox PJ, Evans RD, et al. On the metabolism of exogenous ketones in humans. Front Physiol. 2017;8:848.
- Leckey JJ, Ross ML, Quod M, Hawley JA, Burke LM. Ketone diester ingestion impairs time-trial performance in professional cyclists. Front Physiol. 2017;8:806.
- Poffé C, Ramaekers M, Van Thienen R, Hespel P. Ketone ester supplementation blunts overreaching symptoms during endurance training overload. J Physiol. 2019;597(12):3009–3027.
- Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol. 2017;595(9):2857–2871.
- Valenzuela PL, Morales JS, Castillo-García A, Lucia A. Acute ketone supplementation and exercise performance: a systematic review and meta-analysis of randomized controlled trials. Int J Sports Physiol Perform. 2020;15(3):298–308.
