What to combine exogenous ketones with

Exogenous ketones are rarely taken in isolation: they are mixed with carbohydrate drinks, caffeine, MCT oil, added to a ketogenic diet or to post-workout protein. The editorial team analyzed which combinations have a scientific basis, which are merely a marketing ploy, or may even be harmful.

Ketones and carbohydrates

It may seem paradoxical, but the most studied combination in sport is ketones with carbohydrates. In the study by Cox and colleagues (2016), which launched the wave of interest in ketones, athletes received a ketone ester precisely together with a carbohydrate drink, not instead of it.

The logic of this approach is that ketones cannot fully sustain intense work. For high power, muscles need glucose and glycogen. Ketones in this scenario are considered an additional energy source, not a replacement for the main one.

At the same time it is worth remembering that ketones lower blood glucose and can slightly inhibit its use. Therefore, combining them with carbohydrates also helps avoid an undesirable drop in sugar during prolonged work. However, the overall effect of such a combination on performance was not confirmed as consistent in subsequent studies.

Practical conclusion: if an athlete experiments with ketones during endurance workouts, they should supplement the usual carbohydrate strategy, not displace it. Giving up carbohydrates for the sake of “pure ketosis” during intense work worsens the quality of the workout.

Ketones, protein, and recovery

After a workout, the main tasks of nutrition are to restore glycogen and ensure muscle protein synthesis. Ketones were studied precisely as a supplement to these processes. In the work of Holdsworth and colleagues (2017), a ketone ester taken together with glucose after exhausting exertion was associated with higher glycogen synthesis.

The study by Vandoorne and colleagues (2017) showed that a ketone ester in the recovery period enhanced the mTORC1 signaling pathway associated with protein synthesis when combined with protein and carbohydrates. However, an acceleration of glycogen recovery was not found in this work.

The most convincing data on recovery were obtained in the study by Poffé and colleagues (2019), where a ketone ester was added to the usual nutrition of athletes during a period of very heavy training load. The key word is “added”: the participants did not limit carbohydrates and protein.

So, if you use ketones for recovery, they should be combined with a full meal or a shake with protein and carbohydrates. By themselves, ketones do not replace any of these nutrients.

Ketones and caffeine

Caffeine is one of the most evidence-based ergogenic supplements. The position statement of the International Society of Sports Nutrition (Guest et al., 2021) confirms its effectiveness for a wide range of exertion. That is why manufacturers often add caffeine to ketone products.

The problem is that in such combinations it is difficult to understand what exactly is working. If a person feels a boost of energy and concentration, it is most likely the effect of caffeine, not ketones. There are few studies that would prove synergy of precisely this pair.

In addition, caffeine and ketones can intensify gastrointestinal discomfort, especially on an empty stomach. Caffeine also stimulates the cardiovascular system, which in combination with sodium from salt ketones is undesirable for people with hypertension.

The editorial team advises, if there is a desire to combine these substances, taking them separately in order to control the dose of each and understand how the body reacts to each component. The total daily intake of caffeine from all sources should also be taken into account.

Ketones, MCT, and the ketogenic diet

MCT oil is a precursor of ketones: the liver partially converts medium-chain fatty acids into ketone bodies. Theoretically, combining exogenous ketones with MCT could give both a rapid BHB peak and longer maintenance of ketones, since MCT acts more slowly.

However, such a combination doubles the risk of gastrointestinal symptoms. Both ketones and MCT in large amounts cause discomfort, diarrhea, and cramps. Therefore one should start with small servings of each component separately.

On a ketogenic diet, exogenous ketones are sometimes used to raise BHB levels in the first days or after a “breakdown.” However, they do not accelerate metabolic adaptation to fats and, like any ketones from outside, temporarily inhibit the liver's own ketogenesis.

Salt products on a keto diet can be partly useful as a source of sodium, the loss of which is characteristic at the start of the diet. But for this purpose ordinary salt or broth is enough, and they are much cheaper.

Undesirable combinations

The editorial team considers some combinations undesirable or risky. First — combining ketone products with alcohol. Esters with 1,3-butanediol are themselves metabolized similarly to alcohol, and alcohol additionally loads the liver and affects glucose levels.

Second — taking ketones together with glucose-lowering drugs, especially SGLT2 inhibitors, without agreement with a doctor. This class of drugs is associated with a risk of euglycemic ketoacidosis (Peters et al., 2015).

• Alcohol— additional load on the liver, especially with butanediol-based esters.
• Glucose-lowering drugs— risk of hypoglycemia and ketoacidosis, only under a doctor's supervision.
• Stimulants and “fat burners”— load on the heart and unpredictable interactions.
• Several salt products at once— excess of sodium and other minerals.

Third — combining with aggressive fat burners that contain several stimulants. Such combinations increase the load on the cardiovascular system, and the benefit of ketones in them is doubtful.

Fourth — the simultaneous use of several salt products, for example ketone salts and electrolyte tablets. The total intake of sodium, potassium, or magnesium may turn out to be excessive.

Editorial conclusions

The most justified combination of exogenous ketones is with carbohydrates and protein as a supplement to the usual sports nutrition, not a replacement for it. It is precisely in this context that the most interesting research results were obtained.

Caffeine and MCT can be combined with ketones, but this increases the risk of gastrointestinal symptoms and complicates assessment of the effect. It is better to take the components separately and start with small doses.

Alcohol, glucose-lowering drugs without a doctor's supervision, aggressive fat burners, and an excess of minerals are combinations that should be avoided.

We also recommend reviewing our materials “MCT oil: what it is and how it works,” “How to take exogenous ketones: dosage, timing, duration,” and “Who should not take exogenous ketones.”

References

1. 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.
2. Holdsworth DA, Cox PJ, Kirk T, et al. A ketone ester drink increases postexercise muscle glycogen synthesis in humans. Med Sci Sports Exerc. 2017;49(9):1789–1795.
3. Vandoorne T, De Smet S, Ramaekers M, et al. Intake of a ketone ester drink during recovery from exercise promotes mTORC1 signaling but not glycogen resynthesis in human muscle. Front Physiol. 2017;8:310.
4. 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.
5. Guest NS, VanDusseldorp TA, Nelson MT, et al. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021;18(1):1.
6. Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38(9):1687–1693.
7. Stubbs BJ, Cox PJ, Evans RD, et al. On the metabolism of exogenous ketones in humans. Front Physiol. 2017;8:848.