Who should not take exogenous ketones

Exogenous ketones are sold as dietary supplements, and this creates the impression that anyone can take them. In reality there are groups of people for whom the risks outweigh any hypothetical benefit, and situations where the decision can be made only together with a doctor. The editorial team has systematized these contraindications and cautions.

Why supplements have contraindications

Exogenous ketones are metabolically active substances. They temporarily change glucose levels, acid-base balance, hormonal appetite signals, and, in the case of salts, water-salt metabolism. In a healthy person these changes are small and quickly compensated, but in the case of chronic diseases the compensatory mechanisms may not cope.

The second reason is the composition of the products. Salt forms contain a significant amount of sodium, potassium, calcium, or magnesium. Esters contain 1,3-butanediol, which is metabolized like alcohol. Combination products may include caffeine and other stimulants.

The third reason is a lack of data. Most studies were conducted on healthy young adults, mostly men. For pregnant women, children, older people, and patients with chronic diseases there is practically no information on safety, and the absence of evidence of harm in this case does not mean evidence of safety.

Therefore the editorial team divides situations into three groups: where intake is not recommended, where it is possible only under a doctor's supervision, and where increased caution is needed. Such a division helps orientation but does not replace an individual consultation.

Diabetes and glucose-lowering drugs

People with type 1 diabetes have the highest risk of diabetic ketoacidosis — a life-threatening condition when, against a background of insulin deficiency, ketone bodies accumulate in a very high concentration and acidify the blood. Exogenous ketones do not cause ketoacidosis by themselves, but they add ketones to a system already prone to their excess and can complicate the interpretation of home measurements.

The editorial team pays special attention to SGLT2 inhibitors — drugs for the treatment of type 2 diabetes and heart failure, which increase the risk of so-called euglycemic ketoacidosis, when glucose levels remain almost normal (Peters et al., 2015). The combination of these medications with exogenous ketones has not been studied and, in the editorial team's opinion, is unacceptable without agreement with a doctor.

Another aspect is the reduction of glucose. Exogenous ketones soften the rise of sugar after a glucose load (Myette-Côté et al., 2018). In people receiving insulin or sulfonylurea drugs, this could theoretically contribute to hypoglycemia, especially in combination with physical exertion.

Some studies consider ketones as a potential means of improving glycemic control, but these are scientific hypotheses, not recommendations for independent use. People with diabetes should coordinate any changes in diet and supplements with an endocrinologist.

Kidneys, heart, and blood pressure

The kidneys play a key role in eliminating ketones, regulating acid-base balance, and mineral metabolism. In people with chronic kidney disease these functions are reduced, so an additional load of acids and minerals from salt products is undesirable.

An excess of potassium is especially dangerous. In the case of reduced kidney function or taking drugs that retain potassium in the body (for example, ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics), additional potassium can contribute to hyperkalemia, which threatens heart rhythm disturbances.

People with arterial hypertension and heart failure are usually advised to limit salt. Sodium BHB salts can substantially increase daily sodium intake, which contradicts a therapeutic diet. If the doctor nevertheless does not object, it is worth choosing products with a minimal share of sodium.

People with arrhythmias, especially against a background of taking antiarrhythmic drugs or diuretics, should be careful with any products that change mineral balance. Additional stimulants such as caffeine in combination ketone products only increase this risk.

Pregnancy, children, and other special groups

For pregnant and breastfeeding women, the editorial team does not recommend taking exogenous ketones. The effect of an artificially raised ketone level on fetal development and the composition of breast milk has not been studied, and the potential benefit does not justify the risk.

Ketone supplements are also not indicated for children and adolescents. The only exception is special medical protocols, for example ketogenic diet therapy for some forms of epilepsy, which is carried out in specialized centers under constant medical supervision.

• Rare hereditary metabolic disorders— for example, disorders of fatty acid oxidation or ketone utilization: independent intake is unacceptable.
• Liver diseases and pancreatitis— a doctor's consultation is needed, especially regarding esters and MCT.
• Eating disorders— supplements that suppress appetite can deepen the problem.
• People sensitive to alcohol— products with 1,3-butanediol can cause similar effects.

Older people should be careful due to the more frequent presence of chronic diseases and polypharmacy, that is, taking many medications at once. The risk of unpredictable interactions is higher in this group.

Professional athletes subject to anti-doping control should remember: ketones themselves are not on the WADA Prohibited List, but combination products may be contaminated with banned substances. Preference goes to certified products.

How to make the decision safely

If you have a chronic disease or regularly take medications, the first step should be a conversation with a doctor, not a trial serving. Take the product label with you so the doctor can see the composition, particularly the minerals and additional ingredients.

If the doctor does not object, start with the minimal serving and monitor well-being, blood pressure, and, in the case of diabetes, glucose levels. It is important to record any unusual symptoms and report them to the doctor.

Immediately stop intake and seek medical help if severe abdominal pain, vomiting, frequent deep breathing, marked thirst, weakness, or confusion appears. These may be signs of a serious metabolic disturbance.

Finally, it is worth honestly assessing the need. If the benefit of ketones for your goal is not proven and the risks are real, the safest decision is to forgo the supplement in favor of a balanced diet.

Editorial conclusions

Exogenous ketones are not a neutral product for everyone. For people with diabetes, especially type 1 or against a background of taking SGLT2 inhibitors, insulin, or sulfonylureas, intake is possible only after agreement with a doctor.

Chronic kidney disease, hypertension, heart failure, and rhythm disturbances are grounds to avoid salt forms. For pregnant women, breastfeeding women, and children, supplements are not recommended due to the absence of safety data.

In doubtful situations, the best choice is to refrain from intake. The benefit of exogenous ketones for health and sport is proven much more weakly than the risks for vulnerable groups.

We also recommend reviewing our materials “Side effects of exogenous ketones,” “Exogenous ketones: what they are and how they work,” and “Myths about exogenous ketones.”

References

1. 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.
2. Myette-Côté É, Neudorf H, Rafiei H, Clarke K, Little JP. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. J Physiol. 2018;596(8):1385–1395.
3. Clarke K, Tchabanenko K, Pawlosky R, et al. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012;63(3):401–408.
4. Puchalska P, Crawford PA. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab. 2017;25(2):262–284.
5. Stubbs BJ, Cox PJ, Evans RD, et al. On the metabolism of exogenous ketones in humans. Front Physiol. 2017;8:848.
6. World Anti-Doping Agency. The World Anti-Doping Code: International Standard. Prohibited List. Montreal: WADA; оновлюється щороку.