The ketogenic diet is not for everyone: contraindications, side effects, and drug interactions

The ketogenic diet (KD), initially developed for the treatment of neurological disorders, has gained increasing attention for its potential role in the management of various metabolic diseases. Alongside its expanding clinical use, concerns have emerged regarding its safety, tolerability, and suitability in specific patient populations. This review summarises key contraindications, clinical situations requiring caution, relevant drug interactions, and commonly reported adverse effects associated with KD.

Rare absolute contraindications include selected inborn errors of metabolism affecting pyruvate carboxylase activity, carnitine transport or utilisation, fatty acid oxidation pathways, as well as porphyria. Relative contraindications encompass acute pancreatitis, advanced hepatic or renal disease, familial hypercholesterolaemia, and other conditions that may be aggravated by KD-induced metabolic changes, including concomitant use of propofol. Particular caution is warranted in patients with type 1 or type 2 diabetes receiving specific glucose-lowering therapies, pharmacologically treated hypertension, gallbladder disease or prior cholecystectomy, electrolyte disturbances, cardiac arrhythmias, pregnancy or lactation, underweight status, intense physical activity, significant psychosocial stress, or postoperative recovery.Clinically relevant interactions with medications are reviewed, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, insulin and sulphonylurea derivatives, antiepileptic drugs, diuretics, lipophilic drugs, and corticosteroids. The most frequently reported adverse effects range from transient "keto flu" symptoms (fatigue, headache, nausea) to gastrointestinal disturbances, polyuria, and hypoglycaemia.

KD demonstrates therapeutic potential in the management of a broad range of metabolic and neurological diseases; however, it is not an intervention suitable for all clinical situations. Awareness of existing contraindications, conditions requiring particular caution, and potential drug interactions enables a more responsible, individualised, and safe approach to patient selection and clinical management. In this context, the present paper provides a concise yet comprehensive synthesis to support clinicians and researchers in the rational and effective application of the ketogenic diet in both clinical practice and scientific research.