Who Should Not Do Keto: Contraindications and Drug Interactions
A major review article published in 2025 and indexed in PubMed under PMC12777878 provides the most comprehensive current overview of who should not follow a ketogenic diet and which medications can interact dangerously with it. Published in Annals of Medicine, the paper identifies absolute contraindications (rare inherited metabolic disorders such as fatty acid oxidation defects, carnitine deficiency, and pyruvate carboxylase deficiency), relative contraindications (acute pancreatitis, advanced kidney or liver disease, familial hypercholesterolemia), and clinically significant drug interactions affecting SGLT2 inhibitors, insulin, sulphonylureas, GLP-1 agonists, antiepileptics, and diuretics. The review is required reading for any clinician supervising keto and for any patient on medication who is considering a low-carbohydrate diet, particularly given the rapid blood-sugar shifts that can occur within days of starting.
Absolute contraindications: who must not follow keto
Absolute contraindications are rare but serious. They include inherited metabolic disorders affecting fatty acid oxidation, carnitine transport or utilisation, and pyruvate carboxylase deficiency. Porphyria is also listed as an absolute contraindication. People with these conditions cannot safely metabolise the high-fat, low-carbohydrate substrate that keto provides. Diagnosis of these conditions typically occurs in childhood, but anyone with an undiagnosed metabolic disorder or family history of metabolic disease should be screened before attempting a ketogenic diet.
Relative contraindications: proceed with caution
The review identifies several conditions as relative contraindications, where keto may be possible under close medical supervision but poses meaningful risk without it. These include acute pancreatitis, advanced liver or kidney disease, familial hypercholesterolaemia, and electrolyte disturbances. Advanced chronic kidney disease warrants particular caution because the high protein intake typical on keto can accelerate kidney function decline. Gallbladder disease or cholecystectomy history is also flagged, since rapid fat mobilisation on keto can trigger biliary issues.
Clinically significant drug interactions
The 2026 review outlines several drug classes that interact directly with the ketogenic diet. SGLT2 inhibitors, which are commonly prescribed for type 2 diabetes, carry a risk of euglycaemic diabetic ketoacidosis when combined with keto because both lower blood glucose while allowing ketone production to rise. Metformin, GLP-1 receptor agonists, insulin, and sulphonylureas all require dose adjustments when carbohydrate intake drops significantly. Antiepileptic drugs may need monitoring since the blood pH changes from ketosis can alter their activity. Diuretics may worsen the potassium and magnesium losses that keto can already cause.
Groups that require extra caution
Beyond formal contraindications and drug interactions, the review lists clinical situations that require heightened monitoring. Pregnant or breastfeeding women should avoid strict keto, as the restriction may limit nutrients essential for fetal development. People who are underweight or recovering from major surgery should not follow keto. Athletes engaged in high-intensity training may experience performance decrements during the initial adaptation phase of up to 4 to 6 weeks. Individuals under significant psychosocial stress or with a history of disordered eating should approach ketogenic dieting under professional guidance.
How to start keto safely if you are on medications
If you take any prescription medication, especially for diabetes, heart disease, epilepsy, hypertension, or kidney disease, you should speak with your physician before starting a ketogenic diet. Blood glucose, kidney function markers, electrolytes, and lipid panels should be checked at baseline and monitored during the first few months. Dose adjustments may be needed quickly as carbohydrate restriction takes effect. Stopping or reducing carbohydrates abruptly is particularly risky for insulin-dependent diabetics, who face a risk of hypoglycaemia as their insulin requirement falls rapidly.
FAQ
Can I do keto if I take metformin?
Metformin and keto can be combined, but dose adjustment is often needed because keto improves insulin sensitivity and reduces blood glucose independently of the medication. Your doctor should monitor your blood sugar levels and adjust your dose as necessary. Do not change your metformin dose without medical advice.
Is keto dangerous if you have kidney disease?
Advanced chronic kidney disease is listed as a relative contraindication to keto in the 2026 Annals of Medicine review. High protein intake typical on keto may accelerate decline in kidney function. People with kidney disease should consult a nephrologist before making significant dietary changes.
Can keto cause ketoacidosis if I take an SGLT2 inhibitor?
Yes. Combining SGLT2 inhibitors with a ketogenic diet carries a specific risk of euglycaemic diabetic ketoacidosis, a serious condition where blood pH drops dangerously while blood glucose appears normal. This combination requires close medical supervision and is often avoided entirely in clinical settings.