Nutritional Ketosis
The metabolic state in which the brain uses ketones instead of glucose
Definition
Nutritional ketosis is a metabolic state in which the liver produces ketone bodies (β-hydroxybutyrate, acetoacetate, acetone) from fatty acids, typically due to very low carbohydrate intake (<30-50 g/day), prolonged fasting, or supplementation with exogenous ketones. Plasma β-hydroxybutyrate (BHB) levels between 0.5 and 3.0 mmol/L define nutritional ketosis, clearly distinct from diabetic ketoacidosis (BHB >15 mmol/L, a medical emergency).
Detailed explanation
BHB is not just an alternative fuel — it is a signalling molecule with direct effects on longevity. It inhibits class I histone deacetylase (HDAC), increases expression of FOXO3 (longevity gene) and MnSOD (mitochondrial antioxidant), downregulates the NLRP3 inflammasome (reducing inflammation), and efficiently crosses the blood-brain barrier to fuel neurons with 25% more ATP per unit of oxygen than glucose.
Clinical applications with evidence: paediatric refractory epilepsy (50-70% efficacy since the 1920s), mitochondrial diseases, mild cognitive impairment and early Alzheimer's (Stephen Cunnane's studies), weight control and insulin resistance, sustained mental clarity.
Protocols: strict ketogenic diet (<30 g carbs/day, >70% fat), modified ketogenic diet (30-50 g carbs/day), intermittent ketosis (5 days keto + 2 days refeed), or exogenous ketones (BHB esters or salts) to reach ketosis without carbohydrate restriction. Metabolic adaptation (keto-adaptation) requires 3-6 weeks to reach full efficiency.
Scientific sources
- PubMed — Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor
- PubMed — Ketogenic diet, brain glucose metabolism, and cognitive function
- PubMed — Therapeutic ketosis for neurodegenerative diseases
- PubMed — Cardiovascular and metabolic effects of a ketogenic diet
Related terms
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