Ketones (ketone bodies)

When carbohydrate stores are low (fasting, ketogenic diet, prolonged exercise), the liver converts fatty acids into ketone bodies. These ketones become a substitute fuel, notably for the brain, which cannot burn fat directly.

The original angle (much more than a back-up fuel): ketones were long seen as a simple energy “plan B”. Recent research reveals that they are also signalling molecules with effects of their own:

1. Beta-hydroxybutyrate (BHB) inhibits certain inflammatory pathways (the NLRP3 inflammasome), hence the anti-inflammatory effects being studied
2. Ketones are a “clean” fuel for the brain, hence the interest being studied in epilepsy (the ketogenic diet has treated refractory epilepsy since the 1920s), and under study in Alzheimer’s and Parkinson’s
3. They influence gene expression (through HDAC inhibition)

Nutritional ketosis vs ketoacidosis (a vital distinction):

• Nutritional ketosis: physiological, safe, with ketones at 0.5-3 mmol/L (fasting, keto diet)
• Diabetic ketoacidosis: pathological and dangerous, with ketones > 10 mmol/L, in untreated type 1 diabetes (total lack of insulin). NEVER to be confused

Practical nuances:

• Adapting to ketones (“keto-adaptation”) takes several weeks
• Exogenous ketones (supplements) exist but their real benefits are debated
• Ketosis is not magic for everyone: the response is very individual

Ketones illustrate human metabolic flexibility: our ancestral ability to survive periods of scarcity by switching fuel.