Ketosis - Nature's Backup Fuel
What is ketosis?
When dietary glucose falls, liver HMG-CoA synthase (HMGCS2) converts fatty-acids into the ketone bodies β-hydroxybutyrate (BHB) and acetoacetate, which readily fuel the brain, heart, and skeletal muscle.[1]
Human ketosis levels
| Situation | Typical BHB range | Notes |
|---|---|---|
| Overnight fast | 0.1 – 0.3 mmol L⁻¹ | Baseline in healthy adults[1] |
| Low-carb / ketogenic diet | 0.5 – 3 mmol L⁻¹ | “Nutritional ketosis”; cognitive and metabolic studies target this zone[5] |
| Prolonged total fast (≥ 3 days) | 2 – 7 mmol L⁻¹ | Peaks around day 7; brain now covers > 60 % of ATP with ketones[1] |
| Diabetic or alcoholic ketoacidosis | 10 mmol L⁻¹ + & pH < 7.3 | Medical emergency needing prompt treatment[1] |
Small hibernators: deep nutritional ketosis
Thirteen-lined ground squirrels fast ~6 months; plasma BHB rises from < 0.3 to ≈ 2–3 mmol L⁻¹, supplying more than half of brain ATP while glucose stays low.[2]
Bears: fat burning without strong ketosis
Denning brown bears rely almost entirely on stored fat yet keep BHB below ≈ 1 mmol L⁻¹ thanks to slow metabolic rate and rapid peripheral uptake, sparing glucose without full nutritional ketosis.[3]
Humans: why the switch persists
- Brain safeguard: Ketones cover two-thirds of cerebral fuel after 48 h without food.
- Neonate survival: Newborns, low on glycogen, enter mild ketosis within hours of birth.
- Evolutionary pull: Most placental mammals (humans included) retain functional HMGCS2; only a few lineages (whales, elephants, fruit bats) have lost it, underscoring continuing selection for a famine-buffer pathway.[4]
Children: rapid ketone production
Children transition to ketosis faster than adults. Their higher brain-to-body mass ratio (brain uses ~50% of resting energy in toddlers vs. ~20% in adults) and smaller glycogen reserves mean hepatic stores deplete within 8–12 hours of fasting—roughly half the time needed in adults. Plasma BHB can reach 1–2 mmol L⁻¹ after an overnight fast in young children, a level adults typically achieve only after 24+ hours. This metabolic flexibility has been exploited therapeutically: ketogenic diets have treated pediatric epilepsy since the 1920s, achieving seizure control in ~50–70% of cases by stabilizing neural excitability through ketone-mediated GABAergic signaling and reduced glycolytic flux.[10]
Gestation: ketones before birth
Maternal BHB crosses the placenta within minutes, and the fetus exploits it for energy and lipid synthesis.
- Physiological ketonemia: After an overnight fast, pregnant women usually remain ≤ 0.5–1.0 mmol L⁻¹ BHB.[9]
- Clinical thresholds: UK and ADA guidelines flag BHB > 1.0 mmol L⁻¹ in pregnancy for extra monitoring and recommend urgent assessment at > 3 mmol L⁻¹ because of ketoacidosis risk.[8]
- Outcomes: Persistent BHB ≥ 3 mmol L⁻¹—seen with uncontrolled diabetes, severe vomiting, starvation, or strict ketogenic diets—correlates with lower birth-weight and potential neuro-developmental deficits; obstetric teams therefore discourage deliberate long-term ketosis and track ketone levels in at-risk pregnancies.[6][7]
**Bottom line **Ketosis is an ancient, flexible backup-fuel system—helping squirrels in burrows, bears in dens, humans during fasts, and even fetuses between meals.
[1] Huang J. Update on Measuring Ketones. J Diabetes Sci Technol 2023;18:714-726.
[2] Otis JP et al. Cholesterol and Lipoprotein Dynamics in a Hibernating Mammal. PLoS ONE 2011;6:e29111.
[3] Græsli AR et al. Seasonal Variation in Haematological and Biochemical Variables in Free-Ranging Subadult Brown Bears. BMC Vet Res 2015;11:301.
[4] Jebb D, Hiller M. Recurrent Loss of HMGCS2 Shows That Ketogenesis Is Not Essential for the Evolution of Large Mammalian Brains. eLife 2018;7:e38906.
[5] Hui SA et al. Utility of Blood β-Hydroxybutyrate Measurements in Patients Without Diabetes: A Systematic Review. Syst Rev 2023;12:71.
[6] Qian M et al. Effect of Elevated Ketone Body on Maternal and Infant Outcome in Abnormal Glucose Metabolism Pregnancy. Diabetes Metab Syndr Obes 2020;13:4581-4588.
[7] Tanner HL et al. Ketones in Pregnancy: Why Is It Necessary to Avoid Them and What Is the Evidence Behind Their Perceived Risk? Diabetes Care 2021;44:280-289.
[8] Diabetes Technology Network UK. Best Practice Guide: Using Diabetes Technology in Pregnancy. 2020.
[9] Laffel L. Ketone Bodies: A Review of Physiology, Pathophysiology and Application of Monitoring to Diabetes. Diabetes Metab Res Rev 1999;15:412-426.
[10] Neal EG et al. The Ketogenic Diet for the Treatment of Childhood Epilepsy: A Randomised Controlled Trial. Lancet Neurol 2008;7:500-506.