Ten Days of an 800 kcal Diet: Ketones, Bicarbonate and the Brain
A 45-year-old woman begins a self-prescribed diet of 800 kcal per day, made up almost entirely of fat and protein, with less than 20 g of carbohydrate per day. After 10 days she has lost 3.5 kg, her breath smells of acetone, and her urine contains ketones (3+). Her fasting plasma glucose is 4.3 mmol/L (normal 3.9–5.5), plasma bicarbonate is 20 mmol/L (normal 22–28), and blood pH is 7.36. She feels tired and constipated and is alarmed by the smell. One friend tells her to "eat a spoon of sugar" to stop the ketones; another says that ketones mean she is burning fat and are therefore healthy. She asks whether her brain is being starved of glucose, since her intake is so low.
1. Explain why ketone bodies appear in her breath and urine even though her blood glucose is normal.
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Why ketogenesis is switched on
- A carbohydrate intake below about 20 g per day lowers insulin and raises glucagon.
- Low insulin reduces malonyl-CoA in the liver. Malonyl-CoA normally inhibits carnitine-dependent entry of fatty acids into mitochondria, so low malonyl-CoA allows rapid fatty acid oxidation.
- The liver produces more acetyl-CoA than the citric acid cycle can oxidise, so acetyl-CoA is diverted into ketogenesis: acetoacetate and beta-hydroxybutyrate, with acetone formed by spontaneous decarboxylation.
Why glucose is still normal
- Blood glucose is maintained by gluconeogenesis in the liver, using glycerol from fat breakdown and carbon skeletons from amino acids.
- A normal fasting glucose therefore does not mean carbohydrate intake is adequate; it means the body is making glucose from other sources.
Why ketones appear in breath and urine
- Acetone is volatile and is exhaled, giving the characteristic smell.
- Ketone bodies are water-soluble, filtered by the kidney and excreted in urine, where they are detected as 3+.
All three observations are consequences of the same switch: low carbohydrate supply, high fatty acid oxidation, hepatic ketogenesis.
2. Is her acid–base status dangerous? Interpret the bicarbonate and pH, and explain the buffer cost of ketosis.
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Interpretation
- Blood pH 7.36 is at the lower end of the normal range (7.35–7.45), so there is no severe acidaemia yet.
- Bicarbonate at 20 mmol/L is below normal (22–28). This is the more informative number: it shows that bicarbonate has been consumed and that a metabolic acidosis is present and being compensated.
- The likely compensation is increased ventilation, which lowers carbon dioxide and partly corrects the pH.
Buffer cost of ketosis
- Acetoacetic acid and beta-hydroxybutyric acid are weak acids. At body pH they dissociate, releasing H+.
- H+ is buffered mainly by bicarbonate, forming carbon dioxide and water: H+ + HCO3− → H2CO3 → CO2 + H2O.
- Each ketone anion produced therefore removes one bicarbonate equivalent. The falling bicarbonate and the near-normal pH together show that the buffer system is working but is being depleted.
Judgement: this is not yet a crisis, but it is a warning. If ketone production continues to rise, the bicarbonate reserve will fall further and pH will drop. Acetone itself is not the acid; the danger comes from the other two ketone bodies.
3. Evaluate the two friends' advice and explain what the brain is using for fuel in this state.
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Friend 1 ("eat a spoon of sugar")
- Carbohydrate would raise insulin, restore malonyl-CoA and suppress ketogenesis within hours, so the smell would decrease.
- But a spoon of sugar does not correct the underlying problem: an 800 kcal diet with very low carbohydrate and possibly inadequate protein. It adds energy without fixing nutrient adequacy, and ketones would return.
Friend 2 ("ketones mean healthy fat burning")
- Ketones do show increased fat oxidation, but that is not the same as health. The bicarbonate of 20 mmol/L shows a metabolic acidosis, and the symptoms of tiredness and constipation suggest poor overall intake, low fibre and possible dehydration.
- Without adequate protein, muscle protein is broken down for gluconeogenesis, and vitamin and mineral intake is likely to be deficient.
Brain fuel
- The brain is not simply starved. In early fasting it uses glucose; after several days of sustained ketosis, beta-hydroxybutyrate and acetoacetate can supply a large share of its energy, sparing glucose.
- Some glucose is still required and is supplied by gluconeogenesis. This is an adaptation, not a free lunch: it depends on continued protein and glycerol availability.
Judgement: neither friend's advice is adequate. She needs a balanced diet with adequate carbohydrate, protein, fibre and fluids, and supervision rather than a single spoonful of sugar or reassurance.