Normal Ketone Levels
Normal ketone bodies in blood are present at very low concentrations, typically less than 0.5 mmol/L in healthy individuals, with physiological ketosis during ketogenic diets ranging from 0.3 to 4 mmol/L. 1
Normal Reference Ranges by Clinical Context
Healthy Individuals (Non-Ketogenic State)
- Total serum ketones: <0.5 mmol/L 1
- β-hydroxybutyrate (βOHB): 0 to 0.2 mmol/L 2
- In type 1 diabetic patients on continuous insulin infusion under normal conditions, 81.3% of measurements showed 0 mmol/L, 13% showed 0.1 mmol/L, and only 2% showed ≥0.3 mmol/L 2
Physiological Ketosis (Ketogenic Diet)
- Ketone bodies: 0.3 to 4 mmol/L 1
- This range is characterized by normal pH, low but physiologically normal insulin levels, and normal blood glucose 1
- This state differs fundamentally from pathological ketosis, which shows ketone levels >7-8 mmol/L 1
Critical Thresholds for Clinical Decision-Making
Screening for Diabetic Ketoacidosis (DKA)
- βOHB ≥3.5 mmol/L: 100% specificity and sensitivity for DKA diagnosis 3
- βOHB ≥0.6 mmol/L: Elevated ketone bodies requiring monitoring 4
- Optimal cut-off values for DKA diagnosis: βOHB 6.3 mmol/L, acetoacetate 1.4 mmol/L, total ketone bodies 8.0 mmol/L 5
Monitoring Thresholds for Insulin Pump Users
- βOHB ≥0.3 mmol/L: Threshold for screening insulin deficiency in CSII patients 2
- Only 0.9% of βOHB values were ≥0.3 mmol/L when blood glucose exceeded 250 mg/dL under normal insulin delivery conditions 2
Important Clinical Distinctions
Physiological vs. Pathological Ketosis
Physiological ketosis (as described by Hans Krebs in 1966) is characterized by: 1
- Normal pH
- Low but physiologically normal insulin levels
- Normal blood glucose
- Ketone bodies 0.3-4 mmol/L
Pathological ketosis (DKA) is characterized by: 1
- Low systemic pH
- Absent or severely deficient insulin
- Hyperglycemia
- Very high ketone bodies (>7-8 mmol/L)
Ketone Body Ratios
- Normal ratio of βOHB:acetoacetate is 1:1 6
- In acute DKA, this ratio rises to as high as 10:1 6
- βOHB and acetoacetate are typically present in approximately equimolar amounts under normal conditions 1
Key Measurement Considerations
Preferred Testing Method
- Blood βOHB measurement is preferred over urine ketone testing because urine tests using nitroprusside only detect acetoacetate and acetone, missing βOHB, which is the predominant ketone body 1, 6
- Blood ketone testing provides quantitative results, while urine testing is only semiquantitative 1
Common Pitfalls
- Urine ketone tests may underestimate total ketone body concentration by missing βOHB 1
- During DKA treatment, βOHB converts to acetoacetate, which can falsely suggest worsening ketosis when using nitroprusside-based tests 1
- False-positive urine results can occur with highly colored urine or sulfhydryl drugs like captopril 7
- False-negative urine results occur with prolonged air exposure of test strips or highly acidic urine 7
Clinical Context for Interpretation
When to Measure Ketones
According to the American Diabetes Association, ketone testing should be performed in: 1, 8
- Individuals with type 1 diabetes during illness or unexplained hyperglycemia
- Patients with history of DKA
- Those treated with SGLT2 inhibitors (at risk for euglycemic DKA)
- Presence of symptoms such as abdominal pain or nausea