Beta-Hydroxybutyrate Levels: Normal Values and Diagnostic Thresholds
Normal serum beta-hydroxybutyrate (BHB) levels are below detection limits (<0.3 mmol/L), nutritional ketosis ranges from 0.3–4 mmol/L with normal pH and glucose, while pathological ketosis (diabetic ketoacidosis) is characterized by BHB levels >7–8 mmol/L accompanied by pH <7.30, glucose >250 mg/dL, and bicarbonate <15 mEq/L. 1, 2
Normal and Physiological Ketosis Ranges
Healthy fasting individuals maintain BHB levels below 0.3 mmol/L under normal conditions, with up to 30% of first-morning urine samples showing trace ketones even in asymptomatic adults. 2, 3
Nutritional or physiological ketosis—induced by carbohydrate restriction (<50 g/day), prolonged fasting, or ketogenic diets—produces BHB concentrations of 0.3–4 mmol/L while maintaining normal blood glucose, normal pH, and serum bicarbonate ≥18 mEq/L. 1, 3
During extended fasting, glycogen depletion triggers fatty acid oxidation, generating ketones that serve as alternative fuel for skeletal muscle, cardiac muscle, and other tissues while sparing glucose for the brain. 3
Pathological Ketosis Thresholds
Diabetic ketoacidosis (DKA) requires BHB levels ≥3.8 mmol/L in adults (≥3.0 mmol/L in children) combined with glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, and anion gap >10 mEq/L. 4, 5
Pathological ketosis in decompensated diabetes presents with BHB >7–8 mmol/L, severely low pH, absent or deficient insulin, and hyperglycemia—representing a medical emergency. 1, 3
Research demonstrates that BHB ≥1 mmol/L has 85.1% sensitivity and 95.3% specificity for diagnosing diabetic ketosis/ketoacidosis, while levels <0.66 mmol/L effectively rule out DKA (99.9% negative predictive value). 6
Clinical Action Thresholds
The American College of Clinical Endocrinologists recommends the following blood BHB action thresholds for patients at risk of ketosis: 2, 3
- <0.5 mmol/L: No intervention required
- 0.5–1.5 mmol/L: Initiate sick-day rules (oral hydration, supplemental short-acting insulin with carbohydrate intake, frequent glucose/ketone monitoring)
- ≥1.5 mmol/L: Seek immediate medical attention; intravenous insulin therapy typically required
Critical Diagnostic Considerations
Blood BHB measurement is strongly preferred over urine dipstick testing for all clinical decision-making, because standard urine dipsticks detect only acetoacetate and miss BHB—the predominant ketone body in DKA—leading to significant underestimation of total ketone burden. 2, 3, 4
The nitroprusside method (standard urine dipstick) has sensitivity as low as 35–52% for mild-to-moderate ketosis and should never be used to monitor DKA treatment response, as acetoacetate may paradoxically rise while BHB falls during successful therapy. 2, 4
When evaluating suspected DKA, immediately check blood glucose to distinguish between pathological ketoacidosis and benign starvation ketosis; glucose >250 mg/dL indicates a medical emergency requiring full DKA workup. 2, 3
Special Populations and Pitfalls
SGLT2 inhibitors increase DKA risk and can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis (BHB ≥3.8 mmol/L), complicating timely diagnosis. 2, 4, 7
Pregnant women (with or without diabetes) show positive urine ketones in up to 30% of first-morning samples, reflecting normal metabolic adaptation rather than pathology. 2, 3
Alcoholic ketoacidosis produces positive ketones but typically without hyperglycemia, distinguishing it from DKA. 2
Independent of treatment, DKA risk increases by 18% with each 0.1 mmol/L increase in baseline BHB and by 8% with each 0.1 mmol/L increase from baseline during therapy. 7
High-Risk Patients Requiring Immediate Evaluation
Patients with the following characteristics warrant immediate BHB measurement and DKA evaluation when ketones are detected: 2, 3
- Known type 1 diabetes or history of prior DKA
- Currently on SGLT2 inhibitor therapy
- Unexplained hyperglycemia (>300 mg/dL persistently)
- Acute illness, infection, or physiological stress
- Symptoms of ketoacidosis (nausea, vomiting, abdominal pain, Kussmaul respirations, altered mental status)