What causes ketones in urine in a non-diabetic individual who is not fasting?

Causes of Ketones in Urine in Non-Diabetic, Non-Fasting Individuals

In non-diabetic individuals who are not fasting, ketonuria most commonly results from physiological starvation states (inadequate caloric intake despite not formally "fasting"), alcoholic ketoacidosis, pregnancy, prolonged exercise, very-low-carbohydrate diets, severe illness/sepsis, or vomiting with dehydration. 1, 2, 3

Primary Non-Diabetic Causes

Starvation/Inadequate Caloric Intake

• Even without formal fasting, insufficient caloric intake triggers ketone production as the body metabolizes fat stores for energy when glucose availability is low 1, 4
• Starvation ketoacidosis can develop with prolonged inadequate nutrition, even if the person is consuming some water or supplements 5
• This represents a protective metabolic mechanism where the liver produces ketone bodies as an alternative energy substrate 6, 3

Alcoholic Ketoacidosis

• Alcohol consumption combined with poor nutritional intake is a common non-diabetic cause of significant ketonuria 1, 3
• This occurs through increased lipolysis and altered hepatic metabolism, shifting the redox state toward ketone production 1
• Often overlooked by clinicians due to relative unawareness, leading to misdiagnosis 3

Pregnancy-Related Ketosis

• Up to 30% of first morning urine specimens from pregnant women show positive ketones as a normal physiological finding 2
• Pregnant women are more susceptible to ketosis due to accelerated starvation metabolism 2

Very-Low-Carbohydrate (Ketogenic) Diets

• Intentional dietary carbohydrate restriction induces nutritional ketosis even without caloric restriction 1, 4
• Some individuals following ketogenic diets for weight loss monitor their ketone levels at home 1

Prolonged or Intense Exercise

• Extended physical activity depletes glycogen stores and triggers ketone production as an alternative fuel source 4
• This represents a normal physiological response to low carbohydrate availability 4

Less Common But Important Causes

Severe Illness/Sepsis

• Septic states can induce ketoacidosis even without diabetes, alcohol, or starvation through decreased metabolic function and altered hepatic metabolism 7
• Any condition altering the redox state of hepatic mitochondria (hypoxia, severe illness) shifts equilibrium toward ketone production 1

Vomiting and Dehydration

• Persistent vomiting with inadequate oral intake creates a starvation-like metabolic state 5, 3
• Dehydration compounds the metabolic derangement 3

Physiological Context

Ketone bodies (β-hydroxybutyrate, acetoacetate, and acetone) are normally present in blood and urine at very low concentrations (total serum ketones <0.5 mmol/L) 1

The key mechanisms driving non-diabetic ketonuria include:

• Increased lipolysis releasing free fatty acids that are converted to ketones in the liver 4, 6
• Conditions that increase NADH concentrations in hepatic mitochondria (hypoxia, metabolic disorders, alcohol) shift the equilibrium toward β-hydroxybutyrate production 1
• The ratio of β-hydroxybutyrate to acetoacetate increases from the normal 1:1 to as high as 10:1 in ketoacidotic states 6

Critical Clinical Pitfalls

Testing Limitations

• Standard urine ketone tests using nitroprusside reagents only detect acetoacetate, not β-hydroxybutyrate, which is the predominant ketone body in most ketotic states 1, 2, 6
• This can significantly underestimate total ketone body concentration 1
• False-positive results occur with highly colored urine and sulfhydryl drugs (including captopril) 2
• False-negative results occur with prolonged air exposure of test strips or highly acidic urine 2

When to Escalate Care

Seek immediate medical evaluation if ketonuria is accompanied by:

• Persistent vomiting or inability to tolerate oral hydration 8
• Abdominal pain, nausea, or altered mental status 1, 3
• Signs of dehydration or worsening illness 8
• Rapid, shallow breathing (Kussmaul respirations) 3

Diagnostic Approach

For non-diabetic individuals with ketonuria, systematically assess:

• Recent dietary intake and caloric adequacy (even if not formally "fasting") 5, 3
• Alcohol consumption patterns, particularly with poor nutrition 3
• Pregnancy status 2
• Recent exercise intensity and duration 4
• Presence of vomiting, diarrhea, or acute illness 5, 3, 7
• Adherence to very-low-carbohydrate diets 1, 4

Blood ketone testing measuring β-hydroxybutyrate is preferred over urine testing for accurate assessment of ketone body concentration 2, 8, 6