Breath Acetone as a Measure of Systemic Ketosis Assessed in a Rat Model of the Ketogenic Diet

The mechanism of a high-fat, low-carbohydrate ketogenic diet (KD) in alleviating drug-resistant epilepsy is unknown but may be related to systemic ketosis induced under this treatment. The need for frequent measurement of systemic ketosis, which is essential for improving maintenance of the KD in patients and for studying mechanism of the KD action, has prompted us to validate the breath acetone test as a fast, reliable, and noninvasive tool for ketosis assessment. A rat model of the KD that allowed frequent blood sampling was used to investigate how well breath acetone reflects plasma beta-hydroxybutyrate (beta-HBA), the most commonly measured ketone body. Rat pups (20 days of age) were introduced to and maintained on a KD or control diet for 33 days. During this period, breath acetone, plasma beta-HBA, blood glucose, and body weight were measured approximately every 4th day. A correlational analysis of breath acetone and plasma beta-HBA was conducted. Breath acetone was found to be a significant predictor of plasma beta-HBA over a clinically relevant range of beta-HBA concentrations (r(2) = 0.75; P