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

¹ Department of Nutritional Sciences and
² Department of Pharmacology and Bloorview Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, M5S 1A8 Canada.

^aAddress correspondence to this author at: Department of Pharmacology, University of Toronto, Toronto, M5S 1A8 Canada. Fax 416-971-2433; e-mail sergei.likhodi{at}utoronto.ca.

Background: 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.

Methods: A rat model of the KD that allowed frequent blood sampling was used to investigate how well breath acetone reflects plasma ß-hydroxybutyrate (ß-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 ß-HBA, blood glucose, and body weight were measured approximately every 4th day. A correlational analysis of breath acetone and plasma ß-HBA was conducted.

Results: Breath acetone was found to be a significant predictor of plasma ß-HBA over a clinically relevant range of ß-HBA concentrations (r² = 0.75; P <0.001). We have proposed a general formula that allows the value of plasma ß-HBA to be estimated based on breath acetone measurement.

Conclusions: Breath acetone is an accurate measure of mild to moderate systemic ketosis. The noninvasive nature of this test will be useful for day-to-day implementation of the KD, searching for better forms of this diet, and understanding the role of ketosis in the mechanism of the KD action.

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