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Skin acetone as a clinical diagnostic biomarker of ketosis

By Anh Ngan Nguyen, Oscar Osorio perez, David Jackemeyer, Eliana Terrera, Ayushi Pradhan, Dominguez R. E., Yuyan Hua, Charlotte Chou, Shan Cheng, Erica Forzani
2025
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Background/Objectives: We present the first receiver operating characteristic (ROC) diagnostic analysis of skin-excreted acetone as a biomarker of ketosis.

Participants/Methods: In a pilot study involving 16 healthy participants, we investigated the ability of skin-excreted acetone to differentiate between ketosis and non-ketosis states. Non-ketosis conditions were established under a normal diet and energy balance, while ketosis was induced through dietary and energy manipulations, including a ketogenic diet with energy balance, a normal diet with negative energy balance, and a ketogenic diet with negative energy balance. Alongside skin acetone concentration and excretion rate, we quantified a comprehensive set of ketone body parameters for comparative diagnostic purposes, including breath acetone concentration and excretion rate, blood beta-hydroxybutyrate concentration, urine beta-hydroxybutyrate concentration and excretion rate, urine acetoacetate concentration and excretion rate. Blood beta-hydroxybutyrate concentration (in mM) was included as a benchmark since it is a well-established clinical biomarker of ketosis.

Results: ROC curves were generated to evaluate the diagnostic performance for each biomarker in distinguishing ketosis. Both breath and skin acetone excretion rates achieved an area under the curve (AUC) of 0.83, outperforming several other ketone biomarkers. Similarly, breath acetone concentration and skin acetone concentration also exhibited AUCs of 0.82 and 0.83, respectively. In comparison, blood beta-hydroxybutyrate concentration and urine acetoacetate excretion rate both showed an AUC of 0.81, while urine beta-hydroxybutyrate excretion rate and concentration achieved AUCs of 0.66 and 0.68, respectively. Furthermore, the excretion rates of breath acetone and skin acetone were systematically compared within individual participants and across different participants. The correlation between the two reinforces the significance of skin acetone as a body ketone biomarker that diffuses through the skin representing the body acetone concentrations.

Conclusions: Overall, the results highlight the potential of skin acetone excretion rate as a reliable, non-invasive biomarker for ketosis, offering significant promise for clinical and health monitoring applications.
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