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Background/Objective <p>We present the first receiver operating characteristic (ROC) diagnostic analysis of skin-excreted acetone as a biomarker of ketosis.</p> Participants/Methods <p>In an 8-week controlled crossover pilot study (<i>n</i> = 16), we evaluated the ability of skin-emitted acetone to differentiate metabolic ketosis from non-ketosis states. Non-ketosis was established via a normal diet/energy balance, while ketosis was induced through dietary and energy manipulations, including ketogenic diets and negative energy balances. 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, and urine acetoacetate concentration and excretion rate. Blood BHB (mM) served as the clinical benchmark for ketosis.</p> Results <p>ROC curves were generated to evaluate the diagnostic performance of each biomarker in distinguishing between ketosis and non-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 and skin acetone concentrations 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, breath and skin acetone excretion rates were systematically compared within and across 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’s acetone concentrations.</p> Conclusions <p>Overall, the results highlight the potential of skin acetone excretion rate as a reliable, non-invasive biomarker of ketosis, with diagnostic accuracy comparable to that of blood-based standards, offering significant promise for continuous, wearable metabolic monitoring in clinical and health settings.</p>

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Skin acetone as a clinical diagnostic biomarker of ketosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月7日

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  • Anh Ngan Nguyen,
  • Oscar Osorio-Perez,
  • David Jackemeyer,
  • Eliana Terrera,
  • Shaun Victor,
  • Ayushi Pradhan,
  • Fang Chen,
  • Rodrigo Ezequiel Dominguez,
  • Yuyan Hua,
  • Charlotte Chou,
  • Shan Cheng,
  • Erica Forzani

摘要

Background/Objective

We present the first receiver operating characteristic (ROC) diagnostic analysis of skin-excreted acetone as a biomarker of ketosis.

Participants/Methods

In an 8-week controlled crossover pilot study (n = 16), we evaluated the ability of skin-emitted acetone to differentiate metabolic ketosis from non-ketosis states. Non-ketosis was established via a normal diet/energy balance, while ketosis was induced through dietary and energy manipulations, including ketogenic diets and negative energy balances. 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, and urine acetoacetate concentration and excretion rate. Blood BHB (mM) served as the clinical benchmark for ketosis.

Results

ROC curves were generated to evaluate the diagnostic performance of each biomarker in distinguishing between ketosis and non-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 and skin acetone concentrations 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, breath and skin acetone excretion rates were systematically compared within and across 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’s acetone concentrations.

Conclusions

Overall, the results highlight the potential of skin acetone excretion rate as a reliable, non-invasive biomarker of ketosis, with diagnostic accuracy comparable to that of blood-based standards, offering significant promise for continuous, wearable metabolic monitoring in clinical and health settings.