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Clinical Research

Randomized controlled trial of time-restricted eating: secondary analyses of breath acetone

Abstract

Studies of prolonged fasting produced spectacular weight loss and demonstrated that ketone bodies rise for approximately three weeks before stabilizing as production and utilization rates equilibrate. Although starvation is no longer an accepted obesity treatment, an extended period of fasting is the basis of time-restricted eating which produces metabolic benefits. Nevertheless, the pattern of change in ketone bodies with time-restricted eating has never been investigated. We collected weekly fasting measures of breath acetone from subjects (N = 60) who were on an eight-week, calorie-restricted diet and were randomized to different time-restricted eating windows. Subjects participating in a 14-hour fast, 10-hour eating window (14:10) lost more weight than subjects participating in a 12-hour fast, 12-hour eating window (12:12) as previously reported (Nutr Diabetes 2021; 11(1): 6). Ketone bodies assessed via breath acetone showed an increase for the first three weeks without a significant difference between groups. From weeks four to eight, breath acetone levels were lower in the 14:10 compared to the 12:12 group (between group difference: 5.45 ± 2.1 parts per million, mean ± SE, p = 0.012). We show for the first time that ketone bodies decrease after a period of adaptation to time-restricted eating of a calorie-restricted diet likely from enhanced fat oxidation and ketone utilization.

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Fig. 1: Pattern of change in breath acetone over 8 weeks of time-restricted eating.

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The datasets generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

This study was funded by JC USA, Inc. (Carlsbad, CA). JC USA provided program activities and materials, including discounted prepackaged foods and study equipment, to participants. LEVL devices were provided by Medamonitor, LLC. This work was supported in part by a grant from the National Institute on Aging (CJR, R00AG065419), and from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center (FLG, U54 GM104940).

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FLG, PP, and JCA formulated the research aims and designed the study. PP and RB conducted the research. DZ conducted the statistical analysis. CJR wrote the original draft of the manuscript. All authors reviewed and edited the manuscript.

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Correspondence to Frank L. Greenway.

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RFB was employed by Medamonitor LLC and JCA served as a consultant for Medamonitor LLC. CJR, DZ, PM, and FLG have no declarations of interest.

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Rebello, C.J., Zhang, D., Anderson, J.C. et al. Randomized controlled trial of time-restricted eating: secondary analyses of breath acetone. Int J Obes 49, 1416–1418 (2025). https://doi.org/10.1038/s41366-025-01818-1

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