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

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.