Overnight Fasting and Body Weight: Emulated Target Trial Using Cancer Prevention Study-3 Data.

: Intermittent fasting has gained attention in managing weight, yet its long-term effects remain unclear. We examined the impact of overnight, before-sleep, and after-sleep fasting on body weight over two years using data from the Cancer Prevention Study-3 Diet Assessment Substudy. : We emulated three target trials in 457 adults without diabetes or cancer. Participants were assigned to fasting strategies of <12 vs. ≥12 h overnight, <4 vs. ≥4 h before sleep, and <1 vs. ≥1 h after sleep at baseline (2016). Mean body weight 2 years post baseline was estimated using marginal structural models with stabilized inverse probability weights, adjusting for pre-baseline covariates. : After two years (median [IQR]: 2.0 [1.8-2.0] years), the estimated mean body weight was 79.4 kg (≥12 h overnight) vs. 78.9 kg (<12 h overnight) (mean difference: 0.4 kg; 95% CI: -4.1 to 4.7); 79.4 kg (≥4 h before sleep) vs. 77.5 kg (<4 h before sleep) (mean difference: 1.9 kg; 95% CI: -0.4 to 4.1); and 79.8 kg (≥1 h after sleep) vs. 78.9 kg (<1 h after sleep) (mean difference: 0.9 kg; 95% CI: -4.3 to 4.4). Among men, overnight fasting ≥ 12 h showed a higher weight (100.9 kg vs. 83.9 kg, mean difference: 17.0 kg; 95% CI: 10.8, 23.1), whereas, among women, it was estimated weight was lower (74.3 kg vs. 77.1 kg, mean difference: -2.8 kg; 95% CI: -6.8, 1.2). : Overall, overnight fasting alone may not substantially influence body weight, but sex-specific differences suggest a need for further investigation.