Caution Against Overinterpreting Time-Restricted Eating Results

To the Editor

Lowe et al¹ recently published a randomized clinical trial reporting that extended daily fasting, or time-restricted eating (TRE), does not improve body weight or cardiometabolic risk factors and slightly decreases appendicular lean mass, a surrogate for muscle mass. This important study is the largest published tried of TRE and suggests that TRE does not improve cardiometabolic health, or the effects may be smaller than previously reported.

Some context is merited. First, the control group was an active comparator: participants in that group were not allowed to eat ad libitum but rather were instructed to eat 3 meals per day at specified times. Eating regular meals reduces body weight and postprandial insulin and cholesterol levels,² and some of the previously reported benefits of TRE may be mediated through eating at regular times. The statistical testing, though, did not involve a test of noninferiority for these 2 interventions, as might be expected. Second, the TRE group was instructed to skip breakfast and eat between 12 pm to 8 pm. Key metabolic circadian rhythms peak in the morning or around noontime, and several studies suggest that eating earlier in the daytime increases weight loss and improves cardiometabolic health relative to either eating later or skipping breakfast, which could possibly explain the null results.³ Finally, participants were required to weigh themselves daily and received thrice-daily reminders to comply with study procedures, which may have caused participants in both groups to favorably alter their behavior–a phenomenon known as the Hawthorne effect. This may have limited the ability to detect differences between groups.

Caveats are also merited in interpreting the results. Although not achieving the standard P ≤ .05 threshold for statistical significance, the control group tended to lose weight compared with baseline, and the in-person TRE cohort tended to lose more weight than their control counterparts. And although the reduction in appendicular lean mass was statistically significant, the magnitude of the between-group difference was small (−0.47 kg; 95% CI, −0.82 kg to −0.12 kg). This difference of approximately 1.8% is similar to the cited root-mean-square coefficient of variation of 1.12% to 1.82% for leg and arm lean mass.⁴ It is also likely that only a few individuals exceeded the least significant change, which was estimated at 1.02 kg (4.5%).⁵ The functional implications of these small body composition differences are unclear. We therefore caution against overinterpreting these results. Future larger-scale clinical trials are needed before drawing definitive conclusions.