Stephen D. Anton

Objective A growing body of evidence has supported the health benefits of extended daily fasting, known as time‐restricted eating (TRE); however, whether the addition of TRE enhances the known benefits of calorie restriction (CR) remains unclear. Methods PubMed, Scopus, the Cochrane Library, and Google Scholar were searched through April 2023. This systematic review includes randomized controlled trials (RCTs) that compared CR + TRE with CR alone in energy‐matched conditions of at least 8 weeks in duration that assessed changes in body weight and cardiometabolic disease risk factors in adults with overweight and/or obesity. Results Seven studies were identified ( n = 579). Two studies reported greater weight loss and reductions in diastolic blood pressure with CR + TRE compared with CR alone after 8 to 14 weeks, whereas one study reported greater improvements in triglycerides and glucose tolerance with CR + TRE (3 days/week) compared with CR alone following 26 weeks. One study reported significant increases in homeostatic model assessment of insulin resistance (HOMA‐IR) levels with CR + TRE versus CR alone after 8 weeks. There were no statistically significant differences in any other outcome variable between the two interventions. Conclusions The addition of TRE to CR regimens resulted in greater weight loss and improvements in cardiometabolic risk factors in some studies; however, the majority of studies did not find additional benefits.

It is well recognized that patients with severe obesity exhibit remarkable heterogeneity in response to different types of weight-loss interventions. Those who undergo Roux-en-Y gastric bypass (RYGB) usually exhibit more favorable glycemic outcomes than those who receive adjustable gastric banding (BAND) or intensive medical intervention (IMI). The molecular mechanisms behind these observations, however, remain largely unknown. To identify the plasma metabolites associated with differential glycemic outcomes induced by weight-loss intervention, we studied 75 patients with severe obesity (25 each in RYGB, BAND, or IMI). Using untargeted metabolomics, we repeatedly measured 364 metabolites in plasma samples at baseline and 1-year after intervention. Linear regression was used to examine whether baseline metabolites or changes in metabolites are associated with differential glycemic outcomes in response to different types of weight-loss intervention, adjusting for sex, baseline age, and BMI as well as weight loss. Network analyses were performed to identify differential metabolic pathways involved in the observed associations. After correction for multiple testing (q < 0.05), 33 (RYGB vs. IMI) and 28 (RYGB vs. BAND) baseline metabolites were associated with changes in fasting plasma glucose (FPG) or glycated hemoglobin (HbA1c). Longitudinal changes in 38 (RYGB vs. IMI) and 38 metabolites (RYGB vs. BAND) were significantly associated with changes in FPG or HbA1c. The identified metabolites are enriched in pathways involved in the biosynthesis of aminoacyl-tRNA and branched-chain amino acids. Weight-loss intervention evokes extensive changes in plasma metabolites, and the altered metabolome may underlie the differential glycemic outcomes in response to different types of weight-loss intervention, independent of weight loss itself.