Prolonged Daily Fasting as a Viable Alternative to Caloric Restriction in At-Risk Obese Humans

Aim#1: Evaluate the effect of TRE with ad libitum intake on weight and body composition. H 1.1: Individuals in the TRE and CR groups will have similar weight loss, which will be greater than weight loss achieved in the non-TRE group (primary outcome). H 1.2: TRE will result in greater loss of loss of total body fat (quantified by DXA) and greater loss of hepatic/visceral fat/ectopic fat (quantified by MRI) than CR. Aim#2: Assess the effect of TRE with ad libitum intake on caloric balance. H 2.1: TRE will reduce caloric intake compared with non-TRE \[gold-standard interviewer administered 24-hour dietary recall (primary outcome)\] with similar reduction as with CR, H.2.2: Compared with non-TRE, TRE will result in selection of more nutrient dense foods during a supervised meal within their eating window; this selection will be similar to CR. H 2.3 TRE will not alter physical activity, but will increase fat oxidation compared with CR and non-TRE. Aim#3: Assess the effect of TRE with ad libitum intake on metabolic flexibility. H 3.1: TRE will enhance metabolic flexibility compared with CR and non-TRE as measured by indirect calorimetry \[RQ:Respiratory quotient before and during 2 step 6,6-2H2 hyperinsulinemic-euglycemic clamp: primary outcome\]. H 3.2: TRE will improve insulin sensitivity compared with non-TRE and similar to CR. H 3.3: TRE will augment greater fasting lipolysis compared to CR and non-TRE as measured by \[U-13C\] palmitate and enhance lipolysis suppression during the 2 step 6,6-2H2 hyperinsulinemic-euglycemic clamp. If these hypotheses are confirmed, this project has significant impact. First, it will advance understanding of the mechanisms underpinning this innovative intervention. Second, TRE can be a practical means of implementing prolonged fasting on a large scale, thereby transforming the treatment of obesity. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1-TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.