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Updated: Dec 20, 2025

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Energy Requirement Is Higher During Weight-Loss Maintenance in Adults Consuming a Low- Compared with
Cara B Ebbeling1, Lisa Bielak1, Paul R Lakin2
1New Balance Foundation Obesity Prevention Center, Boston, MA, USA.
Background:
Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized in these studies, involving doubly labeled water (DLW), has been questioned.
Objective:
The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low- compared with high-carbohydrate diet.
Methods:
The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≥25 kg/m2; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA.
Results:
Mean EER was higher in the Low- versus High-Carbohydrate group in models of varying covariate structure involving ITT [ranging from 181 (95% CI: 8-353) to 246 (64-427) kcal/d; P ≤0.04] and PP [ranging from 245 (43-446) to 323 (122-525) kcal/d; P ≤0.02]. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence.
Conclusions:
Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885.
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