ObjectiveTo determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.DesignRandomized trial.SettingMulticenter collaboration at US two sites, August 2014 to May 2017.Participants164 adults aged 18-65 years with a body mass index of 25 or more.InterventionsAfter 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).Main outcome measuresThe primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.ResultsTotal energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (−6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).ConclusionsConsistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.Trial registrationClinicalTrials.gov NCT02068885.

The primary outcome was total energy expenditure, assessed by doubly-labeled water methodology. Secondary outcomes included resting energy expenditure and physical activity, chronic disease risk factors, and variables to inform an understanding of physiological mechanisms by which dietary carbohydrate-to-fat ratio might influence metabolism. Weight change during the ad libitum feeding phase was conceptualized as a proxy measure of hunger.

A research team from Boston Children's Hospital and Harvard Medical School conducted a community-based feeding study in collaboration with Framingham State University (FSU) and Sodexo, the food service contractor at FSU. The study was a randomized controlled trial, implemented on the FSU campus. For the final year of the study, a satellite feeding site was established at Assabet Valley Regional Technical High School. The purpose of the study was to assess the biological effects of different macronutrient diets. An academia-industry partnership was developed to overcome common challenges associated with hospital-based feeding studies. Benefits included the following: a study site outside of Boston (reducing inconvenience for participants), access to a large commercial kitchen and study-specific kiosk (promoting efficiency), collaboration with Sodexo chefs (ensuring palatability of meals), and opportunity to procure food from contracted vendors. The research (academia) and food service (industry) teams worked together to design, plan, and execute intervention protocols using an integrated approach. During execution, the research team was primarily responsible for overseeing treatment fidelity, whereas the food service team provided culinary expertise, with a strong focus on hospitality and food quality. The study was conducted in 3 cohorts between August 2014 and May 2017. Participants received all of their food for ∼30 wk, totaling >160,000 meals. For all 3 cohorts combined, 234 participants provided informed consent, 229 started a standard run-in weight-loss diet, 164 lost a mean ± SD 12% ± 2% of baseline body weight and were randomly assigned to different macronutrient diets for weight-loss maintenance, and 148 completed the study. During the final and largest cohort, as many as 114 participants received daily meals concurrently. The daily cost per participant for preparation and service of weighed meals and snacks was ∼$65. This academia-industry partnership provides a model for controlled feeding protocols in nutrition research, potentially with enhanced cost-effectiveness, practicality, and generalizability. This trial was registered at http://www.clinicaltrials.gov as NCT02068885.

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.