• Kevin D Hall, Juen Guo, Kong Y Chen, Rudolph L Leibel, Marc L Reitman, Michael Rosenbaum, Steven R Smith, and Eric Ravussin.
• National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
• Am. J. Clin. Nutr. 2019 May 1; 109 (5): 1328-1334.

BackgroundLow-carbohydrate diets have been reported to significantly increase human energy expenditure when measured using doubly labeled water (DLW) but not by respiratory chambers. Although DLW may reveal true physiological differences undetected by respiratory chambers, an alternative possibility is that the expenditure differences resulted from failure to correctly estimate the respiratory quotient (RQ) used in the DLW calculations.ObjectiveTo examine energy expenditure differences between isocaloric diets varying widely in carbohydrate and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework.DesignDLW measurements were obtained during the final 2 wk of month-long baseline (BD; 50% carbohydrate, 35% fat, 15% protein) and isocaloric ketogenic diets (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with a BMI of 25-35 kg/m2. Subjects resided 2 d/wk in respiratory chambers to measure energy expenditure (EEchamber). DLW expenditure was calculated using chamber-determined RQ either unadjusted (EEDLW) or adjusted (EEDLWΔRQ) for net energy imbalance using diet-specific coefficients. Accelerometers measured physical activity. Body composition changes were measured by dual-energy X-ray absorptiometry (DXA) which were combined with energy intake measurements to calculate energy expenditure by balance (EEbal).ResultsAfter transitioning from BD to KD, neither EEchamber nor EEbal were significantly changed (∆EEchamber = 24 ± 30 kcal/d; P = 0.43 and ∆EEbal = -141 ± 118 kcal/d; P = 0.25). Similarly, physical activity (-5.1 ± 4.8%; P = 0.3) and exercise efficiency (-1.6 ± 2.4%; P = 0.52) were not significantly changed. However, EEDLW was 209 ± 83 kcal/d higher during the KD (P = 0.023) but was not significantly increased when adjusted for energy balance (EEDLWΔRQ = 139 ± 89 kcal/d; P = 0.14). After removing 2 outliers whose EEDLW were incompatible with other data, EEDLW was marginally increased during the KD by 126 ± 62 kcal/d (P = 0.063) and EEDLW∆RQ was only 46 ± 65 kcal/d higher (P = 0.49).ConclusionsDLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that low-carbohydrate diets substantially increase energy expenditure. This trial was registered at clinicaltrials.gov as NCT01967563.Published by Oxford University Press on behalf of the American Society for Nutrition 2019.

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