Methodologic considerations for measuring energy expenditure differences between diets varying in carbohydrate using the doubly labeled water method

BACKGROUND: Low-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. OBJECTIVE: To 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. DESIGN: DLW 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/m(2). Subjects resided 2 d/wk in respiratory chambers to measure energy expenditure (EE(chamber)). DLW expenditure was calculated using chamber-determined RQ either unadjusted (EE(DLW)) or adjusted (EE(DLWΔRQ)) 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 (EE(bal)). RESULTS: After transitioning from BD to KD, neither EE(chamber) nor EE(bal) were significantly changed (∆EE(chamber )= 24 ± 30 kcal/d; P = 0.43 and ∆EE(bal )= −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, EE(DLW) was 209 ± 83 kcal/d higher during the KD (P = 0.023) but was not significantly increased when adjusted for energy balance (EE(DLWΔRQ) = 139 ± 89 kcal/d; P = 0.14). After removing 2 outliers whose EE(DLW) were incompatible with other data, EE(DLW) was marginally increased during the KD by 126 ± 62 kcal/d (P = 0.063) and EE(DLW∆RQ) was only 46 ± 65 kcal/d higher (P = 0.49). CONCLUSIONS: DLW 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.