Methodologic Issues in Doubly Labeled Water Measurements of Energy Expenditure During Very Low-Carbohydrate Diets

Background Very low-carbohydrate diets have been reported to substantially increase human energy expenditure as measured by doubly labeled water (DLW) but not by respiratory chambers. Do the DLW data reflect true physiological differences that are undetected by respiratory chambers? Alternatively, are the apparent DLW energy expenditure a consequence of failure to fully account for respiratory quotient (RQ) differences between diets?

Objective To examine energy expenditure differences between diets varying drastically 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 two weeks 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 BMI 25-35 kg/m². Subjects resided 2d/week in respiratory chambers to measure energy expenditure (EE_chamber). DLW expenditure was calculated using chamber-determined respiratory quotients (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 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 and EE_DLW∆RQ were marginally increased during the KD by 126±62 kcal/d (p=0.063) and 46±65 kcal/d (p=0.49), respectively.

Conclusions DLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that very low carbohydrate diets substantially increase energy expenditure.