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Potential Bias of Doubly Labeled Water for Measuring Energy Expenditure Differences Between Diets Varying in Carbohydrate

by Kevin D.Hall, JuenGuo, Kong Y.Chen, Rudolph L.Leibel, Marc L.Reitman, MichaelRosenbaum, Steven R.Smith, EricRavussin

Abstract: AbstractObjective To examine possible bias of the doubly labeled water (DLW) method for measuring energy expenditure (EEDLW) in humans consuming a low-carbohydrate diet.Methods EEDLW was measured during the final two weeks of a month-long baseline diet (BD; 50% carbohydrate, 35% fat, 15% protein) as well as a subsequent isocaloric ketogenic diet (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with BMI between 25-35 kg/m2. Physical activity was measured by accelerometers. Subjects resided two days per week in respiratory chambers to measure energy expenditure (EEchamber). Body composition and energy intake measurements were used to calculate expenditure by energy balance (EEbal).Results Neither EEchamber nor EEbal were significantly different during the KD versus the BD phase (ΔEEchamber=24±30 kcal/d; p=0.43 and ΔEEbal=-141±118 kcal/d; p=0.25). Similarly, physical activity (−5.1±4.8%; p=0.3) and the exercise efficiency (−1.6±2.4%; p=0.52) were unchanged. However, EEDLW was 209±83 kcal/d higher during the KD versus the BD (p=0.023).Conclusions The increased EEDLW during the KD was incommensurate with the respiratory chamber, energy intake and body composition measurements and could not be explained by objective measures of physical activity or exercise efficiency. Our data raise the possibility of systematic bias of the DLW method for low-carbohydrate diets.What is already known about this subject?The doubly labeled water (DLW) method has been successfully applied to measuring energy expenditure in humans since the 1980s and has been validated in comparison to respiratory chamber measurements in subjects consuming moderate carbohydrate diets.The DLW has never been validated in humans consuming a very low-carbohydrate diet and there are theoretical reasons why the DLW method might result in a systematic bias when calculating energy expenditure differences between diets widely varying in carbohydrate.What this study addsWhile not designed as a validation experiment, this two-month long inpatient isocaloric feeding study represents the most rigorously controlled investigation of the DLW method during a low-carbohydrate diet in humans.The DLW method calculated a significant increase in energy expenditure after transitioning from a moderate carbohydrate diet to an isocaloric very low carbohydrate, ketogenic diet. However, the increased expenditure measured by the DLW method was inconsistent with both the coincident respiratory chamber measurements, changes in body energy stores, physical activity, and exercise efficiency measurements.Our data raise the possibility that the DLW method results in a systematic bias when calculating energy expenditure differences between diets varying widely in the proportion of carbohydrate.
keto
dlw

17 men were compared on a ketogenic diet (80% fat, 15% protein, 5% carbs) and "baseline" diet (50% carbs, 15% protein, 35% fat). The goal was to compare TEE as measured my metabolic chamber vs. doubly labeled water (DLW). 2 of the 17 had "incompatible" outlier data on DLW. Even after removing those, DLW on the ketogenic diet showed 126±62 kcal/d more TEE than metabolic chamber.

Original source: https://www.biorxiv.org/content/10.1101/403931v1