|Das, Sai Krupa|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2014
Publication Date: 5/1/2014
Citation: Wong, W.W., Roberts, S.B., Racette, S.B., Das, S., Redman, L.M., Rochon, J., Bhapkar, M., Clark, L.L., Kraus, W.E. 2014. The doubly labeled water method produces highly reproducible longitudinal results in nutrition studies. Journal of Nutrition. 144(5):777-783. Interpretive Summary: The doubly labeled water (DLW) method is the reference method for the measurement of energy expenditure in free living conditions because it is noninvasive, nonrestrictive with minimal participant burden, and has no known adverse side effects. The DLW method can also be implemented almost anywhere and the samples can be sent back to the analytical laboratory. Lastly, since the two isotopes 2H and 18O are nonradioactive stable isotopes, they do not decay or emit harmful radiation and thus can be kept for a long time under proper conditions to support longitudinal studies (studies over longer timeframes). However, the long term reproducibility of the DLW method, which is critical for longitudinal studies to monitor changes in energy expenditure and body composition, has not been well documented. The goal of this study was to evaluate the reproducibility of the DLW method using two protocols developed and implemented during the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial. One protocol was based on repeated analysis of dose dilutions over the course of the CALERIE trial, and the other based on repeated but blinded analysis of randomly selected DLW studies. The results of this study showed that the DLW method is reproducible in longitudinal studies. This confirms the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5- 4.4 years. Other laboratories can use these two protocols to document the long term reproducibility of their measurements and to ensure the biological significance of the long term outcomes of interest.
Technical Abstract: The doubly labeled water (DLW) method is considered the reference method for the measurement of energy expenditure under free-living conditions. However, the reproducibility of the DLW method in longitudinal studies is not well documented. This study was designed to evaluate the longitudinal reproducibility of the DLW method using 2 protocols developed and implemented in a multicenter clinical trial-the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). To document the longitudinal reproducibility of the DLW method, 2 protocols, 1 based on repeated analysis of dose dilutions over the course of the clinical trial (dose-dilution protocol) and 1 based on repeated but blinded analysis of randomly selected DLW studies (test-retest protocol), were carried out. The dose-dilution protocol showed that the theoretical fractional turnover rates for 2H and 18O and the difference between the 2 fractional turnover rates were reproducible to within 1% and 5%, respectively, over 4.5 y. The Bland-Altman pair-wise comparisons of the results generated from 50 test-retest DLW studies showed that the fractional turnover rates and isotope dilution spaces for 2H and 18O, and total energy expenditure, were highly reproducible over 2.4 y. Our results show that the DLW method is reproducible in longitudinal studies and confirm the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5-4.4 y. The 2 protocols can be adopted by other laboratories to document the longitudinal reproducibility of their measurements to ensure the long-term outcomes of interest are meaningful biologically.