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Water metabolism may be non-invasively investigated using deuterium elimination from the body. Evaluation of elimination constants (k D ) and pool sizes (N) becomes complicated when turnover rates vary periodically - a realistic scenario in free-living subjects. Unfortunately, phase and frequency of periodic variations are not  a priori  known and can therefore not be used for a sampling protocol. This study investigates the impact of periodical flux variations on the measurement of water turnover. For two models of periodic variation with identical apparent k D , data sets of tracer concentrations in body water were generated for two-hour intervals using a monoexponential decay equation. Data were analyzed using the two- and the multi-point method increasing observation periods stepwise. Apparent values for k D , N and water turnover (R H₂O ) were compared with values originally used in the model. Periodically varying turnover rates introduce considerable errors for k D  and R H₂O  when the two-point method is used. The multi-point method gives a more robust estimate of R H₂O  already after short observation periods, however, due to slope-intercept correlations, still tends to overestimate R H₂O . Errors are more pronounced the more uneven flux rates are distributed. Stepwise analysis of tracer enrichments using the multi-point approach identifies periodical variation of flux rates.

Measurement of Water Turnover Using Deuterium Dilution: Impact of Periodically Varying Turnover Rates on Precision and Accuracy