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Phenotyping in clinical nutrition

Issues related to the assessment of energy balance during short-term over-, under- and refeeding in normal weight men



In humans, it is unclear how different estimates of energy balance (EB) compare with each other and whether the resulting changes in body weight (bw) and body composition (BC) are predictable and reproducible.


This is a secondary data analysis of effects of sequential 7d over- (OF), 21d under- (UF) and 14d refeeding (RF) on EB. Energy intake (EI) was controlled at +/− 50% of energy needs in a 32 normal weight men (see Am J Clin Nutr. 2015; 102:807–819). EB was calculated (i) directly from the difference between EI and energy expenditure (EE) and (ii) indirectly from changes in BC. Changes in fat mass (FM) were compared with predicted changes according to Hall et al. (Lancet 2011; 378:826–37). Finally, within-subject reproducibility of changes in bw and BC was tested in a subgroup.


There were interindividual and day-by-day variabilities in changes in bw and BC. During OF and RF, the two estimates of EB were similar while with UF the indirect approach underestimated the direct estimate by 10593 ± 7506 kcal/21d (p < 0.001). Considerable differences became evident between measured and predicted changes in FM. Adjusting measured for predicted values did not reduce their interindividual variance. During UF, changes in bw and BC were reproducible, while corresponding changes during OF were not.


During hypercaloric nutrition the direct estimate of EB corresponded to the indirect estimate whereas this was not true during UF. Changes in bw and BC in response to OF were not reproducible while they were during UF.

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Fig. 1: Changes in body weight.
Fig. 2: Apparent macronutrient balances during overfeeding (upper panel), underfeeding (middle panel) and refeeding (lower panel) assessed in 32 healthy, young normal weight men.
Fig. 3: Reproducibility of changes in body weight, fat mass (FM) and fat-free mass (FFM) in a subgroup of 8 of the 32 healthy young men undergoing 7 d overfeeding (at +50% of individual energy needs) followed by 7 d underfeeding (at −50% of individual energy needs).

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The study was funded by a grant of the Germany Ministry of Education and Research (BMBF 0315681) and the German Research Foundation (DFG Bo 3296/1-1). Data described in the manuscript, code book, and analytic code cannot be made available because the strict German Data Protection law.

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MJM had the idea and the concept together with ABW. ABW, MJM, WB contributed to data analyses. MJM wrote the 1st version of the manuscript. All authors added to the discussion of the results, the final version and the approval of this manuscript.

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Correspondence to Manfred J. Müller.

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Müller, M.J., Braun, W., Enderle, J. et al. Issues related to the assessment of energy balance during short-term over-, under- and refeeding in normal weight men. Eur J Clin Nutr 77, 538–545 (2023).

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