Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials: Reanalysis of a Metabolic Ward Study

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  • Adrian Soto-Mota
  • Lisa T. Jansen
  • Nicholas G. Norwitz
  • Mark A. Pereira
  • Cara B. Ebbeling
  • Ludwig, David Samuel

An influential 2-wk cross-over feeding trial without a washout period purported to show advantages of a low-fat diet (LFD) compared with a low-carbohydrate diet (LCD) for weight control. In contrast to several other macronutrient trials, the diet order effect was originally reported as not significant. In light of a new analysis by the original investigative group identifying an order effect, we aimed to examine, in a reanalysis of publicly available data (16 of 20 original participants; 7 female; mean BMI, 27.8 kg/m2), the validity of the original results and the claims that trial data oppose the carbohydrate–insulin model of obesity (CIM). We found that energy intake on the LCD was much lower when this diet was consumed first compared with second (a difference of −1164 kcal/d, P = 3.6 × 10-13); the opposite pattern was observed for the LFD (924 kcal/d, P = 2.0 × 10-16). This carry-over effect was significant (P interaction = 0.0004) whereas the net dietary effect was not (P = 0.4). Likewise, the between-arm difference (LCD - LFD) was −320 kcal/d in the first period and +1771 kcal/d in the second. Body fat decreased with consumption of the LCD first and increased with consumption of this diet second (−0.69 ± 0.33 compared with 0.57 ± 0.32 kg, P = 0.007). LCD-first participants had higher β-hydroxybutyrate levels while consuming the LCD and lower respiratory quotients while consuming LFD when compared with LFD-first participants on their respective diets. Change in insulin secretion as assessed by C-peptide in the first diet period predicted higher energy intake and less fat loss in the second period. These findings, which tend to support rather than oppose the CIM, suggest that differential (unequal) carry-over effects and short duration, with no washout period, preclude causal inferences regarding chronic macronutrient effects from this trial.

OriginalsprogEngelsk
TidsskriftJournal of Nutrition
Vol/bind154
Udgave nummer4
Sider (fra-til)1080-1086
ISSN0022-3166
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
We thank Walter Willett for thoughtful review of the manuscript and Shui Yu for verifying the data analyses and statistical code. LTJ was supported by the Center for Childhood Obesity Prevention, funded by the National Institute of General Medicine Sciences of the National Institutes of Health under Award Number P20GM109096 (Arkansas Children’s Research Institute, PI: Weber).

Publisher Copyright:
© 2023 The Author(s)

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