Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials: Reanalysis of a Metabolic Ward Study
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Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials : Reanalysis of a Metabolic Ward Study. / Soto-Mota, Adrian; Jansen, Lisa T.; Norwitz, Nicholas G.; Pereira, Mark A.; Ebbeling, Cara B.; Ludwig, David S.
In: Journal of Nutrition, Vol. 154, No. 4, 2024, p. 1080-1086.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials
T2 - Reanalysis of a Metabolic Ward Study
AU - Soto-Mota, Adrian
AU - Jansen, Lisa T.
AU - Norwitz, Nicholas G.
AU - Pereira, Mark A.
AU - Ebbeling, Cara B.
AU - Ludwig, David S.
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - body composition
KW - clinical trial
KW - insulin
KW - low-carbohydrate diet
KW - low-fat diet
KW - macronutrients
KW - methodology
KW - obesity
U2 - 10.1016/j.tjnut.2023.12.017
DO - 10.1016/j.tjnut.2023.12.017
M3 - Journal article
C2 - 38128881
AN - SCOPUS:85182369796
VL - 154
SP - 1080
EP - 1086
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 4
ER -
ID: 387146190