KD. Hall, J. Guo, AB. Courville, J. Boring, R. Brychta, KY. Chen, V. Darcey, CG. Forde, AM. Gharib, I. Gallagher, R. Howard, PV. Joseph, L. Milley, R. Ouwerkerk, K. Raisinger, I. Rozga, A. Schick, M. Stagliano, S. Torres, M. Walter, P. Walter, S. Yang, et al. (2021). Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake. Nature medicine, 27(2), 344-353. https://doi.org/10.1038/s41591-020-01209-1

PubMed 33479499

[Abstract]
The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m-2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal-1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal-1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d-1 less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d-1 less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .