Alessio Basolo, Paolo Piaggi, Valentina Angeli, Paola Fierabracci, Chiara Bologna, Edda Vignali, Daniela Troiani, Roberta Jaccheri, Caterina Pelosini, Melania Paoli, Guido Salvetti, Luca Chiovato, Jonathan Krakoff, Alberto Landi, Ferruccio Santini
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 12, December 2025, Pages e4158–e4168
https://doi.org/10.1210/clinem/dgaf196
Very-low-calorie ketogenic diet (VLCKD) is used for weight loss and management of obesity-related comorbidities.
We aimed at evaluating the effects of VLCKD on body composition and energy metabolism.
This prospective outpatient study included 17 women with obesity (mean age 41.6 years; body mass index 37.5 kg/m2) who followed a 1-month VLCKD (700-800 kcal/day, carbohydrate 11%, fat 46%, protein 43%) at the University Hospital of Pisa. Measurements of 24-hour energy expenditure (24hEE) and substrate oxidation were conducted in a metabolic chamber at day 1 (V1), day 8 (V2), and day 29 (V3). Body composition was assessed by Dual energy X-ray absorptiometry. Twenty-two women with obesity fed a balanced isocaloric diet served as controls.
Compared with controls, carbohydrate oxidation (CarbOx) was lower, whereas fat oxidation (FatOx) and protein oxidation (ProtOx) were higher in the VLCKD group at V1. CarbOx decreased by 65%, while FatOx increased by 11% at V3. The rate of ProtOx was already higher than in controls at V1 and remained stable throughout the study. After 1 month, body weight decreased by 7%, reflecting an 8.8% reduction in fat mass and a 5.6% reduction in lean soft tissue (LST). A 10% decrease in 24hEE and 24-hour sleeping metabolic rate was observed at V3 compared with V1.
VLCKD promotes weight loss in women with obesity. Our findings highlight the shift in energy metabolism towards increased FatOx accompanied by a modest increase in protein oxidation, a decrease in LST and a reduction in EE.
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