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Updated: May 17, 2026

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of
Thomas P Wycherley1, Lisa J Moran, Peter M Clifton
1Sansom Institute for Health Research, Division of Health Sciences, University of South Australia, Adelaide, Australia. tom.wycherley@unisa.edu.au
Background:
It is currently unclear whether altering the carbohydrate-to-protein ratio of low-fat, energy-restricted diets augments weight loss and cardiometabolic risk markers.
Objective:
The objective was to conduct a systematic review and meta-analysis of studies that compared energy-restricted, isocaloric, high-protein, low-fat (HP) diets with standard-protein, low-fat (SP) diets on weight loss, body composition, resting energy expenditure (REE), satiety and appetite, and cardiometabolic risk factors.
Design:
Systematic searches were conducted by using MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials to identify weight-loss trials that compared isocalorically prescribed diets matched for fat intake but that differed in protein and carbohydrate intakes in participants aged ≥18 y. Twenty-four trials that included 1063 individuals satisfied the inclusion criteria.
Results:
Mean (±SD) diet duration was 12.1 ± 9.3 wk. Compared with an SP diet, an HP diet produced more favorable changes in weighted mean differences for reductions in body weight (-0.79 kg; 95% CI: -1.50, -0.08 kg), fat mass (FM; -0.87 kg; 95% CI: -1.26, -0.48 kg), and triglycerides (-0.23 mmol/L; 95% CI: -0.33, -0.12 mmol/L) and mitigation of reductions in fat-free mass (FFM; 0.43 kg; 95% CI: 0.09, 0.78 kg) and REE (595.5 kJ/d; 95% CI: 67.0, 1124.1 kJ/d). Changes in fasting plasma glucose, fasting insulin, blood pressure, and total, LDL, and HDL cholesterol were similar across dietary treatments (P ≥ 0.20). Greater satiety with HP was reported in 3 of 5 studies.
Conclusion:
Compared with an energy-restricted SP diet, an isocalorically prescribed HP diet provides modest benefits for reductions in body weight, FM, and triglycerides and for mitigating reductions in FFM and REE.
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