Background: To date, no crossover studies have compared the effects of high-protein (HP) and low glycemic index (LGI) diets applied as starting energy-restricted diets. Methods: Thirty-five overweight or obese volunteers with sedentary lifestyles aged 41.4 ± 11.0 years, with body mass index (BMI) of 33.6 ± 4.2 kg/m2, without diabetes, completed an 8-week randomized crossover study of an energy-restricted diet (reduction of 30%; approximately 600 kcal/day). The anthropometric parameters, body composition, 24 h blood pressure, and basic metabolic profile were measured at baseline and after completing the two 4-week diets; i.e., the HP (protein at 30% of the daily energy intake) or LGI diet, followed by the opposite diet. All subjects maintained food diaries and attended six counselling sessions with a clinical dietitian. Results: The final weight loss was not significantly different when the HP diet was used first but was associated with a greater loss of fat mass: 4.6 kg (5.8; 3.0 kg) vs. 2.2 (4.5; 0.8); p < 0.025, preserved muscle mass, and reduced LDL-cholesterol. Conclusions: A short-term HP diet applied as a jump-start diet appeared to be more beneficial than an LGI diet, as indicated by the greater fat mass loss, preservation of muscle mass, and better effects on the lipid profile.

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