Background & aims: The European Food Safety Authority recently recommended an increase in the protein content of total diet replacement (TDR) products from 50 to 75 g/day. The rationale was to minimize reductions in lean mass (LM) and resting metabolic rate (RMR) that occur with weight loss, and thereby facilitate maintenance of lost weight. We sought to directly compare the efficacy of TDR regimens with the new vs the current protein requirement.

Methods: We randomized 108 adults with overweight or obesity (body mass index 28-40 kg/m2) to very-low-calorie diets (VLCD) with either 52 or 77 g/day protein for 8 weeks (total energy intake of 600 or 700 kcal/day, respectively). LM was determined by dual energy X-ray absorptiometry and RMR by indirect calorimetry.

Results: Attrition rate was 22% in both groups. Both VLCDs decreased body weight, fat mass, LM, and RMR (all P < 0.05). Significant time-by-group interactions were detected for weight and fat mass (both P < 0.05), with corresponding reductions being smaller in the higher-protein than the standard-protein VLCD, likely because of the added calories. On the other hand, reductions in LM (6% from baseline) and RMR (9-10% from baseline) did not differ between groups (P = 0.155 and P = 0.389, respectively), and the contribution of LM to total weight loss was identical (27 ± 2% of lost weight, P = 0.973).

Conclusions: Our results indicate that the proposed increase in the protein content of TDR products does not attenuate reductions in LM and RMR in individuals with overweight and obesity who are treated with <800 kcal/day VLCDs for 2 months.

Clinical trial registry: ClinicalTrials.gov # NCT04156165.