4. Discussion
obesity, MM, FM, appetite suppression, weight loss, TG, glucometabolic
OBESITY, SEVERE OBESITY, INSULIN RESISTANCE
VLCKDs are valid and well-recognized strategies in the treatment of severe obesity and the PSMF diet falls into this group of dietary interventions, but its peculiarity is that not only carbohydrates are restricted to less than 30 g/day, but also lipids are limited to less than 20 g/day, making proteins the primary source of calories. This dietary approach seems to have a protein-sparing effect, preventing muscle catabolism. Furthermore, the consistent administration of a whey-protein-rich diet is more effective in preventing lean mass catabolism and inducing appetite suppression [Given this knowledge, we found that the PSMF diet administered by NGT is an effective and safe dietary intervention with a high level of compliance that leads to a rapid improvement in body composition parameters and glucometabolic markers when compared to administering the same diet orally. Specifically, we observed improvements in body composition parameters, with significantly lower levels of FM (kg) and FM (%) and higher levels of FFM (%), MM (%). From a pathophysiological perspective, it is known that nutrition administered via NGT determines a greater suppression of appetite in human subjects due to alterations in appetite-suppressing gut hormones, and may increase the levels of glucagon-like peptide 1 and peptide YY as reported by a recent randomized controlled trial (RCT) [This latter remark could be supported by the conflicting results of the improvement in muscle anabolism when using intermittent boluses of amino acids versus their continuous administration [Another intriguing finding from our study was the possibility of maintaining lean body mass throughout the administration of whey protein as a sole source of protein in PSMF. Whey proteins are rich in leucine, a branched chain amino acid that stimulates human muscle protein synthesis by activating the mTOR signaling pathway independently by Insulin-like growth factor receptor 1, resulting in a muscle anabolism enhancement. Moreover, whey proteins inhibit food intake and tend to improve oxidative balance in rats with obesity as this source of proteins was associated with a slight increase in total glutathione both in the liver and in the blood as compared to a casein-based diet [In our study, we observed a lower level of fasting blood insulin after 150 days of the PSMF diet in the ProMoFasT group compared to the oral group. This effect has several beneficial effects on human health, as it is well known in the literature that an insulin-sensitizing diet can improve strong outcomes in both diabetic and non-diabetic patients such as the reduction in cardiovascular mortality [Although it has been established that prolonged exposure to excessive amino acids diminished AMPK activity leading to insulin resistance [Another interesting result emerging from our study is the significant improvement in the lipid profile of the ProMoFasT group from baseline to follow-up, characterized by a decrease in LDL-C and TG and an increase in HDL-C. On the other hand, patients who received the oral PSMF diet experienced a worsening of LDL-C levels. The different results from baseline to follow-up observed in the ProMoFasT group could be attributed to the levels of fasting blood insulin, which appear to be significantly lower in the ProMoFasT group compared to the oral group. In fact, insulin has a well-recognized stimulatory influence on endogenous cholesterol synthesis [Based on our findings, calcium and phosphorus plasma levels increase in both groups from baseline to follow-up, although it is still possible to hypothesize that a protein-sparing diet may not negatively impact bone metabolism. In fact, it is well-known that a higher protein diet raises insulin-like growth factor-1, a crucial mediator of bone health [Finally, we observed a significant reduction in body weight, BMI and waist circumference during 150-day cycles of PSMF, whether administered via NGT or orally. In this field, a recent study suggested the effectiveness and safety of the PSMF diet as an outpatient weight loss strategy for adolescents affected by severe obesity [To the best of our knowledge, this is the first RCT that compared the safety and the efficacy in terms of body composition and glucometabolic improvement of a PSMF diet administered by NGT, compared to the same diet supplied orally. The limitations of our study include a small sample size and a relative high number of patients lost to follow-up; thus, the findings should be considered as preliminary. Furthermore, the lack of quality-of-life data could be another limitation of the study; in fact, quality of life encompasses significant aspects of well-being such as physical, mental, and emotional health, which are important for assessing the overall effectiveness and sustainability of any dietary intervention in a real-world setting. Another limitation was the non-statistically different distribution of male gender between the two groups, slightly favoring the ProMoFasT group and which may have an impact on the body composition. Nevertheless, we did not observe any differences among all parameters evaluated with the BIA analysis. 