Personalizing Obesity Treatment: Real-World Comparison of a Very-Low-Calorie Ketogenic Diet Versus a Whole-Food Mediterranean Ketogenic Diet Davide Masi, Maria Letizia Spizzichini, Elena Colonnello, Daniel Vasquez Barahona, Lucio Gnessi, et al. Metabolites, 2026 Background/Objectives: Obesity is a chronic, relapsing disease in which lifestyle modification represents the cornerstone of treatment. Among dietary strategies, ketogenic diets can induce rapid weight loss, whereas the Mediterranean diet is associated with established cardiometabolic benefits but typically produces slower weight reduction. Very-low-calorie ketogenic diets (VLCKDs) are effective for weight loss but are often limited by cost, reliance on meal replacements, and reduced long-term feasibility. This study aimed to evaluate whether a whole-food Mediterranean ketogenic diet with moderate caloric restriction (MedKD) could represent a feasible and effective alternative to VLCKD for weight loss and metabolic improvement in adults with obesity. Methods: This 3-month prospective, real-world study compared VLCKD and MedKD in adults with obesity attending a clinical nutrition program. The primary outcome was percentage weight loss. Secondary outcomes included changes in waist circumference, waist-to-height ratio, insulin resistance (HOMA-IR), lipid profile, kidney function, and treatment tolerability. Clinical and biochemical parameters were assessed at baseline and after the intervention. Group differences and time-by-group interactions were analyzed to evaluate changes over the study period. Results: Sixty-two participants were enrolled, and 55 completed the study (27 VLCKD, 28 MedKD). Baseline characteristics were generally comparable, although the MedKD group had a higher prevalence of diabetes and higher baseline insulin resistance and triglyceride levels. Both dietary interventions resulted in substantial and comparable weight loss (approximately 15% of initial body weight), accompanied by significant reductions in waist circumference and waist-to-height ratio. Insulin resistance improved in both groups, with a greater reduction in HOMA-IR observed in the MedKD group (time × group p = 0.031). Serum creatinine decreased in the VLCKD group and slightly increased in the MedKD group (p = 0.025). Changes in lipid profile were not significantly different between groups. No severe adverse events were reported. Conclusions: A whole-food Mediterranean ketogenic diet with moderate caloric restriction achieved weight loss and metabolic improvements comparable to those observed with VLCKD over three months. These findings suggest that MedKD may represent a feasible alternative to formula-based ketogenic programs, supporting more flexible and personalized dietary strategies in the clinical management of obesity.
Matched Analysis of Circulating and Adipose Tissue SIRT1 Protein Level in Human Obesity Luisa Salvatori, Francesca Megiorni, Giorgia Maria Baldazzi, Valentina Ventimiglia, Elena Gangitano, et al. Nutrients, 2026 Background/Objectives: Mammalian sirtuins (SIRTs) are evolutionarily conserved proteins that are epigenetically involved in biological processes such as metabolism and longevity. SIRT1 expression is reduced in metabolic disorders and in complicated diseases such as obesity. However, whether the SIRT1 level in subcutaneous adipose tissue (SAT) matches with its circulating form in obesity is unknown. The aim of our study is to evaluate SIRT1 derived from SAT and plasma of the same subject in individuals with and without obesity to assess whether plasma measurements may provide clinically significant information. Methods: Eleven subjects with obesity (BMI ≥ 30 kg/m2) and six controls without the disease (BMI < 30 kg/m2) were enrolled, and SIRT1 was measured in SAT and plasma by ELISA. Anthropometric parameters, glycemia and transaminases were also assessed. Results: Patients with obesity showed similar levels of SIRT1 in SAT and plasma (1.28 ± 0.45 and 1.9 ± 0.25 ng/mL, respectively, p = 0.243). Patients without obesity showed higher SIRT1 levels in SAT than in plasma (4.19 ± 1.33 and 1.06 ± 0.12 ng/mL, respectively, p = 0.039). An inverse correlation between SAT-derived SIRT1 and BMI was found (r = −0.632, p = 0.007). Conclusions: In this pilot study, our results show that the plasma SIRT1 levels substantially reflect those of SAT in patients with obesity. Given the metabolic role of SIRT1, further comprehensive investigations in larger longitudinal cohorts are needed to support plasma SIRT1 as an eligible diagnostic tool for stratifying metabolic risk associated with fat mass expansion in obesity.
Oxytocin, Weight Loss and Ketosis in Response to a Very-Low-Calorie Ketogenic Diet: An Exploratory Study Elena Gangitano, Rebecca Rossetti, Rossella Tozzi, Paola Nevi, Davide Masi, et al. Nutrients, 2026 Background/Objectives: Obesity is a chronic relapsing disorder associated with many comorbidities. Some evidence suggests that oxytocin (OT) has an anorexigenic effect, but its levels are often increased in obesity. This study investigates the effects of weight loss induced by a very-low-calorie ketogenic diet (VLCKD) on oxytocin levels. Methods: A total of 47 subjects with overweight or obesity, 28 females (60%) and 19 males, with a mean age of 55.5 ± 7.3 years and mean BMI 35.9 ± 4.4 kg/m2, underwent VLCKD for 45 days. We assessed anthropometric parameters, metabolic profile, body composition and OT levels at baseline (t0) and at the end of the diet (t1). Results: After weight loss, plasma OT levels significantly dropped. Baseline OT correlated with BMI, fat mass and trunk fat. A linear relationship was observed between Delta OT levels and Delta BMI. Baseline OT was an independent predictor of weight loss and directly correlated with blood ketone levels at the end of the study. An optimal serum OT cut-off that predicts ketosis occurrence was identified. Conclusions: Weight loss obtained with a VLCKD reduces OT levels in patients with excess weight. Baseline OT predicts weight loss and correlates with ketone body levels during a VLCKD.
The Chronobiology of Hormone Administration: “Doctor, What Time Should I Take My Medication?” Elena Colonnello, Andrea Graziani, Rebecca Rossetti, Giacomo Voltan, Davide Masi, et al. Endocrine Reviews, 2025 Pharmacotherapy involving hormones and hormone-derived molecules has various potential treatment targets. This includes addressing (partial) hormonal deficiencies, pursuing osteoanabolic effects, providing contraceptive options, or supporting gender-affirming transitions. In chronotherapy, the timing of the administration of active ingredients and different pharmaceutical forms is leveraged to maximize therapeutic efficacy while minimizing adverse effects, based on the principle that it is optimal for drugs to be administered according to the body's circadian rhythms. Just as a drummer sets the pace and keeps the rhythm steady for the entire band, the physician, through the application of chronotherapy, ensures the treatment regimen is harmonized with the body's internal clock. However, while this is a consolidated aspect for several endocrine treatments, for others, it represents a novelty. The new advancements in the treatment of osteoporosis, with the latest parathyroid hormone–related protein analogue, abaloparatide, or in congenital adrenal hyperplasia with the new long-lasting hydrocortisone formulation, are notable examples. We herein summarized the state of the art regarding the hormonal circadian rhythm to discuss in depth the evidence available regarding the correct timing of commonly administered hormonal therapies in adult patients. By offering clear indications, this manuscript delves into the importance of harmonizing hormonal therapy with circadian rhythms through chronotherapy, exploring its potential to enhance therapeutic outcomes while minimizing adverse effects.
Obesity may be more associated with disordered eating behaviors, somatization, insecure attachment styles, and sexual dysfunction: An exploratory study Elena Colonnello, Anna Guidi, Beatrice Di Lazzaro, Chandra Massetti, Tommaso B Jannini, et al. Journal of Sexual Medicine, 2025 Background Obesity is a challenging disease due to its multifactorial pathogenesis. However, sexual health is a poorly explored aspect in these patients, and the interaction between eating behavior, psychological factors, and sexual function remains insufficiently characterized, although it may represent a key aspect in clinical management. Aims To provide a characterization of psychological, eating, and sexual function characteristics of patients with obesity through an exploratory analysis. Methods A cross-sectional, single-center study was carried out at Umberto I Hospital of Sapienza University of Rome (Italy), where patients with obesity (body mass index ≥30 kg/m2) were recruited. Additionally, a control group of age-matched, normal-weight (body mass index = 18-25 kg/m2) subjects was enrolled online. All subjects compiled a series of validated psychometric questionnaires that evaluated psychological distress, disordered eating behaviors, attachment styles, and sexual dysfunction. Outcomes To evaluate the psychological distress, attachment style, disordered eating behavior, and sexual dysfunction in patients with obesity and to explore the correlations between these aspects. Results Seventy-two patients (45 women, mean age 51.4 ± 4.3 years and 27 men, mean age 39.6 ± 16.6 years) and 76 controls (51 women, mean age 36.8 ± 14.3 years and 25 men, mean age 39.2 ± 16.6 years) were recruited. Subjects with obesity reported significantly higher scores in somatization and paranoid ideation symptoms, higher scores in food addiction and binge eating domains, and a more fearful attachment style. Women also reported lower sexual desire, arousal, and lubrication, while men showed significantly lower erectile function, orgasmic intensity, and sexual satisfaction. Clinical implications Subjects with obesity are characterized by higher somatization, maladaptive eating behaviors, insecure attachment style, and worse sexual function compared to controls, which highlights the necessity of a multidimensional treatment approach. Strengths and limitations A large and comprehensive battery of questionnaires was employed to examine both the clinical and the control population. However, the absence of stratification by age and the small sample size prevent the generalizability of the results. Conclusion Our results highlight the intricate interplay between psychological, behavioral, and sexual factors in individuals affected by obesity. Further studies should focus on larger and more diverse samples and examine longitudinal trajectories of psychological and sexual health changes in response to weight-loss interventions, to assess how such interconnection may help to improve the personalization of care programs.
