{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:18:55Z","timestamp":1789125535330,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Obesity is a complex, chronic disease with metabolic complications. Many patients respond suboptimally to conventional interventions like the hypocaloric Mediterranean diet (MD), highlighting the need to investigate alternative supervised nutritional strategies in patients with an insufficient response to conventional dietary treatment. Objectives: This study aimed to evaluate the KETOCOMP (Food-Based KETOgenic Nutritional Protocol for Patients with COMPlicated Obesity), a medically and dietitian-supervised, food-based sequential ketogenic nutritional protocol consisting of a ketogenic phase followed by controlled carbohydrate reintroduction, for improving anthropometric and body composition in patients with complicated obesity who were non-responsive to conventional dietary treatment. Methods: In this longitudinal, observational study, adult patients with obesity\/overweight and metabolic comorbidities, previously non-responsive to a hypocaloric MD, were identified. Patients followed a 4-week food-based ketogenic diet (approx. 1200 kcal\/day, &lt;20 g carbohydrate, CHO) followed by a 4-week low-carbohydrate reintroduction phase (approx. 1300 kcal\/day, up to 100 g CHO). Anthropometric and body composition parameters were assessed at baseline (T0), after the MD (T1), after the ketogenic phase (T2), and after the low-carbohydrate phase (T3). Intra-subject comparisons were performed. Results: Across the entire observed nutritional pathway (T0\u2013T3), body weight (BW), body mass index (BMI), and fat mass (FM) decreased by 7.7%, 9.45%, and 23.1%, respectively. Using T1 as the relevant baseline for the second-line KETOCOMP sequence, mean BW and FM decreased by 7.79 kg and 6.29 kg, respectively, from T1 to T3; during the ketogenic phase alone (T1\u2013T2), BW decreased by 6.10 kg and FM by 4.80 kg. Body Cell Mass (BCM) and Phase Angle (PhA) showed no statistically significant changes during the ketogenic and carbohydrate-reintroduction phases, whereas Fat-Free Mass (FFM) decreased significantly. Significant reductions in waist and hip circumferences (WC, HC) were also observed. No serious adverse events were documented among included participants; however, discontinuation rates could not be assessed because completion through T2 formed part of cohort selection. Conclusions: The KETOCOMP protocol may represent a clinically applicable second-line nutritional strategy for patients with obesity and metabolic complications who respond suboptimally to conventional dietary treatment. The observed reductions in body weight and fat mass, together with the absence of significant changes in BCM and PhA, suggest a favorable short-term change in body composition. However, larger prospective controlled studies incorporating standardized clinical and biochemical safety monitoring and direct assessment of skeletal muscle are required to confirm these findings and evaluate longer-term outcomes.<\/jats:p>","DOI":"10.3390\/nu18182982","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:51:37Z","timestamp":1789123897000},"page":"2982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Food-Based Sequential KETOgenic Nutritional Protocol for Mediterranean Diet Non-Responders with COMPlicated Obesity: A Real-World Observational Study (KETOCOMP)"],"prefix":"10.3390","volume":"18","author":[{"given":"Maurizio","family":"Romano","sequence":"first","affiliation":[{"name":"Digestive Disease Center (CEMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-1082","authenticated-orcid":false,"given":"Pauline Celine","family":"Raoul","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Ianiro","sequence":"additional","affiliation":[{"name":"Digestive Disease Center (CEMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3174-5094","authenticated-orcid":false,"given":"Debora","family":"Rondinella","sequence":"additional","affiliation":[{"name":"Digestive Disease Center (CEMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4698-0845","authenticated-orcid":false,"given":"Eleonora","family":"Ribaudi","sequence":"additional","affiliation":[{"name":"Digestive Disease Center (CEMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Sofia","family":"Galli","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-0748","authenticated-orcid":false,"given":"Marco","family":"Cintoni","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Human Nutrition Research Center, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-1779","authenticated-orcid":false,"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"Digestive Disease Center (CEMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Human Nutrition Research Center, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmeralda","family":"Capristo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Obesity Disorders Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8463-7062","authenticated-orcid":false,"given":"Maria Cristina","family":"Mele","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Human Nutrition Research Center, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9165-2367","authenticated-orcid":false,"given":"Emanuele","family":"Rinninella","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. 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