Adaptive Ketogenic–Mediterranean Protocol (AKMP) in Real Clinical Practice: 14-Week Pre–Post Cohort Study on Glucolipid Markers and Safety

Abstract

Background/Objectives: Overweight and obesity are associated with insulin resistance, atherogenic dyslipidemia, and low-grade inflammation. We evaluated analytical safety and within-person metabolic changes under the Adaptive Ketogenic–Mediterranean Protocol (AKMP) in real-world practice. Methods: Single arm, prospective pre–post cohort. We enrolled 112 adults; 105 completed 14 weeks of AKMP (12 in nutritional ketosis ≤ 20 g carbohydrate/day + 2 of gradual reintroduction). Fasting venous samples were analyzed in accredited laboratories (glycolipid profile, hepatic–renal function, inflammatory markers; insulin, thyroid hormones, cortisol). HOMA-IR, TyG, and remnant cholesterol (RC) were calculated; body composition was measured by segmental bioimpedance. Paired analyses were used, with hierarchical gatekeeping for the conditional co-primary outcome and prespecified Δ~Δ correlations. Results: HOMA-IR −52.8% (Δ −1.80; p < 0.001) and RC −35.1% (Δ −10.64 mg/dL; p < 0.001); fasting glucose −13.7 mg/dL, insulin −5.9 μU/L; TyG −0.23 and TG/HDL-c −1.21 (all p < 0.001). Lipids: TG −35.1% and LDL-c −11.2%; HDL-c remained stable. Anthropometry: weight −14.85 kg (−14.7%) and trunk fat −4.88 kg (−22.2%) (p < 0.001). Safety: no serious adverse events; GGT −47.0%, eGFR +11.0%, and CRP −24.6% (p < 0.001). Prespecified correlations supported the internal consistency of the glycolipid axis (e.g., ΔHOMA-IR~ΔTyG; ΔRC~ΔHOMA-IR). Conclusions: In adults with overweight or obesity, the AKMP was associated with improvements in the glucose–insulin axis, atherogenic profile (RC, TG/HDL-c, TG), and body composition, while maintaining a favorable safety profile. The protocol appears feasible in clinical practice and monitorable with routine laboratory tests, although randomized controlled trials are needed to confirm causality and long-term sustainability.