Integrative Carnivore Framework - A Unified Evolutionary, Biochemical, Neurobiological, And Clinical Model Of Human Nutrition

The Integrative Carnivore Framework (ICF) is a comprehensive, multi‑disciplinary theoretical model that reinterprets human metabolism, nutrition, and evolutionary physiology through a mechanistic, systems‑level perspective. This project synthesises evidence from biochemistry, genetics, cell biology, biophysics, anthropology, and environmental toxicology to propose a unified explanation for how humans generate, regulate, and maintain bioavailable chemical potential across diverse dietary environments. The primary purpose of the ICF is to challenge the prevailing calorie‑centric paradigm by demonstrating that human metabolism operates as an open, mass-energy flux system governed by biochemical pathways, mitochondrial energetics, nutrient signalling, and evolutionary constraints rather than by simple caloric arithmetic. The framework integrates molecular mechanisms such as oxidative phosphorylation, ketone metabolism, gluconeogenesis, lipid peroxidation, oxysterol formation, glycation, and redox balance with genotype‑specific factors including APOE isoforms, AMY1 copy‑number variation, SVCT transporter efficiency, and receptor‑mediated lipid clearance pathways. At the physiological and cellular level, the ICF maps how nutrient environments influence mitochondrial function, microglial activation, endothelial integrity, immunometabolic signalling, and neurobiological processes. It incorporates Rc constraints, dynamical systems behaviour, and stoichiometric relationships to explain metabolic flux and energy availability. The model also integrates environmental toxicology: plant secondary metabolites, endocrine disruptors, agricultural chemicals and their interactions with metabolic and immune pathways. Anthropologically, the framework situates human metabolism within a trophic‑level evolutionary context, drawing on Pleistocene archaeological evidence, comparative carnivory, megafaunal exploitation, and species‑specific physiological adaptations. This evolutionary perspective provides a coherent backdrop for understanding modern metabolic phenotypes, dietary responses, and genotype-diet interactions. The expected outcomes of this project include: A unified theoretical model describing human metabolism as an open‑system mass–energy flux process. Mechanistic explanations for metabolic variability across individuals, genotypes, and dietary patterns. A detailed mapping of biochemical, genetic, and physiological pathways relevant to carnivory, ketogenesis, lipid metabolism, and carbohydrate handling. A structured set of falsifiable predictions and measurable biomarkers suitable for future empirical testing. A methodological foundation for improved metabolic research, including assay pipelines, quality‑control standards, and sensitivity analyses. A reframing of human nutrition and metabolic health grounded in evolutionary biology, biophysics, and molecular physiology. Overall, the ICF aims to provide a rigorous, interdisciplinary foundation for understanding human metabolic function, dietary adaptation, and physiological resilience. It is intended as a conceptual and methodological platform for future empirical research, clinical investigation, and evolutionary modelling.