An integrative clinical framework developed by the Pruimboom Institute that applies evolutionary medicine, systems biology, and network physiology to understand and treat chronic disease through the interconnected regulation of psychological, neurological, endocrine, and immune systems. cPNI positions lifestyle interventions as primary medicine, using the AMP metamodel to identify and address root causes of dysregulation.
cPNI operates through five metamodels: (1) Evolutionary Medicine (understanding mismatch between genome and environment), (2) Network Physiology (recognizing interconnected regulatory systems), (3) AMP Model (identifying Associated Molecular Patterns as triggers), (4) Biological Amplification (restoring protective signals through lifestyle), and (5) Resolution Pharmacology (supporting inflammation resolution pathways). The framework emphasizes that psychological stress, immune activation, neuroendocrine signaling, and metabolic function are inseparable—interventions in one domain cascade through all systems. Treatment focuses on removing hazards (AMPs), supporting resolution (SPMs, nutrients), restoring rhythms (circadian, hormonal), and rebuilding resilience (exercise, stress management, social connection).
cPNI represents a paradigm shift from symptom suppression to root-cause resolution. By understanding that chronic diseases (autoimmunity, metabolic syndrome, depression, chronic pain) share common pathophysiology—evolutionary mismatch leading to low-grade inflammation and dysregulated stress axes—practitioners can design comprehensive, personalized interventions. The framework is taught globally and forms the basis for integrative treatment of complex chronic conditions.