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Introduction: Ayurveda describes Ama as an intermediate, improperly metabolized substance that plays a central role in disease pathogenesis. The Samhitas provide detailed insights into the formation, properties, and clinical implications of Ama, correlating it with impaired Agni (digestive/metabolic fire) and disturbed homeostasis. Methods: A structured literature review was conducted using Ayurvedic Samhitas (Charaka, Sushruta, Ashtanga Hridaya), contemporary commentaries, PubMed, Scopus, and Web of Science databases. Inclusion criteria encompassed classical references, clinical studies, experimental research, and modern reviews linking Ama with disease processes. Exclusion criteria included non-Ayurvedic speculative literature and poorly documented case reports. Results: Ama is described as a toxic, sticky, heavy, and obstructive substance formed due to hypofunctional Agni. Classical texts associate it with systemic circulation, obstruction of Srotas (body channels), impairment of Dhatus (tissues), and the manifestation of various diseases including Amavata (rheumatoid arthritis), Amlapitta (acid-peptic disorders), and metabolic syndromes. Modern research parallels Ama with endotoxemia, free radical accumulation, and metabolic inflammation. Several studies support its role in inflammatory and autoimmune conditions. Discussion: Integrating classical concepts of Ama with modern pathophysiology offers novel insights into systemic inflammation, metabolic disorders, and gut dysbiosis. However, gaps remain in experimental validation and standardized biomarkers of Ama. Conclusion: Ama is a fundamental pathogenic concept in Ayurveda that correlates with multiple modern disease mechanisms. Further interdisciplinary research can enhance its clinical applicability and provide holistic therapeutic strategies.

KEYWORDS: Agni, Ama, Ayurveda, Disease pathogenesis, Samhita