Low-Dose, Long-Term Drug Exposure and Epigenetic Changes: Rethinking Drug Evaluation Models

Introduction: Ayurvedic pharmacology, particularly the discipline of Dravyaguna, emphasizes repeated administration of low doses over prolonged durations to achieve stable and sustained therapeutic effects.Such effects are frequently delayed in onset and persist beyond the period of drug administration.However, conventional drug evaluation models, which prioritize high-dose, short-term therapeutic responses, fail to adequately explain these observations.Methods: A conceptual narrative review was conducted focusing on Ayurvedic pharmacological principles related to dosage, repetition, and duration, as discussed in contemporary Ayurveda and integrative medicine literature.These principles were examined in light of current biomedical research on epigenetic regulatory mechanisms to explore a scientific basis for sustained therapeutic effects associated with repeated low-dose, long-term drug exposure.Results: Ayurvedic pharmacological concepts consistently describe drug action as a gradual biological process leading to long-term functional adaptation, rather than immediate pharmacodynamic effects.Modern epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNA regulation provide a plausible explanation for these observations by enabling stable modulation of gene expression without altering the DNA sequence.Discussion: Current drug evaluation frameworks may inadequately capture therapeutic effects emphasized in Ayurveda, as they are optimized for short-term and high-dose interventions.Epigenetic science offers a contemporary explanatory framework that supports Ayurvedic pharmacological principles and highlights the need to reconsider existing drug evaluation models to better assess sustained therapeutic effects.