Nutritional Interventions in Osteoarthritis: Mechanisms, Clinical Evidence, and Translational Opportunities.

Osteoarthritis (OA) is a leading cause of chronic pain worldwide. This is driven by progressive cartilage degradation, inflammation, oxidative stress, and metabolic dysfunction. Current pharmacologic interventions mostly lead to symptomatic relief without actually affecting disease progression. Thus, there is a growing interest in the development of new interventional methods. Our review seeks to synthesize preclinical, translational, and clinical evidence on the impact nutritional methods have on OA management. Whole-diet approaches, such as Mediterranean and plant-based, have been linked to reduced pain, increased physical function, and positive biomarker changes. Bioactive compounds, including curcumin, polyphenols, omega-3 fatty acids, and select herbal extracts, have shown anti-inflammatory, antioxidant, and chondroprotective effects via NF-κB, Nrf2, AMPK, and SIRT1 pathways. This review particularly focuses on plant-derived substances. Emerging nanoparticle technology with regard to advanced delivery systems shows initial promise in nutraceutical pharmacokinetics and tissue targeting. Overall, nutritional interventions are adjunct interventions to OA management. Although these are not full treatment replacements, dietary modifications and targeted nutraceutical strategies with improved delivery systems may lead to more preventive, personalized, and holistic OA management and care.