Walnut (Juglans regia L.) as a Promising Antidiabetic Agent: Mechanistic, Preclinical, and Clinical Evidence.

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder that continues to pose a major healthcare challenge worldwide. Despite the availability of several therapeutic options, achieving sustained glycaemic control and preventing long-term complications remain difficult in many patients. Walnut (Juglans regia L.) has gained attention as a potential complementary approach because of its diverse bioactive constituents and reported metabolic benefits. This review discusses the mechanistic, preclinical, and clinical evidence supporting the role of J. regia in diabetes management. The available studies indicate that walnut contains several phytochemicals, including juglone, flavonoids, polyphenols, and polyunsaturated fatty acids, which may contribute to antioxidant, anti-inflammatory, and insulin-sensitizing activities. Experimental findings suggest that these constituents help improve glucose homeostasis, protect pancreatic β-cells, and regulate insulin-signalling pathways. Preclinical studies consistently demonstrate beneficial effects on glycaemic parameters and pancreatic function, while clinical investigations report modest improvements in fasting blood glucose, HbA1c, and lipid profiles with good tolerability. However, differences in extract preparation, dosage, study design, and duration limit direct comparison among studies and highlight the need for further standardization. Future research should focus on well-designed clinical trials, optimized dosing strategies, and the evaluation of walnut preparations as adjuncts to conventional antidiabetic therapy. Overall, the current evidence supports J. regia as a promising complementary candidate for diabetes management and provides a basis for its further clinical development.