Comparing fermented food and vitamin E on exercise-mediated Nrf2/ARE activation in middle-aged/ elderly: A randomized, double-blind clinical study

Objective: This study investigated the effects of fermented papaya preparation (FPP®) and vitamin E on gene expression in middle-aged/elderly individuals, leveraging FPP’s established antioxidant and immune-regulatory benefits. Methods: Graded Exercise Walking Test was administered twice weekly for 6 months. Total Antioxidant capacity (TAC) and gene expression (Nrf2, NQO1, HO-1) in PBMC were measured monthly. Results: Throughout the 6-month study, routine biochemistry and BMI remained stable. Both treatments significantly improved Total Antioxidant Capacity (TAC), Vitamin E exhibiting earlier effects (3 months). Notably, FPP® supplementation led to sustained over-expression of nuclear Nrf2 in all subjects, surpassing Vitamin E’s effects. NQO1 gene expression was rapidly and consistently upregulated in the FPP group, exceeding baseline and Vitamin E levels throughout the study. HO-1 gene expression was upregulated by FPP at 1 month in younger age quartiles (Q1-2) and at 3 and 6 months in all subjects, regardless of age and gender. In contrast Vitamin E did not significantly impact Nrf2, NQO1, or HO-1 gene expression. Conclusion: These findings demonstrate that FPP, unlike Vitamin E, potentiates Nrf2 signaling, triggering a downstream epigenetic cascade. Notably, our clinical data reveal that physical exercise combined with functional food supplementation partially restores impaired Nrf2 signaling in elderly individuals.