Impact of Polyphenol-Rich Nutraceuticals on Cognitive Function and Neuroprotective Biomarkers: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract

Background: Recent studies have highlighted the neuroprotective effects of polyphenols, particularly their role in enhancing brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) activity. This study aimed to evaluate the relationship between BDNF and CREB levels and cognitive performance in individuals undergoing a polyphenol-rich dietary intervention. Methods: A randomized, crossover, double-blind, placebo-controlled clinical trial was conducted with 92 participants. The intervention involved the daily intake of an encapsulated concentrate of fruit, vegetable, and berry juice powders (Juice Plus+ Premium®) over two 16-week periods, separated by a 4-week washout phase. Cognitive function was assessed using the Stroop Test, Trail Making Test, and Reynolds Intellectual Screening Test (RIST). The plasma levels of CREB and BDNF were measured using ELISA. Results: The polyphenol-rich product significantly improved cognitive performance, as evidenced by higher scores in the Stroop Test and RIST, compared to the placebo. Additionally, the plasma levels of CREB and BDNF were notably elevated in the product condition, indicating enhanced neuroprotective activity. Conclusions: The findings suggest that polyphenol-rich nutraceuticals can modulate neurobiological mechanisms underlying cognitive improvements, primarily through the reduction of oxidative stress and the regulation of signaling pathways associated with synaptic plasticity. These results support the potential of dietary polyphenols in promoting cognitive health and preventing neurodegenerative diseases.