Effects of Polyphenol-Rich Interventions on Cognition and Brain Health in Healthy Young and Middle-Aged Adults: Systematic Review and Meta-Analysis

Abstract

Context: Affecting older and even some younger adults, neurodegenerative disease represents a global public health concern and has been identified as a research priority. To date, most anti-aging interventions have examined older adults, but little is known about the effects of polyphenol interventions on brain-related aging processes in healthy young and middle-aged adults. Objective: This systematic review and meta-analysis aimed to evaluate the acute and chronic effects of (poly)phenol-rich diet supplementation on cognitive function and brain health in young and middle-aged adults. In July 2019, two electronic databases (PubMed and Web of Science) were used to search for relevant trials examining the effect of acute or chronic (poly)phenol-rich supplementation on cognitive function and neuroprotective measures in young and middle-aged adults (<60 years old). A total of 4303 records were screened by two researchers using the PICOS criteria. Fifteen high quality (mean PEDro score = 8.8 ± 0.58) trials with 401 total participants were included in the final analyses. Information on treatment, study design, characteristics of participants, outcomes and used tools were extracted following PRISMA guidelines. When items were shown to be sufficiently comparable, a random-effects meta-analysis was used to pool estimates across studies. Effect size (ES) and its 95% confidence interval (CI) was calculated. The meta-analysis indicated that (poly)phenol supplementation significantly increased brain-derived neurotrophic factor (ES = 3.259, p = 0.033), which was accompanied by higher performance in serial (7s) subtraction (ES = 1.467, p = 0.001) and decreases in simple reaction time (ES = −0.926, p = 0.015) and mental fatigue (ES = −3.521, p = 0.010). Data related to cognitive function were skewed towards an effect from acute compared to chronic polyphenol intervention; data related to BDNF were skewed toward an effect from higher bioavailability phenolic components. Conclusion: This meta-analysis provides promising findings regarding the usefulness of polyphenol-rich intervention as an inexpensive approach for enhancing circulation of pro-cognitive neurotrophic factors. These beneficial effects appear to depend on the supplementation protocols. An early acute and/or chronic application of low- to high-dose phenolic components with high bioavailability rates (≥30%) at a younger age appear to provide more promising effects.

Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera indica L. (Zynamite) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study

“…The results also suggest that the modulation of cerebro-electrical activity (measured using EEG) seen in healthy adults following a single dose of Zynamite mango leaf extract [39] is most likely indicative of a benefit to brain function. The cognitive benefits seen here are broadly in line with previous demonstrations of improved cognitive function following both acute [24][25][26] and chronic administration [27,28] of polyphenol rich extracts. Several polyphenol studies also employed the Cognitive Demand Battery used here (but at a single post-dose time point), with demonstrations of improved performance across all three tasks following cocoa-flavanols [24], improved Serial 3s performance following fruit flavanols [50], but no benefits following resveratrol [51].…”

“…These interactions potentially drive downstream modulation of neuroinflammation, neurotransmission, neurotrophin receptor and signalling pathway interactions, and increased synthesis of neurotrophins and vasodilatory molecules, leading to increased angiogenesis/neurogenesis and local cerebral blood flow [15][16][17][18][19]. These indirect cellular interactions may underlie the consistent demonstrations in humans of increased cerebral blood-flow [51,[65][66][67][68][69] and peripherally measured brain-derived neurotrophic factor [26] seen following diverse polyphenols. Again, potentially diffuse beneficial effects within the brain could be conceived as potentially leading to broad benefits to cognitive function across domains, as seen here.…”

“…In the central nervous system, specific additional interactions attributed to polyphenols include direct neurotransmitter and neurotrophin receptor and signalling pathway interactions, and increased synthesis of neurotrophins and vasodilatory molecules, which, in turn, foster angiogenesis/neurogenesis [15][16][17][18][19][20]. These mechanisms potentially underlie the observation of consistent beneficial cardiovascular effects from meta-analyses of multiple intervention studies [21][22][23], and demonstrations of improved cognitive function [24][25][26][27][28], following diverse polyphenols.…”

Moderators of the Impact of (Poly)Phenols Interventions on Psychomotor Functions and BDNF: Insights from Subgroup Analysis and Meta-Regression

“…Given the decreased activity of many endogenous antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase in aged hippocampus and the cerebral cortex [ 10 , 11 ], a huge array of existing literature has highlighted the importance of exogenous antioxidants as potential anti-aging agents [ 12 , 13 , 14 , 15 , 16 ]. The most widely known exogenous antioxidants are carotenoids (lycopene, lutein, zeaxanthin, α- and β-carotene, β-cryptoxanthin), vitamin E (α- and γ-tocopherol), vitamin C, and (poly)phenols [ 17 ], with the latter exhibiting the highest antioxidant capabilities [ 18 ].…”

“…The most widely known exogenous antioxidants are carotenoids (lycopene, lutein, zeaxanthin, α- and β-carotene, β-cryptoxanthin), vitamin E (α- and γ-tocopherol), vitamin C, and (poly)phenols [ 17 ], with the latter exhibiting the highest antioxidant capabilities [ 18 ]. Considering the increased effectiveness of (poly)phenols in counteracting age-related oxidative stress, recent human studies have examined the role of natural (poly)phenols-rich products in the prevention of cognitive decline and maintenance of brain function [ 15 , 16 ]. Several studies have shown that the consumption of (poly)phenols-rich supplementation can benefit cognitive decline in older adults [ 19 , 20 , 21 ], as well as in young- and middle-aged populations [ 22 , 23 , 24 ].…”