Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial

Abstract

Background: Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown.

Methods: A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry.

Results: A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found.

Conclusions: Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.

Keywords: cerebral blood flow; cognition; flow-mediated dilation; gut microbiota; metabolomics; nutrition; older adults; polyphenol; vascular function; wild blueberry.

FIGURE 1

(A) Study design. (B) Flow diagram outlining study activity and participant numbers throughout the process. ∗Due to COVID-19 pandemic and research disruptions, 7 out of 61 participants did not complete their 12-wk followup study visit. Abbreviations: AIx, augmentation index; BP, blood pressure; CBF, cerebral blood flow; FMD, flow-mediated dilation; PWV, pulse-wave velocity.

FIGURE 2

Differences in vascular and cognitive function of the control group and wild blueberry (WBB)-treated group (n = 27 on each group) at 12 wk following consumption. Flow-mediated dilation (FMD) differences (A) evaluated by linear mixed modeling analysis (<0.001 for an overall WBB treatment effect compared with placebo, adjusted for baseline FMD values as a covariateTotal 24-h (B) systolic blood pressure (SBP) and (C) diastolic blood pressure (DBP) differences following WBB consumption in comparison to placebo. Linear mixed modeling analysis revealed no significance for DBP, and an overall treatment effect in SBP P = 0.037 when compared with the placebo. Baseline blood pressure values were used as a covariate; (D) analysis for mean words recalled for immediate recall (R1) revealed significantly improved performance following WBB consumption in comparison to placebo (P = 0.043). (E) Analysis for mean delayed word recall (R8) revealed a significantly improved performance following placebo consumption relative to WBB (P = 0.029) and (F) analysis for overall TST accuracy scores revealed a significant effect of treatment, with higher overall accuracy for WBB compared with placebo (P = 0.026). AVLT, auditory visual learning task; DBP, diastolic blood pressure; FMD, flow-mediated dilation; SBP, systolic blood pressure; TST, task-switching task; WBB, wild blueberry.

FIGURE 3

Total (A) plasma and (B) 24 h urinary polyphenol metabolites after wild blueberry or placebo consumption for 12 wk, evaluated by linear mixed modeling analysis (n = 27 on each group). No significant differences were found in fasting plasma total (poly)phenols 12 wk after daily consumption of WBB or placebo; however, the WBB group had significantly higher total excreted (poly)phenols in 24 h than the placebo group (P = 0.001).

FIGURE 4

Differences in fecal microbiota composition between the placebo and the blueberry-treatment group (n = 27 on each group). Alpha (A) and beta (B) diversity are compared, as well as relative abundances for the major phyla quantified in this study: Firmicutes (C), Bacteroidetes (D), Proteobacteria (E), and Verrucomicrobiota (F). The 10 most abundant bacteria genera are presented in (G). WBB, wild blueberry.

FIGURE 5

Correlations between plasma metabolites and vascular outcomes (n = 27). Plots show correlations between plasma (poly)phenol metabolites and changes in main cardiometabolic outcomes (FMD and 24 h ambulatory SBP) showing significant changes from WBB treatment; FMD and 24 h SBP. ∗P < 0.05, ∗∗P < 0.001. FMD, flow-mediated dilation; SBP, systolic blood pressure.

FIGURE 6

Correlations between plasma metabolites and cognitive outcomes (n = 27). Plots with correlations between plasma (poly)phenol metabolites and changes in AVLT immediate recall performance showing significant changes from WBB treatment ∗P > 0.05, ∗∗P > 0.001. AVLT, auditory visual learning task; TST, task-switching task.