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

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.

Comparison between dietary assessment methods and biomarkers in estimating dietary (poly)phenol intake.

Background: although widely used, there is limited understanding of the suitability of different dietary assessment tools to estimate (poly)phenol intake. This study aims to compare the agreement between a food frequency questionnaire (FFQ) and a 7-day food diary (7DD) in assessing (poly)phenol intake and explore their associations with the urinary and plasma (poly)phenol metabolites. Methods: healthy free-living participants aged 18-80 years (n = 413) completed a 7DD and an FFQ (EPIC-Norfolk) and provided a 24 h urine and a fasting plasma sample. A comprehensive in-house (poly)phenol database was used to estimate (poly)phenol intake. The phenolic metabolite levels were analysed using a validated LC-MS method. The agreement between dietary assessment methods and biomarkers were evaluated by intraclass correlation coefficients (ICC), weighted kappa, quartile classification, Bland-Altman plots and correlations. Results: the total (poly)phenol intake estimated from FFQ was higher than from 7DD (median 1463 and 1042 mg d-1, respectively). The agreement between FFQ and 7DD were moderate (ICC 0.51-0.59) for total (poly)phenols, flavan-3-ols, total phenolic acids, hydroxycinnamic acids and alkylmethoxyphenols, and were poor for all the other classes and subclasses (ICC 0.00-0.48). Positive correlations with total urine phenolic metabolites were found in FFQ estimated anthocyanins, dihydroflavonols, total lignans, tyrosols, alkylmethoxyphenols, total phenolic acids, and total stilbenes and the 7DD estimated theaflavins and thearubigins (all FDR adjusted p values < 0.1). No significant correlations were found between total plasma phenolic metabolites and (poly)phenol intake. Conclusion: agreements between dietary assessment tools were moderate for the major classes of (poly)phenols, while agreements between (poly)phenol intake and biomarkers were poor. Future research using biomarker approaches to increase the accuracy of estimating (poly)phenol exposure in larger populations is needed.

Dietary Assessment Methods to Estimate (Poly)phenol Intake in Epidemiological Studies: A Systematic Review.

Nutritional epidemiological studies have frequently reported associations between higher (poly)phenol intake and a decrease in the risk or incidence of noncommunicable diseases. However, the assessment methods that have been used to quantify the intakes of these compounds in large-population samples are highly variable. This systematic review aims to characterize the methods used to assess dietary (poly)phenol intake in observational studies, report the validation status of the methods, and give recommendations on method selection and data reporting. Three databases were searched for publications that have used dietary assessment methods to measure (poly)phenol intake and 549 eligible full texts were identified. Food-frequency questionnaires were found to be the most commonly used tool to assess dietary (poly)phenol intake (73%). Published data from peer-reviewed journals were the major source of (poly)phenol content data (25%). An increasing number of studies used open-access databases such as Phenol-Explorer and USDA databases on flavonoid content since their inception, which accounted for 11% and 23% of the data sources, respectively. Only 16% of the studies reported a method that had been validated for measuring the target (poly)phenols. For future research we recommend: 1) selecting a validated dietary assessment tool according to the target compounds and target period of measurement; 2) applying and combining comprehensive (poly)phenol content databases such as USDA and Phenol-Explorer; 3) detailing the methods used to assess (poly)phenol intake, including dietary assessment method, (poly)phenol content data source; 4) follow the Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut) framework; and 5) complementing dietary intake assessment based on questionnaires with measurement of (poly)phenols in biofluids using appropriate and validated analytical methods.

Blueberries and cardiovascular disease prevention.

Blueberries are a rich source of (poly)phenols, particularly anthocyanins. Epidemiological studies indicate that anthocyanin-rich foods including blueberries are associated with a reduction in the risk of cardiovascular disease. These observational findings are supported by a number of randomized-controlled trials showing improvements in biomarkers of cardiovascular disease risk. The beneficial effects of blueberry (poly)phenols are particularly clear when measuring flow-mediated dilation over various timeframes and study populations. However, other outcomes are less clear, such as effects on blood pressure, arterial stiffness and blood lipid profile. This may be due to the heterogeneity existing in study designs, such as duration of the intervention, and the health status of participants. Longer-term RCTs using gold standard methods in relevant populations which can be translated to the general public are needed to clarify and strengthen the evidence available. While circulating phenolic blueberry metabolites have been linked with improvements in vascular function, the biological activities and mechanisms of action of individual metabolites and their interaction in vivo are still unknown. Evaluating the bioactivities of metabolites alone and together, and analysing their structure-activity relationship in well-designed and physiologically relevant experimental and human studies are needed to understand the mechanisms of how these metabolites affect vascular function.

Systematic Review of the Effects of Blueberry on Cognitive Performance as We Age.

The effect of flavonoid-rich food, such as blueberries, on cognitive function has been subject to a growing amount of research interest in recent years. Epidemiological, prospective, preclinical, and clinical trials have revealed positive cognitive benefits from flavonoid interventions, particularly in relation to the amelioration of cognitive decline in older adults. This review will specifically consider the existing clinical research from both acute and chronic blueberry interventions on cognition in human subjects. The results of 11 studies are reported with 4 studies considering blueberry intervention with children aged 7-10 years, 4 considering adults aged 60 years and older, and 3 considering adults suffering from mild cognitive impairment (MCI). Findings from these studies indicate that cognitive benefits may be found for delayed memory and executive function in children and for delayed memory, executive function, and psychomotor function in older healthy and MCI adults. There is less evidence to suggest positive benefits of blueberry intervention on working memory. Recommendations for future research, including dose used, cognitive tasks, and age groups considered, are proposed.

Toxic effects of X-linked adrenoleukodystrophy-associated, very long chain fatty acids on glial cells and neurons from rat hippocampus in culture.

Saturated very long chain fatty acids (VLCFAs; > or =C22:0) accumulate in X-linked adrenoleukodystrophy (X-ALD, OMIM 300100), a severe hereditary neurodegenerative disease, due to peroxisomal impairment. Previous studies analysed the development of X-ALD in humans and gene knockout animal models. However, the toxic effect of VLCFA leading to severe symptoms with progressive and multifocal demyelination, adrenal insufficiency and inflammation still remains unclear. To understand the toxic effects of VLCFA in the brain, here we exposed neural cells to VLCFA and analysed the cellular consequences. We found that oligodendrocytes and astrocytes challenged with docosanoic- (C22:0), tetracosanoic- (C24:0) and hexacosanoic acids (C24:0) die within 24 h. VLCFA-induced depolarization of mitochondria in situ and increased intracellular Ca2+ level in all three brain cell types provides indications about the mechanism of toxicity of VLCFA. Interestingly, VLCFAs affect to the largest degree the myelin-producing oligodendrocytes. In isolated mitochondria, VLCFAs exert a detrimental effect by affecting the inner mitochondrial membrane and promoting the permeability transition. In conclusion, we suggest that there is a potent toxic activity of VLCFA due to dramatic cell physiological effects with mitochondrial dysfunction and Ca2+ deregulation. This provides the first evidence for mitochondrial-based cell death mechanisms in neurodegenerative disease with peroxisomal defects and subsequent VLCFA accumulation.