Development of a (Poly)phenol Metabolic Signature for Assessing (Poly)phenol-Rich Dietary Patterns.

The objective assessment of habitual (poly)phenol-rich diets in nutritional epidemiology studies remains challenging. This study developed and evaluated the metabolic signature of a (poly)phenol-rich dietary score (PPS) using a targeted metabolomics method comprising 105 representative (poly)phenol metabolites, analyzed in 24 h of urine samples collected from healthy volunteers. The metabolites that were significantly associated with PPS after adjusting for energy intake were selected to establish a metabolic signature using a combination of linear regression followed by ridge regression to estimate penalized weights for each metabolite. A metabolic signature comprising 51 metabolites was significantly associated with adherence to PPS in 24 h urine samples, as well as with (poly)phenol intake estimated from food frequency questionnaires and diaries. Internal and external data sets were used for validation, and plasma, spot urine, and 24 h urine samples were compared. The metabolic signature proposed here has the potential to accurately reflect adherence to (poly)phenol-rich diets, and may be used as an objective tool for the assessment of (poly)phenol intake.

Dietary (poly)phenols and cardiometabolic health: from antioxidants to modulators of the gut microbiota.

(Poly)phenols are plant secondary metabolites widely abundant in plant foods and beverages comprising a very large number of compounds with diverse structure and biological activities. Accumulating evidence indicates that these compounds exert beneficial effects against cardiometabolic diseases, and this review will provide a summary of current knowledge in this area. Epidemiological and clinical data collectively suggest that intake of flavonoids reduces the risk of cardiovascular disease (CVD), with the evidence being particularly strong for the flavan-3-ol subclass. However, to provide adequate dietary recommendations, a better understanding of their estimated content in foods and intake among the general public is needed. Regarding mechanisms of action, we now know that it is unlikely that (poly)phenols act as direct antioxidants in vivo, as it was hypothesised for decades with the popularity of in vitro antioxidant capacity assays. One of the reasons is that upon ingestion, (poly)phenols are extensively metabolised into a wide array of circulating metabolites with different bioactivities than their precursors. Well-conducted in vitro and in vivo studies and human nutrigenomic analysis have revealed new molecular targets that may be underlying the health benefits of (poly)phenols, such as the nitric oxide pathway. Recently, a bi-directional relationship was established between (poly)phenols and the gut microbiota, suggesting that individual gut microbial metabolising capacity may be a key factor explaining the variability in the cardiometabolic response to (poly)phenols. Future research is needed to elucidate which are the key factors affecting such capacity, and whether it can be modulated, along with the mechanisms of action.

(Poly)phenol intake, plant-rich dietary patterns and cardiometabolic health: a cross-sectional study.

Diet is an important modifiable risk factor for cardiometabolic diseases. Plant foods contain a complex mixture of nutrients and bioactive compounds such as (poly)phenols. Plant-rich dietary patterns have been associated with reduced cardiometabolic risk in epidemiological studies. However, studies have not fully considered (poly)phenols as a mediating factor in the relationship. A cross-sectional analysis was conducted in 525 healthy participants, aged 41.6 ± 18.3 years. Volunteers completed the validated European Prospective Investigation into Diet and Cancer (EPIC) Norfolk Food Frequency Questionnaire (FFQ). We investigated the associations between plant-rich dietary patterns, (poly)phenol intake, and cardiometabolic health. Positive associations were found between (poly)phenols and higher adherence to dietary scores, except for the unhealthy Plant-based Diet Index (uPDI), which was negatively associated with (poly)phenol intake. Correlations were significant for healthy PDI (hPDI), with positive associations with proanthocyanidins (r = 0.39, p < 0.01) and flavonols (r = 0.37, p < 0.01). Among dietary scores, Dietary Approaches to Stop Hypertension (DASH) showed negative associations with diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (Non-HDL-C) (stdBeta -0.12 to -0.10, p < 0.05). The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) score was positively associated with flow-mediated dilation (FMD, stdBeta = 0.10, p = 0.02) and negatively associated with the 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score (stdBeta = -0.12, p = 0.01). Higher intake of flavonoids, flavan-3-ols, flavan-3-ol monomers, theaflavins, and hydroxybenzoic acids (stdBeta: -0.31 to -0.29, p = 0.02) also showed a negative association with a 10-year ASCVD risk score. Flavanones showed significant associations with cardiometabolic markers such as fasting plasma glucose (FPG) (stdBeta = -0.11, p = 0.04), TC (stdBeta = -0.13, p = 0.03), and the Homeostasis Model Assessment (HOMA) of beta cell function (%B) (stdBeta = 0.18, p = 0.04). Flavanone intake was identified as a potential partial mediator in the negative association between TC and plant-rich dietary scores DASH, Original Mediterranean diet scores (O-MED), PDI, and hPDI (proportion mediated = 0.01% to 0.07%, p < 0.05). Higher (poly)phenol intake, particularly flavanone intake, is associated with higher adherence to plant-rich dietary patterns and favourable biomarkers of cardiometabolic risk indicating (poly)phenols may be mediating factors in the beneficial effects.

Consumption of Stilbenes and Flavonoids is Linked to Reduced Risk of Obesity Independently of Fiber Intake.

BACKGROUND: Polyphenol consumption is implicated in gut microbiome composition and improved metabolic outcomes, but it is unclear whether the effect is independent of dietary fiber. METHODS: We investigated the links between (poly)phenol intake, gut microbiome composition (16s RNA) and obesity independently of fiber intake in UK women (n = 1810) and in a small group of UK men (n = 64). RESULTS: (Poly)phenol intakes correlated with microbiome alpha diversity (Shannon Index) after adjusting for confounders and fiber intake. Moreover, flavonoid intake was significantly correlated with the abundance of Veillonella, (a genus known to improve physical performance), and stilbene intake with that of butyrate-producing bacteria (Lachnospira and Faecalibacterium). Stilbene and flavonoid intake also correlated with lower odds of prevalent obesity (Stilbenes: Odds Ratio (95% Confidence Interval) (OR(95%CI)) = 0.80 (0.73, 0.87), p = 4.90 × 10-7; Flavonoids: OR(95%CI) = 0.77 (0.65, 0.91), p = 0.002). Formal mediation analyses revealed that gut microbiome mediates ~11% of the total effect of flavonoid and stilbene intake on prevalent obesity. CONCLUSIONS: Our findings highlight the importance of (poly)phenol consumption for optimal human health.

Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men.

BACKGROUND: Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. OBJECTIVES: The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. METHODS: A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. RESULTS: Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% ± 0.4% (95% CI: 0.13%, 1.72%) and 1.2% ± 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% ± 0.3%, P = 0.003) and 12 wk later (1.5% ± 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. CONCLUSIONS: In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.

Blood-based redox-signature and their association to the cognitive scores in MCI and Alzheimer's disease patients.

Oxidative stress plays a pivotal and early role in the pathophysiology of Alzheimer's disease (AD). There is convincing evidence that oxidative alterations in AD and in mild cognitive impairment (MCI) patients are not limited to the brain but are extended to the blood compartment. However, the oxidative pattern in plasma is still inconclusive. Moreover, their potential association with the clinical scores MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment) is poorly investigated. The aim of our study was to establish a pattern of blood-based redox alterations in prodromal AD and their evolution during the progression of the disease. Our results showed a reduction in the total antioxidant capacity (TAC) and an increase of the stress-response proteins apolipoprotein J (ApoJ) and Klotho in MCI subjects. For the first time, we evidenced circulating-proteasome activity. We found that the alteration of the circulating-proteasome activity is associated with the accumulation of oxidized proteins in plasma form early AD. Interestingly, the TAC, the levels of vitamin D and the activity of proteasome were positively associated to the clinical scores MMSE and MoCA. The levels of protein carbonyls and of ApoJ were negatively associated to the MMSE and MoCA scores. The levels of apolipoprotein D (ApoD) were not different between groups. Interestingly, the receiver operating characteristic (ROC) curves analysis indicated that these redox markers provide a fair classification of different groups with high accuracy. Overall, our results strengthen the notion that some specific oxidative markers could be considered as non-invasive blood-based biomarkers for an early MCI diagnosis and AD progression.