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The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r2 = 0.74, p < 0.05), driven by caffeic acid 4-O-ß-d-glucuronide, quercetin-3-O-ß-d-glucuronide, ferulic acid 4-O-ß-d-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O-ß-d-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3′-hydroxyphenyl)-γ-valerolactone-4′-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r2 ≥ 0.89, p < 0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

Purpose Wild blueberries (WB) ( Vaccinium angustifolium ) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease. Methods Eighteen male volunteers (ages 47.8 ± 9.7 years; body mass index 24.8 ± 2.6 kg/m 2 ) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed. Results Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5 ± 5.6 % to 9.6 ± 3.5 %, p  ≤ 0.01) and the levels of H 2 O 2 -induced DNA damage (from 45.8 ± 7.9 % to 37.2 ± 9.1 %, p  ≤ 0.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study. Conclusions In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function. This study was registered at www.isrctn.org as ISRCTN47732406.

Purpose Previously, anthocyanin-rich blueberry treatments have shown positive effects on cognition in both animals and human adults. However, little research has considered whether these benefits transfer to children. Here we describe an acute time-course and dose–response investigation considering whether these cognitive benefits extend to children. Methods Using a double-blind cross-over design, on three occasions children ( n  = 21; 7–10 years) consumed placebo (vehicle) or blueberry drinks containing 15 or 30 g freeze-dried wild blueberry (WBB) powder. A cognitive battery including tests of verbal memory, word recognition, response interference, response inhibition and levels of processing was performed at baseline, and 1.15, 3 and 6 h following treatment. Results Significant WBB-related improvements included final immediate recall at 1.15 h, delayed word recognition sustained over each period, and accuracy on cognitively demanding incongruent trials in the interference task at 3 h. Importantly, across all measures, cognitive performance improved, consistent with a dose–response model, with the best performance following 30 g WBB and the worst following vehicle. Conclusion Findings demonstrate WBB-related cognitive improvements in 7- to 10-year-old children. These effects would seem to be particularly sensitive to the cognitive demand of task.

Background/Objectives: Vitamin C is frequently used in several dietary supplements due to its proposed health-promoting properties, while phenolic compounds and especially flavonoids have been suggested to provide synergistic antioxidant and cardiovascular benefits. However, the specific interactions between these compounds and their individual contributions to biological activity remain underexplored. This study aimed to evaluate the antioxidant potential and anti-inflammatory and antiplatelet biological effects of a high-dose (1 g) vitamin C–low-dose (50 mg) bioflavonoid (VCF)-based supplement using both in vitro and in vivo approaches in human platelets. Methods: Total phenolic content was quantified and antioxidant capacity was assessed using DPPH, FRAP, and ABTS assays and compared to individual phenolic standard compounds, including (simple phenolics like gallic acid, flavonoids like quercetin and catechin, and polyphenols like curcumin and tannin), and a standard supplement containing only high-dose vitamin C (VC). ATR-FTIR spectroscopy was used to assess molecular interactions between vitamin C and flavonoids. In vitro anti-inflammatory and antiplatelet activities of all supplements and standards were assessed by quantifying their IC50 values against ADP, PAF, and thrombin-induced platelet aggregation. The in vivo evaluation of the efficacy and synergy of VCF supplement versus VC was achieved by a two-arm clinical study in healthy volunteers by quantifying their platelet reactivity, which was measured via EC50 values on the aforementioned platelet agonists (PAF, ADP, and Thrombin) before (t = 0) and after receiving either solely VC or VCF supplementation for four weeks. Results: From all phenolic standards, the flavonoids and especially a mixture of flavonoids (catechin + quercetin) showed higher in vitro antioxidant capacity and anti-inflammatory and antiplatelet efficacy, followed by polyphenols and then simple phenolics. The VCF supplement showed the most potent antioxidant capacity, but also the strongest anti-inflammatory and antiplatelet activities too, in comparison to the VC and the mixture of flavonoids, suggesting higher synergy and thus bio-efficacy as a result of the co-presence of flavonoids and vitamin C in this supplement. Platelet reactivity decreased over time for PAF and thrombin in both arms of the trial, but no significant differences were observed between treatment groups, suggesting that the number of flavonoids used was not sufficient to translate the in vitro findings to the in vivo setting. Conclusions: VC-containing supplements provide antioxidant, anti-inflammatory, and antiplatelet benefits, while the incorporation of flavonoids may provide synergistic health benefits, but more in vivo assessment is needed to fully evaluate the dose efficacy.

Purpose Berry-derived phenolic compounds found in grapes have been associated with a number of health benefits, including the augmentation of human brain function and cognition. Previous intervention studies of Concord grape juice have demonstrated improvement to memory and driving ability following 3- to 4-month supplementation in middle-aged and older adults. However, no studies to date have demonstrated acute cognitive benefits of grape juice, and investigation of these effects in young adults is lacking. Methods This randomised, placebo-controlled, double-blind, counterbalanced-crossover study, assessed the effects of 230 ml purple grape juice or sugar-matched control in 20 healthy young adults. Computerised measures of episodic memory, working memory, attention and mood were completed at baseline and following a 20-min absorption period. Results Purple grape juice significantly improved reaction time on a composite attention measure ( p  = 0.047) and increased calm ratings ( p  = 0.046) when compared to placebo. Order effects also indicated an enduring positive effect on pre-dose memory reaction time ( p  = 0.018) and post-dose calm ratings ( p  = 0.019) when purple grape was consumed first. Conclusions These findings in a small sample of healthy young adults suggest that purple grape juice can acutely enhance aspects of cognition and mood. No significant effects of juice were observed on memory measures, suggesting that these may be less susceptible to manipulation following acute supplementation in healthy young adults. Potential mechanisms underlying these effects include modulation of cerebral blood flow, glucoregulation and inhibition of monoamine oxidase activity, all of which require further exploration.

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Epidemiological evidence suggests that consumption of flavonoids (usually via fruits and vegetables) is associated with decreased risk of developing depression. One plausible explanation for this association is the well-documented beneficial effects of flavonoids on executive function (EF). Impaired EF is linked to cognitive processes (e.g., rumination) that maintain depression and low mood; therefore, improved EF may reduce depressionogenic cognitive processes and improve mood. Study 1: 21 young adults (18–21 years old) consumed a flavonoid-rich blueberry drink and a matched placebo in a counterbalanced cross-over design. Study 2: 50 children (7–10 years old) were randomly assigned to a flavonoid-rich blueberry drink or a matched placebo. In both studies, participants and researchers were blind to the experimental condition, and mood was assessed using the Positive and Negative Affect Schedule before and 2 h after consumption of the drinks. In both studies, the blueberry intervention increased positive affect (significant drink by session interaction) but had no effect on negative affect. This observed effect of flavonoids on positive affect in two independent samples is of potential practical value in improving public health. If the effect of flavonoids on positive affect is replicated, further investigation will be needed to identify the mechanisms that link flavonoid interventions with improved positive mood.

Background: Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers. Methods: Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species—ROS, Total Antioxidant Capacity—TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples. Results: Si.Pi.Mi intake reduced circulating ethanol after 120 min (−33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9–12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range −22–27%), were observed too. Conclusion: After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested.

Background: Gingival inflammation is highly prevalent and may impact systemic health. While professional mechanical plaque removal (PMPR) is the standard treatment, dietary interventions may provide additional benefits. The French maritime pine bark extract Pycnogenol® has anti-inflammatory and antioxidant properties, but its impact on inflammatory biomarkers in saliva and serum has not been studied in a controlled clinical trial. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 91 participants received Pycnogenol® (100 mg twice daily; n = 46) or a placebo (n = 45) following PMPR. Saliva and serum samples were collected at baseline, and after two and three months. Inflammatory biomarkers (IL-1β, IL-6, MMP-8, and MMP-9) and polyphenol concentrations were analyzed using ELISA and LC-MS/MS. Results: Pycnogenol® supplementation significantly reduced salivary MMP-8 levels (p = 0.0261), and serum IL-6 levels compared to placebo (p = 0.0409). Additionally, ferulic acid, caffeic acid, and the gut microbial metabolite 5-(3,4-dihydroxyphenyl)-γ-valerolactone (M1) significantly increased in saliva following Pycnogenol® intake. A correlation analysis revealed a significant inverse association between bleeding on probing and M1 concentration in saliva (r = −0.3476, p = 0.0167). Conclusions: Dietary supplementation with Pycnogenol® significantly reduced key inflammatory biomarkers and increased polyphenol concentrations in saliva, suggesting a potential anti-inflammatory effect of Pycnogenol® on gingival inflammation. Trial registration: ClinicalTrials.gov (NCT05786820).

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20–39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women.