Rafaela G. Feresin

Wild blueberries (Vaccinium angustifolium Ait.) are North American perennial plants rich in polyphenols, including flavonoids, beneficial to human health. This article provides a summary of the evidence and perspectives presented at an expert symposium that focused on wild blueberries and cardiometabolic health. Topics covered include historical perspectives, food matrix and bioavailability, clinical and translational evidence on blueberries and cardiometabolic health, mechanisms of action, the role of the gut microbiome, knowledge gaps, and future research. Overall, data support that acute and chronic wild blueberry consumption can favorably affect measures of cardiometabolic health and related health outcomes such as the gut microbiota and cognitive function. Mechanistically, data suggest wild blueberry polyphenols, particularly anthocyanins, mediate the cardiometabolic benefits of dietary blueberries by acting on multiple targets. However, the cardiometabolic health benefits of wild blueberry consumption are equivocal, and future research should aim to understand factors and mechanisms contributing to individual and subgroup responses. Future studies should also investigate comprehensive biomarkers of cardiometabolic health and explore standardized methodological and precision nutrition approaches. Finally, evaluation and confirmation of wild blueberry phytochemicals, dosing strategies and food matrix interactions are needed to strengthen clinical trial designs and extend dietary recommendations to broader public health benefits.

Hypothesized model by which a plant-based diet can prevent and treat hypertension-induced renal and hepatic dysfunction.

Hypertension (HTN) and intestinal permeability (IP) are increasingly recognized as interrelated processes driven by shared oxidative and inflammatory mechanisms. This review synthesizes evidence linking HTN-induced vascular dysfunction to alterations in intestinal barrier integrity and explores the potential of dietary flavonoids as modulators of these pathologies. A narrative approach was used to synthesize findings from cellular, animal, and human studies that specifically address how flavonoids influence the molecular pathway connecting HTN and IP. Emerging evidence suggests that HTN-driven vascular injury, which is characterized by reduced nitric oxide bioavailability, increased reactive oxygen species, and pro-inflammatory signaling, contributes to tight junction disruption and increased IP. Mechanistic evidence indicates that flavonoids exert both direct antioxidant effects and indirect actions via the modulation of key cellular pathways. Preclinical and clinical data demonstrate that flavonoid-rich foods and isolated compounds can lower blood pressure, enhance endothelial function, and preserve intestinal barrier integrity by stabilizing tight junction proteins and attenuating pro-inflammatory signaling. Together, these findings highlight flavonoids as cross-system modulators that may mitigate HTN-associated increases in IP. Further research addressing sex, race, and age differences, as well as flavonoid bioavailability and dose optimization, is needed to clarify their translational potential.

Background: Coronary microvascular dysfunction (CMD) is associated with adverse cardiovascular outcomes. CMD is driven by endothelial and vascular smooth muscle cell (VSMC) dysfunction. We aimed to test whether CMD could be mitigated by a plant‐based diet (PBD) in an animal model of hypertension. Methods: We compared 28‐ and 40‐week‐old female normotensive Wistar–Kyoto and spontaneously hypertensive rats (SHRs), maintained, from age 4 weeks, on a control refined diet or a PBD, composed of 28% fruits, vegetables, nuts, and legumes. A subset of control SHRs was switched to the PBD at 28 weeks. CMD was assessed by coronary flow reserve via echocardiogram. Cardiac microvascular endothelial function was assessed via cardiac magnetic resonance imaging. Endothelial and VSMC function were assessed in the left ventricle or in isolated VSMCs. The role of gut microbiota was probed via 16S sequencing and antibiotics. Cardiac inflammation, oxidative stress, and fibrosis were also explored. Results: SHRs exhibited endothelial dysfunction and likely VSMC dysfunction. A PBD did not ameliorate their hypertension but, nonetheless, prevented and reversed CMD. The PBD’s mitigation of CMD was associated with improved endothelial nitric oxide synthase function and nitric oxide–mediated VSMC signaling, as well as reductions in left ventricular oxidative stress, inflammatory signaling, and fibrosis. A PBD altered the gut microbiota, although antibiotic studies failed to establish its importance in ameliorating CMD. Conclusions: A PBD prevented CMD development and reversed established CMD in SHRs. Such benefits of PBD, which occurred without alleviating hypertension, were possibly due to improved endothelial function and likely improved VSMC function. These results support clinical trials to test PBDs in human CMD.

Background and aims: Coronary microvascular dysfunction (CMD) is associated with adverse cardiovascular outcomes. CMD is driven by endothelial and vascular smooth muscle cell (VSMC) dysfunction. We aimed to test whether CMD could be mitigated by a plant-based diet (PBD) in an animal model of hypertension. Methods: We compared 28- and 40-week-old female normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) rats, maintained, from age 4 weeks, on a control refined diet or a PBD, comprised of 28% fruits, vegetables, nuts and legumes. A subset of control SHRs were switched to the PBD at 28 weeks. CMD was assessed by coronary flow reserve via echocardiogram. Cardiac microvascular endothelial function was assessed via cMRI. Endothelial and VSMC function were assessed in the left ventricle (LV) or in isolated VSMCs. The role of gut microbiota was probed via 16S sequencing and antibiotics. Cardiac inflammation, oxidative stress, and fibrosis were also explored. Results: SHRs exhibited endothelial dysfunction and likely VSMC dysfunction. PBD did not ameliorate their hypertension but, nonetheless, prevented and reversed CMD. PBD’s mitigation of CMD was associated with improved endothelial nitric oxide synthase function and NO-mediated VSMC signaling, as well as reductions in LV oxidative stress, inflammatory signaling, and fibrosis. PBD altered the gut microbiota, although antibiotic studies failed to establish its importance in ameliorating CMD. Conclusions: A PBD prevented CMD development and reversed established CMD in SHRs. Such benefits of PBD, which occurred without alleviating hypertension, were possibly due to improved endothelial function and likely improved VSMC function. These results support clinical trials to test PBDs in human CMD. Graphical A plant-based diet prevented and reversed CMD without attenuating hypertension. Such amelioration of CMD was not negated by antibiotics and correlated with improved endothelial and VSMC function. Legend: ABX, antibiotics; BP, blood pressure; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; PBD, plant-based diet; PKG, protein kinase G; PLN, phospholamban; SHR, spontaneously hypertensive rat; SR, sarcoplasmic reticulum; VSMC, vascular smooth muscle cell.

This study investigates the effect of OCP phase on in vivo microvascular endothelium-dependent vasodilation and explores underlying mechanisms. Present findings suggest OCP phase does not affect overall microvascular endothelium-dependent dilation but does affect the underlying mechanisms. In women using OCP, there is a robust reliance on EDHF pathways and the COX pathway moderates basal microvascular blood flow and demonstrates a phase-dependent restraint of the NO pathway.

Background: Quercetin (QCT) and citrulline (CIT) have been independently associated with improved antioxidant capacity and nitric oxide (NO) production, potentially enhancing cardiovascular function and exercise performance. This study aimed to evaluate the combined and independent effects of QCT and CIT supplementation on NO metabolites and antioxidant biomarkers in 50 trained cyclists undergoing a 20 km cycling time trial (TT). Methods: In a randomized, double-blind, placebo-controlled design, forty-two male and eight female trained cyclists were assigned to QCT + CIT, QCT, CIT, or placebo (PL) groups. Supplements were consumed twice daily for 28 days. Biochemical assessments included NO metabolites (nitrate/nitrite), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD) activity, and antioxidant capacity, measured pre- and post-TT. Results: NO metabolites were significantly elevated post-supplementation (p = 0.03); however, no significant interaction effects were observed for NO metabolites, FRAP, SOD, or antioxidant capacity across the groups (p > 0.05). Post-hoc analyses revealed that QCT significantly reduced FRAP concentrations compared to PL (p = 0.01), while no significant changes in SOD or antioxidant capacity were found across any groups. Conclusions: These findings suggest that combined and independent QCT and CIT supplementation did not significantly improve these biomarkers, suggesting that baseline training adaptations, supplementation timing, and individual variability may influence the efficacy of these compounds in enhancing exercise performance and oxidative stress markers. The ergogenic efficacy of QCT + CIT on antioxidant-related markers remains inconclusive.

There is growing interest in the use of nutrition and dietary supplements to optimize training and time-trial (TT) performance in cyclists. Separately, quercetin (QCT) and citrulline (CIT) have been used as ergogenic aids to improve oxygen (VO₂) kinetics, perceived effort, and cycling TT performance. However, whether the combination of QCT and CIT can provide additive benefits and further enhance cycling performance production is currently unknown. We examined 28-days of QCT + CIT supplementation on TT performance and several performance measures (i.e. mean power, VO₂, respiratory exchange ratio (RER), and rate of perceived exertion (RPE)). Forty-eight highly trained cyclists were assigned to one of four supplementation groups: (1) QCT + CIT (QCT: 500 mg, CIT: 3000 g), (2) QCT (500 mg), (3) CIT (3000 mg), or (4) placebo (3500 mg of a zero-calorie flavored crystal light package). Supplements were consumed two times per day for 28 consecutive days. Participants performed a 20-km cycling time-trial race, pre- and post-supplementation to determine the impact of the combined effects of QCT + CIT. There were no potential benefits of QCT +CIT supplementation on TT performance and several performance measures. However, there was an improvement in VO₂ from pre-to-post-supplementation in QCT (p = 0.05) and CIT (p = 0.04) groups, but not in the QCT+CIT and PL groups. QCT + CIT does not seem beneficial for 20-km TT performance; further exploration with a focus on an increase in cycling duration or QCT+CIT combined with additional polyphenols may amplify any perceived bioactive or metabolic effects on cycling performance. The efficacy of QCT + CIT supplementation to improve cycling performance remains ambiguous.