Protective effects of blueberries on vascular function: A narrative review of preclinical and clinical evidence

Abstract

Blueberries are rich in nutrients and (poly)phenols, popular with consumers, and a major agricultural crop with year-round availability supporting their use in food-based strategies to promote human health. Accumulating evidence indicates blueberry consumption has protective effects on cardiovascular health including vascular dysfunction (i.e., endothelial dysfunction and arterial stiffening). This narrative review synthesizes evidence on blueberries and vascular function and provides insight into underlying mechanisms with a focus on oxidative stress, inflammation, and gut microbiota. Evidence from animal studies supports beneficial impacts on vascular function. Human studies indicate acute and chronic blueberry consumption can improve endothelial function in healthy and at-risk populations and may modulate arterial stiffness, but that evidence is less certain. Results from cell, animal, and human studies suggest blueberry consumption improves vascular function through improving nitric oxide bioavailability, oxidative stress, and inflammation. Limited data in animals suggest the gut microbiome mediates beneficial effects of blueberries on vascular function; however, there is a paucity of studies evaluating the gut microbiome in humans. Translational evidence indicates anthocyanin metabolites mediate effects of blueberries on endothelial function, though this does not exclude potential synergistic and/or additive effects of other blueberry components. Further research is needed to establish the clinical efficacy of blueberries to improve vascular function in diverse human populations in a manner that provides mechanistic information. Translation of clinical research to the community/public should consider feasibility, social determinants of health, culture, community needs, assets, and desires, barriers, and drivers to consumption, among other factors to establish real-world impacts of blueberry consumption.

Keywords: Anthocyanins; Arterial stiffness; Blueberry; Cardiovascular disease; Endothelial function; Polyphenols.

Fig. 1 –

Visual representation of blueberry (poly)phenol digestion, absorption, metabolism, and elimination that includes examples of (poly)phenol metabolites produced through phase I and II and gut microbial metabolism. Following ingestion of blueberries, their (poly)phenols travel through the gastrointestinal tract, where a minor amount is absorbed in the stomach following release from the food matrix and hydrolysis. Approximately 5% to 10% are absorbed in the small intestine following deconjugation reactions, and the remainder (~ 90%–95%) go to the large intestine for gut microbial and phase II metabolism. Following absorption and further metabolism in the liver, (poly)phenol metabolites enter systemic circulation for travel to target tissues and/or are eliminated through urine or feces. This figure was created with Biorender (https://www.biorender.com).

Fig. 2 –

Graphical schematic of the impact of blueberry consumption on endothelial function and arterial stiffness (i.e., vascular dysfunction) and potential major mechanisms based on evidence from cell, animal, and human studies. Vascular dysfunction occurs with aging and is accelerated by chronic disease risk factors and contributes to cardiovascular disease (CVD). Evidence indicates major mediators include oxidative stress, inflammation, and the gut microbiome. Preclinical and clinical evidence supports that blueberries improve vascular function, particularly endothelial function. The evidence supporting effects on arterial stiffness is less conclusive. Effects are mediated through modulation of oxidative stress and inflammation, and potentially the gut microbiome. This figure was created with Biorender (https://www.biorender.com).

Fig. 3 –

Potential mechanisms by which blueberries, their components, and/or resulting metabolites improve endothelial function based on evidence from cell, animal, and human studies. Evidence indicates blueberries may improve endothelial function through antioxidant defense (i.e., Nrf2/Keap1/ARE), reduced free radical production/oxidative stress (i.e., NADPH oxidase), reduced inflammation (i.e., iNOS, NF-κB, COX-2), endothelial cell nitric oxide production (i.e., eNOS), and gut microbiota modulation. This figure was created with Biorender (https://www.biorender.com). Abbreviations: COX-2, cyclooxygenase-2; eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B; NADPH oxidase, nicotinamide adenine dinucleotide phosphate oxidase; Nrf2/Keap1/ARE, nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1/antioxidant response element.

Fig. 4 –

Knowledge gaps and suggestions for future research with blueberries related to cardiovascular health in humans. Major knowledge gaps related to blueberry consumption in humans were identified include dose-dependent and time-course clinical efficacy, underlying mechanisms and factors contributing to efficacy, and translation to clinical/medical, community, and public health settings. This figure was created with Biorender (https://www.biorender.com). Abbreviations: CVD, cardiovascular disease; FMT, fecal microbiota transplant; RCTs, randomized controlled trials.