'Compelling data': RCT shows blueberry flavonoids boost endothelial function and heart health

The improvements in vascular function in healthy men were linked to both the time and dose of blueberry flavonoids, report scientists from the University of Reading (UK), the University Düsseldorf (Germany), and the University of Northumbria (UK).

“Our data suggest that the consumption of blueberry at dietary intakes (100–240 g; equivalent to 319, 639, and 766 mg total polyphenols) may have public health relevance in maintaining circulatory function,” ​they wrote in the American Journal of Clinical Nutrition​​.

“Furthermore, such an intake of polyphenols need not be restricted to blueberry alone but may be achieved through the intake of other berries and anthocyaninrich foods and beverages. ​

“With regard to the higher intakes reported in the current study, we suggest that these intakes are most likely through novel, functional foods and beverages in which polyphenols have been incorporated.”​

The study used test material donated by the Wild Blueberry Association of North America.

‘Well-designed’​

Commenting independently on the study, Navindra Seeram, PhD, associate professor in the Bioactive Botanical Research Laboratory at the University of Rhode Island, told NutraIngredients-USA that previous human intervention data, obtained from a variety of polyphenol-rich foods and beverages, have yielded still unclear conclusions due to lack of randomized controlled trials and polyphenol quantification in the various food matrices. 

“Remarkably, here the authors have addressed these issues by conducting two separate randomized, controlled, double-blind, crossover studies, and by delivering known quantities of polyphenols, to support their overall hypothesis. ​

“Moreover, the authors have also addressed the important issues of bioavailability and metabolism of polyphenols by conducting plasma metabolite analyses and have provided mechanistic insights to support their findings. In sum, this is a well-designed human study showing that blueberry intake improves vascular function in male volunteers.”​

Study details​

The research, led by Dr Jeremy Spencer from the University of Reading, investigated the impact of blueberry flavonoids on the function of the cells lining blood vessels (endothelium) in healthy men. They conducted two randomized, controlled, double-blind, crossover human-intervention trials with 21 healthy men. For the first study, they assessed the effect of different doses of blueberry flavonoids (766, 1278, and 1791 mg total blueberry polyphenols) on flow-mediated dilation (FMD) – a measure of the elasticity of blood vessels – at different times (1, 1, 2, 4, and 6 hours). These were compared to a control drink containing no blueberry polyphenols.

The second study investigated the effects of 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols between time zero and one hour later.

Results of the first study showed that the FMD increased at two moments – at 1-2 hours after consumption, and again at 6 hours after consumption.

At 1-2 hours after consumption of the blueberry polyphenols, the researchers found that ferulic acid, isoferulic acid, vanillic acid, 2-hydroxybenzoic acid, benzoic acid, and caffeic acid were significantly increased.

“Improvements in FMD at 6 h after consumption were correlated with the appearance of metabolites derived from anthocyanin and chlorogenic acid, notably hippuric, hydroxyhippuric acid, and homovanillic acid,” ​they added. “Because intact anthocyanin and flavanol glucuronides and sulfates are not expected in plasma at 6 h post-consumption, this finding suggests that these smaller phenolic derivatives are more likely to have mediated the observed vascular effects.”​

There were no significant differences observed for the doses studied in this trial (766, 1278, and 1791 mg total blueberry polyphenols).

The second study revealed that a dose-response was observed for intakes up to 766 mg total blueberry polyphenol intake. Above 766 mg, FMD was found to plateau.

Compelling data​

Amy Howell, PhD, associate research scientist at the Marucci Center for Blueberry Cranberry Research at Rutgers University, told us that the new study provides “compelling data suggesting positive effects of blueberry on endothelial function over the first 6 hours following consumption.​ 

“The biological effects on FMD were well-correlated with circulating levels of blueberry polyphenolic metabolites and their effects on an enzyme important in cardiovascular health.  The effect on FMD was biphasic, highly significant after only one hour, and reached a threshold after 766 mg of blueberry polyphenols (240 g of fruit) were ingested.  ​

“It is important to note that the bioactive dosages of 100-240 g of blueberries are very achievable for daily consumption by consumers.  Although studies on the long-term effects of blueberry consumption on FMD are needed, this latest study provides additional evidence for the positive effects of blueberries on maintenance of heart health.”​  

Potential mechanism​

Dr Spencer and his co-workers noted that the increases in FMD were also linked to decreases in the activity of the enzyme called nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. This enzyme generates superoxide, and by inhibiting its activity the vaso-dilating compound nitric oxide is spared.

“To our knowledge, our data provide the first evidence that circulating small phenolic metabolites derived from blueberry polyphenols may be partly responsible for acute improvements in endothelial function in healthy individuals, and these improvements may be dependent on the potential of such metabolites to inhibit neutrophil NADPH oxidase,” ​they wrote.  

“However, the causal relation, clinical relevance, and potential long-term health benefits of blueberry polyphenols on vascular function remain to be established.”​

Source: American Journal of Clinical Nutrition​​
Published online ahead of print, doi: 10.3945/​ajcn.113.066639
“Intake and time dependence of blueberry flavonoid–induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity”​
Authors: A. Rodriguez-Mateos, C. Rendeiro, T. Bergillos-Meca, S. Tabatabaee, T.W. George, C. Heiss, J.P.E. Spencer