Over 20 Years of Health Research

Since 1997, the Wild Blueberry Association of North America (WBANA) has been collaborating with elite scientists to help study the health benefits of wild blueberries. WBANA is dedicated to furthering research that explores the health potential of wild blueberries and annually funds research studies that help advance the understanding of the nutritional and human health benefits of wild blueberries.

Each year, WBANA has hosts the Wild Blueberry Health Research Summit in Bar Harbor, Maine, a worldwide gathering of renowned scientists and researchers from leading institutions representing broad disciplines — from cardiovascular health to cancer to heart disease, osteoporosis, neurological diseases of aging, and more. Their work is leading the way to learn more about the health benefits of wild blueberries, and their findings, which use rigorous methodology, are documented in a growing number of published studies on the potential health and disease-fighting benefits of wild blueberries. All published research studies are written by and submitted to peer-reviewed journals by the researcher, independent of WBANA.

Below are scientific research papers that provide more detail into the role wild blueberries may play in promoting human health.

Total phenolics content and antioxidant capacities of microencapsulated blueberry anthocyanins during in vitro digestion

Flores, F. P.; Singh, R. K.; Kerr, W. L.; Pegg, R. B.; Kong, F.
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The goal of this research was to investigate the change in phenolics content and antioxidant capacity of microencapsulated anthocyanins (ACNs) digested in vitro. Blueberry ACN microcapsules were prepared from two wall materials (whey protein isolate and gum arabic) and ACN powder, previously extracted with three solvent systems (acetonic, ethanolic, methanolic); this was then spray-dried. The physicochemical properties and release characteristics of the microcapsules were evaluated. Rehydrated gum arabic microcapsules retained more total ACNs but less ferric reducing power than did whey protein microcapsules. Ethanolic extracts retained most of the total ACNs while methanolic extracts possessed the highest antioxidant capacity. During in vitro digestion, gum arabic microcapsules had high release rates of phenolics with high antioxidant activity during the gastric phase. Whey protein microcapsules had comparably lower release rates but high antioxidant activity throughout digestion.


Blueberry polyphenols prevent cardiomyocyte death by preventing calpain activation and oxidative stress

Louis, X. L.; Thandapilly, S. J.; Kalt, W.; Vinqvist-Tymchuk, M.; Aloud, B. M.; Raj, P.; Yu, L.; Le, H.; Netticadan, T.
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The purpose of this study was to examine the efficacy of an aqueous wild blueberry extract and five wild blueberry polyphenol fractions on an in vitro model of heart disease. Adult rat cardiomyocytes were pretreated with extract and fractions, and then exposed to norepinephrine (NE). Cardiomyocyte hypertrophy, cell death, oxidative stress, apoptosis and cardiomyocyte contractile function as well as the activities of calpain, superoxide dismutase (SOD) and catalase (CAT) were measured in cardiomyocytes treated with and without NE and blueberry fraction (BF). Four of five blueberry fractions prevented cell death and cardiomyocyte hypertrophy induced by NE. Total phenolic fraction was used for all further analysis. The NE-induced increase in oxidative stress, nuclear condensation, calpain activity and lowering of SOD and CAT activities were prevented upon pretreatment with BF. Reduced contractile function was also significantly improved with BF pretreatment. Blueberry polyphenols prevent NE-induced adult cardiomyocyte hypertrophy and cell death. The protective effects of BF may be in part attributed to a reduction in calpain activity and oxidative stress.


[Blueberry anthocyanins induce G2/M cell cycle arrest and apoptosis of oral cancer KB cells through down-regulation methylation of p53]

Qi, C.; Li, S.; Jia, Y.; Wang, L.
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Blueberries are an excellent source of dietary polyphenols such as anthocyanins and phenolic acids. In this study, we investigated the ability of anthocyanins from the wild blueberries of Inner Mongolia to suppress the growth of the oral cancer cell line KB. The blueberry anthocyanins were extracted with methanol-containing 0.1% (v/v) hydrochloric acid. Fourteen unique anthocyanins were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The anticancer bioactivity of the extracts on KB cells was analyzed using methylthiazolyl-tetrazolium (MTT), flow cytometry (FCM) and immunocytochemistry. It was shown that the blueberry anthocyanins suppressed the proliferation of KB cells in a dose-dependent manner, as well as induced G2/M cell cycle arrest and apoptosis of oral cancer KB cells. Immunocytochemistry analysis showed that the expression of caspase-9 and cytochrome c were obviously increased after the anthocyanins treatment. Western blot analysis also indicated that the expression of p53 was increased. Methylation-specific PCR (MSP) showed that the amount of unmethylated p53 increased, indicating that the anthocyanins can down-regulate the methylation of p53.


Can transcriptomics provide insight into the chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

van Breda, S. G.; Wilms, L. C.; Gaj, S.; Jennen, D. G.; Briede, J. J.; Helsper, J. P.; Kleinjans, J. C.; de Kok, T. M.
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Abstract Blueberries contain relatively large amounts of different phytochemicals, which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a 4-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in four subgroups. The magnitude of the preventive effect after the intervention differed between these four subgroups. Furthermore, subjects in two groups carried genetic polymorphisms that were previously found to influence the chemopreventive response. Pathway analysis of the identified genes showed strong but complex gene expression changes in pathways signaling for apoptosis, immune response, cell adhesion, and lipid metabolism. These pathways indicate increased apoptosis, upgraded growth control, induced immunity, reduced platelet aggregation and activation, blood glucose homeostasis, and regulation of fatty acid metabolism. Based on these observations, we hypothesize that combining transcriptomic data with phenotypic markers of oxidative stress may provide insight into the relevant cellular processes and genetic pathways, which contribute to the antioxidant response of complex mixtures of phytochemicals, such as found in blueberry-apple juice. Antioxid. Redox Signal. 20, 2107-2113.


Can transcriptomics provide insight into the chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

van Breda, S. G.; Wilms, L. C.; Gaj, S.; Jennen, D. G.; Briede, J. J.; Helsper, J. P.; Kleinjans, J. C.; de Kok, T. M.
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Abstract Blueberries contain relatively large amounts of different phytochemicals, which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a 4-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in four subgroups. The magnitude of the preventive effect after the intervention differed between these four subgroups. Furthermore, subjects in two groups carried genetic polymorphisms that were previously found to influence the chemopreventive response. Pathway analysis of the identified genes showed strong but complex gene expression changes in pathways signaling for apoptosis, immune response, cell adhesion, and lipid metabolism. These pathways indicate increased apoptosis, upgraded growth control, induced immunity, reduced platelet aggregation and activation, blood glucose homeostasis, and regulation of fatty acid metabolism. Based on these observations, we hypothesize that combining transcriptomic data with phenotypic markers of oxidative stress may provide insight into the relevant cellular processes and genetic pathways, which contribute to the antioxidant response of complex mixtures of phytochemicals, such as found in blueberry-apple juice. Antioxid. Redox Signal. 20, 2107-2113.


Can transcriptomics provide insight into the chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

van Breda, S. G.; Wilms, L. C.; Gaj, S.; Jennen, D. G.; Briede, J. J.; Helsper, J. P.; Kleinjans, J. C.; de Kok, T. M.
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Abstract Blueberries contain relatively large amounts of different phytochemicals, which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a 4-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in four subgroups. The magnitude of the preventive effect after the intervention differed between these four subgroups. Furthermore, subjects in two groups carried genetic polymorphisms that were previously found to influence the chemopreventive response. Pathway analysis of the identified genes showed strong but complex gene expression changes in pathways signaling for apoptosis, immune response, cell adhesion, and lipid metabolism. These pathways indicate increased apoptosis, upgraded growth control, induced immunity, reduced platelet aggregation and activation, blood glucose homeostasis, and regulation of fatty acid metabolism. Based on these observations, we hypothesize that combining transcriptomic data with phenotypic markers of oxidative stress may provide insight into the relevant cellular processes and genetic pathways, which contribute to the antioxidant response of complex mixtures of phytochemicals, such as found in blueberry-apple juice. Antioxid. Redox Signal. 20, 2107-2113.


Berries and human health: research highlights from the fifth biennial berry health benefits symposium

Seeram, N. P.
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The fifth biennial Berry Health Benefits Symposium showcased recent research supporting the positive effects of berry consumption on human health and disease. Remarkably, the vast majority of oral papers covered data accumulated from in vivo studies, which underscores how berry health research has advanced since the inception of this symposium in 2005. Similar to the past, research presented at this meeting was primarily focused on the major commercially cultivated berries in North America, namely, blackberry, blueberry, black raspberry, cranberry, red raspberry, and strawberry. Despite this, on the basis of similar compositional chemistry, it is possible that similar biological effects may also be extended to other small soft-fleshed “berry-type” fruits popular in other parts of the world including Europe, Asia, and South America. Overall, this symposium continues to add to the growing body of data supporting the positive impact of berry fruit consumption on human health promotion and disease risk reduction.


Effects of Soluble and Insoluble Fractions from Bilberries, Black Currants, and Raspberries on Short-Chain Fatty Acid Formation, Anthocyanin Excretion, and Cholesterol in Rats

Jakobsdottir, G.; Nilsson, U.; Blanco, N.; Sterner, O.; Nyman, M.
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Dietary fiber and flavonoids, important components in berries, are suggested to improve metabolic health. This study investigates whether soluble and insoluble fractions isolated from bilberry, black currant, and raspberry affect the formation of short-chain fatty acids (SCFAs), uptake and excretion of flavonoids, and levels of cholesterol differently. Cecal SCFA pools were higher in rats fed the soluble than the insoluble fractions (525 vs 166 mumol, P < 0.001), whereas higher concentrations of butyric acid were found in the distal colon and serum of rats fed the insoluble fractions (5 vs 3 mumol/g and 58 vs 29 mumol/L, respectively, P < 0.001). The soluble bilberry fraction gave lower amounts of liver cholesterol (56 mg) than the other berry fractions (87 +/- 5 mg), formed the highest amount of SCFAs (746 vs 266 +/- 21 mumol), and contributed the highest intake of anthocyanins. Cyanidin-3-glucoside monoglucuronide was detected in the urine of all groups, whereas anthocyanins were found only in groups fed soluble black currant and raspberry.


Cronobacter sakazakii reduction by blueberry proanthocyanidins

Joshi, S. S.; Howell, A. B.; D’Souza, D. H.
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Blueberry juice and blueberry polyphenols reportedly have antimicrobial properties against foodborne pathogens, without much currently known on their effects against Cronobacter sakazakii. This study evaluated the antimicrobial effects of blueberry proanthocyanidins (PAC) and commercial blueberry juice (BJ) against two strains of C. sakazakii, ATCC 29004 and 29544. BJ (pH 2.8), blueberry PAC (5 mg/ml) and controls (phosphate buffered saline (PBS), pH 7.2, and malic acid pH 3.0) were mixed with equal volumes of washed overnight cultures of C. sakazakii and incubated for 30 min, 1 h, 3 h and 6 h at 37 degrees C. Reductions of approximately 1 and 1.50 log CFU/ml were obtained for strains 29004 and 29544, respectively after 30 min with BJ or blueberry PAC. Both C. sakazakii strains 29004 and 29544 were reduced to undetectable levels from 8.25 +/- 0.12 log CFU/ml and 8.48 +/- 0.03 log CFU/ml, respectively with BJ (pH 2.8) or blueberry PAC after 1 h, while malic acid (pH 3.0) showed approximately 1.3 log CFU/ml reduction for both strains. Scanning electron microscopy studies showed differences in cell membrane morphology with clumping and formation of blebs of the treated strains compared to untreated controls. These results warrant further in vivo studies with blueberry bioactives to determine potential for preventing and treating C. sakazakii infections.


Diet-derived phenolic acids regulate osteoblast and adipocyte lineage commitment and differentiation in young mice

Chen, J. R.; Lazarenko, O. P.; Zhang, J.; Blackburn, M. L.; Ronis, M. J.; Badger, T. M.
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A blueberry (BB)-supplemented diet has been previously shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and they were found in the serum of rats fed BB-containing diet. We conducted in vitro studies with PAs and demonstrated stimulation of osteoblast differentiation and proliferation. On the other hand, adipogenesis was inhibited. To more fully understand the mechanistic actions of PAs on bone formation, we administered hippuric acid, one of the major metabolites found in animal circulation after BB consumption, to prepubertal female mice for 2 weeks. We found that hippuric acid was able to stimulate bone-forming gene expression but suppress PPARgamma expression, leading to increased bone mass dose-dependently. Cellular signaling studies further suggested that the skeletal effects of PAs appeared to be mediated through activation of G-protein-coupled receptor 109A and downstream p38 MAP kinase and osterix. In conclusion, PAs are capable of altering the mesenchymal stem cell differentiation program and merit investigation as potential dietary therapeutic alternatives to drugs for degenerative bone disorders. (c) 2014 American Society for Bone and Mineral Research.


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Looking for more health research?

Contact KIT BROIHIER, resident nutrition adviser to the Wild Blueberry Association of North America

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Kit Broihier, MS, RD, LD is the Nutrition advisor and spokesperson for the Wild Blueberry Association of North America. She is a Registered and Licensed Dietitian with a Masters Degree in Nutrition and is the owner of NutriComm Inc., a food and nutrition communications consulting company.

Ms. Broihier received a Bachelor of Science degree in Dietetics from Michigan State University and a Master of Science degree in Nutrition Communications from Boston University.