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.

Role of a prudent breakfast in improving cardiometabolic risk factors in subjects with hypercholesterolemia: A randomized controlled trial

Adamsson, V.; Reumark, A.; Marklund, M.; Larsson, A.; Riserus, U.
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BACKGROUND & AIMS: It is unclear whether advising a prudent breakfast alone is sufficient to improve blood lipids and cardiometabolic risk factors in overweight hypercholesterolemic subjects. The aim of this study was to investigate whether a prudent low-fat breakfast (PB) rich in dietary fiber lowers low-density lipoprotein cholesterol (LDL-C) and other cardiometabolic risk factors in subjects with elevated LDL-cholesterol levels. METHODS: In a parallel, controlled, 12-week study, 79 healthy overweight subjects (all regular breakfast eaters) were randomly allocated to a group that received a PB based on Nordic foods provided ad libitum or a control group that consumed their usual breakfast. The primary outcome was plasma LDL-C. Secondary outcomes were other blood lipids, body weight, sagittal abdominal diameter (SAD), glucose tolerance, insulin sensitivity and inflammation markers (C-reactive protein [CRP] and tumor necrosis factor receptor-2 [TNF-R2]), and blood pressure. The PB was in accordance with national and Nordic nutrition recommendations and included oat bran porridge with low-fat milk or yogurt, bilberry or lingonberry jam, whole grain bread, low-fat spread, poultry or fatty fish, and fruit. RESULTS: No differences were found in LDL-C, other blood lipids, body weight, or glucose metabolism, but SAD, plasma CRP, and TNF-R2 decreased more during PB compared with controls (p < 0.05). In the overall diet, PB increased dietary fiber and beta-glucan compared with controls (p < 0.05). CONCLUSIONS: Advising a prudent breakfast for 3 months did not influence blood lipids, body weight, or glucose metabolism but reduced markers of visceral fat and inflammation. The trial was registered in the Current Controlled Trials database (http://www.controlled-trials.com); International Standard Randomized Controlled Trial Number (ISRCTN): 84550872.


Chemopreventive and Therapeutic Activity of Dietary Blueberry against Estrogen-Mediated Breast Cancer

Jeyabalan, J.; Aqil, F.; Munagala, R.; Annamalai, L.; Vadhanam, M. V.; Gupta, R. C.
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Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17beta-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-alpha gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.


Chemopreventive and Therapeutic Activity of Dietary Blueberry against Estrogen-Mediated Breast Cancer

Jeyabalan, J.; Aqil, F.; Munagala, R.; Annamalai, L.; Vadhanam, M. V.; Gupta, R. C.
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Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17beta-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-alpha gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.


Protective effects of bilberry and lingonberry extracts against blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro

Ogawa, K.; Kuse, Y.; Tsuruma, K.; Kobayashi, S.; Shimazawa, M.; Hara, H.
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BACKGROUND: Blue light is a high-energy or short-wavelength visible light, which induces retinal diseases such as age-related macular degeneration and retinitis pigmentosa. Bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea) contain high amounts of polyphenols (anthocyanins, resveratrol, and proanthocyanidins) and thus confer health benefits. This study aimed to determine the protective effects and mechanism of action of bilberry extract (B-ext) and lingonberry extract (L-ext) and their active components against blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage. METHODS: Cultured murine photoreceptor (661 W) cells were exposed to blue LED light following treatment with B-ext, L-ext, or their constituents (cyanidin, delphinidin, malvidin, trans-resveratrol, and procyanidin B2). 661 W cell viability was assessed using a tetrazolium salt (WST-8) assay and Hoechst 33342 nuclear staining, and intracellular reactive oxygen species (ROS) production was determined using CM-H2DCFDA after blue LED light exposure. Activation of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor-kappa B (NF-kappaB), and LC3, an ubiquitin-like protein that is necessary for the formation of autophagosomes, were analyzed using Western blotting. Caspase-3/7 activation caused by blue LED light exposure in 661 W cells was determined using a caspase-3/7 assay kit. RESULTS: B-ext, L-ext, NAC, and their active components improved the viability of 661 W cells and inhibited the generation of intracellular ROS induced by blue LED light irradiation. Furthermore, B-ext and L-ext inhibited the activation of p38 MAPK and NF-kappaB induced by blue LED light exposure. Finally, B-ext, L-ext, and NAC inhibited caspase-3/7 activation and autophagy. CONCLUSIONS: These findings suggest that B-ext and L-ext containing high amounts of polyphenols exert protective effects against blue LED light-induced retinal photoreceptor cell damage mainly through inhibition of ROS production and activation of pro-apoptotic proteins.


Berry antioxidants: small fruits providing large benefits

Manganaris, G. A.; Goulas, V.; Vicente, A. R.; Terry, L. A.
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Small berry fruits are consumed because of their attractive colour and special taste, and are considered one of the richest sources of natural antioxidants. Their consumption has been linked to the prevention of some chronic and degenerative diseases. The term ‘berry fruits’ encompasses the so-called ‘soft fruits’, primarily strawberry, currants, gooseberry, blackberry, raspberry, blueberry and cranberry. The objective of this review is to highlight the nutraceutical value of berries and to summarize the factors affecting berry fruit antioxidants. Particular attention is given to postharvest and processing operation factors that may affect fruit phytochemical content. The structure-antioxidant relationships for phenolic compounds – the main group of antioxidants in this fruit group – are presented and major areas for future research are identified. (c) 2013 Society of Chemical Industry.


Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model

Hara, S.; Morita, R.; Ogawa, T.; Segawa, R.; Takimoto, N.; Suzuki, K.; Hamadate, N.; Hayashi, S. M.; Odachi, A.; Ogiwara, I.; Shibusawa, S.; Yoshida, T.; Shibutani, M.
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To investigate the protective effect of bilberry extracts (BBE) and enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We examined the modifying effect of co-administration with BBE or EMIQ on the liver tissue environment including oxidative stress responses, cell proliferation and apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth factor (TGF)-beta/Smad signalings on the induction mechanism of preneoplastic lesions during early stages of hepatocellular tumor promotion. PBO increased the numbers and area of glutathione S-transferase placental form (GST-P)+ liver cell foci and the numbers of Ki-67+ proliferating cells within GST-P+ foci. Co-administration of BBE or EMIQ suppressed these effects with the reductions of GST-P+ foci (area) to 48.9-49.4% and Ki-67+ cells to 55.5-61.4% of the PBO-promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid-reactive substances to 78.4% of the PBO-promoted cases. PBO increased the incidences of phospho-PTEN- foci, phospho-Akt substrate+ foci, phospho-Smad3- foci and Smad4- foci in GST-P+ foci. Both BBE and EMIQ decreased the incidences of phospho-PTEN- foci in GST-P+ foci to 59.8-72.2% and Smad4- foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the incidence of phospho-Akt substrate+ foci in GST-P+ foci to 75.2-75.7% of the PBO-promoted cases. These results suggest that PBO-induced tumor promotion involves facilitation of PTEN/Akt and disruptive TGF-beta/Smad signalings without relation to oxidative stress responses, but this promotion was suppressed by co-treatment with BBE or EMIQ through suppression of cell proliferation activity of preneoplastic liver cells.


Detection of anthocyanins/anthocyanidins in animal tissues

Aqil, F.; Vadhanam, M. V.; Jeyabalan, J.; Cai, J.; Singh, I. P.; Gupta, R. C.
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Dietary polyphenols may contribute to the prevention of several degenerative diseases, including cancer. Anthocyanins have been shown to possess potential anticancer activity. The aim of this study was to determine anthocyanin bioavailability in lung tissue of mice fed with a blueberry diet (5% w/w) for 10 days or a bolus dose (10 mg/mouse; p.o.) of native mixture of bilberry anthocyanidins. All five anthocyanidins present in the blueberry were detected in the lung tissue using improved methods. We analyzed effect of various solvents on stability of anthocyanins and their recovery from biomatrix. Detection of anthocyanins and their metabolites was performed by UPLC and LC-MS. Though, anthocyanins were not detected, cyanidin was detected by UPLC-PDA and other anthocyanidins by LC-MS, following conversion to anthocyanidins and selective extraction in isoamyl alcohol. The results show that anthocyanins can be detected in lung tissue of blueberry fed mice and thus bioavailable beyond the GI track.


Protective effect of Vaccinium myrtillus extract against UVA- and UVB-induced damage in a human keratinocyte cell line (HaCaT cells)

Calo, R.; Marabini, L.
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Recently, the field of skin protection have shown a considerable interest in the use of botanicals. Vaccinium myrtillus contains several polyphenols and anthocyanins with multiple pharmacological properties. The purpose of our study was to examine whether a water-soluble V. myrtillus extract (dry matter 12.4%; total polyphenols 339.3mg/100gfw; total anthocyanins 297.4mg/100gfw) was able to reduce UVA- and UVB-induced damage using a human keratinocyte cell line (HaCaT). HaCaT cells were pretreated for 1h with extract in a serum-free medium and then irradiated with UVA (8-40J/cm(2)) and UVB (0.008-0.72J/cm(2)) rays. All experiments were performed 24h after the end of irradiation, except for oxidative stress tests. The extract was able to reduce the UVB-induced cytotoxicity and genotoxicity (studied by comet and micronucleous assays) at lower doses. V. myrtillus extract reduced lipid peroxidation UVB-induced, but had no effect against the ROS UVB-produced. With UVA-induced damage V. myrtillus reduced genotoxicity as well as the unbalance of redox intracellular status. Moreover our extract reduced the UVA-induced apoptosis, but had no effect against the UVB one. V. myrtillus extract showed its free radical scavenging properties reducing oxidative stress and apoptotic markers, especially in UVA-irradiated cells.


The antibiofilm effect of blueberry fruit cultivars against Staphylococcus epidermidis and Pseudomonas aeruginosa

Zimmer, K. R.; Blum-Silva, C. H.; Souza, A. L.; Wulffschuch, M.; Reginatto, F. H.; Pereira, C. M.; Macedo, A. J.; Lencina, C. L.
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The antibiofilm and antibacterial properties against Pseudomonas aeruginosa and Staphylococcus epidermidis and chemical characterization of six hydroethanolic blueberry extracts (blueberry rabbiteye-Vaccinium virgatum) from different cultivars and means of propagation were investigated. The total flavonoid, anthocyanin, and phenolic contents were determined by specific and well-established methods. Among the cultivars, Briteblue showed the lowest content of all metabolites analyzed, while Bluegem showed the highest concentrations of these compounds. All the micropropagated cultivars presented the highest amounts of chlorogenic acid. The blueberry fruit extracts showed strong activity against S. epidermidis biofilm (up to 84% inhibition) without inhibiting bacterial growth. Likewise, Bluegem micropropagated extract, which had the highest anthocyanin, flavonoids, and phenolic compound content, demonstrated the highest S. epidermidis biofilm inhibitory effect. Finally, a linear correlation between the total phenolic content and the percentage of biofilm inhibition was observed.


A novel cobiotic containing a prebiotic and an antioxidant augments the glucose control and gastrointestinal tolerability of metformin: a case report

Greenway, F.; Wang, S.; Heiman, M.
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The gut microbiome plays an important role in regulation of metabolic processes, including digestion, absorption, and synthesis of bioactive molecules that signal physiological host mechanisms. Changes in the human gut microbiome are associated with type 2 diabetes and insulin resistance. Water-soluble dietary fibres like inulin and beta-glucan are fermented in the colon, and beta-glucan increases viscosity. Blueberries improve insulin sensitivity through an antioxidant effect. A cobiotic, consisting of purified inulin, sugar-free blueberry pomace extract, and an oat preparation of purified beta-glucan was developed for twice a day (bid) consumption as a smoothie drink to repair the gastrointestinal dysbiosis in type 2 diabetes. A 30-year-old man presented with new onset type 2 diabetes and a fasting glucose (FBS) of 375 mg/dl. Metformin 500 mg bid was initiated and increased to 1 g bid after 1 week. During the first 9 days of metformin treatment, he developed diarrhoea, but his FBS only dropped to 325 mg/dl. The cobiotic bid was added on the 9th day of metformin treatment, and after 2 days, his FBS dropped to 175 mg/dl. After 8 weeks on metformin and the cobiotic, his blood sugar was 100 mg/dl and he lost 5.5 kg. His stools became soft and formed on the cobiotic, reverted to diarrhoea when off of it for 2 days, and returned to normal on resuming the cobiotic formulation. Metformin is a safe, effective and inexpensive generic medication favouring weight loss, recommended as initial treatment of type 2 diabetes by the American Diabetes Association. However, a 20% incidence of diarrhoea limits its tolerability. A safe food supplement that can increase the efficacy of metformin and its tolerability, as occurred in this case report, would have significant positive public health consequences. A controlled clinical trial of the cobiotic with metformin is planned.


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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.