Health Benefits of Berries: Blueberries

Anti-Diabetic Properties of the Canadian Lowbush Blueberry Vaccinium Angustifolium Ait.
Martineau, L. C. ; Couture, A. ; Spoor, D. ; Benhaddou-Andaloussi, A. ; Harris, C. ; Meddah, B. ; Leduc, C. ; Burt, A. ; Vuong, T. ; Le, P. M. ; Prentki, M. ; Bennett, S. A. ; Arnason, J. T. ; Haddad, P. S.
Phytomedicine, 2006, 13(9-10), 612-623

Differential Effects of Blueberry Proanthocyanidins on Androgen Sensitive and Insensitive Human Prostate Cancer Cell Lines
Schimidt, B. M. ; Erdman, J. W. ; Lila, M. A.
Cancer Letters, 2006, 231(2), 240-246

Total Antioxidant Power in Sled Dogs Supplemented with Blueberries and the Comparison of Blood Parameters Associated with Exercise
Dunlap, K. L.; Reynolds, A. J.; Duffy, L. K.
Comparative Biochemistry and Physiology A-Molecular & Integrative Physiology, 2006, 143(4), 429-434

Blueberry Polyphenols Increase Lifespan and Thermotolerance in Caenorhabditis Elegans
Wilson, M. A.; Shukitt-Hale, B.; Kalt, W.; Ingram, D. K.; Joseph, J. A.; Wolkow, C. A.
Aging Cell, 2006, 5(1), 59-68(10)

Effects of Phenolic Compounds in Blueberries and Muscadine Grapes on Hepg2 Cell Viability and Apoptosis
Yi, W.; Akoh, C. C.; Fischer, J.; Krewer, G.
Food Research International, 2006, 39(5), 628-638

Blueberry Supplemented Diet Reverses Age-Related Decline in Hippocampal HSP70 Neuroprotection
Galli, R. L.; Bielinski, D. E. ; Szprengiel, A. ; Shukitt-Hale, B. ; Joseph, J. A.
Neurobiology of Aging, 2006, 27(2), 344-350

Safety and Whole-Body Antioxidant Potential of a Novel Anthocyanin-Rich Formulation of Edible Berries
Bagchi, Debasis; Roy, Sashwati; Patel, Viren; He, Guanglong; Khanna, Savita; Ojha, Navdeep; Phillips, Christina; Ghosh, Sumona; Bagchi, Manashi; Sen, Chandan
Molecular and Cellular Biochemistry2006, 281(1-2), 197-209

Phenolic Compounds from Blueberries Can Inhibit Colon Cancer Cell Proliferation and Induce Apoptosis
Yi, W. G.; Fischer, J.; Krewer, G.; Akoh, C. C.
Journal of Agricultural and Food Chemistry, 2005, 53(18), 7320-7329

Reversing the Deleterious Effects of Aging on Neuronal Communication and Behavior: Beneficial Properties of Fruit Polyphenolic Compounds
Joseph, J. A.; Shukitt-Hale, B.; Casadesus, G.
American Journal of Clinical Nutrition , 2005, 81(1), 313S-316S Suppl.

Blueberries in the American Diet
Lewis, N. M.; Ruud, J.
Nutrition Today, 2005, 40(2), 92-96


This article reviews the history and nutritional attributes of the native American blueberry and describes the available research to date on the relationship between blueberries and health and disease.

Reversing the Deleterious Effects of Aging on Neuronal Communication and Behavior: Beneficial Properties of Fruit Polyphenolic Compounds
Joseph JA; Shukitt-Hale B; Casadesus G 
The American journal of clinical nutrition, 2005, 81(1) Supp, 313S-316S


Despite elegant research involving molecular biology studies and determination of the genetic mechanisms of aging, practical information on how to forestall or reverse the deleterious effects of aging may be years away. If this is the case, then it is prudent to try to establish other methods that can be used now to alter the course of aging. Numerous epidemiologic studies have indicated that individuals who consume diets containing large amounts of fruits and vegetables may reduce their risk for developing age-related diseases such as Alzheimer disease. Research from our laboratory suggested that dietary supplementation with fruit or vegetable extracts high in antioxidants (eg, blueberry or spinach extracts) might decrease the enhanced vulnerability to oxidative stress that occurs in aging. These reductions might be expressed as improvements in motor and cognitive behavior. Additional research suggested that mechanisms in addition to antioxidant and antiinflammatory activities might be involved in the beneficial effects of these extracts; the most important of these might be their ability to increase cellular signaling and neuronal communication.

Wild Blueberry-Rich Diets Affect the Contractile Machinery of the Vascular Smooth Muscle in the Sprague-Dawley Rat
Norton, Cynthia; Kalea, Anastasia Z.; Harris, Patrick D.; Klimis-Zacas, Dorothy J. 
Journal of Medicinal Food, 2005, 8(1), 8-13


Weanling male SpragueDawley rats were randomly fed a control diet (AIN-93) (C) or a blueberry diet (B) for 13 weeks, or a reverse diet (R) (C diet for 13 weeks, switched to the B diet for 8 weeks). Aortas were excised, and two intact and two endothelium-denuded rings were immersed in tissue baths containing physiological salt solution at 37°C and aerated with 95% O2 and 5% CO2 (pH 7.4). Following equilibration and preconditioning under 1.5-g preload, cumulative doseresponse curves were generated with six doses of the 1-adrenergic receptor-selective agonist L-phenylephrine (L-Phe, 1083 106 M) and relaxed with one dose of acetylcholine (3 106 M) to assess intact endothelium. The maximum force of contraction (Fmax) and vessel sensitivity (pD2) were determined in intact and endothelium-denuded rings. A two-way analysis of variance test revealed that blueberry-fed animals (B and R diets) developed a significantly lower F max (0.873 ± 0.0463 and 0.9266 ± 0.0463 g, respectively) when contracted with L-Phe, compared with the animals on the C diet (1.109 ± 0.0463 g) (P < .05). The pD2 of the intact rings was not significantly different among diet groups. Additionally, diet did not significantly affect the mean F max or pD2 of endothelium-denuded rings. Our results indicate for the first time that wild blueberries incorporated into the diet affect the vascular smooth muscle contractile machinery by suppressing the 1-adrenergic receptor agonist-mediated contraction while having no effect on membrane sensitivity of the endothelial or vascular smooth muscle cell layer. Furthermore, their mechanism of action seems to be accomplished through an endothelium-dependent pathway.

Bluberry Extract Enhances Survival of Intraocular Hippocampal Transplants
Willis L; Bickford P; Zaman V; Moore A; Granholm AC 
Cell Transplantation, 2005, 14(4), 213-23


Transplantation of neural tissue has been explored as a potential therapy to replace dead or dying cells in the brain, such as after brain injury or neurodegenerative disease. However, survival of transplanted tissue is poor, especially when the transplant recipient is of advanced age. Recent studies have demonstrated improvement of neuronal deficits in aged animals given a diet supplemented with blueberry extract. The present study focuses on the survival of fetal hippocampal transplants to young (4 months) or middle-aged (16 months) animals with or without dietary supplementation with blueberry extract. Results indicate that fetal hippocampus transplanted to middle-aged host animals exhibits poor survival characterized by reduced growth and compromised tissue organization. However, when middle-aged animals were maintained on a diet supplemented with 2% blueberry extract, hippocampal graft growth was significantly improved and cellular organization of grafts was comparable to that seen in tissue grafted to young host animals. Thus, the data suggest that factor(s) in blueberries may have significant effects on development and organization of this important brain region.

Blueberry Supplemented Diet: Effects on Object Recognition Memory and Nuclear Factor-Kappa B Levels in Aged Rats
Goyarzu, P.; Malin, D. H.; Lau, F. C.; Taglialatela, G.; Moon, W. D.; Jennings, R.; Moy, E.; Moy, D.; Lippold, S.; Shukitt-Hale, B.
Nutritional Neuroscience, 2004, 7(2), 75-84


It has been reported that an antioxidant-rich, blueberry-supplemented rat diet may retard brain aging in the rat. The present study determined whether such supplementation could prevent impaired object recognition memory and elevated levels of the oxidative stress-responsive protein, nuclear factor-kappa B (NF-B) in aged Fischer-344 rats. Twelve aged rats had been fed a 2% blueberry supplemented diet for 4 months prior to testing. Eleven aged rats and twelve young rats had been fed a control diet. The rats were tested for object recognition memory on the visual paired comparison task. With a 1-h delay between training and testing, aged control diet rats performed no better than chance. Young rats and aged blueberry diet rats performed similarly and significantly better than the aged control diet group. Levels of NF-B in five brain regions of the above subjects were determined by western blotting assays. In four regions, aged control diet rats had significantly higher average NF-B levels than young animals on the control diet. In four regions, aged blueberry diet rats had significantly lower levels of NF-B than aged control diet rats. Normalized NF-B levels (averaged across regions and in several individual regions) correlated negatively and significantly with the object memory scores

Blueberry Supplementation Enhances Signaling and Prevents Behavioral Deficits in an Alzheimer Disease Model
Joseph, J. A.; Denisova, N. A.; Arendash, G.; Gordon, M.; Diamond, D.; Shukitt-Hale, B.; Morgan, D.
Nutritional Neuroscience, 2003, 6(3), 153-162


Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP+PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.

The Effect of Freeze-Dried Blueberries on N-nitrosomethylbenzylamine Tumorigenesis in the Rat Esophagus
Aziz R.M.; Nines R.; Rodrigo K.; Harris K.; Hudson T.; Gupta A.; Morse M.; Carlton P.; Stoner G.D.
Pharmaceutical Biology (Formerly International Journal of Pharmacognosy), 2002, 40(1), Suppl., 43-49


Previous studies in our laboratory have demonstrated the inhibitory effects of freeze-dried strawberries and black raspberries on N -nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. In addition, organic extracts from strawberries and black raspberries were shown to inhibit benzo[a]pyrene-induced transformation of Syrian hamster embryo (SHE) cells in vitro . In the present study, we evaluated blueberries for their ability to inhibit NMBA tumorigenesis in the rat esophagus. Blueberries, like strawberries and black raspberries, contain multiple cancer preventive agents, and are among the most heavily consumed berries in the American diet. They differ from strawberries and black raspberries, however, in that they contain only small amounts of the chemopreventive agent ellagic acid. Two weeks prior to NMBA treatment, animals were placed on a control diet or diets containing 5 and 10% freeze-dried blueberries. The animals were fed berry diets or control diets for the duration of the study. NMBA treatment was once per week for 15 weeks. At 25 weeks, 5 and 10% blueberries produced no significant differences in tumor incidence, multiplicity, or size when compared to NMBA-treated controls. In addition, blue-berries did not reduce the formation of NMBA-induced O 6 -methylguanine adducts in esophageal DNA when fed at 10% of the diet. Blueberries appear to lack components that inhibit the initiation and progression of NMBA-induced tumorigenesis in the rat esophagus.

Feeding Rats Diets Enriched in Lowbush Blueberries for Six Weeks Decreases Ischemia-Induced Brain Damage
Sweeney, M.I.; Kalt, W.; MacKinnon, S.L.; Ashby, J.; Gottschall-Pass, K.T. 
Nutritional Neuroscience, 2002, 5, 6, 427-431

Oxidative stress is an important element in the etiology of ischemic stroke. Lowbush blueberries (Vaccinium angustifolium Aiton) have a high antioxidant capacity and thus we determined whether consumption of lowbush blueberries would protect neurons from stroke-induced damage. Rats were fed AIN-93G diets containing 0 or 14.3% blueberries (g fresh weight/100 g feed) for 6 weeks. Stroke was then simulated by ligation of the left common carotid artery (ischemia), followed by hypoxia. One week later, plasma and urine were collected, and neuronal damage in the hippocampus was determined histologically. In control rats, hypoxia-ischemia resulted in 40 +/- 2% loss of neurons in the hippocampus of the left cerebral hemisphere, as compared to the right hemisphere. Rats on blueberry-supplemented diets lost only 17 +/- 2% of neurons in the ischemic hippocampus. Neuroprotection was observed in the CA1 and CA2 regions, but not CA3 region, of the hippocampus. The blueberry diet had no detectable effects on the plasma or urine oxygen radical absorbance capacity (ORAC) or plasma lipids. We conclude that consumption of lowbush blueberries by rats confers protection to the brain against damage from ischemia, suggesting that inclusion of blueberries in the diet may improve ischemic stroke outcomes.

Fruit Polyphenolics and Brain Aging: Nutritional Interventions Targeting Age-Related Neuronal and Behavioral Deficits
Galli RL; Shukitt-Hale B; Youdim KA; Joseph JA 
Annals of the New York Academy of Sciences, 2002, no. 959, 128-32


Nutritional interventions, in this case, increasing dietary intake of fruits and vegetables, can retard and even reverse age-related declines in brain function and in cognitive and motor performance in rats. Our lab has shown that as Fischer 344 rats age their brains are increasingly vulnerable to oxidative stress. Dietary supplementation with fruit or vegetable extracts high in antioxidants (e.g., blueberry, BB, spinach, respectively) can decrease this vulnerability to oxidative stress as assessed in vivo by examining reductions in neuronal signaling and behavioral deficits and in vitro via H2O2-induced decrements in striatal synaptosomal calcium buffering. Examinations have also revealed that BB supplementations are effective in antagonizing other age-related changes in brain and behavior, as well as decreasing indices of inflammation and oxidative stress in gastrocnemius and quadriceps muscles. In ongoing studies we are attempting to determine the most effective BB polyphenolic components. To date, the anthocyanins show the most efficacy in penetrating the cell membrane and in providing antioxidant protection. In sum, our results indicate that increasing dietary intake of fruits and vegetables high in antioxidant activity may be an important component of a healthy living strategy designed to maximize neuronal and cognitive functioning into old age.

Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells
Wedge, D. E.; Meepagala, K. M.; Magee, J. B.; Smith, S. H.; Huang, G.; Larcom, L. L.
Journal of Medicinal Food, 2001, 4(1), 49-52


Freeze-dried fruits of two strawberry cultivars, Sweet Charlie and Carlsbad, and two blueberry cultivars, Tifblue and Premier, were sequentially extracted with hexane, 50% hexane/ethyl acetate, ethyl acetate, ethanol, and 80% acetone/water at ambient temperature. Solvents were then evaporated at 40° C. The extracts were tested against in vitro cultures of two aggressive cervical cancer cell lines (CaSki and SiHa) and two breast cancer cell lines with different requirements for estrogen (MCF-7 and T47-D). The metabolic activity of the cultures was assessed with MTS viability assay. The Ames assay for mutagenesis was used to evaluate the anticarcinogenic effects of phytochemicals with a 90% accuracy. Ethanol extracts from all four fruits strongly inhibited CaSki and SiHa cervical cancer cell lines and MCFF-7 and T47-D breast cancer cell lines. An unfractionated aqueous extract of raspberry and the ethanol extract of Premier blueberry significantly inhibited mutagenesis by both direct-acting and metabolically activated carcinogenesis.

Health Functionality of Blueberries
Kalt, Willy; Dufour, Dominique
HortTechnology, 1997, 7(3), 216


Blueberries (Vaccinium sp.) have a long history of use in native and folk medicine in North America and Europe. Today the European blueberry (bilberry) is used in a variety of pharmaceutical and food supplement products that are recommended for treating blood vessel disorders and ophthalmological conditions. Anthocyanins, the pigments that impart the blue colour to blueberries, are considered the active ingredient in bilberry health products, although other related flavonoids are biomedically useful. Vaccinium flavonoids are antioxidants and are also recognized for their anticarcinogenic properties and usefulness in treating urinary tract infections. The most immediate, and perhaps greatest, opportunity for a health market for North American blueberries may be in promoting blueberries as a healthy food. As researchers continue to explore the biomedical usefulness of blueberries, the bluberry food industry should strive to retain the healthful phytochemical in their products