Health Benefits of Berries: Blueberries

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.

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.

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.

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.

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

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.

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.

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.

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.

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