Blueberry Clinical Report Summary

 

Blueberry is most common as an important supplement for improved eye health; and research supports its use in inhibiting cancer cells, cell mutations and its potential use in combating Alzheimer's disease.  As a fruit with many health-promoting antioxidants, blueberry has been shown to be in the top quartile of most common fruits in terms of Oxygen Radical Absorbance Capacity (ORAC) activity, which may explain why that even with inconclusive data, blueberry maintains its high reputation for eye health (1).  It is perhaps because of this activity as well that in vitro studies involving blueberries have also found blueberry beneficial in inhibiting breast and cervical cancer cells and in decreasing the production of cell mutation by mutagen in vitro by 24-49% (2, 3).  In regards to brain and memory, the work of Jim Joseph provides the most suggestive research; in a study, Joseph fed the equivalent of one cup per day to lab mice before running them through various tests.  At the end of the test, the group receiving blueberries showed significantly higher motor ability than the control group (4).  Another study by Joseph involved mice with similar cognitive loss to those suffering from Alzheimer's.  The study found that the group of mice who received blueberries showed less functional damage than the control group (5).

 

Blueberry Overview

 

Blueberries were originally used in tonics and teas by Native Americans, but the large amounts of antioxidants contained in this fruit are becoming popular today for a variety of health issues.   Aside from being high in natural dietary fiber and vitamin C, blueberries are rich in antioxidants like flavonols, beta-carotene, glutathione, anthocyanidins, and many other health-promoting antioxidants. The antioxidant anthocyanin, in particular, has shown especial properties that benefit eye health (6). Much like its antioxidant-rich cousin the bilberry, blueberries are often used to promote eye health, although most research that has been done in this field is not conclusive. While there is still a good deal of human research to be done on the efficacy of blueberries as a dietary supplement, work done on animal and in-vitro models has been promising.

 

Safe Use of Blueberry

 

There are no known drug or food interactions with blueberries, although those taking anti-diabetic drugs are not strongly recommended to consume the fruit in large quantities as it may lower blood glucose (7). Because blueberries are primarily used as a food, such as in baking, cooking, jams, jellies and various other preparations, there is no recommended supplementary dose, although one study used the equivalent of one cup per day in its research (4).

 

Clinical Studies for Eye Health

 

1. Antioxidant Properties in Blueberry

 

Antioxidant Properties of Prepared Blueberry (Vacciunium myrtillus) Extracts.  Faria A, Oliveira J, Neves P, Gameiro P, Santos-Buelga C, Freitas V, Mateus N.

A blueberry extract (A) and two anthocyanin-derived extracts (B and C) were prepared. The contents of polyphenols, flavonoids, anthocyanins, and anthocyanin-derived pigments of the extracts were determined for the first time. The pigment profile of blueberry extract A corresponded to 15 anthocyanins, whereas extract B was mainly composed of anthocyanin-pyruvic acid adducts of the blueberry original anthocyanins and extract C was mainly composed of the respective vinylpyranoanthocyanin-catechins (portisins). The extracts' abilities to inhibit lipid peroxidation, induced by 2,2'-azobis(2-methyl-propanimidamide) dihydrochloride in a liposomal membrane system were examined. The antioxidant capacities of the extracts were evaluated through monitoring oxygen consumption and by measuring the formation of conjugated dienes. All of the extracts provided protection of membranes against peroxyl radicals by increasing the induction time of oxidation. This effect increased with the polyphenol content and with the structural complexity of the anthocyanin-derived pigments of the extracts. The pigments present in extract C seemed to induce a higher protection of the liposome membranes toward oxidation. In addition, the antiradical properties and the reducing power of the extracts were determined by using DPPH and FRAP methods, respectively. The results from these assays were in agreement with those obtained with the liposome membranes.

 

Oxygen Radical Absorbance Capacity (ORAC) and Phenolic and Anthocyanin Concentrations in Fruit and Leaf Tissues of Highbush Blueberry. Ehlenfeldt MK, Prior RL.

Antioxidant capacity, as measured by oxygen radical absorbance capacity (ORAC), and total phenolic and total anthocyanin contents were evaluated in fruit tissues of 87 highbush blueberry (Vaccinium corymbosum L.) and species-introgressed highbush blueberry cultivars. ORAC and phenolic levels were evaluated in leaf tissues of the same materials. Average values for ORAC, phenolics, and anthocyanins in fruit were 15.9 ORAC units, 1.79 mg/g (gallic acid equivalents), and 0.95 mg/g (cyanidin-3-glucoside equivalents), respectively. Cv. Rubel had the highest ORAC per gram of fresh weight values, at 31.1 units, and cv. Elliott had the highest values on the basis of ORAC per square centimeter of surface area. In leaf tissue, values for both ORAC and phenolics were significantly higher than in fruit tissue, with mean values of 490 ORAC units and 44.80 mg/g (gallic acid equivalents), respectively. Leaf ORAC had a low, but significant, correlation with fruit phenolics and anthocyanins, but not with fruit ORAC. An analysis of ORAC values versus calculated midparent values in 11 plants from the 87-cultivar group in which all parents were tested suggested that, across cultivars, ORAC inheritance is additive. An investigation of ORAC values in a family of 44 cv. Rubel × Duke seedlings showed negative epistasis for ORAC values, suggesting Rubel may have gene combinations contributing to ORAC that are broken up during hybridization.

 

2. Blueberry and Cancer Inhibition

 

Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells. David E. Wedge, Kumudini M. Meepagala, James B. Magee, S. Hope Smith, George Huang, Lyndon L. Larcom.

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 70% acetone/water at ambient temperature. Each extract was tested separately for in vitro anticancer activity on cervical and breast cancer cell lines. Ethanol extracts from all four fruits strongly inhibited CaSki and SiHa cervical cancer cell lines and MCF-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 carcinogens.

 

3. Blueberry and Brain and Memory

 

Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B, Morgan D.

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.

 

Blueberry References

 

1. Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL. Lipophilic and hydrophilic antioxidant capacities of common foods in the United States. Journal of Agricultural and Food Chemistry, 2004, 52:4026-4037.
2. David E. Wedge, Kumudini M. Meepagala, James B. Magee, S. Hope Smith, George Huang, Lyndon L. Larcom. Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells. Journal of Medicinal Food. 2001, 4(1): 49-51.
3. S. Hope Smith, Patricia L. Tate, George Huang, James B. Magee, Kumudini M. Meepagala, David E. Wedge, Lyndon L. Larcom. Antimutagenic Activity of Berry Extracts. Journal of Medicinal Food. 2004, 7(4): 450-455.
4. Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci. 1999 Sep 15;19(18):8114-21.
5. Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B, Morgan D. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci. 2003 Jun;6(3):153-62.
6. Zadok D, Levy Y, GLovinsky Y. The effect of anthocyanosides in a multiple oral dose on night vision. Eye 1999, vol. 13 (6), pp. 734-736 (16 ref).
7. Cignarella A, Nastasi M, Cavalli E, Puglisi L. Novel lipid-lowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. Thromb Res 1996;84:311-22.
8. Faria A, Oliveira J, Neves P, Gameiro P, Santos-Buelga C, Freitas V, Mateus N. Antioxidant Properties of Prepared Blueberry (Vacciunium myrtillus) Extracts.  J Agric Food Chem, 2005; 53 (17): 6896-6902.
9. Ehlenfeldt MK, Prior RL. Oxygen Radical Absorbance Capacity (ORAC) and Phenolic and Anthocyanin Concentrations in Fruit and Leaf Tissues of Highbush Blueberry. J Agric Food Chem 2001; 49 (5): 2222-2227.