Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA.

The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study.

We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance.

To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects.

How Blueberry Works

PMID: 16441844 [PubMed – indexed for MEDLINE]

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 Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC.

United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA.

Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function.

The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

PMID: 10479711 [PubMed – indexed for MEDLINE]

Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.

Nutr Neurosci. 2003 Jun;6(3):153-62

Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B,

Morgan D.

USDA-HNRCA at Tufts University, 711 Washington Street, Boston, MA 02111, USA.

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.

PMID: 12793519 [PubMed – indexed for MEDLINE]

Blueberry as Antioxidant

A 2005 study which was published in the Journal of Agricultural food Chemicals compared the antioxidant properties of prepared blueberry with two anthocyanin-derived extracts. 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 ( J.Agric Food Chem. 2005 Aug 24;53(17):6896-902).

A 2005 study conducted by Han, Li, Mazza and Yang in Beijing, China examined the effect of anthocyanin rich fruit extract (blueberry, blacjcurrant, chokeberry) on PGE2 produced by Endothelia Cells. When stimulated by LPS, the production of PGE2 by endothelial cells were increased two fold. Blueberry extract inhibit such action. 100 microg/ml of Blueberry extract keeps the production of PGE2 in normal level. 700 microg/mL of Blackcurrant extract and 500 microg/ml Chokeberry extract also inhibit the releasing of PGE2 (Biochem Cell Biol. 2005 Oct;83(5):637-43).

A 2003 study, published in the Journal of Agriculture and Food Chemistry, compared the antioxidant ability of blueberries with that of red wine. Researchers found that a moderate drink (about 4 ounces) of white wine contained .47 mmol of free radical absorbing antioxidants, red wine provided 2.04 mmol, and a wine made from high-bush blueberries delivered 2.42 mmol of these protective plant compounds (Sanchez-Moreno C, Cao G, Ou B, Prior RL. Anthocyanin and proanthocyanidin content in selected white and red wines. Oxygen radical absorbance capacity comparison with nontraditional wines obtained from high-bush blueberry. J Agric Food Chem. Aug 13;51(17):4889-96).

Blueberry Extract Benefits

Clinical Abstracts

Antioxidant properties of prepared blueberry (Vaccinium myrtillus) extracts.

J Agric Food Chem. 2005 Aug 24;53(17):6896-902

Faria A, Oliveira J, Neves P, Gameiro P, Santos-Buelga C, de Freitas V, Mateus N.

Centro de Investigacao em Quimica, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.

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.


PMID: 16104817 [PubMed – indexed for MEDLINE]