You love 'em in pancakes, muffins, pies, and cobblers. Now it turns out that blueberries may actually be able to reverse the aging process—at least it does in rats!

Even when there's no disease, neurological changes that occur as we age can cause cognitive, motor, and behavioral problems. Recent research suggests that one important reason for these changes is the body's reduced ability to fight oxidative stress, damage to cells caused by the by-products of converting oxygen into energy. Oxidative stress has also been linked to the decline in patients with Alzheimer's and Parkinson's disease.

Researchers have been looking at the phytochemicals in plants as a source of antioxidants, substances that help fight oxidative stress. A study last year at the U.S. Department of Agriculture's Human Nutrition Research Center on Aging at Tufts University in Boston showed that when adult rats were fed chow supplemented with fruits and vegetables, the natural decline usually seen with aging was slowed. Fruits and vegetables have also been shown to help protect humans from cancer and cardiovascular disease.

In the latest study, the Tufts researchers worked again with rats—this time, elderly male rats the age-equivalent of men in their 70s. Forty of these rats were randomly assigned to receive either regular chow or chow supplemented by extract from blueberries, strawberries, or spinach. The four groups of rats were tested on cognitive and motor tasks after eight weeks on their special diets.

Rats who got blueberry supplements out-performed the other groups on tests of coordination and balance. All the rats who received supplemented chow performed better than the control group on tests of learning and memory. When the researchers analyzed the rats' brain tissue, they found that those who got supplements had better neural functioning.

The researchers hypothesized that in addition to protecting against oxidative stress, fruits and vegetables may allow nutrients to pass through the cell membranes more easily, helping to improve neural functioning.

Noting that this is the first study to find that antioxidant-rich fruits and vegetables can actually reverse aspects of the aging process, the researchers concluded that "nutritional intervention with fruits and vegetables may play an important role in reversing the deleterious effects of aging on neuronal function and behavior." Their report was published the September issue of the "Journal of Neuroscience."

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Blueberries: New Thrills for Those Over the Hill

For centuries, people have enjoyed blueberries for their flavor and color. In a new research study,animals fed a blueberry extract diet, rich in naturally-derived antioxidants, showed fewer age-related motor changes and outperformed their study counterparts on memory tests.
Indeed, blueberries and other foods containing antioxidants may act to protect the body against damage from oxidative stress, one of several biological processes implicated in aging and in the development of a number of neurodegenerative diseases. The National Institute on Aging (NIA) and the U.S. Department of Agriculture funded the study.

In the study, three groups of older rats were fed an 8-week-long diet supplemented with fruit or vegetable extracts with potential antioxidant effects. A fourth group of animals did not receive the special diet. The group of animals that received the supplements showed some improvement on key indicators of age-related decline.

The study was conducted by James Joseph, Ph.D. of the U.S. Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University in Boston, and Paula C. Bickford, Ph.D. of the University of Colorado Health Sciences Center and the Department of Veterans Affairs Medical Center in Denver.

The animals that received supplements were given either blueberry, strawberry, or spinach extracts. Investigators found that the group of rats that was fed blueberry supplements came out on top in tests of balance and coordination. The two groups given strawberry or blueberry supplements showed the most compelling evidence of protection against oxidative stress in their brains. On tests of working memory, all three groups receiving supplements outperformed their control counterparts. fn addition, the groups receiving supplements all showed signs of the presence of vitamin E, a key antioxidant, in their brains.

"The exciting finding from this study is the potential reversal of some age-related impairments in both memory and motor coordination, especially with blueberry supplements," said Molly Wagster, Ph.D., a Health Scientist Administrator with the NIA's Neuroscience and Neurospsychology of Aging Program. "For these animals at least, investigators were able to produce a noticeable improvement within a relatively short period of time. A next important step in the research will be to see if the improvements are long lasting."

When a cell converts oxygen into energy, tiny molecules called free radicals are made. When produced in normal amounts, free radicals work to rid the body of harmful toxins, thereby keeping it healthy. When produced in toxic amounts, however, free radicals damage the body's cellular machinery, resulting in cell death and tissue damage. This process is called oxidative stress.

"Whether results found in this study will also prove true for humans remains to be seen," says Marcelle Morrison-Bogorad, Ph.D., who directs the NIA's Neuroscience and Neuropsychology of Aging Program. "The only way to determine whether particular food ingredients actually work to slow age-related cognitive decline in humans as well is to conduct controlled clinical trials." The NIA has recently funded additions to two ongoing clinical trials testing whether a number of over-the-counter agents, including antioxidants such as vitamin E, influence the rate of cognitive decline in older women.

Plant chemicals, called phytochemicals, are present in fruits and vegetables and may have additional beneficial propertie,5 beyond the antioxidant activity. The authors believe that
the phytochemicals present in blueberries, strawberries, and spinach may have properties that increase cell membrane fluidity, allowing important nutrients and chemical signals to pass in and out of the cell, thereby reducing inflammatory processes in tissues.

Recent studies suggest that a diet rich in fruits and vegetables---natural dietary sources of antioxidants-- may have a beneficial anti-cancer effect. Orange and yellow vegetables, fruits, and whole grains are all rich in natural antioxidants. Several currently popular substances, including vitamin E, beta carotene, vitamin C, and selenium, are also thought to have antioxidant effects in the body, but how they actually work is not entirely understood. Scientists are studying the effectiveness of these and other agents for their antioxidant properties and for their ability to protect cells against damage and death associated with oxidative stress.

"When we hear these promising results, we also may hear an echo of our wise mothers' voices-Eat your fruits and vegetables," says Dr. Wagster.

The National Institute on Aging, part of the National Institutes of Health (NIH), located in Bethesda, Maryland, leads the Federal effort supporting basic, clinical, epidemiological and social research on aging and the special needs of older people.

BLUEBERRIES

Blueberry Health Benefits : From research labs all across the country and the world, there is growing evidence that blueberries could be powerful little disease fighters.  Here is what we have learned so far.  (summary)

Anti-Aging.   In another USDA Human Nutrition Center (HNRCA) lab, neuroscientists discovered that feeding blueberries to laboratory rats slowed age-related loss in their mental capacity, a finding that has important implications for humans.  Again, the high antioxidant activity of blueberries probably played a role. 

Disease Prevention - Blueberries may reduce the build up of so called "bad" cholesterol that contributes to cardiovascular disease and stroke, according to scientists at the University of California at Davis.  Antioxidants are believed to be the active component. 

Eating blueberries may help you remember where you placed your car keys—important findings if you’d like to keep Alzheimer’s and heart disease at bay.

The research was presented Monday, August 19, at the ACS national meeting in Boston.

In one study, Jim Joseph, director of the neuroscience laboratory in the USDA Human Nutrition Center (HNRCA) , fed blueberry extractions—the equivalent of a human eating one cup of blueberries a day—to mice and then ran them through a series of motor skills tests.

He found that the blueberry-fed mice performed better than their control group counterparts in motor behavioral learning and memory, and he noticed an increase in exploratory behavior. When he examined their brains, he found a marked decrease in oxidative stress in two regions of the brain and better retention of signal-transmitting neurons compared with the control mice.

The chemical that appears responsible for this neuron protection, anthocyanin also gives blueberries their color and might be the key component of the blueberry’s antioxidant and anti-inflammatory properties. Blueberries, along with other colorful fruits and vegetables, test high in their ability to subdue oxygen free radicals. These oxygen radicals, which can damage cell membranes and DNA through a process known as oxidative stress, are blamed for many of the dysfunctions and diseases associated with aging.

These findings could become increasingly important as the U.S. population ages. It is projected that by 2050, more than 30% of Americans will be over 65 and will have the decreased cognitive and motor function that accompanies advanced age. Joseph is currently testing the effects of blueberries on humans. Preliminary results show that people who ate a cup of blueberries a day have performed 5–6% better on motor skills tests than the control group.

The following summarizes some of the published research in the area of nutraceuticals and health.

The belief that food products have medicinal properties has been celebrated in folk medicine for centuries. Today food properties are being explored by the medical and scientific fields. Some cultures have long valued many naturally occurring substances believed to have preventative and therapeutic value. In the United States, nutraceuticals are part of a rapidly expanding area of biomedical research, generating considerable interest among consumers, manufacturers, and regulators alike. This is a progressive area; the field is continually conducting studies and discovering possible benefits.

Though blueberries themselves are not a cure-all, they contain a number of substances which are thought to have health benefits. These substances include, but are not limited to fructose, fiber, vitamins and antioxidants. Antioxidants thus far, seem to have the most conclusive role in the prevention/ delaying of such diseases as cancer, heart disease and the aging process however, a limited number of studies, especially long term and on human beings, are not available at this time.

Nutraceutical- Any substance that may be considered a food or part of a food that provides health benefits, including the prevention or treatment of disease. They range from isolated nutrients to genetically engineered "designer foods".

The term "nutraceutical" was coined by The Foundation for Innovation in Medicine in 1989 to provide a name for this area of biomedical research, and has since become part of the standard lexicon in both the medical - scientific community and in the food and drug industries (The Foundation for Innovation in Medicine, 1991). The wide acceptance of this term itself provides ample testimony that a new product category is ready to be born. Largely based on their cultural and historical beliefs, Japan and many European countries hold established places in the international marketplace for nutraceuticals. They have long valued many natural substances that hold preventative and therapeutic values, and have a rapidly expanding body of research to back them up. The United States, however, is at the beginning of this process. Nutraceuticals have become a focal point for updating the U.S. economic and regulatory system in response to worldwide medical and scientific trends.

Free Radicals - Antioxidants:

Antioxidants are thought to help protect the body against the damaging effects of free radicals and the chronic diseases associated with the aging process (Ames, 1993). Fresh fruits (blueberries) and vegetables contain many of these naturally occurring antioxidants such as vitamins A, C and E.

Blueberries contain 0.04 mg of beta-carotene, 13 mg of vitamin C and 1 mg vitamin E per 100 g of blueberries.  Blueberries contain 10 RE (Retinol Equivalents, a unit of vitamin A) of vitamin A per 100 grams of blueberries.  The RDA for vitamin A is 1000 RE for men and 800 RE for women.  In addition, blueberries contain anthocyanins and phenolics that can also act as antioxidants.
 

Ellagic and Folic Acid:

Although their modes of action is still poorly understood, it appears that these acids may inhibit cancer initiation. Ellagic acid (in its most biologically active form, ellagitannin) is found in blueberries and some other berries. (Stoner, 1989).

Folic acid may help guard against cervical cancer (Toufexis, 1992), and may benefit the fetus during pregnancy. Blueberries contain 6 ug./ 100g of folic acid. The RDA for women is 180 ug.

Other Substances: Antibacterial Agents

In Sweden, dried blueberries are used to treat childhood diarrhea (Kowalchuk, 1976). This use is attributed to anthocyanosides, a natural substance found in blueberries which is believed to be "lethal" to E. Coli (a bacteria sometimes linked to the infection).

Fiber: Multiple Health Benefits

Considerable evidence collected over the last 20 years has proven the numerous advantages of high fiber diets (Potter, 1986). Blueberries are a source of dietary fibers: 2.7g/100g. A diet containing 25g. of dietary fiber per day is generally recommended.

Blueberries contain a variety of compounds. These include: antioxidants, anthocyanosides, bacterial inhibitors, folic acid, vitamins A and C, carotenoids, ellagic acid, folic acid, and dietary fibers. The significance of their presence and modes of action remain largely unexplored.

Sources:

1. The Foundation for Innovative Medicine, The Nutraceutical Initiative: A Proposal for Economic and Regulatory Reform. December1991
2. Kowalchuk J. Antiviral Activity of Fruit Extracts. J Food Science. 41: 1013-1017, 1976
3. Potter N. Food Science 4^th ed. Conn: A VI 1986
4. Potter N. Do Functional Foods Raise the Health Threshold. The World of Ingredients. Oct.-Nov. 54-55, 1994
5. Stoner G.. Ellagic acid: A Naturally Occurring Inhibitor of Chemically-Induced Cancer. 1989
6. Toufexis A. The New Scoop on Vitamins. Time 139(14). 1992
7. Ames BN, Shigenaga MK, Hagen TM. Oxidants antioxidants, and the degenerative diseases of aging.  Proc. Natl. Acid. Sci. USA 90:7915-7922, 1993.
   

Total antioxidant capacity, measured as ORAC, ranged from a low of 13.9 to 44.6 mmol TE/g fresh berries in the acetonitrile extracts of the different cultivars of blueberries (Tables 1 and 2). The overall mean of all commercially available cultivars was 24.0±2.0. The highbush varieties of "Rancocas", "Rubel", "Bladen", and the late harvest on the rabbiteye cultivars "Tifblue" and "Brightwell" had ORAC values (i.e. 32.4, 37.1, 42.3, 37.8, and 34.3 respectively) that approached that observed for the Bilberry (44.6). There appears to be two clusters of ORAC values in the lowbush blueberries. The first included lowbush from Prince Edward Island and Nova Scotia, and Fundy lowbush blueberries which were relatively high in ORAC (mean: 41.8), anthocyanins, and total phenolics. The second cluster included lowbush from Maine, "Cumberland", and "Blomidin"lowbush blueberries which were lower in ORAC (mean: 27.5). At this point, it is not clear as to the source (genetics, location, maturity, etc.) of this variation. Anthocyanins in the lowbush blueberries were not as high as the bilberry relative to ORAC values as reflected in the ratio of anthocyanins to ORAC (0.37 vs. 0.57).

The relationship between ORAC and total anthocyanin or total phenolic content in all these different blueberry samples is presented in Figures 1 and 2. A significant linear relationship was observed between ORAC and total anthocyanin or total phenolic content. The correlation coefficient was much higher between ORAC and total phenolics (r_xy = 0.85) compared to ORAC and anthocyanins (r_xy = 0.77) (Figures 1 and 2).

Ascorbate concentrations (1.3-16.4 mg/100 g) showed a significant variability between cultivars and species. Although most of the samples had an ascorbate concentration between 9-16 mg/100 g, no consistent pattern emerged relative to ORAC or anthocyanins or to total phenolics. Using an ORAC value for ascorbate of 5.6 mmol TE/g, it was calculated that the antioxidant capacity contributed by ascorbate to the total antioxidant capacity, measured as ORAC, was 2.3% for the highbush and rabbiteye berries. Ascorbate in lowbush berries contributed only 1.5% while in the bilberry sample, the contribution of ascorbate to ORAC was only 0.2%. Thus, it is clear that ascorbate does not make a major contribution to the antioxidant capacity of any of the blueberries sampled. In calculations with other fruits, ascorbate has generally contributed less than 10% of the total antioxidant capacity (Wang et al., 1996).

Maturity effects: Maturity at harvest had a marked effect on ORAC, total anthocyanins and total phenolics of the berries, for the "Brightwell" and "Tifblue" cultivars of rabbiteye blueberries which were the only two cultivars evaluated. Berries harvested immediately after turning blue had lower ORAC and total anthocyanins than berries well matured that were harvested 49 days later. ORAC and total anthocyanins increased 224% and 261% respectively, in the "Brightwell" cultivar, while in "Tifblue" they increased 164% and 176% respectively, with increasing maturity. Total phenolics increased by 169% and 113% in the "Brightwell" and "Tifblue" cultivars, respectively, with increased maturity.

The results presented in this presentation represent the first data on the total antioxidant capacity in blueberries. On a fresh weight basis, blueberries have the highest antioxidant capacity of all the fresh fruits and vegetables tested to date. However, considerable variability seemed to exist among the initial analyses that were performed on blueberry samples obtained from the commercial supermarket, suggesting that variation exists in the antioxidant capacity of different varieties of the Vaccinium species. We have previously analyzed the antioxidant capacity of anthocyanins (Wang et al., 1997) and other flavonoids (Cao et al., 1997) and found them to have 2 to 6 times the activity found in common antioxidants such as ascorbate, glutathione, etc. Thus, in our current studies, we also determined the anthocyanin and total phenolic concentrations in the different blueberry samples. Previous reports of anthocyanin content in blueberries have also indicated a large variation (Mazza and Miniati, 1993). Highbush blueberries have been reported to have an anthocyanin content of 25-495 mg/100 g (Mazza and Miniati, 1993). Highbush blueberry (V. cormbosum L.) and lowbush blueberry (Vacccinium angustifolium Ait.) are the primary species of blueberries used by the food industry in the United States. Rabbiteye blueberries (Vacccinium ashei Reade) grown in the southern U.S., have been reported to have an anthocyanin content of 210- (Tifblue) to 272- (Bluegem) mg/100 g (Gao and Mazza, 1994). Gao and Mazza (1994) reported, using HPLC techniques to measure anthocyanins, that most lowbush blueberry cultivars contained 150-200 mg anthocyanins/100 g and highbush blueberry samples contained about 100 mg anthocyanins/100 g. Bilberry (Vacccinium myrtillus L.), native to parts of Europe and northern regions of Asia, has been reported to have the highest anthocyanin content (300-698 mg anthocyanin/100 g)(Mazza and Miniata, 1993). Lowbush blueberries (V. angustifolium Ait.), which are grown in Maine and Eastern Canada, are reported to have about 138 mg anthocyanins per 100 g (Kalt and McDonald, 1996). We observed anthocyanin concentrations in the range of 62 mg/100 g for "Reveille" blueberries to 300 mg/100 g for bilberries (V. myrtillus L.). Our results in general seem to be a little lower than some of the other reports; however, the particular anthocyanin compound used as a standard and its associated molar absorption coefficient can influence the absolute amounts calculated. The 3-glucoside(s) and 3-galactoside(s) of delphinidin, malvidin, petunidin, cyanidin and peonidin are the primary anthocyanins that have been identified in blueberries (Mazza and Miniati, 1993; Gao and Mazza, 1994). Bilyk and Sapers (1986) found that 4 varieties of highbush blueberry ("Earliblue", "Weymouth", "Coville" and "Bluetta") had total anthocyanin concentrations that varied by about 15%. Anthocyanin content of the different blueberry samples was linearly related to the ORAC measurement (r_xy = 0.77; p<0.01) (Fig. 2), however, the agreement as indicated by the correlation coefficient was not as high as between total phenolics and ORAC (r_xy = 0.85; p<0.01) (Fig. 3) although both were significant.

The phytochemicals responsible for the antioxidant capacity most likely can be accounted for by the phenolic acids, anthocyanins and other flavonoid compounds (Cao et al., 1997). We are in the process of identification of the compounds represented in our HPLC chromatograms, the results of which will be published at a later time.

The polyphenolic components present within blueberries may have multiple health benefits which at this point are difficult to understand. The potential beneficial effects of the high antioxidant capacity and protection of cells from free radical attack seem clear, but other possible effects which might be independent of antioxidant effects remain open to question. Anthocyanins in blueberries may have potential health benefits that are independent of or in addition to their antioxidant effects. Based upon our measurements of antioxidant capacity, other Vaccinium species might be equally good as a source of anthocyanins and other antioxidants as bilberry.