BLUEBERRIESOne of Nature's Most Potent Antioxidants

Ojfers Powerful Neuroprotective and Other Benefits

By Russell Martin

When it comes to brain protection, there is nothingquite Hke blueberries," accordingtojames Joseph,PhD, lead scientist in the Laboratory of Neuro-

science at the I'SDA Human Nutrition Research Center on Agingat Tufts University. "Call the blueberry the brain berry," saysDr. Joseph.'

Dr. Joseph's claim was made with the publication of hislandmark blueberry research. It has since been bolstered byanimal studies demonstrating that daily consumption ofmodest amounts of blueberries dramatically slows impair-ments in memory and motor coordination that normallyaccompany aging. Moreover, a wealth of exciting newresearch clearly establishes that in addition to promotingbrain health, this long-prized native North American fruit—whether consumed fresh, frozen, canned, or as an extract—may confer a range of diverse health benefits. > > >

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After testing 24 varieties of freshfruit, 23 vegetables, 16 herbs andspices, 10 different nuts, and 4 driedfruits, the US Department of Agri-culture determined that blueberriesscored highest overall in totalantioxidant capacity per serving. Asmost health-conscious adults areaware by now, antioxidants are vitalin countering free radicals, theharmful byproducts of cellularmetabolism that can contributeto cancer and other age-relateddiseases.'

Separate studies show that blue-berries may help to lower bloodcholesterol,' promote urinary tracthealth, and reduce the risk of uri-nary infections/^ Studies in Europehave documented the relationshipbetween consumption of bilberries{the blueberry's close Europeancousin) and eye health, highlightingthe berries' ability to improve nightvision, halt cataract progression,and protect against glaucoma." Newstudies also support blueberries'ability to reduce age-associatedlipid peroxidation,' a contributor tocardiovascular disease, and to sup-press the growth of several types ofcancer cells,"" suggesting that blue-berry phytochemicals may well playa future role in human cancer treat-ment. And you can add to the man-ifold health benefits of blueberriesat least one more reason to eat themdaily: virtually everyone agrees thatthey are delicious.

When the Plymouth colonistsarrived in what is now Mas-sachtisetts, native Americaninhabitants shared with them theblue-tinged fruit of a low woodyshrub whose calyx forms a delicatefive-point star. Eor centuries,native American cultures had con-sumed "star berries" not only asfood but also as medicine, drinkingblueberry juice to relieve coughs,brewing a tea from blueberryleaves as a tonic, and eating fresh,dried berries to sharpen theirvision.'"

Blueberries and bilberriesbelong to the genus Vaccinium,which includes more than 450plants grown in all parts of theworld. Members of the Vacciniumgenus possessing the darkest-colored fruits appear to provide thegreatest health benefits, a factthat scientists attribute to thecompounds that give the plantstheir dark pigmentation. Thesebioflavonoids include antho-cyanins and their precursor,proanthocyanidins, both of whichare voracious scavengers of freeradicals." " Research demonstratesthat blueberry consumptionboosts serum antioxidant status inhumans." Elevated antioxidantlevels in the body may protectagainst damage to cells and cellu-lar components, thus helping toreduce the risk of many chronicdegenerative diseases.'^

How BlueberriesCombat Brain Aging

In Dr. foseph's groundbreakingwork at Tufts, 19-month-old labora-tory rats—the equivalent of 60- to 65-year-old humans—were fed driedblueberry extract at a dose the inves-tigators calibrated to be the humanequivalent of one-half cup of blue-berries per day. Three other groups ofrats received spinach extract, straw-berry extract, or a control diet. Aftereight weeks on the regimen, theinvestigators evaluated the rats—now equivalent in age to 70- to 75-year-old humans—using varioustests of memory function.

Compared to a control group fedonly a standardized diet, each of thethree supplemented groups per-formed at least marginally better onmemory and learning tests.' In testsof neuromotor function, however,the blueberry-fed rats significantlyoutperformed the other groups.These rats were much better able towalk the length of a narrow rod andbalance on an accelerating rotatingrod compared to the other groups.This was indeed a stunning finding,as scientists have for some time tend-ed to accept as established fact thatage-related neuromotor dysfunctionis irreversible. Dr. Joseph's findingsappear to flatly contradict thisnotion. Blueberry extract, he discov-ered, was clearly capable of reversingthis particular aging process as noother agent had ever heen demon-strated to do. Dr. Joseph concluded:

"This is the first study that hasshown that dietary supplementa-tion with fruit and vegetableextracts that are high in phyto-nutrient antioxidants can actuallyreverse some of the aging-related-neuronal/behavioral dysfunction."^*

Dr. Joseph's blueberry-supple-mented rats also demonstratedimproved learning and memoryskills as they navigated mazes andfound— and then remembered—thelocation of an underwater platformon which they could rest from swim-ming. When Dr. Joseph and his

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colleagues examined the brain tis-sues of these rats in vitro, they foundthat dopamine levels were muchhigher than in the brains of rats in theother groups. Dopamine is an essen-tial neurotransmitter that enablessmooth, controlled movements aswell as efficient memory, attention,and problem-solving function. Dr.Joseph speculated that blueberryextract might also increase brain cellmembrane fluidity while reducinglevels of inflammatory compounds,thus slowing the brain's normal agingprocess.'^

To other researchers, Dr. Joseph'sstudy seemed especially promisingin its implications for aging humans.Older adults tend to fall or stumble—sometimes with catastrophic conse-quences—because their brainsbecome less adept at monitoring andmodulating swaying motion, as con-duction of neural signals in the brainslows with aging. Older people like-wise tend to suffer memory loss andan inability to learn new behaviors inways that can starkly limit their abil-ity to lead productive, satisfying lives."People are told once you're old,there's nothing you can do," noted Dr.Joseph's colleague and study coau-thor Dr. Barbara Shukitt-Hale. "Thatmight not be true.""

New Studies ConfirmBrain Benefits

Dr. Joseph's findings not onlyspurred scientific research into thehealth properties of blueberries, butalso greatly increased public aware-ness of this remarkable fruit. Eiveimportant new studies support andexpand on Dr. Joseph's originalresearch.

In a 2005 article published in thejournal Neurobiology of Aging,Rachel Galli and her colleagues, alsobased at Tufts, reported discovering aspecific mechanism by which blue-berries help reverse the neurologicalaging process."' The Galli study—which included Drs. Joseph andShukitt-Hale as co-investigators—sought to measure the heat-shockprotein response in the brains of bothyoung and aged rats supplemented

with blueberr>' extract compared to acontrol group of aged rats. A protec-tive mechanism produced in thebrains of most animals (andhumans), heat-shock proteins fightfree radicals and inflammation-inducing agents, acting similarly toantioxidants to support healthybrain tissues. As people age, howev-er, their ability to generate heat-shock proteins in sufficient quantitydeclines,'' sometimes dramatically.The Tufts researchers sought todetermine whether blueberriescould help restore the heat-shockprotein response in rats."'

After 10 weeks, the scientists sub-jected brain tissues from the rats toan inflammatory challenge and thenmeasured the subsequent heat-shock protein response. As pre-sumed, the brains of young rats thathad consumed blueberries produceda strong heat-shock proteinresponse, unlike the brains of theaged rats that did not consume blue-berry extract. The significant finding,however, was that the brains of agedrats fed blueberries were as success-ful at initiating the heat-shock pro-tein response as the brains of youngrats. The blueberry extract provedcapable of entirely restoring theheat-shock protein response in thetest animals, suggesting that blue-berries may protect against neurode-generative processes associated withaging."^

Last year, the journal NutritionalNeuroseience published an impor-tant new study by scientists at the

University of Barcelona. The Spanishresearchers previously had demon-strated blueberries' effectiveness inreversing age-related deficits in neu-ronal signaling. They now sought todetermine whether the active phyto-chemicals that give blueberries theirsignificant neurological benefits doindeed cross the blood-brain barrier.Examining the brains of rats that hadbeen fed blueberry extract for 10weeks, they were able to isolate blue-berry-specific agents in the rats' cere-bellum, cortex, hippocampus, andstriatum—brain areas that controlmemory and learning processes.Most striking, the scientists were ableto correlate the presence of blueber-ry phytochemicals in the rat braincortices they examined withimproved cognitive performance intests initiated at the end of the 10-week supplementation period.'"

Blueberries may also prove capa-ble of helping humans whose brainshave been damaged by a loss of bloodflow and the critical oxygen andnutrients it provides, a conditionknown as ischemia (one of the twoprincipal causes of stroke). In a May2005 study published in the journalExperimental Neurology, researchersdocumented how three groups of ratswhose diets were supplemented withblueberries, spinach, and spirulina,respectively, all suffered less braincell loss and were better able torecover lost function following artifi-cially induced ischemia than rats in anon-supplemented control group. Atautopsy, the scientists observed that

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Jthe physical extent of ischemic dam-age to the brains of rats that had beenfed the three supplements was sig-nificantly less than that suffered bythe control group."

Similarly, the Tufts scientists whohave been in the forefront of blue-berry research reported an addition-al study in the Augnst 2005 issue ofNeurobiology of Aging. In this study,they demonstrated that the auditoryprocessing speed of aged rats sup-plemented with blueberries nearlymatched the lightning-fast auditoryprocessing speeds of young rats,while the speeds of a control group ofnon-supplemented aged rats weredramatically slower. According to theresearchers, "These results suggestthat the age-related changes in tem-poral processing speed in (the prima-ry auditory cortex] may be reversed bydietary supplementation of blueberryphytochemicals."-"

Another recent study suggeststhat blueberries may have applica-tions in the developing field ofneural transplants, which manyneuroscientists believe hold promiseas a means of replacing vital brainstructures destroyed or damagedby brain injury or degenerative dis-ease. Unfortunately, the survival oftransplanted tissue is often poor,especially in older recipients. Whenresearchers gave blueberry supple-ments to middle-aged rats receivingneural implants, the growth of theirhippocampal grafts was markedlymore vigorous than that of identical

grafts in a cotitrol group, and cellularorganization was comparable to thatin tissue grafted into young laborato-ry animals. Blueberries may some-day play an important role inensuring that surgically grafted tis-sues thrive in the new host, wherethey may help to restore lost motorand cognitive functions.-'

Benefits for Other Body Systems

Blueberries' benefits for neuro-logical health and vigor are so wellestablished as to make daily con-sumption of the fruit a "no-brainer"for virtually everyone. Moreover,new studies continue to confirmblueberries' remarkable health-pro-moting effects in other areas of thehuman body.

For decades, researchers inEurope have documented evidenceof the ability' of bilberries to combata range of eye disorders. DuringWorld War II, French researchers whoexamined bilberry extract's effectsin pilots found that bilberry helpedimprove nighttime visual acuity,adjustment to darkness, and recov-ery from glare.'' In another study, alleight patients with glaucoma whowere given a single oral dose of bil-berry extract demonstrated improve-ments based on electroretinography,a measure of electrical responsive-ness of the retinal cells. Bilberry'santioxidant properties may protectagainst glaucoma by supportinghealthy intraocular pressure.'' In a

clinical study, the combination of bil-berry extract with vitamin E stoppedthe formation of senile corticalcataracts in 48 of 50 patients.^Researchers believe that the antho-cyanins and proanthocyanidinsfound in blueberries might similarlyoffer benefits for eye health.

In an article in X\\e Journal of Agri-cultural and Food Chemistry in 2004,researchers announced that theyhad isolated three compounds inblueberries and other dark-pig-mented berries known to lowercholesterol levels.-^ In a follow-upstudy, one of the three phytochemi-cals—pterostilbene—showed a par-ticularly potent effect in stimulatinga receptor protein in cells that playsan important role in loweringcholesterol and other blood fats.'"We are excited to learn that blue-berries, which are already known tobe rich in healthy compounds, mayalso be a potent weapon in the bat-tle against obesity and heart dis-ease," lead author Agnes Rimandotold members of the AmericanChemical Society.'--'

Blueberry juice or extract mayhelp avert urinary tract infectionscommonly suffered by women. Sci-entists formerly hypothesized thatdark-pigmented berries such ascranberry help fight infectionthrough an antibacterial effectcaused by the acidification of urine.'Current research suggests thatberries, including cranberry andblueberry, may fight bacterial uri-nary infections by preventing E. coliand other forms of bacteria fromadhering to cells lining the walls ofthe urinary tract."

Blueberries also may slow thegrowth of cancer cells. In 2001, Uni-versity of Mississippi researchersconducting in-vitro tests found thatblueberry and strawberry extractswere remarkably successful in slow-ing the growth of two aggressive cer-vical cancer cell lines and twofast-replicating breast cancer celllines, with the blueberry extract per-forming best against the cervicalcancer cells." Last year, a Universityof Georgia study similarly demon-strated blueberry extract's ability to

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inhibit cell proliferation in twoseparate lines of colon cancer cells,reducing by more than 50% the rateat which the cells otherwise multi-plied. Further studies are indicatedto determine whether phytochemi-cals from dark-pigmented berriesmay affect very early growth ofmalignant cells in the bodies ofhumans as well.

Conclusion

Although no studies to date havecompared the relative efficacy offresh blueberries versus frozenberries, canned berries, or berryextracts, each form of the fruit hasbeen shown to contain the essentialanthocyanins and proanthocyani-dins that make blueberries one of themost exciting nutraceuticals beingresearched and consumed today.Blueberry extracts have the advan-tage of delivering the fruit's phyto-chemicals in a simple, standardizeddose, while consuming blueberriesas food offers the benefit of flavor.

Regardless of how they are con-sumed, blueberries should be con-sidered a mainstay of every healthydiet. This remarkable fruit, knownfor centuries for its medicinal prop-erties, continues to prove itself inresearch laboratories around theworld, demonstrating a wide arrayof dramatic, health-enhancingbenefits. I

NEW FINDINGS ON BLUEBERRIES

New research reported in peer-reviewed journals by scientists around the world confirmsthe wide range of health benefits attributed to blueberries, while pointing to promising newtherapeutic applications:

In a study published in the journalNutritional Neuroseience,^' a blueberry-supplemented diet was found to greatlyenhance the spatial memory of labora-tory animals. When later studied invitro, the animals' brains demonstratedstructural changes associated with animproved capacity for learning.Researchers believe the two findingsare directly correlated.In a study reported in the Journal ofAgricultural and Food Chemistry,cold-pressed blueberry, Marion berry,boysenberry, and red raspberry seed oilswere evaluated for their fatty acidcomposition. The oils were found tocontain antioxidants with a highcapacity to absorb oxygen radicals, andwere deemed potent sources oftocopherols, carotenoids, and naturalantioxidants."

The journal of Medicinal Food reportedthat in an in-vitro study of aortic tissueof young rats, wild blueberriesincorporated in the diet positively affectthe plasticity of vascular smoothmuscle, but have no deleterious effecton membrane sensitivity. This findingsuggests that blueberries may haveapplications in helping prevent heartdisease and stroke in humans.^'

In a similar study published in theJournal of Nutritional Biochemistry,researchers demonstrated that in rataortic tissue, compounds from berryextracts caused cell changes that mayaffect cellular signal transductionpathways and contribute to improvedcardiovascular health."Research published in the journalNeurobiology of Aging s\]Qm6 thatnutritional antioxidants found inblueberries can reverse age-relateddeclines in neuronal signal transductionas well as cognitive and motor deficits.The investigators speculated thatblueberry supplementation may alsohelp slow declines in brain function thataccompany diseases such as amy-otrophic lateral sclerosis, Alzheimer'sdisease, and Parkinson's disease. ''In an in-vitro study published inBiochemistry and Cell Biology, 24 hoursof exposure to extracts of blueberryantioxidants sharply reduced the pro-duction of matrix metalloproteinases—enzymes believed to play key roles inmalignant tissue metastasis—inhuman prostate cancer cells. This ledthe researchers to postulate thatblueberry supplementation may helpprevent tumor metastasis."

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