Re:Blueberries Rock! :)- Blueberries & Brain

August 29, 2004

http://www.lef.org/magazine/mag2000/mar00-cover1a.html

LE Magazine March 2000

Antioxidant Power

Blueberries and bilberries slow brain aging and protect vision

by Ivy Greenwell

When it comes to antioxidant power, according to a measure called

ORAC (oxygen radical absorbance capacity), blueberries are at the

top of the USDA chart-ahead of blackberries, garlic, kale and

strawberries, and far ahead of broccoli and spinach. Not only that,

but they taste delicious. Here, nature has been gracious to us: a

favorite food has been found to be a powerhouse of antioxidants.

Talk about a miracle anti-aging food that is actually a treat!

Now, by all means keep eating spinach and kale-these vegetables

contain the powerful carotenoids, lutein and zeaxanthin, as well as

a sulfur-containing antioxidant, lipoic acid-nutrients that help

protect us against macular degeneration and cataracts, and probably

against cardiovascular disease and other aging-related disorders as

well. Eating spinach, kale and other green leafy vegetables at least

twice a week is highly recommended. But do consider consuming half a

cup or more of blueberries every day in addition to all the

vegetables and fruit you already consume. Yes, you've read that

correctly: this article is urging you to eat blueberries every day.

Why? Because adding blueberries to your daily diet could double your

antioxidant intake from food. Frozen blueberries are fine when fresh

ones are out of season. Wild blueberries may be more potent than the

larger, sweeter cultivated blueberries, but even the cultivated

blueberries apparently can pack a ferocious punch against free

radicals.

Why this sudden urgency about eating blueberries? It started with

the scientists at the USDA Nutrition Research Center on Aging at

Tufts University in Boston. They have discovered that the blueberry

comes close to being a miracle food, considering the important

health and anti-aging benefits it offers. It is rumored that the

Tufts researchers themselves have begun to eat blueberries by the

pint during the berry season; off-season, their freezers are stacked

with frozen blueberries. Dr. ph, a senior scientist at

Tufts, admits that he started adding blueberries to his morning

protein shake after he saw the results of his own research. This

comes as no surprise: scientists have known for a long time that

restoring and maintaining youthful brain function is key in slowing

aging.

European bilberries (Vaccinium myrtillus) and North American

blueberries (Vaccinium corymbosum) are closely related; cranberries

(Vaccinium macrocarpon) are also close cousins to blueberries.

Scientists think that the antioxidant and general anti-aging

benefits of the Vaccinium species berries come from the compounds

that give them their deep pigmentation. These compounds are a class

of flavonoids (phenolic compounds) called anthocyanins, which often

occur together with proanthocyanidins. Proanthocyanidins are the

precursors of anthocyanins, and also excellent antioxidants in their

own right.

Sometimes these complex flavonoids are referred to by an older term

that seems to be regaining popularity, namely " condensed tannins. "

It is these tannins that give flowers, vegetables and fruit hues

that include deep red, purple, mauve, blue, all the way to the

extremely dark blue of Northern European bilberries, which can

appear practically black. Thus, the redness of strawberries and

raspberries and the blueness of blueberries are due to the same

class of compounds. Elderberry, persimmon, tart red cherries

(tartness indicates the presence of condensed tannins), red and

purple grapes, beets, purple cabbage, and the peel of the purple

eggplant also contain anthocyanins and proanthocyanidins.

So do many flowers-the very names of certain anthocyanins such as

petunidine, malvidine, delphynidine, and peonidine indicate in which

flowers these anthocyanins were first discovered. The anthocyanins

in hydrangea have the interesting property of imparting mauve-pink

color when the plant grows in acid soil, and blue color in alkaline

soil. The red-mauve hues of autumn leaves are also due to these

complex polyphenols. Those stunning scarlets of New England in

October are the gift of anthocyanins. The astringent taste of wine

and unripe fruit is also due to various condensed tannins.

In addition, one of the most potent flavonoids-quercetin-widely

researched due to its powerful anti-cancer, anti-inflammatory, and

cardioprotective properties, is chemically closely related to

anthocyanins. Quercetin is present in wine, ginkgo, onions, apples,

black tea and grapefruit. But berries appear to have something

possibly even more potent in some ways than quercetin: a simple

phenolic compound called ellagic acid, which has emerged as a star

in natural chemoprevention.

Please note that green tea contains mainly catechins, which are

relatively simple phenolic compounds. " Simple " doesn't mean that

they are less beneficial. Black tea and many fruits and vegetables

contain mainly complex polyphenols, also called polymeric

polyphenols, or condensed tannins. Both simple and complex

polyphenols, often present side by side, have been found to have a

wide range of health benefits. Ellagic acid, for instance, a

powerful anti-carcinogen, is also present in many kinds of berries,

including blueberries and raspberries, as well as in cherries and

pomegranates. Catechins are found not only in green tea, but also in

red wine and dark chocolate (cocoa powder and bittersweet chocolate

are good sources; " white chocolate " does not contain polyphenols).

Likewise, coffee contains not only caffeine (an alkaloid; by the

way, caffeine is also a strong antioxidant), but also catechins, as

well as simple phenolic acids, such as chlorogenic acid, caffeic

acid, and tannic acid. Hence, for instance, the well-established

effectiveness of coffee in decreasing iron levels, or helping fight

certain bacterial and viral infections.

Tannins are very common in the plant world. Apart from the sources

already mentioned, they are also found in the bark of various trees-

the best-known bark extract, Pycnogenol, comes from the bark of the

French Maritime Pine, Pinus maritima. The wide distribution of

tannins in the plant kingdom is probably related both to their

antioxidant and antimicrobial properties. The presence of tannins in

wood, for instance, is likely to be a key reason for the durability

of wood. The fact that chocolate doesn't spoil in spite of its high

fat content is also due to these fascinating polyphenols. Also, in

spite of containing sugar, chocolate, like tea and other flavonoid-

rich foods, appears to help prevent cavities. There is emerging

evidence that thanks to their antimicrobial action, flavonoids can

help prevent dental decay and oral diseases.

Bioflavonoids in general are amazingly bioactive with a wide range

of benefits. Like many other powerful antioxidants, they show a

biphasic action, depending on the dose. Lower doses, available from

diet and supplements (even if you take several capsules per day of

various flavonoid extracts, it is still a fairly low dose) act as

antioxidants and raise the levels of reduced glutathione (GSH) and

vitamin C. Negative effects such as pro-oxidant action and

glutathione depletion become an issue only if huge megadoses are

taken over a longer period of time. Again: neither blueberry eaters

nor supplement takers need worry, since it would be very difficult

and extremely expensive to reach the kind of tissue concentrations

at which damage from flavonoids might occur. As Dr. Shukitt-Hale

says, " You can't overdose on blueberries. "

At the same, we badly need more research to investigate some

unanswered questions about the dose range that produces optimum

results. And of course, as usual, there are questions about in-vivo

effects and complex interactions. Taking a single very potent

flavonoid such as quercetin in megadoses (several grams a day, for

instance) for an extended period of time should not be done without

the supervision of an experienced clinician. We must remember that

flavonoid research is still in infancy, and our knowledge is partial

at best.

A lot of the benefits of phenolic compounds stem from their

antioxidant properties. Flavonoids are powerful scavengers of free

radicals. They also enter the body's antioxidant network, boosting

the levels of vitamin C and of our chief endogenous antioxidant,

glutathione. Higher levels of ascorbate and glutathione mean better

protection of DNA and cell proteins against free radical damage.

Higher levels of glutathione also mean better recycling of other

antioxidant compounds, including, very importantly, estrogens, to

their reduced (antioxidant) form so that these substances do not

produce damage. Estrogens are excellent at protecting neural

membranes from peroxidation and preventing neural death-but only if

there is sufficient glutathione to keep recycling these powerful

hormones to their antioxidant form. Thus, the ability of phenolic

compounds such as anthocyanins to raise glutathione levels is

extremely important. This, together with the inhibition of the

enzymes needed for cell proliferation, such as tyrosine kinase and

ornithine decarboxylase, leads to a longer cell cycle and a lower

cellular turnover, since fewer damaged cells need to be replaced.

The implications for anti-aging and cancer prevention are profound.

Hormone-like?

You may wonder why flavonoids have such a wide range of

physiological effects, resembling those of hormones. Apparently this

stems from the fact that flavonoids have chemical and structural

similarities to steroid hormones, thyroid hormones, prostaglandins,

retinoids, and fatty acids. Thus it should not be altogether

surprising that flavonoids can even affect gene expression-both the

expression of our own genes, and the genes of the various bacteria

and viruses that may invade us.

Flavonoids can also attach themselves to proteins, modulating the

action of enzymes. They inhibit certain digestive enzymes and also

the kinase enzymes necessary for cell proliferation. This partly

explains how flavonoids can serve as a valuable adjunct cancer

therapy for many kinds of cancer. When very high doses of flavonoids

are used, the proliferation of normal cells is also inhibited, but

that generally doesn't hurt these cells, which just " sit. " In fully

developed cancer, however, tumor cells cannot survive in the resting

state.

On the other hand, very high levels of flavonoids are undesirable

for women seeking to become pregnant, since these compounds are also

known to decrease fertility, possibly by modulating hormone levels

and even by interfering with the critical early stages of pregnancy.

Soy and red clover phytoestrogens are a particular culprit here,

acting as endocrine disruptors because of their high ability to bind

to estrogen receptors. Less estrogenic flavonoids may have less

impact on the menstrual cycle and other aspects of fertility. A lot

remains to be explored.

We are barely beginning to research flavonoids and other

phytochemicals in the kind of depth they deserve. For a long while

it has been known that people who consume more vegetables and fruit

showed significantly superior health compared to those eating the

least, especially in regard to lower rates of cardiovascular disease

and cancer. Now the reasons for this are emerging. While eating a

wide variety of plant foods is highly recommended, due to the

synergy of various phytochemicals, we are discovering that certain

compounds are particularly valuable. The phytochemicals in

blueberries and bilberries are now at the top of the list.

What is so special about blueberries and bilberries? They are the

richest known source of anthocyanins. But it's possible that it is

the synergy of the various compounds these berries contain that is

responsible for the dramatic results recently obtained at Tufts

University in Boston.

Continued

http://www.lef.org/magazine/mag2000/mar00-cover1a.html

LE Magazine March 2000

Continued from

Antioxidant Power

Blueberries and bilberries slow brain aging and protect vision

by Ivy Greenwell

Repairing the aging brain

The main reason there has been a recent flurry of articles and media

reports on blueberries is the groundbreaking research at Tufts

University in Boston, conducted under the direction of Dr.

ph.

Nineteen-month-old Fisher rats, the equivalent of 60- to 65-year-old

humans, were fed dried aqueous blueberry extract in a dose assumed

by the investigators to be the human equivalent of one-half cup of

blueberries a day. Other experimental groups received either vitamin

E, dried aqueous spinach extract, or strawberry extract. After eight

weeks in which the rats were the equivalent of 70- to 75-year-old

humans, the control rats and rats supplemented with strawberry,

blueberry, and spinach extracts were subjected to various tests of

memory and motor function. The latter included such challenging

tasks as walking on a narrow rod and, most difficult of all, staying

on an accelerating rotating rod (the researchers jocularly referred

to these tests as the " rat Olympics " ).

While all supplemented rats showed some improvement on memory and

learning tasks, only the rats fed blueberry extract showed a

dramatic improvement in balance and motor coordination compared to

unsupplemented rats. Rats fed blueberries could run faster and stay

longer on the narrow rod and on the rotating rod. In fact, on the

average they managed to stay on almost twice as long as all the

other aged rats before falling off.

The blueberry-supplemented rats even came close to the youthful norm

on maintaining balance while walking on the narrow rod. Young rats

can stay on for 13 seconds; old rats fall off after five seconds.

Rats in the groups receiving vitamin E, spinach extract, and

strawberry extract fell off just as quickly as control rats. But the

blueberry-supplemented old rats managed to stay on for 10 to 11

seconds.

All these feats show a reversal of the usual aging-related

dysfunction in motor behavior, balance and coordination. Again, the

blueberry-supplemented animals were the only group to show reversals

in motor-behavioral deficits. Neither vitamin E, spinach extract or

strawberry extract produced these rejuvenating effects on the motor

function.

In his paper in the September 1999 issue of the Journal of

Neuroscience, Dr. ph states, " This is the first study that has

shown that dietary supplementation with fruit and vegetable extracts

that are high in phytonutrient antioxidants can actually reverse

some of the aging-related neuronal/behavioral dysfunction. " The

dryness and formality of this statement should not obscure the fact

that something extraordinary has been discovered. We do not know of

any other agent that can reverse the deterioration of motor function

with aging. And yet daily doses of blueberry extract have done just

that.

An impaired sense of balance is one of the telltale signs of aging.

For instance, a young person can usually stand on one leg, even with

eyes closed, much longer than an older person, who begins to sway

and quickly needs to put down the raised leg in order to prevent a

fall. The elderly are also notorious for falling down for no

apparent reason. We maintain our posture by automatically correcting

against swaying motion; when the conduction of neural signals slows

down due to aging, we easily lose our balance. The phytochemicals in

the blueberry extract appear to have speeded up neural communication.

The next project is to start feeding blueberry extract to very young

rats, to see to what extent the age-related deterioration in both

cognitive and motor function can be prevented. Previous Tufts

studies have already shown that if rats are fed antioxidants

beginning at six months of age, their aging process is partly slowed

down (in animal studies, various antioxidants have been found to

extend the average life span by 10% to 30%). It would be interesting

to see if any of the fruit- or vegetable-extract supplemented diets

also extend longevity. The fact that blueberry extract resulted in

greater ability to release dopamine may be significant for

longevity. Several nutrients that increase dopamine (and thus also

growth hormone) have been shown to increase the average life span.

The supplemented rats also showed improved learning and short-term

memory, performing closer to youthful levels in tests such as

navigating mazes and finding an underwater platform. One possible

explanation is vision improvement, since flavonoids and other

compounds found in berries and spinach are known for their benefits

to the eyes. However, an improvement in memory and cognition in

general is also likely to be involved. This is to be expected when

the levels of neurotransmitters, which typically decline with

advancing age, are raised through a powerful antioxidant

intervention. In separate studies, it has also been found that

phytochemicals contained in blueberry, strawberry and spinach

extracts prevented cell death and the loss of nerve growth factors.

When the brain tissue from the blueberry-supplemented rats was

subjected to various in-vitro tests, it was discovered that it

showed the greatest dopamine release, and the best ability to handle

calcium ions. " It appears that blueberry supplementation may be

effective in reversing the deleterious effects of aging on calcium

homeostasis, " Dr. ph states in his paper. Other changes also

confirmed that the neurons from blueberry-supplemented rats had the

best ability to communicate with other cells. Dr. ph speculates

that mechanisms other than the antioxidant protection may be

involved here, mainly an increase in membrane fluidity and lower

levels of inflammatory compounds. An increase in glutathione was

also found, but it did not reach statistical difference.

A co-author of the study, Barbara Shukitt-Hale, said in an

interview, " People are told once you're old, there's nothing you can

do. That might not be true. " You may chuckle at this truism. Coming

from the scientific establishment, however, the suggestion that

nutrients easily obtained from the diet might at least partially

reverse aging-related impairment is quite revolutionary. Up to now,

the belief has been that the decline in brain function, both the

cognitive and motor aspects, is inevitable and irreversible. Now,

more and more evidence points the opposite way.

If simply eating one-half cup of blueberries a day might produce

dramatic changes (though of course this is yet to be documented in

humans), then a more aggressive and multi-factorial approach might

yield even more profound results. For instance, we know that certain

hormones have a profound impact on brain function. In terms of motor

function, coordination has been shown to improve when the levels of

estradiol and progesterone are high. Likewise, postmenopausal women

have shown faster reaction time and improved manual dexterity when

put on hormone replacement. A popular old definition of flavonoids

used to be " weak plant estrogens. " These compounds often bind to the

newly discovered human Type II estrogen receptors. A great deal of

exploration remains to be done.

Are there yet other possible mechanisms through which blueberries

might work to protect and repair neural tissue? One interesting

property of polyphenols is their ability to modulate the production

of nitric oxide. In correct amounts, nitric oxide is extremely

useful. In excess, it is neurotoxic. Phenolic compounds seem

particularly effective in terms of keeping nitric oxide within the

correct range, thus improving circulation and reducing free-radical

damage from nitrogen peroxides.

Another important property of flavonoids is their ability to raise

the levels of glutathione. Glutathione is arguably the most

important neuroprotector, being not only our primary antioxidant

defense, but also an effective suppressor of chronic inflammation,

known to be a significant factor in all the major diseases related

to aging. Victims of Parkinson's disease show low levels of

glutathione in brain tissue. It's interesting to speculate that

perhaps compounds that raise glutathione, such as lipoic acid, NAC,

and the potent phenolics found in berries, cherries and walnuts,

might be able to help prevent the development of Alzheimer's disease

and Parkinson's disease, two of the most feared and disabling

degenerative disorders of old age. Both could be called " death in

life " and are a tragedy for both the victim and the nearest family

members. What if it turned out that simply eating half a cup of

blueberries every day could largely prevent an enormous amount of

suffering later! (For even better prevention, one needs to boost the

entire antioxidant network-see the review of Packer's Antioxidant

Miracle in the June 1999 issue of Life Extension magazine. -Eds.)

Flavonoids also tend to lowerblood sugar, and thus glycation. An

extract of blueberry leaves has been a traditional folk remedy

against diabetes. Glycation and its toxic end product, known as AGEs

(a singularly apt acronym for " advanced glycation end products " ),

are regarded as one of the important factors in the development and

progression of brain diseases such as Alzheimer's disease.

In addition, bilberry extract has been shown to enhance the blood-

brain barrier, which tends to become impaired with aging, showing a

decrease in vascular density, increased permeability and other

abnormalities. The normal functioning of blood-brain barrier is

important not only for keeping out toxins and undesirable compounds,

but also for glucose transport to the brain. Anthocyanins and

related compounds seem able to decrease capillary permeability

(possibly by stabilizing membrane phospholipids). Animal studies

have also shown that if the blood-brain barrier becomes damaged and

too permeable, anthocyanins help restore normal permeability.

In general, we have plenty of evidence that Dr. Packer is right when

he says, " Flavonoids are a brain booster. " But their action goes

beyond mere " boosting. " At least some flavonoids can apparently

repair the age-related damage to the neurons-and here the

anthocyanins and proanthocyanidins in blueberries, bilberry extract

and grape seed extract (or red wine and purple grape juice) are the

best candidates for this starring new role in the anti-aging regimen.

Berries, true eye-openers

The public became interested in bilberry extract after the news

about its vision-improving benefits. Bilberry flavonoids appear to

protect the retina and enhance the production of rhodopsin, also

called the visual purple. Rhodopsin is a protein necessary for near

vision. Exposure to light, particularly bright daylight, high-

contrast lights or even computer screens deplete rhodopsin,

resulting in poor night vision. A sufficient dose of bilberry

anthocyanins apparently leads to an increase in rhodopsin.

The first anecdotal reports about the effectiveness of bilberries

came from British pilots who consumed bilberry jam in order to

improve their night vision. This story became so widely known to the

readers of popular alternative health magazines that unfortunately

for quite a while the public assumed that the only benefits of

bilberry extract relate to night vision. Later on we learned about

bilberry in relation to enhanced mirocirculation in the retina. Even

now, many people assume that the benefits of bilberry extract are

confined to vision. This is reminiscent of a similar development in

regard to glutathione. Because glutathione is present in especially

high levels in the lens of the eye, early research focused on the

role of glutathione in vision; the understanding of glutathione's

primary role as the body's main antioxidant, detoxifier, anti-

inflammatory and possibly the key anti-aging compound came only

later.

This is not to deny that the protection of the retina is indeed

extremely important. Interestingly, it was not in England, but in

Italy that most studies on bilberry extract and vision were

performed, mostly in the late 1980s. One study achieved an

unprecedented 97% success in halting cataract progression using

bilberry extract and vitamin E. In another exciting study,

bilberryextract improved vision in 75% of nearsighted subjects. A

German study using a combination of vitamin E and anthocyanins found

either a stabilization of myopia or an actual improvement in visual

acuity in the majority of patients, whereas the control group showed

further deterioration. The progressive nature of myopia is one of

axioms of traditional ophthalmology: once you become near-sighted,

the older you get, the more near-sighted you get, requiring a

stronger prescription every couple of years. Hence, it is truly

revolutionary to note that a group of naturally occurring flavonoids

has been shown to either arrest or even reverse the progression of

myopia.

Please note: those who wish to experiment with bilberry extract for

reversing myopia should understand that there is no guarantee of

this benefit. On the other hand, there is nothing to lose, since it

is likely that at least the progressive deterioration of vision can

be arrested. In addition, bilberry extract has many other health

benefits, typical for phenolic antioxidants.

Of special interest in various ophthalmic pathologies are the anti-

angiogenic properties of certain flavonoids, when these

phytonutrients are used in the correct dosage range. Catechins,

anthocyanins and proanthocyanidins have been found to inhibit the

growth of abnormal blood vessels. This happens to be one of the

mechanisms through which phenolic compounds can inhibit the growth

and spread of tumors. But it also applies to the growth of abnormal

blood vessels involved in the " wet, " or advanced macular

degeneration.

But perhaps the greatest enemy of good eye health is elevated blood

glucose. You do not need to be diagnosed with diabetes to suffer

some degree of damage to the tiny blood vessels of the retina

(microvascular damage) due to the destructive action of glucose.

Serum glucose levels typically rise with age. Apart from a low-

carbohydrate diet combined with exercise, can anything be done? Here

again the finding that various kinds of polyphenols lower blood

sugar is of great relevance.

Interestingly, Chinese medicine recommends raspberries for vision

improvement. Close enough: raspberries contain many of the same

flavonoids as blueberries and bilberries. For vision improvement,

think in terms of deeply colored berries (and probably cherries and

plums as well). Red wine may also help: one study found that red

wine drinkers were 20% less likely to develop macular degeneration.

And since we have mentioned Oriental medicine, ginkgo too has been

shown to have benefits for the retina, thanks to its antioxidant

properties, its ability to raise glutathione levels, and its

enhancement of the blood-retinal barrier. To put it simply, various

potent flavonoids have similar effects, whether on the brain,

eyesight or the vascular system.

Again, a reminder that vegetables and/or supplements containing

lutein and zeaxanthin are also a must if you wish to protect your

vision against aging-related deterioration. Egg yolks are a rich

source of lutein, as is spinach. Vitamins E and C (800 mg/d), as

well as zinc, have also been documented to help prevent cataracts.

In addition, antioxidant hormones such as estrogens and DHEA may

also be protective. Finally, the alkaloid vinpocetine (an extract of

the lesser periwinkle, Vinca minor) is a promising new addition to

the growing arsenal of compounds that can help protect our eyesight.

The omega-3 fatty acid known as DHA (docosahexaenoic), richly

present in fish oil, also appears to be important for protecting

vision. When you use a variety of protective supplements are used,

you lower your chances of developing the " inevitable " senile

cataracts and other age-related eye problems.

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Li JJ et al. Age-dependent accumulation of advanced glycosylation

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Quotations by Shukitt-Hale - " A berry good nutrition tip, " AARP

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1999.

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