~ Very Berry - and Grape too! Benefits Abound: An Update on Blueberries, Bilberry Extract, Cranberry Extract, and Grape Seed Extract, Part 2

Potent anticarcinogens

Epidemiological studies confirm that those who consume plenty of polyphenol-rich foods and beverages have a lower risk of cancer. We are always being urged to eat more fruits and vegetables. There has been little guidance, however, as to which fruits and vegetables should be particularly emphasized. There is reason to think that berries should be very high on the list. Raspberries and strawberries contain a potent anti-carcinogenic compound called ellagic acid, which is well documented, however flavonoids in general are known to inhibit the bioactivation of carcinogens.

Blueberries and other berries, notably raspberries and strawberries, contain a potent anticarcinogenic compound called ellagic acid. While the anticarcinogenic properties of ellagic acid are particularly well documented, polyphenols in general are known to inhibit the bioactivation of carcinogens. They also exert antiproliferative (anti-mitotic) effects that are particularly pronounced in tumor cells. Add to this the growing evidence that some classes of phenolic compounds, including anthocyanins and proanthocyanidins, have an anti-angiogenic effect (that is, they prevent the development of new blood vessels).

Red wine and grape seed extract also show a great promise in the prevention of cancer. Resveratrol in particular has been extensively studied for its anticarcinogenic properties. Its action on tumor cells has been found to be dose-dependent. Very low doses appeared to increase proliferation; higher doses decreased proliferation and induced apoptosis (programmed cell death). Exposure of colon cancer cells to resveratrol resulted in growth inhibition through cell-cycle arrest and an inhibition of polyamine synthesis, apparently through inhibition of a crucial enzyme, ornithine decarboxylase. Resveratrol also strongly inhibited the proliferation of liver-cancer cells. Interestingly, ethanol (the alcohol present in wine) lowered the threshold for the effectiveness of resveratrol, again showing that alcohol can enhance the action of polyphenols. Resveratrol and quercetin have also been shown to some effectivess against leukemia.

Grape seed extract has been found to provide greater protection against DNA damage than vitamins C, E and beta-carotene. In addition, grape seed extract has proven effective in vitro in arresting the growth of human breast cancer, lung and gastric adonocarcinoma. In animal studies, topical application of grape seed extract has been shown to provide excellent protection against skin cancer. Of special interest is the recent finding that grape seed extract may also work against prostate cancer. Up to 98% growth inhibition was obtained in a dose- and time-dependent manner. Another study found that resveratrol downregulates androgen-upregulated genes, thus inhibiting androgen-stimulated cell growth. It should be stressed that while resveratrol is often referred to as a phytoestrogen, it has no feminizing side effects.

The fact that polyphenols raise glutathione levels is also of great importance in cancer prevention. Glutathione is one of the chief factors in the defense of DNA. In fact, one of the many jobs performed by glutathione is activating the enzymes that repair damaged DNA. The liver also needs enormous amounts of glutathione to detoxify the endless carcinogens and other toxins to which we are constantly exposed. By boosting glutathione levels with various polyphenols, we increase our ability to detoxify harmful chemicals.

People who show a slow rate of aging and a resistance to cancer (both thought to be due to "centenarian genes") tend to have higher levels of glutathione than their chronological peers. Conversely, people suffering from age-related diseases are deficient in glutathione. Likewise, animal studies have shown that raising glutathione levels can extend life span. Thus, if we can keep our glutathione levels from declining with age, it is likely that we will age more slowly and will be more resistant to cancer. Dr. Packer, for one, thinks that reaching 100 should not be a difficult feat as long as we can maintain youthful levels of glutathione. Dr. Packer, of course, advocates the boosting of the entire antioxidant network, which means consuming an antioxidant-rich diet and supplementing with a variety of antioxidants, including a mix of polyphenols.

Supplementation with oral glutathione is controversial because of uncertainty as to its absorption in the reduced state. However, there is reason to think that if glutathione is taken together with sufficient amount of bilberry extract, it can be absorbed in the reduced (antioxidant) state. It may still be more cost-effective, however, simply to consume a lot of polyphenol-rich food and/or take supplements that contain a mixture of various phenolic compounds, along with lipoic acid, also known to be very effective at raising the levels of glutathione.

Packer also reports the findings that Pycnogenol enhances the immune function, increasing the production of Interleukin 2 and stimulating natural killer cell activity. A healthy immune system is regarded as one the crucial factors in resistance to cancer.

Preventing UTIs and dental decay

No, you don't need to drink huge amounts of cranberry juice! In fact, cranberries are not the only berry that can fight urinary infections. A cup of blueberries a day ought to do the trick. Dr. Amy Howell at the Rutgers Blueberry Cranberry Research Center at Rutgers University in New Jersey was part of the team that discovered the anti-UTI effect of blueberries. She admits that she eats blueberries by the pint when in season.

What is the secret of the antibacterial effectiveness of these amazing berries? According to Dr. Howell, it is the condensed tannins in blueberries that prevent bacteria from adhering to the wall of the bladder, literally making it difficult for the infection "to take hold." Thus, these tannins could be called "anti-adhesins." By the way, part of the mechanism through which blueberry polyphenols fight dental decay is the same as the way they fight urinary infections: they interfere with the ability of the bacteria to adhere to dental surfaces.

Recent research has confirmed this and identified specific proanthocyanidins, composed of epicatechin units, that appears to be the most bioactive anti-adhesive polyphenols.

But anti-adhesive activity is probably not the only mechanism of action. Tannins in general have been found to have an antimicrobial effect. The growth of many bacteria, viruses, yeasts and fungi is inhibited by these compounds. Very likely, they interfere with genetic signaling in the microbial cells. (Note that polyphenols are generally anti-proliferative, inhibiting even the proliferation of normal cells, but affecting especially cancer cells and pathogenic organisms.) Remember, however, that dosage is critical for effectiveness. At this point, we have barely begun to investigate these effects in a controlled manner.

This is not to say that you should forget about cranberries. Cranberries (Vaccinium macrocarpon) are the cousins of blueberries. It is not surprising that, in addition to preventing and relieving bladder infections, cranberries too have been shown to have considerable cardiovascular and anti-cancer benefits, similar to those of other berries. Unfortunately, cranberries are usually prepared with a lot of sugar. This makes the relatively low-glycemic blueberries (fresh or frozen) a better choice for daily consumption. As a bonus, slowly chewing blueberries is probably excellent against tooth decay. Drinking tea also has that effect. Polyphenols in general have an anti-bacterial and anti-viral effect.

If you prefer the traditional remedy of drinking cranberry juice by the quart, try the unsweetened variety. The typical commercial cranberry cocktails contain so much sugar that there is a danger of suppressing your immune system and thus possibly making the infection even worse. The best and most practical solution appears to be taking cranberry extract in the supplement form.

Why consider berries and berry extracts for urinary tract infections when we have antibiotics? One reason is the development of bacterial resistance due to the overuse of antibiotics. Another excellent reason for decreasing the use of antibiotics is that these are not harmless compounds. They have side effects, such as diarrhea. The killing off of friendly bacteria often results in an overgrowth of harmful organisms such as Candida. Many women experience a miserable vaginal Candida infection practically every time they use antibiotics. The use of a potent cranberry extract has no side effects, while producing multiple benefits.

Since it is women who tend to suffer more frequently from urinary tract problems, it may be worth mentioning here that according to alternative clinicians, menstrual problems typical of perimenopause can also be alleviated with large doses of flavonoids, including the powerful anthocyanins in bilberry extract. According to an Italian study, high intake of bilberry flavonoids (anthocyanins) may also decrease or even eliminate the soreness in fibrocystic breasts. This may be due mainly to the anti-inflammatory action of these phytonutrients and also to their probable ability to bind to Type II estrogen receptors and exert hormone-like effects, counteracting too much estrogenic stimulation.

Polyphenols slow aging

In his excellent book, The Antioxidant Miracle, Dr. Lester Packer reports that antioxidants such as vitamin E and the pine-bark polyphenols (similar to those contained in grape seed extract) have shown in vitro the ability to slow cellular aging. In the case of the pine-bark proanthocyanidins (Pycnogenol), Packer demonstrated that these polyphenols could protect brain cells against apoptosis (programmed cell death) in an experimental model that mimics the aging process.

Research has also established that the rate of telomere shortening in dividing cells and thus, indirectly, the rate of aging, can be significantly modified by the amount of oxidative stress. (Telomeres are end points of each chromosome; their length decreases with each cell division until the telomeres become so short that the cell can no longer replicate.) It has been shown that if oxidative stress is lowered through enrichment with potent antioxidants, the rate of telomere shortening is slowed down. Mixtures of anthocyanins and proanthocyanidins are among the most powerful antioxidants yet discovered. Likewise, the accidental discovery by Dr. Winter that regular consumption of ginkgo may extend both the average and the maximum life span in rats could prove to be very important. It would be interesting to repeat his study using grape seed extract, since the proanthocyanidins found in grape seed extract show some of the same properties (e.g. inhibiting platelet aggregation and improving microcirculation) as the compounds found in ginkgo.

There is extensive epidemiological evidence that populations consuming larger quantities of polyphenols show less obesity and lower cardiovascular, cancer and Alzheimer's disease mortality. Take Eastern Asia, for instance, with its high intake of green tea, miso, ginger and a great variety of vegetables; Southern France and other Mediterranean countries, with their high consumption of red wine and olive oil, both known to be rich in phenolic compounds. Chocolate too may have similar benefits, due to its high content of proanthocyanidins similar to those found in red wine. Epidemiological studies tend to confirm a correlation between low risk for various degenerative disorders and high consumption of polyphenols. If red wine and chocolate do not agree with you, you can always reach for grape seed extract.

One of the most anti-aging important properties of anthocyanins and simpler phenolic compounds such as ellagic acid and quercetin is their ability to recycle glutathione. Glutathione is one of our most important antioxidant defenses. It is a tripeptide consisting of amino acids glutamate, glycine and cysteine. Some experts call glutathione the "ultimate antioxidant" and regard high glutathione levels as the key to longevity. Higher than average glutathione does indeed seem to be one of the characteristics of centenarians. Those of us who do not happen to have centenarian genes (and that means practically all of us) can perhaps compensate by eating a lot of berries and/or taking bilberry extract in order to raise our glutathione levels (lipoic acid and n-acetyl-cysteine also raise glutathione). If you wish to take oral glutathione, it might be a good idea to take a high dose of bilberry extract with the glutathione capsule in order to help prevent glutathione from being oxidized right in the gastrointenstinal tract.

High serum glucose is a major factor in accelerated aging. Simple sugars such as glucose, fructose and galactose can act as free radicals. They can also attach themselves to amino acids, thus damaging proteins. Polyphenols, especially the large polymers often called "condensed tannins," can protect against this damage by lowering blood sugar, as well as through their antioxidant action. Diabetics especially should take note of the finding that consuming more polyphenols is likely to lower the rate of glycosylation, a process of sugar-induced protein damage that leads to severe problems such as cataracts, neuropathy and even kidney failure. Eating the whole fruit may be of special value for lowering blood sugar, since the pectin in blueberries also has a hypoglycemic (glucose-lowering) effect.

Lower serum glucose and low insulin levels are among the dramatic biomarkers of slower aging in calorie-restricted animals. This effect very likely applies to humans. A massive National Institute of Health study has already established that older men with the lowest insulin are the healthiest. Low-normal blood sugar generally goes hand-in-hand with healthy-range blood lipids. All in all, reduced absorption of both proteins and carbohydrates due to high polyphenol intake results to some degree in calorie restriction. Since the individual is eating his or her customary portions of food, this is calorie restriction without the discomfort of hunger. While tannins have a bad reputation in animal husbandry because they slow down the animals' growth and help prevent fattening up, the implications for humans are quite positive. Calorie restriction is well known to be an effective way to slow aging.

Unfortunately, very few individuals are able to practice it by limiting their food intake. Adding blueberries, red wine and other sources of polyphenols to the diet might at least partly help this problem by slowing down digestion (by inhibiting enzymes such as amylase) and reducing absorption.

For now, we can only make an educated guess that blueberries and bilberry extract, as well as grape seed extract, with their spectacular antioxidant power, have anti-aging benefits and may even be able to extend life span if consumed daily in sufficient doses. This is highly likely in view of the documented antioxidant, chelating, hypoglycemic, antiatherogenic, anticarcinogenic, anti-inflammatory, immunostimulating and enzyme-modulating effects of polyphenols.

Our whole notion of the "inevitable" disabilities of so-called "normal aging" (isn't this like saying "normal cancer"?) is undergoing a revolutionary change. The stereotype of a "little old lady" or a "little old man" evokes the image of someone shrunken and stooped, wrinkled, forgetful and confused, hardly able to walk, weak and shaky, falling down for no apparent reason, part-blind and deaf and so on. These horrors have traditionally been shrugged off as simply "aging," with the implication that nothing can be done.

Now we are discovering that in fact a lot can be done. Aging can be slowed down and some aspects of it can even be reversed. Not too long ago, if anyone should have dared suggest that something as simple as eating blueberries could reverse aging-related loss of motor function, s/he would have been dismissed as a na´ve optimist who doesn't understand the fundamental laws of biology. The official belief was that if we live long enough, we are doomed to develop cataracts, dementia, bone and muscle loss and so forth. Not any more. Now the evidence to the contrary is beginning to pour in. The belief that growing older is synonymous with becoming senile and decrepit is being rapidly eroded.

Since even blueberries can get boring when eaten every day, it is good to try all kinds of berries and other antioxidant-rich fruit in order to enjoy variety.

So, based on this new evidence, it is wise to consume plenty of berries, cherries and plums and a moderate amount of red wine-the richest natural sources of proanthocyanidins, anthocyanins, simple phenolic acids and other phenolic compounds-and to initiate or continue a standard anti-aging regimen. Since even blueberries can get boring when eaten every day, it is good to try all kinds of berries and other antioxidant-rich fruit in order to enjoy variety. Blackberries, for instance, are also an extremely rich source of phenolic antioxidants. Likewise, tart cherries, now available in the dried form, are a delicious source of anthocyanins and ellagic acid. Unsweetened prunes are also high on the list of antioxidant-rich fruit. Think in terms of rich, deep pigments and somewhat tart taste-these signal the presence of the beneficial polyphenols.

In order to get the full benefits of blueberries and/or bilberry extract, you should eat an adequate amount and/or take an adequate dose. Half a cup of blueberries a day is probably the minimum needed to provide benefits for the brain; a whole cup works better for preventing bladder infections. The elderly who wish to reverse motor dysfunction may also consider consuming a larger amount, or else supplement their berry consumption with high-potency bilberry extract. You may want to experiment to see what dosage range works best for you in terms of vision improvement or arthritis relief. If you have arthritis and want to wake up free from stiffness and pain, you might also consider taking 300 mg of grape seed extract at bedtime. For anti-aging purposes, however, you can adjust the dose according to your age, body size and other antioxidants currently taken.

Much higher doses of anthocyanins may be needed as an adjunct treatment of diabetes and its complications, such as diabetic retinopathy, but such treatment requires the guidance of an experienced alternative clinician. The general rule is that a synergistic mixture of antioxidants works much better than relying on a single agent.

In summary, getting sufficient doses of polyphenols from diet and supplements should be an important part of any serious anti-aging regimen.

References . . .

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