Very Berry - and Grape Too!
Benefits Abound: An Update on Blueberries, Bilberry Extract, Cranberry Extract, and Grape Seed ExtractMarch 2001
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 naïve 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.
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.
Agarwal C et al. Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis. Mol Carcinog 2000; 28:129-38.
Andriambeloson E et at. Natural dietary polyphenolic compounds cause endothelium-dependent vasorelaxation in rat thoracic aorta. J Nutr 1998;128: 2324-33.
Arteel GE et al. Reactions of peroxynitrite with cocoa procyanidin oligomers. J Nutr 2000; 130 (8S Suppl): 2100S-4S.
Asgary S et al. Antioxidant effect of flavonoids on hemoglobin glycosylation. Pharma Acta Helv 1999; 73:223-6.
Atkins, R. The Vita-Nutrient Solution. Simon and Schuster, 1999, pp. 310-311.
Bagchi D et al. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 2000; 148:187-97.
Baker ME. Flavonoids as hormones. A perspective from an analysis of molecular fossils. Adv Exp Med Biol 1998;439:249-67.
Bomser J et al. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996; 62:212-6.
Canali R et al. Reduction of oxidative stress and cytokine-induced neutrophil chemoattractant expression by red wine polyphenols in zinc deficiency induced intestinal damage in rat. Free Radic Biol Med 2000; 28:1661-70.
Cao G et al. Hyperoxia-induced changes in antioxidant capacity and the effect of dietary antioxidants. J Appl Physiol 1999; 86:1917-22.
Cignarella A et al. Novel lipid-lowering properties of Vaccinium myrtillus leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. Thromb Res 1996; 84:311-22.
Chung KT et al. Tannins and human health: a review. Crit Rev Food Sci Nutr 1998; 38:421-64.
Da Luz PL et al. The effect of red wine on experimental atherosclerosis: lipid-independent protection. Exp Mol Pathol 1999; 65:150-59.
Delmas D et al. Inhibitory effect of reveratrol on the proliferation of human and rat hepatic derived cell lines. Oncol Rep 2000; 7:847-52.
Demrow HS et al. Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 1995; 91:1182-88.
Ferrandiz ML, Alcaraz MJ. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Actions 1991; 32:283-88.
Foo LY et al. The structure of cranberry proanthocyanidins which inhibit adherence to uropathogenic P-fimbriated E. coli in vitro. Phytochemistry 2000; 54: 173-81.
Furumoto K et al. Age-dependent telomere shortening is slowed down by enrichement of introcellular vitamin C via suppression of oxidative stress. Life Sci 1998; 63:935-48.
Howell A et al. Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial cell surfaces by proanthocyanidin extracts from cranberries. N Engl J Med 1998; 339:1085-6.
Hung LM et al. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res 2000; 47:549-55.
Iijima K et al. Red wine polyphenols inhibit proliferation of vascular smooth muscle cells and downregulate expression of cyclin A gene. Circulation 2000; 101:805-11.
Khanduja KL et al. Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. Food Chem Toxicol 1999; 37:313-8.
King A, Young G. Characteristics and occurrence of phenolic phytochemicals. J Am Diet Assoc 1999; 99:213-8.
Koga T et al. Increase of antioxidant potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds. J Agric Food Chem 1999;47: 1892-97.
Leonardi M. [Treatment of fibrocystic disease of the breast with myrtillus anthocyanins. Our experience.] Minerva Ginecol 1993; 45:617-21.
Lin JK, Tsai SH. Chemoprevention of cancer and cardiovascular disease by resveratrol. Proc Natural Sci Counc Repub China B 1999; 23:99-106.
Manna SK et al. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappaB, activator protein-1 and apoptosis: potential role of oxygen intermediates and lipid peroxidation. J Immunol 2000;164:6509-19.
Man-Ying Chan M et al. Synergy between ethanol and grape polyphenols, quercetin and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol 2000; 60:1539-48.
Mian E et al. Anthocyanosides and the walls of the microvessels: further aspects of the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med 1977; 68:3565-81.
Mitchell SH et al. Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res 1999; 59:5892-95.
Mizutani K et al. Resveratrol inhibits AGEs-induced proliferation and collagen synthesis activity in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. Biochem Biophys Res Commun 2000; 274:61-67.
Nagata H et al. Antioxidant action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase. Tokai J Exp Clin Med 1999; 24:1-11.
Narayanan BA et al. P53/p21 expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett 1999; 136:215-21.
Packer L and Colman C. The Antioxidant Miracle. John Wiley and Sons, 1999.
Packer L et al. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine bark, pycnogenol. Free Radic Biol Med 1999; 27:704-24.
Pignatelli P et al. The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am J Clin Nutr 2000; 72:1150-55.
Sakagami H et al. Prevention of oral diseases by polyphenols. In Vivo 1999; 13:155-7.
Sato M et al. Cardioprotective effects of grape seed proanthocyanidins against ischemic reperfusion injurty. J Mol Cell Cardiol 1999; 31:1289-97.
Schneider R et al. Anti-proliferative effects of resveratrol on human colonic cancer cells. Cancer Lett 2000; 158:85-91.
Stein JH. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation 1999; 100:1050-55.
Szende B. Dose-dependent effect of resveratrol on proliferation and apoptosis in endothelial and tumor cell cultures. Exp Mol Med 2000; 32:88-92.
Takahashi T et al. Procyanidin oligomers selectively and intensively promote proliferation of mouse hair epithelial cells in vitro and activate hair follicle growth in vivo. J Invest Dermatol 1999; 112:310-16.
Thompson, LU et al. Relationship between polyphenol intake and blood glucose resonse of normal and diabetic individuals. Am J Nutr 1984;39:745-51.
Virgili F. Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages. Free Radic Biol Medicine 1998; 24:1120-29.
Winter JC. The effects of an extract of ginkgo biloba on cognitive behavior and longevity in the rat. Physiol Behav 1998; 63:425-33.
Yamakoshi J et al. Proanthocyanidin-rich extract from grape seeds atttenuates the development of aortic atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 1999; 142:139-49.
Youdim KA et al. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radic Biol Medicine 2000; 29:51-60.
Youdim KA, Shukitt-Hale B et al. Polyphenolics enhance red blood cell resistance to oxidative stress in vitro and in vivo. Biochim Biophys Acta 2000; 1523:117-22.