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02.2005

Massachusetts Beverage Business

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Article By: Harvey Finkel, MD

First, let us revisit what is known of increased cancer risk associated with drinking. Alcohol (and its first breakdown product, acetaldehyde) is the only component of wine that may be inculpated, then almost exclusively when chronically abused. Spirits and beer appear to be associated with more risk than wine. It is generally accepted that prolonged excessive consumption of alcohol, especially when combined with smoking, leads to an increased incidence of aerodigestive cancers (mouth, throat, larynx, esophagus, perhaps stomach). Chronic liver damage of any cause (viral hepatitis, alcohol abuse, toxic damage, as by iron overload) increases the risk of liver cancer. Alcohol abuse may indirectly and rarely promote pancreatic cancer.

The influence, if any, of even moderate drinking on the risk of breast and colorectal cancers remains unclear, and, at worst, small. Information available on possible associations, beneficial or adverse, between alcohol and other cancers is mostly trivial and immature. The venerable Framingham Study has indicated no increase in the risk of breast cancer resulting from drinking, although others are not finally reassured. A recently published multinational study of 489,979 men and women followed from six to sixteen years suggests no increase in risk of colorectal cancer at intakes of alcohol less than eleven ounces of wine per day, or the equivalent in other beverages - the type of beverage did not matter. Risk rose moderately with higher consumption. We should factor in the beneficial cardiovascular effects (improved health, reduced mortality) of moderate drinking. Then, the net general result is clearly favorable. Individual assessment is necessary for individual advice.

Another red flag has arisen for pregnant women. As recently reported in the British Journal of Cancer, the female offspring of rats fed alcohol during pregnancy developed breast tumors more readily than did the progeny of abstinent mothers. We do not yet have a clue whether this is relevant to humans. Research done in Spain, the US and the Netherlands during the past year suggests that moderate consumption of red wine reduces the risks of lung and prostate cancers, two of our most frequent causes of death.

It appears that the anti-cancer capabilities possessed by potables reside in wine's polyphenolic compounds, generally referred to as antioxidants, for their best-known function. Other functions, in the vine (among which, protection from fungus), in the wine (preservation, perhaps), and in the drinker (best known for cardiac protection), are incompletely understood. Of the dozens of such compounds, quercetin and resveratrol are most familiar. The cancer-protective effects of the antioxidants probably work by a multiplex of mechanisms, especially by inhibition of carcinogenic oxidative reactions promoted by excessive alcohol and acetaldehyde in the liver and upper aerodigestive tract.

The phenolics of wine are believed to help eliminate infection of the stomach by Helicobacter pylori, a bacterium that causes chronic gastritis, most ulcers, and a significant proportion of cancers of the stomach. They inhibit the reactions which induce malignant mutations by damaging DNA. They induce the activity of enzymes which protect DNA and repair damage to our genetic material. Red-wine solids delay the formation of tumors in mice genetically engineered to be afflicted with them.

Quercetin-rich diets in China are associated with reduction of the high frequency of stomach cancer. Quercetin is found in abundance in grape skins and in allium vegetables (onion, scallion, leek, shallot, garlic) and broccoli. It has been demonstrated to inhibit the growth of the cells of leukemia and ovarian and uterine cancers, and to enhance the effectiveness of cisplatin, a widely used chemotherapeutic agent.

Resveratrol is esteemed for its likely cardiac protection in humans. Its mechanisms of cancer protection include modulation of the inflammatory reactions that may damage tissues and lead to cancer; promotion of normal cellular differentiation and maturation, the opposite of cancer growth; inhibition of cancer formation; countering the unbalanced effects of estrogen, which, when unopposed, may lead to breast and uterine cancer. Evidence has lately appeared that resveratrol may increase lifespan.

A provocative research paper confirms and elaborates the kind of antioxidant activity of quercetin that surely has relevance to both cardiovascular and cancer protection. A main pathway in the formation of cancer is considered to be repetitive tissue injury by highly chemically reactive free radicals (not a political term) and avid oxidants. The study by Huk et al. demonstrated that quercetin reduced injury to tissue by scavenging destructive superoxide and by increasing the tissue concentration of protective nitric oxide.

Another research report is astonishing. It presents direct evidence that resveratrol causes the death of cancer cells. Clement et al. studied the effects of resveratrol on human leukemia cells, breast-cancer cells and normal cells. The resveratrol initiated a series of biochemical events within the leukemia and the cancer cells that resulted in programmed cell death, a process called "apoptosis". Normal cells were not harmed. The death cascade proceeded by a chiefly enzymatic pathway induced by resveratrol, really a tumor suicide. The novel mechanism, the selective targeting of cancer cells, and the lack of toxicity to normal cells, excites interest in clinical trials in the prevention and treatment of cancer, perhaps in combination with other anti-cancer drugs and with immune defenses against cancer.

I must emphasize that the practical clinical applicability of this data is unclear, and will take quite some time to determine - but isn't it fascinating?

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