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Medicine

Dr Bacchus prescribes

Studies suggest that wine compounds increase longevity

Probably, most of the present-day studies about the possible benefic effects of red wine or grape byproducts lies in the area of cardiology. In Brazil, it is no different. Pharmacologist Roberto Soares de Moura, from the Rio de Janeiro State University (UERJ), in an article published in 2002 in the Journal of Pharmacy and Pharmacology, suggested, as other authors had done, that the moderate consumption of red wine may stimulate the dilation of the blood vessels and reduce the levels of blood pressure. Over 30 days, the researcher gave rats with induced hypertension a non-alcoholic extract obtained from the skin of Isabel grapes, a variety used to produce ordinary wines. “The reduction in the pressure was significant”, says Moura. Before this work, he had achieved similar results in an experiment with a non-alcoholic extract from the skin of Cabernet Sauvignon grapes, a noble variety.

In both cases, the ethanol was taken out of the preparation administered to the animals, so as for there to be no doubt that the positive effects derive from its non-alcoholic part. “We now have the patent over the method for getting the extract, and the idea is for us to produce a drug with effects similar to those of red wine”, says Moura. Without ethanol, the extract can be recommended for people who need to bring down their blood pressure and cannot drink alcoholic beverages. Pregnant women who suffer from eclampsia (a kind of hypertension that endangers the life of the mother and the baby) could be users of the product, according to the pharmacologist from UERJ.

Before the 1990’s, health research with wine and its compounds, of which resveratrol is today the biggest star, used to be viewed with a certain disdain by the scientific community. This view was understandable and justifiable. Between the end of the 19th century and the beginning of the 20th, medical science began to clearly associate a series of health problems with the excessive ingestion of alcohol. Today, over 60 diseases show alcohol as a risk factor, and the World Health Organization estimates that 4% of deaths derive from health problems related to the uncontrolled consumption of alcohol. Even so, historically, it cannot be denied that between Antiquity and the 18th century, wine had a central role in medicine. Almost five centuries before Christ, the Greek Hippocrates, the so-called “father of medicine” gave several uses for wine, as a disinfectant, a remedy for various clinical conditions, a vehicle for other drugs, and part of a healthy diet. Until the end of the 19th century, diluted, the beverage went so far as to be used to disinfect water to be drunk. Without denying the obvious evils of alcohol in excess, contemporary work about the possible benefits to health of the parsimonious consumption of red wine is redeeming, without the mystic nature and exaggerations of the olden days, the controlled adoption of this beverage as one component of a healthy diet. The discovery of the so-called French paradox was fundamental for the change of attitude.

Lifestyle
The year was 1992, and a study showed that the French, in spite of consuming food rich in saturated fat, had a low rate of cardiovascular problems, when compared with the inhabitants of other countries with similar diets. Serge Renaud, the main author of the work, attributed the low incidence of heart attacks to the consumption of wine, a deep-rooted habit in the land of Napoleon. “It was an epidemiological work, which did not establish a cause and effect relationship between alcoholic beverages and cardiovascular diseases”, comments cardiologist Protásio Lemos da Luz, from the Heart Institute of the Faculty of Medicine of the University of São Paulo, who is studying the benefic action of components of wine and grape juice in dilating the arteries and veins and in reducing the formation of plaques of fat in the blood vessels (please see article in issue nº 109 of Pesquisa FAPESP).

“Other components of the diet, the habit of smoking, genetic factors, stress and the practice of exercise could play a role in the paradox.” That is true. There is no doubt that people’s biology and lifestyle, which far transcends the habit of drinking wine or otherwise, are determinant in the genesis of the ills of the heart, cancer and other diseases. Now, judging from the scientific evidence that is building up, humanity’s primordial beverage, blessed by the Catholic Church with divine metaphors, can be benefic, if consumed with moderation.

White with the effects of red
If the researches prosper of enologist Mauro Celso Zanus, from Embrapa Grapes & Wine, in Bento Gonçalves, Brazilians will shortly have a domestic white wine rich in flavonoids, among which the much fêted resveratrol. Due to its traditional production process, this kind of wine usually shows only 10% of the compounds apparently benefic to health, contained in red wine. “We want to make a white wine with about 40% of the flavonoids of Cabernet Sauvignon, and we are almost getting there”, explains Zanus, who is carrying out his work with BRS Lorena, an aromatic white grape cultivar launched by Embrapa four years ago. To reach the objective, the researcher introduces maceration, a procedure adopted normally in the manufacture of red wines, into the process for producing the wine made with Lorena.

Maceration consists of leaving, for a few days, the juice of the recently fermented grape in contact with the skins. The objective of this is to extract a series of phenolic compounds present in this part of the fruit, such as coloring material and flavonoids. You cannot, though, get the recipe wrong in maceration, under penalty of completely mischaracterizing the final product or offending the palate of more demanding consumers. The beverage may turn out very bitter. “Some experiments abroad with Chardonnay (a white grape) resulted in unattractive wines”, the enologist ponders. As Embrapa is going to ask for a patent over the recipe for producing white wines with more flavonoids, some details of the experiment cannot be disclosed. But the ideal time for the maceration of the Lorena must not exceed 15 days. In 2006, the tests should be finished and, in the following year, if the researches do not turn sour, a commercial product will be launched by Embrapa.

Scientists ought to avoid using words like “miraculous”. But, if there is perchance a reason for admitting an exception, it is resveratrol. This small non-toxic molecule found in medicinal herbs from Asia and in red wine is being tested clinically on humans to treat bowel cancer and oral herpes; in rodents, it provides protection against inflammatory disorders, strokes, myocardial infarction, traumas in the spinal cord and cardiac diseases, and is one of the most effective preventive chemical agents against cancer to be known. Nobody really knows how resveratrol these feats, but there is little doubt that this knowledge could open up new avenues for the development of really revolutionary drugs.

The above text, not at all moderate, was taken literally from the opening paragraph of an article published in April by David Sinclair, a 36-year-old pathologist from the Harvard Medical School, in Nature Genetics, one of the scientific magazines of greatest impact. Sinclair is the head of a team of researchers that, two years ago, increased by 70% the lifetime of the Saccharomyces cerevisiae yeast, just by administering resveratrol. This substance belongs to the category of flavonoids – compounds that bring color, flavors and sensations like bitterness and astringency to wines –, to which vasodilator and antioxidant properties are attributed. Like yeast, other organisms, such as the Caenorhabditis elegans worm, attest to the positive effects of resveratrol as a candidate for being the molecule of longevity, in experiments done at various laboratories in the world. Including in Brazil.

Geneticist Gilson Cunha, from the Pontifical Catholic University of Rio Grande do Sul (PUC-RS), verified that tiny doses of the substance increased by 30% the longevity of Drosophila melanogaster, popularly known as the fruit fly. “Studies with invertebrates, mammals and on tissue cultures suggest that resveratrol could, up to a certain point, imitate some benefic effects of a diet that restricts calories, a procedure that induces the prolonging of life”, says Cunha, who, at the beginning of June was to take part in the International Wine and Health Symposium, in Bento Gonçalves, in the Hills fo Rio Grande do Sul, by the Brazilian Agricultural Research Corporation (Embrapa) Grapes & Wine and the Brazilian Wine Institute (Ibravin). The same biological circuits activated by the daily habit of ingesting food moderately, a family of genes called sirtuins, could be linked to the thrifty consumption of the grape. “In the last analysis, what this group of genes does is to control the activity of functions that are vital for the maintenance of the survival of the cells”, Cunha explains.

Two glasses
For the time being, and probably forever, the most agreeable way of taking a daily dose of resveratrol is to uncork a good red wine, the first alcoholic beverage invented by man, 9 thousand years ago. And preferably wine based on Pinot Noir or Merlot, two varieties of grape that usually produce the compound in a larger quantity, and to drink it moderately. Something like two or three glasses, no more than 300 milliliters for men and a bit less for women. Various epidemiological studies suggest that the risk of death from cardiac problems and even cancer is lower amongst people who imbibe low quantities of alcohol, above all red wine, than amongst the abstemious. “In relation to the cardiovascular diseases, the evidences appear to be more convincing. As to cancer, care is needed in the interpretation of the studies”, explains oncologist Gilberto Schwartsmann, from the Medical School of the Federal University of Rio Grande do Sul (UFRGS).

More in the Brazilian Merlot
Alcohol is known to have a carcinogenic effect on animals, and abusive consumption of it favors the appearance of several kinds of cancer in man. “However, some work suggests that red wine, in low doses, may partly attenuate this risk, probably for containing significant quantities of substances with a potentially protective effect”, Schwartsmann ponders. Although there is no consensus, some studies indicate that grape juice could have effects almost equal to those of wine, which would be an alternative for people who do not want or who cannot drink alcohol.

If the effects of resveratrol are similar to the hypotheses raised by the scientists, there are plenty of reasons for proposing a toast. And it is not even necessary to resort to the imported product. Work done by chemist André Souto, from the School of Chemistry of PUC, Rio Grande do Sul, indicates that the concentration of resveratrol in Brazilian red wines is one of the highest in the world. The researcher analyzed the concentrations of transresveratrol, one form of the molecule, in 36 samples of Brazilian red wines, and arrived at an average rate of 2.57 milligrams of the compound per liter of the beverage. “I only know of higher average concentrations in French wines”, says Souto, who published the study in 2001, in the Journal of Food Composition and Analysis. The highest levels of the compound were found in products made with the Merlot grape.

One explanation for the strong presence of resveratrol in Brazilian red wine could be the climate of the hills of Rio Grande of Sul, where about 90% of the domestic wine is produced. The region is humid and the vines are more subject to attacks from funguses and microorganisms. In danger, the plant increases the production of resveratrol, which protects it from the action of the pathogens. The process for producing red wines makes them have more flavonoids than the white ones. To reduce the difference, experiments at Embrapa are trying to increase the levels of resveratrol and other compounds in white wine.

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