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Wine and Health Trailblazers

Five European researchers push the frontiers of knowledge -- and hope

Per-Henrik Mansson
Posted: December 5, 2001

  The Researchers:  
  Serge Renaud  
  Morten Grønbaek  
  Serenella Rotondo  
  Jean-Marc Orgogozo  
  Elias Castanas  
  Related Wine and Health Stories:  
  Eat Well, Drink Wisely, Live Longer
The science behind a healthy life with wine
  The Case for Red Wine  
Serge Renaud: The man behind the French Paradox

We all aspire to a healthy and long life, and Serge Renaud believes he has found a recipe for increasing life expectancy dramatically. Drinking red wine is part of the secret.

Nobody has done more than Renaud to popularize the notion that wine is good for you. "He symbolizes the advantages of wine for the entire world," says Jean-Marc Orgogozo, a fellow researcher in Bordeaux, where Renaud is currently based.

As a boy, Renaud lived on a vineyard in the Gironde area, near Bordeaux, with his grandparents and great-grandparents; these forebears drank moderate amounts of wine every day and each reached an age of between 80 and 90 years. Renaud concluded that wine in low doses could never be harmful.

Although he didn't coin the term "French Paradox," he is widely considered the father of the concept, which became famous worldwide after he was interviewed on the CBS television program 60 Minutes for its 1991 segment called "The French Paradox."

In 1992, Renaud drew on the epidemiological research available at the time, looked at it from a new angle, added some new data of his own and made a coherent case for the existence of the French Paradox in an article in The Lancet, the influential English medical journal.

He tried to explain why the French died from heart disease at less than half the rate recorded in the United States. This was an unexpected finding, since the French eat a great deal of cream and butter, consume the same amount of saturated fat as the Americans and have higher levels of cholesterol.

For a possible explanation, Renaud turned to the consumption of alcohol in France. In earlier laboratory tests with rats, the Frenchman had documented that alcohol reduced the risk of heart and arterial disease by decreasing the frequency and severity of blood clots. In The Lancet, he reported that 20 to 30 grams of alcohol a day (about two to three standard glasses of wine) could reduce the risk of dying from a heart attack by 40 percent.

At the time, Renaud now says, he didn't know whether it was wine or the alcohol it contained that was the important factor. But since the French took most of their alcohol in the form of wine, Renaud concluded that the high consumption of wine probably explained this French paradox. "In France, the untoward effects of saturated fats are counteracted by intake of wine," he wrote.

A maverick scientist, he has challenged several medical sacred cows over the years. "Serge Renaud has been challenging dogma and winning medical bets for more than 50 years," wrote The Lancet last year. "He is best-known for his work on the link between wine, diet and thrombosis." Thrombosis consists of life-threatening, circulation-restricting blood clots in the arteries and heart cavity and can lead to sudden death.

Renaud emigrated in 1951 from France to Canada, where he became fascinated with heart and circulatory disease, which is the leading cause of death in Western industrialized countries. He decided to do research instead of working as the veterinarian he had studied to be in Montreal. He showed his talent as a researcher early on, when he demonstrated that aspirin (which, like alcohol, thins the blood) protects against heart disease.

In 1973, he returned to France. Soon after, he headed a research team at INSERM, the national health and research institute in Lyon. His work there established him as one of the leading epidemiologists in the world.

In 1986, he began the Lyon diet heart study, which duplicated in France what he called the Cretan Mediterranean diet. He invented a margarine that was based on rapeseed (canola) oil and other ingredients. The margarine was rich in alpha-linolenic acid, which was found in abundance in the blood serum of the Cretans, and which Renaud figured accounted for their exceptional life expectancy and health.

The diet, which included moderate consumption of wine, produced dramatic results. It reduced deaths and the incidence of serious heart complications by more than 70 percent within two months. "The Cretan diet is absolutely extraordinary," says Renaud, who eats what he preaches. He consumes a healthy Cretan-like diet of fruit, vegetables, olive oil, red wine in moderation, and alpha-linolenic acid from his special margarine. He's lean and fit, with the energy one normally associates with a much younger man.

The septuagenarian has put his retirement on hold to allow more time to fight for his precepts. He's courteous, but doesn't relax or smile easily. He estimates that millions of people would benefit from the Cretan diet, and he's more at ease talking about the challenges ahead than past successes. "If I stopped giving lectures and doing research, my work might be forgotten," he says.

Morten Grønbaek: Danish epidemiologist champions wine

In May 1995, Morten Grønbaek didn't have the slightest idea that he was about to become famous. The young Danish scientist had never heard of the CBS program 60 Minutes or of the correspondent, Morley Safer, who faced the researcher as a television crew set up in a borrowed university office in Copenhagen.

Earlier that month, the British Medical Journal had published an article by Grønbaek and his colleagues detailing some of the most significant research ever produced on the health benefits of wine. Grønbaek found himself in the spotlight because the large-scale study had made a clear distinction between different alcoholic drinks, concluding that wine drinkers enjoyed healthier lives.

As the cameras began to roll, the Dane looked a bit nervous, but not because of Safer's questions. A tall, marathon runner with steely blue-gray eyes, Grønbaek, then 35, was expecting a call from his wife, Lisa, who was scheduled to give birth that day. As it turned out, the baby boy was born later, and Grønbaek was able to detail his findings.

"What surprised us the most," said Grønbaek on the television show, "is that even a moderate intake of wine ... implied a significantly lower mortality." Shortly after the broadcast, called "To Your Health," aired in November 1995, wine sales in America soared.

"I had my 20 minutes of fame," Grønbaek says, smiling as he enjoys a couple of glasses of 1998 Mâcon from Jean-Paul Thévenet during a recent lunch in the Danish capital. He remains in the public eye because he and his team at the Copenhagen University Hospital's Institute of Preventive Medicine have published at a prolific rate.

Perseverance accounts for Grønbaek's success. As a doctoral student in Denmark, his thesis was about alcohol, but he had a hunch that the health benefits of wine specifically, not just any beverage containing ethanol, were the real story. Although his thesis advisers discouraged him, he came back to wine later and started sifting through the considerable data available in Denmark. His team can now draw from data on 33,000 men and women, collected since 1976 at the Copenhagen Center for Prospective Population Studies.

In his 1995 Copenhagen city heart study, Grønbaek researched the health and drinking patterns of 13,285 men and women aged 30 to 79 years.

Previous studies had found that consumption of alcohol increased the risk of stroke. But the Dane found that this was not the case with wine. Three to five glasses of wine a day actually reduced the risks of heart and stroke diseases by 60 percent. However, drinking only one to two drinks of spirits daily increased these risks by 16 percent, which climbed to 35 percent with three to five drinks a day.

In dozens of articles over the past few years, Grønbaek and his colleagues have confirmed the health advantages to wine drinkers over beer and spirits drinkers. Wine drinkers have significantly lower risks of throat and lung cancer. They even suffer hip fractures slightly less frequently than beer and spirits drinkers do.

The Danish team also assessed the risks of dying from other causes, not just heart disease. Until Grønbaek came along, many studies had found that alcohol increased overall mortality; drinking protected against heart disease but not against cancer, the thinking went. "But when we separated out the different types of beverages, we found that wine lowered the risk of lung cancer, and this was very surprising," said Grønbaek.

Scientists have said that light to moderate wine-consumption extends life expectancy by three to four years beyond that of teetotalers. By drinking one to two glasses a day, wine drinkers reduced their overall mortality by 40 percent compared with teetotalers', according to Grønbaek. Drinking a bit more was even better; those who averaged three to five glasses enjoyed a reduced mortality rate of 50 percent compared with teetotalers'. Beer drinkers didn't enjoy such protection, however. And spirits drinkers increased their risk of dying by a third with three to five drinks a day, again compared with results for nondrinkers.

Breaking new ground is all in a day's work for Grønbaek, now 40. And more good news about wine is on the way, as 10 assistants currently work under the Danish research director. "Soon there will be an explosion of published papers from us," promises assistant Majken Jensen.

Serenella Rotondo: Focusing on the high-fat diet

If you want to eat rich food, do yourself a favor: Drink red wine to help counterbalance the ill effects of a high-fat diet. At least that's how it worked out for laboratory rats during experiments conducted by Serenella Rotondo and her colleagues in southern Italy.

Rotondo, 40, stands in the dark behind a dais, only her face and short, black, curly hair illuminated by a small lamp and the blue glow of a portable computer. Graphs and statistics are projected on a screen behind her at the click of a button. She is one of the scientists describing the relationship between wine and health during a seminar held this spring at the 35th annual meeting of the European Society for Clinical Investigation, convened in Barcelona, Spain.

Her topic -- "Vascular and Blood Cell Function and Interaction: Modulation by Wine Compounds" -- may seem esoteric. But the results of her studies of rats at Consorzio Mario Negri Sud, a research center in central Italy, may have practical implications for anyone who loves food and wine.

Imagine going on a gastronomic tour of France. You eat your fill every day, starting with croissants in the morning and ending with five-course dinners rich in cream, butter and saturated fat. That's the sort of diet that Rotondo's colleagues replicated with the rats before testing what happened to the animals when they were fed red and white wine.

The health implications of bad and good diets, and the role of wine in them, are part of Rotondo's specialty in the center's vascular medicine and pharmacology department. She studied biology and got her start in basic cell research at Baylor College of Medicine in Houston in the 1980s.

"We say fruit is good, wine is good, but why are they good and how?" asks Rotondo, whose recent published work has focused on ways a polyphenol-rich, Mediterranean-style diet protects against heart disease. "We need to explain the mechanism responsible for the beneficial effect of the diet."

Such was the objective with the rats bred at the research institute, where Rotondo works with test tubes, animals and computers. The researchers fed the rats a high-cholesterol diet for six months, then induced a blood clot, or thrombosis, in the abdominal aorta.

"A high-fat diet accelerates thrombosis. That's why fat people have thrombosis more frequently than fit people," says Rotondo. Thrombosis occurs when blood platelets stick to the arterial wall and cause an inflammation, which produces blood clots that can lead to death from a stroke or heart attack.

The rats consumed either red wine (1995 Montepulciano d'Abruzzo), white wine (1996 Trebbiano d'Abruzzo), ethyl alcohol or alcohol-free red wine. Control group rats were fed water.

Compared with those rats on a water diet, red wine—fed rats saw blood clotting reduced by nearly 60 percent, whereas white wine and ethyl alcohol produced only a "slight, nonsignificant" reduction in the illness. "With red wine, the problem can be partially reversed," says Rotondo. "What makes red wine different [from alcohol, white wine and water] is the high content of polyphenols." In fact, those rats fed red wine had three times higher concentration of antioxidants, compared with rats fed white wine or alcohol.

Scientists are interested in polyphenols because they are rich in antioxidants, which are known to fight a variety of illnesses. Polyphenols exist in considerable quantities in grape stems, seeds and skins. And red wine, which is fermented with grape skins, is rich in polyphenols.

If this laboratory test can be confirmed with humans, it means that red wine could dramatically reduce the risk of developing thrombosis from eating fatty food. Other studies do suggest that humans also benefit from red wines.

Rotondo warns that her research shouldn't encourage people to indulge in an unhealthy diet. "Don't say to yourself, 'I can eat fatty food as long as I drink red wine,'" she says. "We know fat is bad for your health." Besides, the experiment was on rats, not people.

But the research confirms that polyphenols are good for us, and the results aren't lost on Rotondo, a wine lover. "Wine is first of all part of a good life. It's an enjoyable part of the Mediterranean diet," says Rotondo, who drinks wine every night with meals. "The best thing is to have wine daily in the context of a healthy diet."

Jean-Marc Orgogozo: Recommending alcohol for the elderly

Myths and misconceptions cloud much contemporary thinking about the relationship between wine drinking and good health. But an intrepid French neuropsychologist has shot down one of the most persistent misunderstandings in medical history.

Jean-Marc Orgogozo, 53, is chairman of the neurology department of the University Hospital Pellegrin in Bordeaux. In landmark research, he asserts that wine consumption can help prevent the onset of dementia and its most common type, Alzheimer's disease.

"Many doctors are saying to their elderly patients, 'You are now too old, so you should no longer drink,'" says Orgogozo. But according to Orgogozo's 13-year epidemiological research of elderly residents in Dordogne and Gironde, the areas around Bordeaux, those well-meaning doctors are wrong.

In 1988, Orgogozo and a colleague, Jean-François Dartigues, decided to test the conventional medical wisdom that moderate drinking was toxic for the elderly. The hypothesis was that the elderly were at risk, even when drinking just a couple of glasses a day, because their livers had slowed and their brains were more fragile.

This epidemiological project in southwestern France monitored and analyzed the health and drinking habits of 3,777 residents. All were 65 or older at the start of the study and were selected from dozens of villages and towns in the area around Bordeaux. Of the 60 percent who drank regularly, 95 percent drank wine, most of it red.

The results were dramatic. Compared with nondrinkers, those who drank a moderate amount of wine reduced their risks of dementia by 80 percent and of Alzheimer's disease by 75 percent during the first five years of the study. The protection from wine declined slightly as the subjects grew older and more of them were struck by the illness. However, eight years into the study, those who had kept drinking moderate amounts of wine still enjoyed a 50 percent reduction in the risk of developing Alzheimer's disease and dementia, compared with the nondrinkers.

"It seems that there is no medical rationale to advise people over 65 to quit drinking wine moderately, as this habit carries no specific risk and may even be of some benefit for their health," wrote Orgogozo and colleagues. The paper, published in 1997 in Revue Neurologique, with more details given in the American Journal of Epidemiology in 1998, showed typical professional reserve, but in person Orgogozo is more direct: "It's fantastic. No drug can do that. If a drug could do that, it would be an immense success. Even a drug that would reduce these risks by just 15 percent would immediately be accepted by the Food and Drug Administration."

The study defined "moderate" daily drinking for women as two to three standard glasses; for men, moderation ranged from three to four glasses a day, with a 4.5-ounce serving equaling one glass of wine.

It was important to stick to these rather generous quantities of wine to benefit fully from the protection. "Mild" consumption -- two glasses (9 ounces) a day or less -- seemed to give no protection against the onset of Alzheimer's disease and dementia, according to a prominent French study of aging. Heavier drinking was too infrequent (3 percent of the subjects) to allow conclusions.

Only a few hundred women in the study drank regularly, but their results were surprising: In a 10-year follow-up, not a single one of the women who drank three to four glasses of wine per day had developed Alzheimer's disease or dementia. "Normally, we should have found several cases [in this group]," says Orgogozo, as women are more prone to Alzheimer's disease than men are.

"There is really a threshold. You have to drink three to four glasses a day, which isn't bad," says Orgogozo, raising a glass of '99 red Burgundy during a recent dinner in Bordeaux. He has taken after his subjects and averages three glasses nightly. But he doesn't hold himself to this conservative limit on special occasions. His rotund constitution betrays his love of the good life.

Orgogozo, a native of the French Basque region, is warm, charming and expansive. His knowledge about wine, health, strokes and Alzheimer's has led to expert positions in French and European official organizations as well as to consulting roles for several companies.

It's far from certain that nondrinkers who start to consume wine when they grow old would receive the same protective benefits as the Bordeaux residents monitored in the French study. They may have built up protection against the diseases through a lifelong moderate consumption of wine.

"If you have always had water, and you start drinking at 65 to avoid the risk of Alzheimer's disease -- nothing proves it would work," says Orgogozo. "But for those who did drink moderately, our study affirms that there is no danger to continue doing so, and it's probably beneficial."

Elias Castanas: How wine may prevent cancer

"Scientists and artists are paid to follow their imagination," says Elias Castanas, professor of experimental endocrinology at the University of Crete's School of Medicine in Iráklion. But the Athens-born researcher never imagined he might prove that wine could perhaps cure cancer.

Castanas, 50, has found evidence suggesting that drinking one or two glasses of red wine per day might inhibit breast and prostate cancer. His results have scientists around the world scratching their heads in disbelief. Castanas, who is a medical doctor with a Ph.D. in biochemistry, understands their skepticism.

"My first reaction was, there must be a mistake," said Castanas. "I didn't believe that with one or two glasses [of wine] you could stop the proliferation of cancer cells. That was really new. But we ran the tests again and again and again, and it was true."

Castanas repeated his tests several times, with identical results, but they were so unexpected that the first two journals he approached refused to publish them. In early 2000, however, a third publication, the Journal of Cellular Biochemistry, published his paper entitled "Potent Inhibitory Action of Red Wine Polyphenols on Human Breast Cancer Cells." The same year, the journal Nutrition and Cancer published another paper written by Castanas and colleagues entitled "Wine Antioxidant Polyphenols Inhibit the Proliferation of Human Prostate Cancer Cell Lines."

Castanas is a dogged researcher, a wine lover and a bon vivant. When he isn't enjoying the best restaurants on the island of Crete, he might be found in the lab analyzing wine for vintner friends. These extracurricular activities are welcome distractions from his job. Most of his time is spent manipulating cancer cells.

Castanas' possible breakthrough was triggered three years ago, when he was approached by a group of French scientists. They knew Castanas was studying the action of various food substances on cancer, and sent him purified polyphenols they had extracted from Cabernet Sauvignon.

Castanas used polyphenols, such as quercetin, against cancer lines in his laboratory tests.

In Crete, Castanas' team proceeded with meticulous precision. In separate tests, the researchers seeded and incubated human cells that had characteristics of advanced breast and prostate cancer. They then added polyphenols derived from de-alcoholized wine to the cultures. Because cells are sensitive to alcohol, alcohol was eliminated in all the experiments, but after two days of incubation, the phenolic substance inhibited cell proliferation. Castanas found that the polyphenol quercetin he had obtained from the French efficiently inhibited the spread of prostate cancer cells at very low doses, the equivalent of one or two glasses of wine daily.

The Cretan researchers reached a promising conclusion. "Low concentrations of polyphenols, and consequently, consumption of moderate quantities of wine, could have a beneficial antiproliferative effect on breast and prostate cancer cell growth," they said.

Breast and prostate cancers are among the most common malignancies in Western society, so researchers like Castanas might one day become medical heroes. For the moment, however, the conclusions are based on laboratory tests, and Castanas warns that quercetin, or other wine-related polyphenols, may not have the same effect in the human body as they do in test tubes.

"What we've done is study cells, not humans. Cancer cells are inhibited by wine, but I'm not saying wine cures breast or prostate cancer," says Castanas. "All we can say is that wine may be good against breast cancer because it inhibits cancer cells at different stages of their evolution."

Castanas believes science is five years away from proving whether wine's antioxidant polyphenols do kill breast and prostate cancer cells in humans. However, he said preliminary animal studies seem to back his laboratory, or in vitro, research. "This isn't science fiction, but science fact. I think I will be right. But for the moment, I have to be cautious. We shouldn't give false hopes to people having cancer."

Personally, the Greek scientist isn't waiting for confirmation to indulge with gusto his love for a fine wine. Raising a glass of a fragrant, rich 1998 Cabernet Sauvignon made by a doctor friend in Crete, he says, "Wine is good and it's good to your health."

This article appears in the Dec. 15, 2001, issue of Wine Spectator magazine, page 55. (Subscribe today)

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