FEATURE

Serge Renaud: from French paradox to Cretan miracle ow in his ~OS, Serge Renaud has N b e e n challenging dogma and winning scient& bets for more than 50 years. As a student in Montreal, Canada, in the 195Os, Renaud showed in a fortnight that an experimental animal polyarthritis-held for 2 years to be stress induced-was caused by an infectious agent. But what he is best known for is his work on the link between wine, diet, and thrombosis. “If 1 hadn’t lived with my grandparents and great-grandparents on a vineyard near Bordeaux, perhaps mis idea wouldn’t have occurred to me. When you see people reach the age of 80 or 90 years, who have been drinking small amounts of wine every day, you don’t believe wine in low doses is harmful”, says Renaud. Renaud started his medical ² ing in France in 1949, but realising that he wanted to do research, he moved to Canada 2 years later. “Research was something you could hardly earn your keep with in France”, he explains. In Canada, the “incredible coronary mortality” made a deep impression on him, but the concept of wine’s benefits came later. In 1970, Renaud heard how, in the Framingham study, low-dose alcohol had protected against death from coronary heart disease. This result was not published for a while, he recalls, because “the [US] National Institutes of Health feared it might encourage drinking”. In 1973, Renaud returned to France to investigate the behaviour of platelets in animals and people. He found that platelet aggregation was reduced in rats that had been fed alcohol. On alcohol withdrawal, there was a rebound effect and the platelets became stickier than normal. “The human corollary of this is ischaemic events after binge drinking”, he notes. In French and British farmers, platelet aggregation also decreased after low doses of alcohol, but in the French farmers there was no rebound effect when alcohol (wine) was withdrawn. After further study, Renaud reported that alcohol causes a dose-dependent inhibition of adenosine-diphosphate-induced platelet aggregation, as does aspirin. “Aspirin and alcohol share effects and mechanisms”, he noted in 1990. Then, in 199 1, Renaud was asked on US television for his explanation of the “French paradox”-the lowerthan-expected coronary mortality in France. “Low-dose alcohol 48

consumption”, he replied. Renaud stressed then, as he does now, that alcohol is a hazard except at low doses, but the US Administration demanded that he justify his comment. “That is how my paper on the French paradox, written with Michel de Lorgeril and published in 7’he Lancet, originated. Had my results not been convincing 1 think INSERM [Institut National de Santé et de la Recherche Médicale, Renaud’s employer] would have fired me.” Renaud kept his job but not everyone agrees with his ideas about the French paradox. No magie pill “Coronary incidence data now deny there is a French paradox”, notes Pierre Ducimetière (INSERM, Villejuif, France). The lower coronary mortality in France compared with other countries “is a consequence of different ways of coding coronary mortality”, he asserts, not a view that Renaud agrees with. Renaud’s interest in how table habits affect health does not stop with alcohol. “More than almost any other investigator, Renaud has helped us appreciate the role of diet in coronary heart disease, pointing out how dietary factors affect its development other than through their effect on blood cholesterol”, says R Curtis Ellison (Boston University, MA, USA). This side of Renaud’s work goes back to 1960 when, against prevailing opinion, Renaud postulated that thrombosis is crucial in acute coronary syndromes. He then went on to show that in-vitro aggregation of platelets from people in the Moselle region of France where there is a high incidence of coronary disease could be brought to coincide with that of platelets from people living in Provence, a low incidence region, by means of a diet rich in oleic and a-linolenic fatty acids. “It was diet that made the difference, not genes or environment”, says Renaud. Then, “when 1 saw the results of the Seven Countries Study in 1980”, .‘he recalls, “1 thought, Cretans must be doing-or eating-something right”. Crete had by far the lowest coronary mortality of the cotmtries studied. Yet, serum cholesterol concentrations were higher in Crete than in other countries with higher coro-

nary mortalities. “Something protects Cretans which does not reduce their cholesterol”, proposed Renaud. Renaud guessed that the difference was a-linolenic acid and set up the Lyon Diet Heart Study in 1985, a secondary prevention trial. Overall, deaths and cardiovascular events were reduced by at least 70%, with the protective effect occurring within 2 months. This study, which was published in The Lancet in 1994, was initially rejected by the New England J o u r n a l Medicine because the

“intervention induced no changes in serum lipids”, a- fact that left the referees “wondering how such a large mortality reduction could have possibly been achieved”. Renaud’s answer is simple. The participants in the Lyon study ate like Cretans: no butter, cream, or milk; lots of vegetables, fruit, bread, and cereals; and little meat. For the study, Renaud designed a margarine similar in composition to olive oil, but enriched in o-linolenic acid. Patients ate cheese (“a 9000 year old invention not linked to coronary disease”) and, of course, drank wine. Other linolenic acid-rich ingredients of the Cretan diet-walnuts, snails, and purslane-were replaced by his margarine. Although linolenic acid’s protective effects have been corroborated in other studies, Ducimetière wams that “the extraordinary [Lyon] results await conlïrmation”. Renaud is now retired but has yet another diet-related hunch: that the Cretan diet Will prevent arrhythmias, an idea prompted by the reduction in ventricular fibrillation in the Lyon study. Summing up his life’s work, Renaud says it has made him “wonder about the origins of civilisations. It is intriguing that ancient Asian and Mediterranean civilisations used natural oils in cooking-colza and olive-with similar fatty acid compositions”. And because of his belief in ancient wisdom when it cornes to diet and health, Renaud ends his book Le régime santé (Odile Jacob, Paris, 1998) with a waming: “Don’t look for a pi11 that replaces [the Cretan diet] . There is no such thing.”

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THE LAh’CET * Vol 355 . January

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