A quick online search for 鈥渞esveratrol supplements鈥� finds dozens produced by various companies. They contain anywhere from 50 to 500 mg resveratrol per capsule and sport labels that scream 鈥渟ource of antioxidants.鈥� But there is no mention of any condition that resveratrol is expected to treat or prevent. For good reason! While there is plenty of speculation about what this compound can do based on laboratory experiments that use cell cultures, yeasts, worms, flies or rodents, it is best to remember that humans are not giant test tubes or colossal rodents. Clinical evidence for any benefit of resveratrol supplements in people is sparse, but there are some interesting possibilities as researchers aim to develop special formulations of resveratrol that increase its absorption and therefore levels in the blood previously not achievable.
Why should there be any interest in more absorbable formulations of a compound that our body does not naturally produce? That interest traces back to the observation in the 1970s that the incidence of coronary disease in France was lower than in North America. The coronary arteries supply blood to the heart muscle and derive their name from the Latin word for 鈥渃rown鈥� because they encircle the heart like a crown. A narrowing or blocking of these arteries聽by a buildup of cholesterol and fatty deposits, known as 鈥減laque,鈥� results in decreased blood flow, and consequently reduced oxygen delivery to the heart muscle. This reduced oxygen supply can lead to the injury or death of muscle cells that then presents as a heart attack, or in medical terms, a 鈥渕yocardial infarction (MI).鈥�
Why were the French less prone to coronary disease? That was a surprising finding given that in the 1950s American physiologist Ancel Keys had presented data linking a diet high in saturated fats to heart disease. How was it then that the French, with their penchant for buttery croissants, fatty cheeses and cholesterol-laden goose liver seemed to be protected from the buildup of plaque in their arteries? That was a paradox, a 鈥淔rench Paradox!鈥�
Were the French doing something that protected then from the condition that was rampant on this side of the ocean? An obvious difference was that they were drinking more wine. Thirty times more!聽Could there be some sort of protective factor in wine, scientists wondered? Attention began to focus on resveratrol, a compound first detected in red wine in 1992 by Cornell University researchers. They were studying why some red grapes are more resistant to fungal attack and found that the resistant grapes produce resveratrol in their skin as a defensive compound. That prompted an investigation of red wine to see if it also contained the antifungal compound. It did! Ten years earlier, Japanese researchers had also come across resveratrol as they investigated the chemical composition of the Japanese knotweed plant because of the plant鈥檚 history of medicinal use. One of the compounds they isolated was resveratrol that they subsequently found reduced deposition of fats in rat liver.
Resveratrol turned out to belong to a family of compounds known as 鈥減olyphenols鈥� that had drawn interest since the 1930s when Hungarian Nobel Laureate Albert Szent-Gyorgyi isolated several, specifically rutin and hesperidin, from plant sources such as lemons or paprika. He discovered that these compounds reduced the fragility of capillaries, the body鈥檚 smallest and most delicate blood vessels. Obviously, polyphenols had biological activity.
The stage was now set. Red wine had been found to contain resveratrol, a compound linked with reducing fatty deposits. It also belonged to the family of polyphenols, some of which had been shown to reduce blood vessel fragility. The French drank more red wine. Could it then be that it was the resveratrol they were consuming that offered protection from heart disease? The American media ran with that story and sales of red wine mushroomed. But 鈥渨hoa,鈥� scientists said. This needs more investigation. And investigate they did.
In the lab, resveratrol was found to reduce inflammation, lower the risk of blood clot formation, improve blood vessel flexibility, neutralize tissue damaging free radicals, and activate genes that code for the production of enzymes known as sirtuins that research linked to increased longevity in yeast, worms and flies. But there were flies in that ointment. The activation of the sirtuin genes turned out to be due to a faulty assay and the doses of resveratrol used in the cell culture and animal studies are not achievable in humans. Furthermore, any benefit found in humans was in terms of some improvement in biomarkers such as insulin resistance, not in any change in hard outcomes like fewer heart attacks or slower dementia progression or increased longevity.
A major problem with human trials is that resveratrol has very low solubility and when used as a dietary supplement fails to be absorbed to any significant degree. Any that is absorbed is quickly metabolized with the metabolites being excreted. Since taking standard oral supplements of resveratrol is therefore essentially useless, researchers are now focusing on versions with enhanced absorbability. Jupiter Neurosciences has managed to develop 鈥淛otrol,鈥� a drug in which resveratrol is encapsulated in a proprietary lipid coating that results in nine times higher bioavailability than conventional resveratrol. In mouse models, the drug has been shown to cross the blood-brain barrier and offers protection against Parkinson鈥檚 disease. The deposition of amyloid proteins, characteristic of Alzheimer鈥檚 disease, was also reduced. Clinical trials are now underway to see if Jotrol can deliver benefits for humans.
Maybe specially designed absorbable forms of resveratrol will turn out to have some benefit, maybe even on cardiovascular disease. But that will not justify the effusive articles that have appeared in the media about the French Paradox being explained by resveratrol in wine. That is total nonsense. The amount of resveratrol in wine is miniscule, way too little to have any biological effect.
What then explains the French Paradox? There are suggestions that statistics are skewed because in France some fatalities are just listed as 鈥渟udden death鈥� and do not appear in coronary disease statistics. Still, there is general agreement among epidemiologists that France really does have a lower rate of heart disease. Maybe it is because the French eat smaller portions, consume fewer processed foods, walk more, take longer vacations, don鈥檛 eat large American style breakfasts, have their main meal in the middle of the day and place more emphasis on leisure activities and social life. It is certainly not because of resveratrol, or anything else, in red wine.
So, what are people getting when they are scoffing large doses of resveratrol supplements spurred by the gushy stories about resveratrol in red wine? Nothing other than a chance of gastrointestinal symptoms and the risk of interaction with prescription drugs they may be taking. I鈥檇 leave the supplement on the shelf.
As far as red wine goes, it has no health benefits. Pliny the Elder, the Roman historian opined that 鈥渋n wine there is truth.鈥� The truth is that early studies about a glass of red wine a day being 鈥渉ealthy鈥� have been debunked, and the scientific consensus now is that even one drink a day increases the risk of cancer, cardiovascular disease, liver disease and all cause early mortality. That being said, I do think that the current statement circulating that 鈥渢here is no safe amount of alcohol鈥� is a little extreme. I doubt that the occasional glass of red wine will shorten life. But it will certainly not extend it.
