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The Cellar Dweller


Jury still out on the substance that appears tomake wine amagic elixir.


I


doubt that anyone in the world who has an association with grapes and wine has not heard that red wine helps you to live a longer, healthier life. A much smaller population has heard of resveratrol, the substance that is mostly credited with the health-boosting effects of red wine, and to a lesser extent white wines.


I’ll bet you didn’t know that you can also get your daily dose of resveratrol from peanuts, blueberries or cranberries. Make mine wine, please. I’ve been following the resveratrol story for about 15 years. I just did a search of my data drive for resveratrol and 439 files were listed. Where do I start?


Twenty years ago the public interest began when 60 Minutes did a story on a research study that compared middle- aged men in the United States and France, and exposed that the French lived longer and were healthier in spite of their evil behaviours of smoking and drinking red wine. A few years after that the word got around that resveratrol appeared to be the substance responsible for most of the effects. Interestingly, one of the pioneers in this search was Dr George Soleas, who was then head of wine research for Andres Wines and is now vice president in charge of quality control and logistics for the Liquor Control Board of Ontario. Another early entrant into the field was wine writer, Bill Sardi, from California. He was convinced of the value of resveratrol as a dietary supplement and opened a small company to manufacture pills containing resveratrol.


Sardi and I have been exchanging correspondence about resveratrol for about 12 years.


In winemaking, resveratrol is released from red grapes during the skin maceration extraction of colour (anthocyanins) and tannins (polyphenolics). Tannins contribute astringency and antioxidant activity to red wines.


Within the phenolic fraction of wines 30


there is a group of compounds called flavones. All of the flavones have antioxidant activity and many of them have biological activity, which makes them useful as dietary supplements. Flavones are important in winemaking because they participate in a reaction called copigmentation which enhances red wine colour and stability. Resveratrol, a flavone, is also a phytoalexin, which means that it is produced by some plants in order to ward off infections from bacteria, fungi, and insects. The level of resveratrol in plants is thus related to that plant’s constitutive resistance to infection, but it can also be related to the cultural conditions.


Grapes grown in humid regions with higher incidence of mildew tend to have higher resveratrol content than grapes grown in low humidity with reduced mildew risk. On the other hand, resveratrol content is enhanced in grapes whose roots have been inoculated with symbiotic fungi of the Mycorrhizae group. Another early entrant into the field was David Sinclair, a molecular biologist at Harvard Medical School. He founded a company called Sirtris. The name was based on a group of genes that were thought to be affected by resveratrol. The sirtuins (there are seven known) comprise a group of genes that have a role in human ageing and in prevention of metabolic disorders such as diabetes. Sinclair’s thought was that resveratrol-like compounds could be valuable pharmaceuticals. Sirtris, founded in 2004, was sold in 2008 to London-based pharmaceutical company GlaxoSmithKline (GSK) for $720


By Gary Strachan Unravelling the mysteries of resveratrol million.


There’s more to the story. An editorial in the March 25 issue of Nature came close to calling Sinclair a charlatan. An earlier issue of Nature (Jan. 19) questioned that the results of the Sirtris trials were third party reproducible. Further investigation published online by the magazine on Marh 24 reviewed experimental results in which the biological activity of the Sirtris compounds lost their biological activity unless they were joined to fluorescing proteins used to trace them. There are a lot of unanswered questions but GSK still contends it will have an anti-aging pill on the market within two years The Wall Street Journal reported on May 4 that GSK has suspended clinical trials of its experimental SRT501, “for safety reasons”.


Sardi contends that Sirtris has been on the wrong track from the beginning. The observation from population studies was that drinking two or three glasses of red wine per day is beneficial to health. This would contain resveratrol in the range of 100 to 300 mg.


Sirtris has contended that up to 5,000 mg/day of resveratrol is required for biological activity. Sirtris’ study initiated the rumour that it required


consumption of 1,000 bottles of wine to achieve a beneficial effect from resveratrol.


Sardi has cited animal studies in which the Sirtris-recommended dose caused kidney toxicity. The Journal of Biological Chemistry has published a study which says that Sirtuin 1 is not the target gene of resveratrol or the Sirtris analogues that were tested in their study.


There have been a lot of biochemical studies to determine the target genes and biochemical activity of resveratrol. Perhaps some day we’ll have the full answer. Sardi has regular discussions with academic researchers who are studying resveratrol and he has a wealth of information about the substance. I expect he’d like to make a $720 million sale, but the pills that he blends don’t have the flashy cachet of Sirtis synthesized products.


I think I’ll have a glass of red wine while I consider the question. — Gary Strachan can be reached at gestrachan@alum.mit.edu.


British Columbia FRUIT GROWER • Summer 2010


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