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Wine IS Medicine Georges M. Halpern, MD, PhD

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1 Wine IS Medicine Georges M. Halpern, MD, PhD
Distinguished Professor of Pharmaceutical Sciences Hong Kong Polytechnic University HK PolyU 23/02/05

2 Disclaimer This presentation is exclusively prepared for education and information. It was not supported by any commercial company, or wine industry-related institution. All references are available on PubMed/Medline (National Library of Medicine). I do not support, encourage or condone alcoholism, or any form of abuse of wine. HK PolyU 23/02/05

3 What is Wine. German JB, Walzem RL. The health benefits of wine
What is Wine? German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000;20: The term wine describes a diverse commodity class composed of the yeast fermentation products of the must, or juice, pressed from grapes, the fruit of genus Vitis. Wine is a fruit product, but fermentation produces a variety of chemical changes in the must, and so wine is not simply grape juice with ethanol added. Fermentation alters the must by altering the conjugation of organic acids and phenolics, by extraction and formation of copigments and the development of an anaerobic and protective redox potential. HK PolyU 23/02/05

4 Wine & Ethanol German JB, Walzem RL. Annu Rev Nutr 2000;20:561-593
Wine contains 8-15% ethanol by weight. The effects of ethanol on overall mortality in modern western populations follow a J-shaped curve. In such a relationship, moderate ethanol intakes produce a significant reduction in mortality relative to abstinence from ethanol, but, beyond moderate intakes, mortality rises sharply. HK PolyU 23/02/05

5 Is Wine Different from Other Alcoholic Beverages. Burns J, Crozier A
Is Wine Different from Other Alcoholic Beverages? Burns J, Crozier A. Lean ME. Alcohol consumption and mortality: is wine different from other alcoholic beverages? Nutr Metab Cardiovasc Dis 2001;11: Both clinical and experimental evidence suggest that red wine offers greater protection to health.; this is attributed to grape-derived antioxidant polyphenolics found particularly in red wine. HK PolyU 23/02/05

6 Composition of Wine Excluding Phenolic Acids and Polyphenols
Component Concentration (g/100ml) Water 80-90 Carbohydrates/sugars Alcohols (mostly ethyl) Glycerol Aldehyde Organic Acid (e.g. tartaric, etc.) Nitrogenous compounds Mineral Compounds (K, etc.) HK PolyU 23/02/05

7 Summary of Phenolic Acid and Polyphenol Components of Red and White Wines
Concentration (mg/L) Component Red Wine White Wine Nonflavonoids: Hydroxybenzoic acids, Hydroxycinnamic acids, Stilbenes Flavonoids: Flavonols, Flavanols, Anthocyanins 25-30 Total phenolic acids and polyphenols 1200 ( ) 200 ( ) HK PolyU 23/02/05

8 The Antioxidant Activity in 1 Glass of Red Wine (150 ml) is Equivalent to that Found in:
12 glasses of White Wine 2 cups of Tea 5 Apples 5 (100g) port. of Onion 5.5 port. of Eggplant 3.5 gl. of Black Currant juice 500 ml of Beer 7 glasses of Orange juice 20 glasses of Apple juice HK PolyU 23/02/05

9 Pharmacokinetic Parameters of Wine and Food Flavonoids
Quercetin Epicatechin Catechin Parameter Fried Onions Apples Nestlé Noir 40g Nestlé Noir 80g Wine - Ethanol Wine + Ethanol Dose (mg) 68 98 82 164 35 E1/2(h) 28 23 1.9 2.3 3.8 3.1 Tmax(h) 0.7 2.5 2.0 2.6 1.5 Cmax(mmol liter-1) 740 300 355 675 81 91 HK PolyU 23/02/05

10 The ONLY Thing that Improves with Age is Wine
The ONLY Thing that Improves with Age is Wine! Burns J, Gardner PT, Matthews D, et al. Extraction of phenolics and changes in antioxidant activity of red wines during vinification. J Agriic Food Chem 2001;49: 4 wines were tested. 9 days after vinification the total phenolic content was comparable to the one of a bottled wine, but the antioxidant activity, due to larger polyphenolics that appear during aging, was significantly lower. HK PolyU 23/02/05

11 Catechin is Present as Metabolites in Human Plasma after Consumption of Red Wine Donovan JL, Bell JR, Kasim-Karakas S, German JB, Walzem RL et al. J Nutr 1999;129: Catechin is present almost exclusively as metabolites in plasma after consumption of red wine. Flavonoids are extensively conjugated after absorption from foods; it is the metabolites, and not the forms that exist in foods, that require attention. HK PolyU 23/02/05

12 Catechins from Red Wine are Absorbed and Excreted, Regardless of Alcohol Content Donovan JL, Kasim-Karakas S, German JB, Waterhouse AL. Urinary excretion of catechin metabolites by human subjects after red wine consumption. Br J Nutr 2002;87:31-7.                                           Catechin in all urine samples was present as metabolites, without differences between red wine and de-alcoholized red wine (120 ml/day). HK PolyU 23/02/05

13 Red Wine >White Wine on Platelets Pignatelli P, Lenti L, Pulcinelli FM, et al. Red and white wine differently affect collagen-induced platelet aggregation. Pathophysiol Haemost Thromb 2002;32: 20 healthy subjects randomly consumed 300ml/day x 2w of red or white wine (same % ethanol). At +2w, red wine subjects had lower response to platelet agonist (p<0.005). This is probably due to the higher concentration in polyphenols in red wine. HK PolyU 23/02/05

14 Consumption of Red Wine with Meals Reduces the Susceptibility of Human Plasma and Low-Density Lipoprotein to Lipid Peroxidation Fuhrman B, Lavy A, Aviram M. Am J Clin Nutr 1995;61: Red wine consumption [400 mL/day x 2 wk] resulted in 20% reduction of plasma lipid peroxidation (TBARS), reduced LDL lipid peroxidation (Cu ions), and prolonged the lag phase required for LDL oxidation. White wine consumption resulted in 34% increase in plasma lipid peroxidation, and 41% increase of LDL lipid peroxidation. Vitamin E or beta-carotene did not change; red wine polyphenols were elevated in plasma and LDL. HK PolyU 23/02/05

15 Red Wine Protects Against Cigarette Papamichael C, Karatzis E, Karatzi K et al. Red wine’s antioxidants counteract acute endothelial dysfunction caused by cigarette smoking in healthy nonsmokers. Am Heart J 2004;147:274. Acute smoking of 1 cigarette in 16 healthy volunteers caused a reduction in flow-mediated dilatation (p<.001). Simultaneous ingestion of red wine or dealcoholized red wine abrogated this effect on FMD, and harmful effects on endothelium. HK PolyU 23/02/05

16 Drink Wine With Meals Trevisan M, Schisterman E, Menotti A et al
Drink Wine With Meals Trevisan M, Schisterman E, Menotti A et al. Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project. Ann Epidemiol 2001;11: 8647 men and 6521 women, age at baseline were followed for 7 years. Drinkers of wine outside meals exhibited higher death rates (all causes, non CV, cancer) as compared to drinkers of wine with meals. HK PolyU 23/02/05

17 Red Wine vs. High-fat Meals Ventura P, Bini A, Panini R, Marri L, Tomasi A, Salvioli G. Red wine consumption prevents vascular oxidative stress induced by a high-fat meal in healthy volunteers. Int J Vitam Nutr Res 2004;74: Ingestion of red wine during a high-fat meal significantly reduces oxidative stress without inducing any significant modification in postprandial lipemia. HK PolyU 23/02/05

18 Copenhagen City Heart Study Gronbaek M et al. BMJ 1995;310:1165-1169
HK PolyU 23/02/05

19 Copenhagen City Mortality Study Gronbaek M et al
Copenhagen City Mortality Study Gronbaek M et al. Ann Intern Med 2000;133: During person-years of follow-up, 4833 participants died. Wine drinkers had significantly lower mortality from both coronary heart disease and cancer than did non-wine drinkers (p=0.007 and p=0.004, respectively). Wine intake may have a beneficial effect on all-cause mortality that is additive to alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer. HK PolyU 23/02/05

20 Does Wine Work? Goldberg D. Clinical Chemistry 1995;41:14-16
If every North American drank 2 glasses of wine each day, cardiovascular disease, which accounts for almost 50% of deaths in this population, would be cut by 40%, and $40 billion could be saved annually. HK PolyU 23/02/05

21 Wine beats Valium® Paladini AC et al
Wine beats Valium® Paladini AC et al. Flavonoids and the CNS: from forgotten factor to potent anxiolytic compounds. J Pharm Pharmacol 1999:51; Some natural occurring wine flavonoids, e.g. chrysin and apigenin, selectively bind with high affinity to the central benzodiazepine receptor, and exert powerful anxiolytic effects. HK PolyU 23/02/05

22 Wine Protects the Brain of the Elderly Orgogozo JM, Dartigues JF, Lafont S et al Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.Rev Neurol [Paris] 1997;153: 3777 community residents ≥65 y were enrolled; 3 y later 2273 subjects were studied. 318 drank ml/d of wine; OR was 0.18 for incident dementia (p<0.01) and 0.25 for Alzheimer’s (p<0.03) when compared to 971 non-drinkers. There is no medical rationale to advise people >65 to quit drinking wine moderately. HK PolyU 23/02/05

23 Wine Sharpens Your Brain. Britton A, Singh-Manoux A, Marmot M
Wine Sharpens Your Brain! Britton A, Singh-Manoux A, Marmot M. Alcohol consumption and cognitive function in the Whitehall II study. Am J Epidemiol 2004;160: Increasing levels of alcohol (mostly wine) consumption (>240g/week) in middle-aged subjects (4,272 ♂, 1761 ♀; 46-68y) were associated with better cognitive function: memory test, AH4, Mill-Hill, phonetic and semantic fluency. The effect was stronger for women, and not explained by confounding factors. HK PolyU 23/02/05

24 A Pleasant Way to Protect Diabetics: Red Wine Ceriello A, Bortolotti N, Motz E, et al. Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes. Eur J Clin Invest 2001;31: Free radicals are produced in the absorptive phase, with reduced serum antioxidant capabilities, LDL oxidation, and activation of coagulation. Moderate consumption of red wine, during a meal, preserves plasma antioxidation and reduces both LDL oxidation and thrombotic activation, in diabetics. Some of the symptoms of diabetes are: Frequent urination Excessive thirst Extreme hunger Unusual weight loss Increased fatigue Irritability Blurry vision HK PolyU 23/02/05

25 Wine and Retina Obisesan TO, Hirsch R, Kosoko O, et al
Wine and Retina Obisesan TO, Hirsch R, Kosoko O, et al. Moderate wine consumption is associated with decreased odds in developing age-related macular degeneration in NHANES-1. J am Geriatr Soc 1998;46:1-7 In a study of >3,000 adults, alcohol consumers (wine drinkers in particular) were found to be at reduced risk for AMD. The effects of wine as antioxidant, and on platelet aggregability are associated with reducing the odds of developing AMD. HK PolyU 23/02/05

26 Wine and Gallstones in Italy Attili AF, Scafato E, Marchioli R, Marfisi RM, Festi D. Diet and gallstones in Italy: the cross-sectional MICOL results. Hepatology 1998;27: After analyzing data from >15,000 men and >13,000 women, they observed a decreasing risk of GS and increasing serum HDL levels by increasing daily wine consumption. HK PolyU 23/02/05

27 Antibacterial Activity of Wine vs
Antibacterial Activity of Wine vs. Salmonella enteritidis: pH or alcohol? Marimon JM, Bujanda L, Gutierrez-Stampa MA, et al. J Clin Gastroenterol 1998;27: Red wine’s bactericidal effect was large and greater than the same ethanol concentration at the same pH. Polyphenols may well have a bactericidal effect. [The same group confirmed bactericidal effect vs. H. Pylori. AJG 1998;93:1392] HK PolyU 23/02/05

28 Wine –not Beer or Alcohol- Protects vs
Wine –not Beer or Alcohol- Protects vs. Common Cold Takkouche B, Regueira-Mendez C, Garcia-Closas R, et al. Intake of wine, beer, and spirits and the risk of clinical common cold. Am J Epidemiol 2002;155: When drinkers of >14 glasses of wine/week were compared to teetotalers, the r risk was 0.6. Wine intake (red wine) may have a protective effect vs. common cold, while beer, spirits and total alcohol intake did not affect the incidence. HK PolyU 23/02/05

29 Wine as Digestive Aid Weisse ME, Eberly B, Person DA
Wine as Digestive Aid Weisse ME, Eberly B, Person DA. BMJ 1995;311: HK PolyU 23/02/05

30 Wine as a Digestive Aid Weisse ME, Eberly B, Person DA
Wine as a Digestive Aid Weisse ME, Eberly B, Person DA. BMJ 1995;311: Undiluted red and white wine, and bismuth salicylate (Pepto-Bismol®) were both effective in reducing the number of viable Salmonella, Shigella, and Escherichia coli (by CFUs) after minutes. Dilutions of wine were much more effective in decreasing colony counts than were similar dilutions of bismuth salicylate. The antibacterial property of wine is largely responsible for wine’s reputation as a digestive aid. HK PolyU 23/02/05

31 Red Chilean Wines Kill H
Red Chilean Wines Kill H. pylori Daroch F, Hoeneisen M, Gonzalez CL, et al. In vitro antibacterial activity of Chilean red wines against Helicobacter pylori. Microbios 2001;104:79-85. 16 Chilean red wines (Cabernet Sauvignon, Cabernet Merlot, Cabernet Organic & Pinot noir), and the active extracts of 2 randomly selected wines did demonstrate antibacterial activity vs. 6 strains of H. Pylori isolated from gastric biopsies. Activity depended mainly on resveratrol. HK PolyU 23/02/05

32 Wine, Osteoporosis and Hip Fracture Hoidrup S, Gronbaek M, Gottschau A, Lauritzen JB, Schroll M. Am J Epidemiol 1999;149: Research included 32,000 patients. A light to moderate alcohol intake does not influence the risk of hip fracture. Preferrers of wine tend to have a lower risk of hip fracture as compared to preferrers of other alcoholic drinks. HK PolyU 23/02/05

33 Resveratrol vs. Human Breast Cells Mgbonyebi OP, Russo J, Russo IH
Resveratrol vs. Human Breast Cells Mgbonyebi OP, Russo J, Russo IH. Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. Int J Oncol 1998;12: The effect of resveratrol is consistent with the activity of other anti-cancer drugs. It is a potential chemopreventive agent for both hormone responsive and non-responsive breast cancers. HK PolyU 23/02/05

34 Suppression of Aromatase by Red Wine Eng ET, Williams D, Mandava U, et al. Suppression of aromatase (estrogen synthetase) by red wine phytochemicals. Breast Cancer Res Treat 2001;67: Aromatase converts androgen to estrogen, hence promoting proliferation of breast cancer cells. Red wine was shown to be much more effective than white wine in suppression of aromatase. This was demonstrated in different cell models, and in a model of transgenic mouse in which aromatase is over-expressed in the mammary tissue. HK PolyU 23/02/05

35 Resveratrol and Quercetin Modulate Oral Cancer Cell Growth El Attar TM, Virji AS. Modulating effect of resveratrol and quercetin on oral cancer growth and proliferation. Anticancer Drugs 1999;10: Resveratrol or a combination of resveratrol and quercetin, in concentrations equivalent to that present in red wines, are effective inhibitors of oral squamous carcinoma cell growth and proliferation. HK PolyU 23/02/05

36 Intake of Wine is Associated with a Reduced Risk of Lung Cancer Prescott E, Gronbaek M, Becker U, Sorensen TI. Alcohol intake and the risk of lung cancer: influence of type of alcoholic beverage. Am J Epidemiol 1999;149: Data from 3 prospective studies of >28,000 subjects confirmed that intake of wine was associated with a reduced risk of lung cancer. This seemingly protective effect may be related to the antioxidant properties of wine. HK PolyU 23/02/05

37 Red Wine, but not White Wine Decreases the Risk of Lung Cancer Ruano-Ravina A, Figueiras A, Barros-Dios JM. Type of wine and risk of lung cancer: a case-control study in Spain. Thorax 2004;59:981-5 In , a study was conducted on 319 subjects (132 cases, 187 controls). A slight but significant (OR 1.2/each daily glass) was observed between lung cancer and white wine consumption. But red wine had an inverse association (OR 0.87). HK PolyU 23/02/05

38 Wine Does Not Increase the Risk of Prostate Cancer Sesso HD, Paffenbarger RS Jr, Lee IM. Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study. Int J Epidemiol 2001;30: 7612 Harvard alumni (~66.6y) were prospectively followed from 1988 through 1993; 366 cases of prostate cancer occurred. Liquor, but not wine or beer, consumption was positively associated with prostate cancer                                  HK PolyU 23/02/05

39 Polyphenols in Red Wine Impair Prostate Cancer Cell Line Romero I, Paez A, Ferruelo A, Lujan M, Berenguer A. Polyphenols in red wine inhibit the proliferation and induce apoptosis of LANCaP cells. BJU Int 2002;89: Quercetin, rutin, morin, gallic acid and tannic acid, from red wine, inhibited the growth of prostate cancer LANCaP cells at different concentrations, and induced apoptosis. HK PolyU 23/02/05

40 Beethoven Should Have Drunk Wine
Beethoven Should Have Drunk Wine! Becker U, Gronbaek M, Johansen D, Sorensen TI. Lower risk for alcohol-induced cirrhosis in wine drinkers. Hepatology 2002;35: Individuals who drank >5 drinks/day had a relative risk of for developing cirrhosis. If wine was 16-30% of total intake, risk was 0.4; if wine was >51%, risk was 0.3. Compared to beer and spirits, wine carries a much lower risk. HK PolyU 23/02/05

41 Wine is Safe for Asthmatics
Two studies Halpern GM et al. Ann Allergy 1985;55:686-69; Vally H et al. J Allergy Clin Immunol 1999;103:41-46 have confirmed that consumption of wine with normal levels of sulfites is safe in most asthmatics. Only a very limited number of exquisitely sensitive patients may suffer, mostly after very high exposure to sulfites. Histamine content does not influence wine tolerance in normal subjects Kanny G et al. Allergie & Immunologie 1999;31: No [n=8] subject reacted after ingesting wine, rich or poor in histamine. There were no changes in plasma histamine, nor in plasma or urinary methyl histamine. The amount of histamine in wine has no clinical or biological effect in healthy subjects. HK PolyU 23/02/05

42 “Moderate” Drinking During Pregnancy: Cause for Concern. Abel EL
“Moderate” Drinking During Pregnancy: Cause for Concern? Abel EL. Clinica Chemica 1996:246:149154 Weighing the issues, the greatest danger to the life of an unborn child does not come from a drink per day but from alarmism over what might be the harm to the child, which could result in termination of an otherwise healthy pregnancy, or psychological distress that might itself lead to an unhealthy pregnancy. HK PolyU 23/02/05

43 Wine Drinkers are Smarter and Richer Mortensen EL, Jensen HH, Sanders SA, Reinish JM. Better psychological functioning and higher social status may largely explain the apparent health benefits of wine: a study of wine and beer drinking in young Danish adults. Arch Intern Med 2001;161: In 363 men and 330 women aged 29-34, wine drinking was significantly associated with higher IQ, parental educational level, and socioeconomic status. Beer drinking was associated with significantly lower scores. Wine drinking is a general indicator of optimal, social, cognitive, and personal development. HK PolyU 23/02/05

44 Drink your Bordeaux in <90” Lupi-Pegurier L, Muller M, Leforestier E, Bertrand MF, Bolla M. In vitro action of Bordeaux red wine on the microhardness of human dental enamel. Arch Oral Biol 2003;48: Wine has no disastrous effect on the microhardness (Vickers; scanning electron microscopy) of dental enamel if contact is <90 s. When exposure is >120 s, the decrease in the microhardness of enamel was significant (P<0.05). HK PolyU 23/02/05

45 The Champagne Angle Pemberton PL, Calder I, O’Sullivan C, Crockard HA
The Champagne Angle Pemberton PL, Calder I, O’Sullivan C, Crockard HA. The Champagne angle. Anaesthesia 2002;57; The cranio-cervical extension required to drain a glass of wine was 40° with a narrow flute, 22º with a wide flute, 26º with a wine glass, and 0º with a champagne saucer. The narrow flute requires 73% of the total available cranio-cervical extension. HK PolyU 23/02/05

46 Cork Injury to the Eye Cavallini GM, Lugli N, Campi L, Pagliani L, Saccarola P. Bottle-cork injury to the eye: a review of 13 cases. Eur J Ophthalmol 2003;13: Bottle-cork injuries account for 10.8% of post-trauma admission in Modena. Most are due to sparkling white wine served at room temperature. There is no correlation between ocular injury and the eye-bottle distance or the type of cork. HK PolyU 23/02/05

47 Enjoy in the Right Shape of Glass Huttenbrink KB, Schmidt C, Delwiche JP, Hummel T. The enjoyment of red wine is influenced by the shape of the wine glass. Laryngorhinootologie 2001;80: Egg-shaped glasses, compared to “tulip” or “beaker” glasses, appear to produce higher intensity and higher complexity of wine odors. HK PolyU 23/02/05

48 Wine May Make you Live 10 More Years
Wine May Make you Live 10 More Years! Howitz KT, Bitterman KJ, Cohen HY, Lamming DW et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003 Aug 24 [Epub ahead of print] Resveratrol, a potent activator of sirtuins, lowers the Michaelis constant of SIRT1 (a human deacetylase) and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. Resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by…70%! HK PolyU 23/02/05

49 Salute! 干杯! Cheers! Santé! Salud! Skål! HK PolyU 23/02/05

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