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Georges M. Halpern, MD, PhD
Distinguished Professor of Pharmaceutical Sciences
Hong Kong Polytechnic University firstname.lastname@example.org
HK PolyU 23/02/05 1
This presentation is exclusively prepared for education and information. It was not supported by any commercial company, or wine industryrelated 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
What is Wine?
German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000;20:561-593
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 3
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
HK PolyU 23/02/05 5 . Alcohol consumption and mortality: is wine different from other alcoholic beverages? Nutr Metab Cardiovasc Dis 2001..11:249-258. this is attributed to grape-derived antioxidant polyphenolics found particularly in red wine. Lean ME. Both clinical and experimental evidence suggest that red wine offers greater protection to health. Crozier A.Is Wine Different from Other Alcoholic Beverages? Burns J.
09 Mineral Compounds (K.01-0.40 Aldehyde 0. etc.15-0.0-15.01-0.)HK PolyU 23/02/05 0.2-0. etc.) 0.30-1.10 Nitrogenous compounds 0.3-1.g. tartaric.45 Alcohols (mostly ethyl) 8.3 Glycerol 0.Composition of Wine Excluding Phenolic Acids and Polyphenols Concentration (g/100ml) Water 80-90 Carbohydrates/sugars 0.40 6 Component .050 Organic Acid (e.
Anthocyanins Total phenolic acids and polyphenols 1200 (900-2500) HK PolyU 23/02/05 200 (190-290) 7 .Summary of Phenolic Acid and Polyphenol Components of Red and White Wines Concentration (mg/L) Component Nonflavonoids: Hydroxybenzoic acids. Stilbenes Red Wine 240-500 750-1060 White Wine 160-260 25-30 Flavonoids: Flavonols. Flavanols. Hydroxycinnamic acids.
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 Black Currant juice 500 ml of Beer 7 glasses of Orange juice 20 glasses of Apple juice HK PolyU 23/02/05 8 .5 gl. of Eggplant 3.5 port. of Onion 5.
5 81 35 3.7 740 98 23 2.Pharmacokinetic Parameters of Wine and Food Flavonoids Quercetin Parameter Dose (mg) E1/2(h) Tmax(h) Cmax(mmol liter-1) Fried Onions Apples Epicatechin Nestlé Nestlé Noir 40g Noir 80g Catechin Wine Ethanol Wine + Ethanol 68 28 0.1 1.5 91 9 HK PolyU 23/02/05 .8 1.9 2.5 300 82 1.3 2.6 675 35 3.0 355 164 2.
9 days after vinification the total phenolic content was comparable to the one of a bottled wine. Extraction of phenolics and changes in antioxidant activity of red wines during vinification. was significantly lower.The ONLY Thing that Improves with Age is Wine! Burns J.49:5797-5808. HK PolyU 23/02/05 10 . Matthews D. et al. J Agriic Food Chem 2001. but the antioxidant activity. due to larger polyphenolics that appear during aging. Gardner PT. 4 wines were tested.
129:1662-1668 Catechin is present almost exclusively as metabolites in plasma after consumption of red wine. German JB. it is the metabolites. that require attention. J Nutr 1999. Bell JR.Catechin is Present as Metabolites in Human Plasma after Consumption of Red Wine Donovan JL. HK PolyU 23/02/05 11 . and not the forms that exist in foods. Kasim-Karakas S. Flavonoids are extensively conjugated after absorption from foods. Walzem RL et al.
German JB. Regardless of Alcohol Content Donovan JL. without differences between red wine and dealcoholized red wine (120 ml/day). Catechin in all urine samples was present as metabolites. HK PolyU 23/02/05 12 .Catechins from Red Wine are Absorbed and Excreted. Br J Nutr 2002. Urinary excretion of catechin metabolites by human subjects after red wine consumption.87:31-7. Kasim-Karakas S. Waterhouse AL.
Lenti L. red wine subjects had lower response to platelet agonist (p<0. Pathophysiol Haemost Thromb 2002. This is probably due to the higher concentration in polyphenols in red wine.Red Wine >White Wine on Platelets Pignatelli P.005). HK PolyU 23/02/05 13 .32:356-358. 20 healthy subjects randomly consumed 300ml/day x 2w of red or white wine (same % ethanol). Red and white wine differently affect collagen-induced platelet aggregation. At +2w. Pulcinelli FM. et al.
Aviram M. Vitamin E or beta-carotene did not change. White wine consumption resulted in 34% increase in plasma lipid peroxidation. reduced LDL lipid peroxidation (Cu ions). HK PolyU 23/02/05 14 . and prolonged the lag phase required for LDL oxidation. Am J Clin Nutr 1995. red wine polyphenols were elevated in plasma and LDL. and 41% increase of LDL lipid peroxidation.Consumption of Red Wine with Meals Reduces the Susceptibility of Human Plasma and LowDensity Lipoprotein to Lipid Peroxidation Fuhrman B. Lavy A.61:549-554 Red wine consumption [400 mL/day x 2 wk] resulted in 20% reduction of plasma lipid peroxidation (TBARS).
Red Wine Protects Against Cigarette Papamichael C. Karatzi K et al. HK PolyU 23/02/05 15 . Red wine’s antioxidants counteract acute endothelial dysfunction caused by cigarette smoking in healthy nonsmokers.147:274. Am Heart J 2004.001). and harmful effects on endothelium. Acute smoking of 1 cigarette in 16 healthy volunteers caused a reduction in flowmediated dilatation (p<. Simultaneous ingestion of red wine or dealcoholized red wine abrogated this effect on FMD. Karatzis E.
Drinkers of wine outside meals exhibited higher death rates (all causes.Drink Wine With Meals Trevisan M. Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project.11:312-319 8647 men and 6521 women. Menotti A et al. HK PolyU 23/02/05 16 . Ann Epidemiol 2001. age 30-59 at baseline were followed for 7 years. Schisterman E. non CV. cancer) as compared to drinkers of wine with meals.
Tomasi A.Red Wine vs. Bini A. Marri L. Red wine consumption prevents vascular oxidative stress induced by a high-fat meal in healthy volunteers. HK PolyU 23/02/05 17 .74:137-43. Panini R. Salvioli G. High-fat Meals Ventura P. Int J Vitam Nutr Res 2004. Ingestion of red wine during a high-fat meal significantly reduces oxidative stress without inducing any significant modification in postprandial lipemia.
BMJ 1995.310:1165-1169 HK PolyU 23/02/05 18 .Copenhagen City Heart Study Gronbaek M et al.
Wine drinkers had significantly lower mortality from both coronary heart disease and cancer than did non-wine drinkers (p=0. respectively). HK PolyU 23/02/05 19 .007 and p=0. Wine intake may have a beneficial effect on allcause mortality that is additive to alcohol.Copenhagen City Mortality Study Gronbaek M et al. 4833 participants died.004. This effect may be attributable to a reduction in death from both coronary heart disease and cancer. Ann Intern Med 2000.133:411-419 During 257 859 person-years of follow-up.
41:14-16 If every North American drank 2 glasses of wine each day. and $40 billion could be saved annually. which accounts for almost 50% of deaths in this population. cardiovascular disease. HK PolyU 23/02/05 20 .Does Wine Work? Goldberg D. would be cut by 40%. Clinical Chemistry 1995.
J Pharm Pharmacol 1999:51. e.Wine beats Valium® Paladini AC et al. HK PolyU 23/02/05 21 .g. Flavonoids and the CNS: from forgotten factor to potent anxiolytic compounds. and exert powerful anxiolytic effects. selectively bind with high affinity to the central benzodiazepine receptor.519-526 Some natural occurring wine flavonoids. chrysin and apigenin.
25 for Alzheimer’s (p<0. Dartigues JF.Wine Protects the Brain of the Elderly Orgogozo JM.153:185-192 3777 community residents ≥65 y were enrolled. 3 y later 2273 subjects were studied. There is no medical rationale to advise people >65 to quit drinking wine moderately.03) when compared to 971 non-drinkers.01) and 0. 318 drank 250-500ml/d of wine. 22 HK PolyU 23/02/05 .Rev Neurol [Paris] 1997. OR was 0.18 for incident dementia (p<0. Lafont S et al Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.
phonetic and semantic fluency.160:240-247 Increasing levels of alcohol (mostly wine) consumption (>240g/week) in middle-aged subjects (4.Wine Sharpens Your Brain! Britton A. The effect was stronger for women. 1761 ♀. HK PolyU 23/02/05 23 . AH4. Alcohol consumption and cognitive function in the Whitehall II study. 46-68y) were associated with better cognitive function: memory test. Singh-Manoux A. and not explained by confounding factors. Am J Epidemiol 2004.272 ♂. Mill-Hill. Marmot M.
Motz E. with reduced serum antioxidant capabilities.31:322-328. Moderate consumption of red wine. HK PolyU 23/02/05 24 . in diabetics. during a meal. and activation of coagulation. A Pleasant Way to Protect Diabetics: Red Wine Some of the symptoms of diabetes are: •Frequent urination •Excessive thirst •Extreme hunger •Unusual weight loss •Increased fatigue •Irritability •Blurry vision Free radicals are produced in the absorptive phase. et al. preserves plasma antioxidation and reduces both LDL oxidation and thrombotic activation. Bortolotti N. Eur J Clin Invest 2001.Ceriello A. LDL oxidation. Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes.
000 adults. J am Geriatr Soc 1998. Moderate wine consumption is associated with decreased odds in developing age-related macular degeneration in NHANES-1.Wine and Retina Obisesan TO. The effects of wine as antioxidant. et al. Kosoko O. Hirsch R. and on platelet aggregability are associated with reducing the odds of developing AMD. alcohol consumers (wine drinkers in particular) were found to be at reduced risk for AMD.46:1-7 In a study of >3. HK PolyU 23/02/05 25 .
Marchioli R. they observed a decreasing risk of GS and increasing serum HDL levels by increasing daily wine consumption. Diet and gallstones in Italy: the crosssectional MICOL results. Hepatology 1998. Festi D.000 women. Scafato E. HK PolyU 23/02/05 26 .Wine and Gallstones in Italy Attili AF. Marfisi RM.000 men and >13.27:1492-1498 After analyzing data from >15.
et al. Pylori. Polyphenols may well have a bactericidal effect. Bujanda L. H. Gutierrez-Stampa MA. AJG 1998.27:179-180 Red wine’s bactericidal effect was large and greater than the same ethanol concentration at the same pH. Salmonella enteritidis: pH or alcohol? Marimon JM.93:1392] HK PolyU 23/02/05 27 . J Clin Gastroenterol 1998.Antibacterial Activity of Wine vs. [The same group confirmed bactericidal effect vs.
Wine –not Beer or AlcoholProtects vs.6. beer. When drinkers of >14 glasses of wine/week were compared to teetotalers. Wine intake (red wine) may have a protective effect vs. Regueira-Mendez C. Common Cold Takkouche B. common cold. and spirits and the risk of clinical common cold. Am J Epidemiol 2002. while beer. et al. HK PolyU 23/02/05 28 . the r risk was 0. spirits and total alcohol intake did not affect the incidence. Garcia-Closas R.155:853-858. Intake of wine.
Person DA.311:1657-1660 HK PolyU 23/02/05 29 .Wine as Digestive Aid Weisse ME. BMJ 1995. Eberly B.
HK PolyU 23/02/05 30 . Person DA. Dilutions of wine were much more effective in decreasing colony counts than were similar dilutions of bismuth salicylate.311:1657-1660 Undiluted red and white wine. and bismuth salicylate (Pepto-Bismol®) were both effective in reducing the number of viable Salmonella. Shigella. Eberly B. and Escherichia coli (by 105-106 CFUs) after 20-30 minutes. BMJ 1995.Wine as a Digestive Aid Weisse ME. The antibacterial property of wine is largely responsible for wine’s reputation as a digestive aid.
Activity depended mainly on resveratrol. and the active extracts of 2 randomly selected wines did demonstrate antibacterial activity vs. pylori Daroch F.Red Chilean Wines Kill H. 16 Chilean red wines (Cabernet Sauvignon. Pylori isolated from gastric biopsies.104:79-85. Cabernet Merlot. Cabernet Organic & Pinot noir). Gonzalez CL. 6 strains of H. Microbios 2001. et al. HK PolyU 23/02/05 31 . In vitro antibacterial activity of Chilean red wines against Helicobacter pylori. Hoeneisen M.
Wine. HK PolyU 23/02/05 32 . Preferrers of wine tend to have a lower risk of hip fracture as compared to preferrers of other alcoholic drinks. Gronbaek M. Am J Epidemiol 1999.000 patients.149:9931001 Research included 32. A light to moderate alcohol intake does not influence the risk of hip fracture. Osteoporosis and Hip Fracture Hoidrup S. Lauritzen JB. Schroll M. Gottschau A.
Antiproliferative effect of synthetic resveratrol on human breast epithelial cells.12:865-869 The effect of resveratrol is consistent with the activity of other anticancer drugs. HK PolyU 23/02/05 33 . Russo J. Human Breast Cells Mgbonyebi OP. Int J Oncol 1998. Russo IH. It is a potential chemopreventive agent for both hormone responsive and nonresponsive breast cancers.Resveratrol vs.
Red wine was shown to be much more effective than white wine in suppression of aromatase. and in a model of transgenic mouse in which aromatase is over-expressed in the mammary tissue. HK PolyU 23/02/05 34 . Suppression of aromatase (estrogen synthetase) by red wine phytochemicals.67:133-146. Williams D. hence promoting proliferation of breast cancer cells. Breast Cancer Res Treat 2001. Mandava U. This was demonstrated in different cell models. Aromatase converts androgen to estrogen.Suppression of Aromatase by Red Wine Eng ET. et al.
Anticancer Drugs 1999. Virji AS. are effective inhibitors of oral squamous carcinoma cell growth and proliferation.Resveratrol and Quercetin Modulate Oral Cancer Cell Growth El Attar TM. HK PolyU 23/02/05 35 . in concentrations equivalent to that present in red wines. Modulating effect of resveratrol and quercetin on oral cancer growth and proliferation.10:187-193 Resveratrol or a combination of resveratrol and quercetin.
Becker U. Alcohol intake and the risk of lung cancer: influence of type of alcoholic beverage. HK PolyU 23/02/05 36 .149:463-470 Data from 3 prospective studies of >28. This seemingly protective effect may be related to the antioxidant properties of wine. Gronbaek M.000 subjects confirmed that intake of wine was associated with a reduced risk of lung cancer. Sorensen TI. Am J Epidemiol 1999.Intake of Wine is Associated with a Reduced Risk of Lung Cancer Prescott E.
187 controls).2/each daily glass) was observed between lung cancer and white wine consumption. HK PolyU 23/02/05 37 .59:981-5 In 1999-2000. Barros-Dios JM. Type of wine and risk of lung cancer: a case-control study in Spain.Red Wine. but not White Wine Decreases the Risk of Lung Cancer Ruano-Ravina A. A slight but significant (OR 1. Figueiras A. Thorax 2004. a study was conducted on 319 subjects (132 cases. But red wine had an inverse association (OR 0.87).
366 cases of prostate cancer occurred. Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study. Paffenbarger RS Jr. Liquor.30:749-755 7612 Harvard alumni (~66.Wine Does Not Increase the Risk of Prostate Cancer Sesso HD. Int J Epidemiol 2001. but not wine or beer. consumption was positively associated with prostate cancer HK PolyU 23/02/05 38 . Lee IM.6y) were prospectively followed from 1988 through 1993.
and induced apoptosis. rutin. BJU Int 2002. morin.89:950-954. Polyphenols in red wine inhibit the proliferation and induce apoptosis of LANCaP cells. gallic acid and tannic acid. HK PolyU 23/02/05 39 . Paez A. inhibited the growth of prostate cancer LANCaP cells at different concentrations. from red wine. Berenguer A. Ferruelo A. Quercetin.Polyphenols in Red Wine Impair Prostate Cancer Cell Line Romero I. Lujan M.
Sorensen TI. Lower risk for alcohol-induced cirrhosis in wine drinkers. Gronbaek M. if wine was >51%.3. Compared to beer and spirits.35:868-875.4. risk was 0. If wine was 16-30% of total intake.Beethoven Should Have Drunk Wine! Becker U. wine carries a much lower risk. Hepatology 2002. HK PolyU 23/02/05 40 . Johansen D. risk was 0. Individuals who drank >5 drinks/day had a relative risk of 14-20 for developing cirrhosis.
mostly after very high exposure to sulfites. nor in plasma or urinary methyl histamine.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. rich or poor in histamine. Allergie & Immunologie 1999. Histamine content does not influence wine tolerance in normal subjects Kanny G et al.31:45-47.Wine is Safe for Asthmatics Two studies Halpern GM et al. The amount of histamine in wine has no clinical or biological effect in healthy subjects. No [n=8] subject reacted after ingesting wine. Vally H et al. J Allergy Clin Immunol 1999. Ann Allergy 1985. There were no changes in plasma histamine. HK PolyU 23/02/05 41 .55:686-69.
which could result in termination of an otherwise healthy pregnancy. Clinica Chemica 1996:246:149154 Weighing the issues.“Moderate” Drinking During Pregnancy: Cause for Concern? Abel EL. or psychological distress that might itself lead to an unhealthy pregnancy. 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. HK PolyU 23/02/05 42 .
and personal development. cognitive.161:1844-1848 In 363 men and 330 women aged 29-34. and socioeconomic status. Arch Intern Med 2001. Sanders SA. social. Reinish JM. Jensen HH. 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. wine drinking was significantly associated with higher IQ. parental educational level.Wine Drinkers are Smarter and Richer Mortensen EL. Beer drinking was associated with significantly lower scores. Wine drinking is a general indicator of optimal. HK PolyU 23/02/05 43 .
In vitro action of Bordeaux red wine on the microhardness of human dental enamel. Bertrand MF.48:141-145 Wine has no disastrous effect on the microhardness (Vickers. HK PolyU 23/02/05 44 .Drink your Bordeaux in <90” Lupi-Pegurier L. Bolla M.05). the decrease in the microhardness of enamel was significant (P<0. Muller M. scanning electron microscopy) of dental enamel if contact is <90 s. Leforestier E. When exposure is >120 s. Arch Oral Biol 2003.
The narrow flute requires 73% of the total available cranio-cervical extension.402-403. The Champagne angle.The Champagne Angle Pemberton PL.57. Crockard HA. 26º with a wine glass. HK PolyU 23/02/05 45 . 22º with a wide flute. and 0º with a champagne saucer. Anaesthesia 2002. O’Sullivan C. Calder I. The cranio-cervical extension required to drain a glass of wine was 40° with a narrow flute.
Saccarola P. Lugli N.13:287-291 Bottle-cork injuries account for 10. Pagliani L. HK PolyU 23/02/05 46 . Eur J Ophthalmol 2003. Campi L. There is no correlation between ocular injury and the eyebottle distance or the type of cork. Most are due to sparkling white wine served at room temperature.8% of post-trauma admission in Modena. Bottle-cork injury to the eye: a review of 13 cases.Cork Injury to the Eye Cavallini GM.
compared to “tulip” or “beaker” glasses. Egg-shaped glasses. Schmidt C. Hummel T. Delwiche JP. The enjoyment of red wine is influenced by the shape of the wine glass. appear to produce higher intensity and higher complexity of wine odors.80:96-100.Enjoy in the Right Shape of Glass Huttenbrink KB. HK PolyU 23/02/05 47 . Laryngorhinootologie 2001.
Cohen HY.Wine May Make you Live 10 More Years! Howitz KT. a potent activator of sirtuins. increasing DNA stability and extending lifespan by…70%! HK PolyU 23/02/05 48 . Bitterman KJ. Resveratrol mimics calorie restriction by stimulating Sir2. Nature 2003 Aug 24 [Epub ahead of print] Resveratrol. Lamming DW et al. lowers the Michaelis constant of SIRT1 (a human deacetylase) and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
Salute! 干杯！ Cheers! Santé! Salud! Skål! HK PolyU 23/02/05 49 .