Wine IS Medicine

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Wine IS Medicine

• Georges M. Halpern, MD, PhD
• Distinguished Professor of Pharmaceutical
  Sciences
• Hong Kong Polytechnic University
• drgeorges_at_drgeorges.net

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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.

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What is Wine?German JB, Walzem RL. The health
benefits of wine. Annu Rev Nutr 200020561-593

• 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.

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Wine EthanolGerman JB, Walzem RL. Annu Rev
Nutr 200020561-593

• 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.

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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 200111249-258.

• 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.

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Composition of WineExcluding Phenolic Acids and
Polyphenols
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Summary of Phenolic Acid and Polyphenol
Components of Red and White Wines
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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

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Pharmacokinetic Parameters of Wine and Food
Flavonoids
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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
2001495797-5808.

• 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.

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Catechin is Present as Metabolites in Human
Plasma after Consumption of Red WineDonovan JL,
Bell JR, Kasim-Karakas S, German JB, Walzem RL et
al. J Nutr 19991291662-1668

• 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.

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Catechins from Red Wine are Absorbed and
Excreted, Regardless of Alcohol ContentDonovan
JL, Kasim-Karakas S, German JB, Waterhouse AL.
Urinary excretion of catechinmetabolites by
human subjects after red wine consumption. Br J
Nutr 20028731-7.

• Catechin in all urine samples was present as
  metabolites, without differences between red wine
  and de-alcoholized red wine (120 ml/day).

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Red Wine White Wine on PlateletsPignatelli P,
Lenti L, Pulcinelli FM, et al. Red and white wine
differently affect collagen-induced platelet
aggregation. Pathophysiol Haemost Thromb
200232356-358.

• 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 (phigher concentration in polyphenols in red wine.

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Consumption of Red Wine with Meals Reduces the
Susceptibility of Human Plasma and Low-Density
Lipoprotein to Lipid PeroxidationFuhrman B, Lavy
A, Aviram M. Am J Clin Nutr 199561549-554

• 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.

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Red Wine Protects Against CigarettePapamichael
C, Karatzis E, Karatzi K et al. Red wines
antioxidants counteract acute endothelial
dysfunction caused by cigarette smoking in
healthy nonsmokers. Am Heart J 2004147274.

• Acute smoking of 1 cigarette in 16 healthy
  volunteers caused a reduction in flow-mediated
  dilatation (pred wine or dealcoholized red wine abrogated this
  effect on FMD, and harmful effects on endothelium.

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Drink Wine With MealsTrevisan M, Schisterman E,
Menotti A et al. Drinking pattern and mortality
the Italian Risk Factor and Life Expectancy
pooling project. Ann Epidemiol 200111312-319

• 8647 men and 6521 women, age 30-59 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.

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Red Wine vs. High-fat MealsVentura 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 200474137-43.

• Ingestion of red wine during a high-fat meal
  significantly reduces oxidative stress without
  inducing any significant modification in
  postprandial lipemia.

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Copenhagen City Heart StudyGronbaek M et al. BMJ
19953101165-1169
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Copenhagen City Mortality StudyGronbaek M et al.
Ann Intern Med 2000133411-419

• During 257 859 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 (p0.007 and p0.004, 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.

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Does Wine Work?Goldberg D. Clinical Chemistry
19954114-16

• 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.

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Wine beats ValiumPaladini AC et al. Flavonoids
and the CNS from forgotten factor to potent
anxiolytic compounds. J Pharm Pharmacol
199951519-526

• 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.

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Wine Protects the Brain of the ElderlyOrgogozo
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 1997153185-192

• 3777 community residents 65 y were enrolled 3 y
  later 2273 subjects were studied. 318 drank
  250-500ml/d of wine OR was 0.18 for incident
  dementia (p(pis no medical rationale to advise people 65 to
  quit drinking wine moderately.

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Wine Sharpens Your Brain!Britton A, Singh-Manoux
A, Marmot M. Alcohol consumption and cognitive
function in the Whitehall II study. Am J
Epidemiol 2004160240-247

• 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.

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A Pleasant Way to Protect Diabetics Red
WineCeriello 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 200131322-328.

• 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.

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Wine and RetinaObisesan 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 1998461-7

• 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.

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Wine and Gallstones in ItalyAttili AF, Scafato
E, Marchioli R, Marfisi RM, Festi D. Diet and
gallstones in Italy the cross-sectional MICOL
results. Hepatology 1998271492-1498

• 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.

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Antibacterial Activity of Wine vs. Salmonella
enteritidis pH or alcohol?Marimon JM, Bujanda
L, Gutierrez-Stampa MA, et al. J Clin
Gastroenterol 199827179-180

• Red wines 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 1998931392

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Wine not Beer or Alcohol- Protects vs. Common
ColdTakkouche 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 2002155853-858.

• 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.

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Wine as Digestive AidWeisse ME, Eberly B, Person
DA. BMJ 19953111657-1660
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Wine as a Digestive AidWeisse ME, Eberly B,
Person DA. BMJ 19953111657-1660

• 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 105-106 CFUs)
  after 20-30 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 wines reputation as a digestive
  aid.

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Red Chilean Wines Kill H. pyloriDaroch F,
Hoeneisen M, Gonzalez CL, et al. In vitro
antibacterial activity of Chilean red wines
against Helicobacter pylori. Microbios
200110479-85.

• 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.

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Wine, Osteoporosis and Hip FractureHoidrup S,
Gronbaek M, Gottschau A, Lauritzen JB, Schroll M.
Am J Epidemiol 1999149993-1001

• 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.

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Resveratrol vs. Human Breast CellsMgbonyebi OP,
Russo J, Russo IH. Antiproliferative effect of
synthetic resveratrol on human breast epithelial
cells. Int J Oncol 199812865-869

• 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.

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Suppression of Aromatase by Red WineEng ET,
Williams D, Mandava U, et al. Suppression of
aromatase (estrogen synthetase) by red wine
phytochemicals. Breast Cancer Res Treat
200167133-146.

• 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.

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Resveratrol and Quercetin Modulate Oral Cancer
Cell GrowthEl Attar TM, Virji AS. Modulating
effect of resveratrol and quercetin on oral
cancer growth and proliferation. Anticancer
Drugs 199910187-193

• 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.

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Intake of Wine is Associated with a Reduced Risk
of Lung CancerPrescott E, Gronbaek M, Becker U,
Sorensen TI. Alcohol intake and the risk of lung
cancer influence of type of alcoholic beverage.
Am J Epidemiol 1999149463-470

• 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.

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Red Wine, but not White Wine Decreases the Risk
of Lung CancerRuano-Ravina A, Figueiras A,
Barros-Dios JM. Type of wine and risk of lung
cancer a case-control study in Spain. Thorax
200459981-5

• In 1999-2000, 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).

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Wine Does Not Increase the Risk of Prostate
CancerSesso HD, Paffenbarger RS Jr, Lee IM.
Alcohol consumption and risk of prostate cancer
The Harvard Alumni Health Study. Int J Epidemiol
200130749-755

• 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

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Polyphenols in Red Wine Impair Prostate Cancer
Cell LineRomero I, Paez A, Ferruelo A, Lujan M,
Berenguer A. Polyphenols in red wine inhibit the
proliferation and induce apoptosis of LANCaP
cells. BJU Int 200289950-954.

• 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.

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Beethoven Should Have Drunk Wine!Becker U,
Gronbaek M, Johansen D, Sorensen TI. Lower risk
for alcohol-induced cirrhosis in wine drinkers.
Hepatology 200235868-875.

• Individuals who drank 5 drinks/day had a
  relative risk of 14-20 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.

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Wine is Safe for Asthmatics

• Two studies Halpern GM et al. Ann Allergy
  198555686-69 Vally H et al. J Allergy Clin
  Immunol 199910341-46 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 19993145-47. No n8
  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.

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Moderate Drinking During Pregnancy Cause for
Concern?Abel EL. Clinica Chemica 1996246149154

• 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.

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Wine Drinkers are Smarter and RicherMortensen
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
20011611844-1848

• 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.

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Drink your Bordeaux in 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 200348141-145

• Wine has no disastrous effect on the
  microhardness (Vickers scanning electron
  microscopy) of dental enamel if contact is When exposure is 120 s, the decrease in the
  microhardness of enamel was significant (P

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The Champagne AnglePemberton PL, Calder I,
OSullivan C, Crockard HA. The Champagne angle.
Anaesthesia 200257402-403.

• 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.

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Cork Injury to the EyeCavallini GM, Lugli N,
Campi L, Pagliani L, Saccarola P. Bottle-cork
injury to the eye a review of 13 cases. Eur J
Ophthalmol 200313287-291

• 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.

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Enjoy in the Right Shape of GlassHuttenbrink KB,
Schmidt C, Delwiche JP, Hummel T. The enjoyment
of red wine is influenced by the shape of the
wine glass. Laryngorhinootologie 20018096-100.

• Egg-shaped glasses, compared to tulip or
  beaker glasses, appear to produce higher
  intensity and higher complexity of wine odors.

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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 by70!

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Salute!

• ??!
• Cheers!
• Santé!
• Salud!
• Skål!