Rami Khouzam, MD
Alcohol
(Pros & Cons)
The word "toast" meaning a wish of
good health, started in ancient Rome,
where a piece of toasted bread was
dropped into wine
• “In Vino veritas: In wine
is truth”, old latin saying
• "In water you see your
own face, but in wine
the heart of its garden”,
ancient Egyptian
proverb
• Hippocrates illustrated
the value of wine as a
medicine. “Wine is vital
to a healthy diet”
• Paracelsus a German
physician of the 16th
century: “Whether wine
is a nourishment,
medicine or poison is a
matter of dosage”
Beyond the French Paradox: The Impact
of Moderate Beverage Alcohol & Wine
Consumption in the Prevention of
Cardiovascular Disease
Cardiology Clinics, Volume 21. Number 3. August 2003
Tedd M. Goldfinger, DO, FACC
• “Telling people to avoid any alcohol
consumption , because of the potential dangers
of heavy use may not be in the best health
interest of the public”
• In our society, CVD is the leading cause of
death and prevention is vital to longer life and
better health
• Many epidemiologic and observational studies
indicate that a healthy lifestyle including
cigarette avoidance, low fat high fiber diet, lean
body weight, regular exercise and small
amounts of daily beverage alcohol, is protective
against CHD
History of Alcohol & Health
• Through the ages, alcohol, particularly wine: elixir for
better health
• Ancient societies:
– Evidence of wine consumption in moderation.
– Earliest wine consumers: better nourished and less
prone to sickness
• Judaic records: “Wine is at the head of all medicines”
& “Where wine is lacking, drugs are necessary”
Wine in Ancient Egypt
According to William
Younger in his book,
“Gods, Men and
Wine”:
“It is in Egypt where
we must go for our
fullest knowledge of
man's early and
deliberate growing of
wine”
• In Ancient Egypt wine was
regarded as a gift from the
gods. This belief may have
come from the fact that
Egyptian wine was only
available to the socially
elite classes
• Wine was used in funeral
rites as well. The higher the
social status of the
deceased, the greater
quantity of wine was used
to anoint his body and
belongings before
entombment
• Some Pharaohs, such as
King Tutankhamen, were
given jars of wine in
their tombs in order to
accompany the royal
spirit on its journey to
the underworld
• 36 Jars were found!
• 20th century: epidemiologic reports: an inverse
relationship between alcohol consumption and
atherosclerotic disease
– Heavy drinkers: highest mortality
– Abstainers: prone to a higher mortality
– Moderate drinkers: lowest mortality
• Cirrhosis: sparing of vascular intima from
atherosclerosis particularly in the coronary
circulation  anti-atherosclerosic effect of
alcohol & a salutary effect on the endothelium
Studies & facts
• Copenhagen Center for Population Studies
• At all levels of alcohol intake, wine drinkers
were at significantly lower risk than nonwine drinkers for all cause mortality
(p<0.001)
• Non-drinkers: Relative risk for death from
CHD of 0.76, and wine drinkers had a risk of
0.58
• 6051 men and 7234 women aged 30 to 70 of
the Copenhagen City Heart Study: the risk for
dying steadily decreased with an increasing
intake of wine
• Neither beer nor spirits was associated with a
reduced risk
• The association between alcohol intake
and CHD was studied prospectively
among 51,529 male health professionals
• Alcohol consumption was consistently
associated with a reduced risk for a fatal
and non-fatal myocardial infarction and
the need for (CABG) or (PCI)
• A meta-analysis of studies involving
209,413 persons: relationship between
wine & beer consumption and risk for fatal
and non-fatal vascular events
• The relative risk for vascular endpoints
among wine drinkers was 0.68 (CI, 0.590.77) relative to non-drinkers
How Much Is Too Much?
• A significant inverse relationship was found
at a daily intake of 150 ml of wine; a
maximum risk reduction was predicted at
750 mL/day
• A risk reduction in favor of beer drinkers
was also noted with a RR of 0.78 (CI, 0.700.86). There was no observed dose
relationship
Thomas Jefferson:
“Wine of long habit has
become indispensable
to my health”, “I think
it is a great error to
consider a heavy tax on
wine as a tax on luxury.
On the contrary, it is a
tax on the health of our
citizens”
Biology of Alcohol & Wine
• Mechanism of CVD risk reduction for
alcohol drinkers caused by significant rise
in HDL-C
• At least 50% of the benefit has been
attributed to HDL-C rise
• Alcohol intake may be the strongest
positive predictor for an increased HDLC in men and women
(at present, lifestyle factors, such as
aerobic exercise, and lipid lowering
drugs, produce only small increases in
HDL-C)
• In 1992, Renauld and DeLongeril: the
French Paradox, enhancing an interset in
wine worldwide
• Mortality rate for CHD in France was
paradoxical and unexpectedly lower than
other industrialized countries such as the
USA and the UK, despite similarly high
dietary intake of saturated fat
• The ontoward effects of saturated fats are
counteracted by the intake of wine
• Serum concentrations of HDL-C were seen,
however, to be no higher in France than
other European countries
• A critical effect on hemostasis at levels of
moderate alcohol intake:
– Decrease in platelet reactivity and aggregability
in humans
– Dramatic and significant decrease in
intravascular platelet deposition in a normal
laminar flow state and high shear flow states
across a stenotic atherosclerotic lesion
• Effect of a single alcohol beverage on
the bleeding time, a sensitive measure
of platelet function, is increased and
lengthened, when consumed with
aspirin or within thirty six hours after
aspirin ingestion
• Louis Pasteur, French
biologist: “Wine is the most
healthful and hygienic of
beverages”
• William Heberden’s classic
description of angina
pectoris in 1786 included
the statement:”Wine and
spiritious liquors afford
considerable relief” and
postulated that alcohol was
a coronary vasodilator
Alcohol & Wine in Vascular Biology
• Wine is a rich source of flavonoid phenolics
such as resveratrol
• Substances giving wine its astringency and
bitterness and are the foundation of long
aging since they are effective antioxidants
• Red wines, unlike white wines, are high in
concentrations of these substances and age
gracefully
• Derived from the skins and seeds of red wine
grapes
• Moderate wine consumption increases
measurable plasma antioxidant activity, and
inhibits the oxidation of LDL-C
• Whitehead: 18% increase in serum
antioxidant capacity in subjects who drank
300 mL of red wine, compared with a 4%
increase for the same amount of white wine
• Anderson: addition of a potent antioxidant to
a regimen of aggressive lipid lowering
produced enhanced endothelial-dependent
vasodilatation
(Red wine, de-alcoholized red wine, purple
grape juice)
• Resveratrol (a red wine polyphenol):
– Inhibits a number of (PMN) functions
considered to contribute to the pathogenesis and
evolution of acute and chronic CHD:
 Inhibiting toxic reactive oxygen species
produced by activated PMNs, B-glucuronidase
and elastase release, proteolytic enzymes
responsible for acute vascular damage
• Resveratrol: also inhibits the
production of 5-lipooxygenase derived
metabolites which are chemotactic for
neutrophils, esinophils and monocytes
 Blunting the inflammatory response
of neurophil aggregation,
degranulation and superoxide
production
• Leikert & colleagues: increase in endothelial
nitric oxide synthase (eNOS) enhanced
transcription of the eNOS gene in human
endothelial cells exposed to alcohol-free red
wine polyphenol extract
• This effect may not be common to all red wines
• French red wines, not German red wines
increase endothelial nitric oxide mRNA protein
• Endothelin-1 (ET-1): a potent vasoconstrictor
• Khan & associates: a concentration dependent
inhibition of ET-1 from a cabernet sauvignon
wine
• One investigator suggested:
–
–
–
–
Differences in grape variety
Regions of production
Cultivation
Method of post fermentation processing
may be important variables for health
benefits
• Flesch & colleagues: Red wines
produced “en barique” that is small
barrels, typical of French Bordeaux
produced a particularly pronounced
vasodilatory effect compared with
other red wines
• Châteauneuf du Pape and Bordeaux
The Heart in Ancient Egypt
• The heart was considered the most
important of the body's organs
• The Egyptians believed that the
heart, rather then the brain, was
the source of the human wisdom,
the emotions, the memory, the
soul and the personality itself
• Notions of physiology and disease
were all connected in concept to
the heart, and it was through the
heart that god spoke, giving
ancient Egyptians knowledge
Inflammation & Vascular
Remodeling
• C-reactive protein is an emerging marker
for acute CHD
• Associated with a significantly higher
mortality in patients presenting with ACS
• Moderate red wine consumption has antiinflammatory properties and is associated
with a lowered level of CRP
• In a study of 2008 men & women, ages 1888 years, alcohol consumption showed a Ushaped association with mean values of
CRP
• Effect of red wine on vessel wall remodeling
including:
– Neointimal hyperplasia
– Monocyte recruitment & adhesion to the
endothelium
– Inhibition of intracellular adhesion molecules
– Foam cell accumulation
– Smooth muscle cell (SMC) proliferation and
migration
– Abnormal expression of intracellular tissue factor
• Feng & colleagues: a significant reduction
in Monocyte Chemotactic Protein (MCP1) expression and reduced neointimal
thickening in rabbits fed a high
cholesterol diet with red wine after
balloon injury
• In a study of 247 patients undergoing
PCI, nondrinkers compared with alcohol
drinkers had a 5-fold increase in risk of
cardiac death, non-fatal MI, and other
adverse end points
• Despite the ancient Egyptians’
seemingly advanced medical and
surgical knowledge, the heart's role
in blood circulation was not
precisely understood
• It was felt that the heart channels
(metu) linked all parts of the body
together
• These channels delivered not only
blood, but also air, tears, saliva,
mucus, sperm, nutriment and even
bodily waste
• The only real function of the brain
was thought to be to pass mucus to
the nose, so it was one of the organs
that were discarded during
mummification
Amount & Type of Alcohol and Risk of
Dementia: The Copenhagen City Heart
Study
Neurology- 12 NOV-2002; 59 (9): 1313-9
TruelsenT
Objective:
To assess whether amount or type of
alcohol is associated with risk of dementia
Methods & subjects:
Case-control, a cohort study among
participants in the third Copenhagen City
Heart Study (1991-1994), aged 65 years
and more. Mini-Mental State Examination
Results:
• Monthly and weekly intake of wine was
significantly associated with a lower risk
of dementia
• The effect of alcohol on risk of dementia
did not differ between men & women
Conclusions:
Monthly and weekly intake of wine is
associated with a lower risk of dementia
Alcohol is not associated with increased
risk of heart failure
Walsh C, Larson M, Evans J.
Alcohol consumption & risk for CHF in the
Framingham Heart Study
Ann Intern Med 2002; 136(3): 181-191
Background:
• Excessive alcohol consumption can be
harmful, little is known about whether
alcohol increases the risk of CHF
• Some studies have suggested that moderate
alcohol intake has a protective effect
Objective:
Examine the relationship between alcohol
consumption and risk of CHF
Setting:
United states; recruitment from 1948, data
collected 1971-1995
Method:
Community-based prospective
observational study
Participants:
6289 in the Framingham Heart Study
without CHF or coronary heart disease at
baseline
Main Results:
• Heart failure risk was lower among men
who consumed any level of alcohol
compared to non-drinkers
• After adjusting for confounders, there was
no association between alcohol intake and
heart failure in women
Authors’ Conclusions:
• Even among heavy drinkers (>15 drinks/wk
in men & >8 drinks/wk in women) , alcohol
consumption is not linked with increased risk
of CHF
• When consumed in moderation ( 8-14
drinks/wk in men & 3-7 drinks/wk in
women), alcohol may have a protective effect
& a lower hazard ratio compared to less than
one drink/wk
• How might alcohol benefit the heart?
Alcohol may impact on other cardiac risk factors
• Improvements in lipid profile and anti-oxidant effect,
among others...
• Alcohol in moderation may therefore have beneficial
cardiovascular effects, however, high intake and
binge drinking are not supported by this study
• In the Final Judgment portrayed
by the Book of the Dead, the
heart of the deceased was shown
being weighed against the
feather of Ma’at, a symbol of
universal truth, harmony and
balance
• For this reason, the heart was
one of the only organs not
removed from the body during
mummification
Summary
• Alcohol beverages, particularly red wine,
when consumed in moderation reduce the
risk of acute CVD and death
• The mechanism for alcohol beverage
benefit is complex; includes an
independent benefit of ethyl alcohol
• The multiplicity of effects identified for the
non-alcohol components of red wine play a
role in improved endothelial physiology and
enhance vascular homeostasis
• CAD begins early in life, and it progresses
over decades
• Prospective studies of alcohol or wine
consumption in the young, middle and older
aged persons would be interesting
• It is prudent for physicians to discuss the
harmful effects of alcohol with their
patients while at the same time, not
discourage a potentially healthy practice
of wine in moderation (eg, with meals)