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 2003Tedd 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 non-wine 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, 0.59-0.77) 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, 0.70-0.86). 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 HDL-C 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 anti-inflammatory properties and is associated with a lowered level of CRP

• In a study of 2008 men & women, ages 18-88 years, alcohol consumption showed a U-shaped 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 (MCP-1) 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 StudyAnn 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)