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Alcohol consumption: an overview of benefits and risks.

Abstract: Published health benefits of regular light-to-moderate alcohol consumption include lower myocardial infarction rates, reduced heart failure rates, reduced risk of ischemic stroke, lower risk for dementia, decreased risk of diabetes and reduced risk of osteoporosis. Numerous complimentary biochemical changes have been identified that explain the beneficial effects of moderate alcohol consumption. Heavy alcohol consumption, however, can negatively affect neurologic, cardiac, gastrointestinal, hematologic, immune, psychiatric and musculoskeletal organ systems. Binge drinking is a significant problem even among moderate drinkers and is associated with particularly high social and economic costs. A cautious approach should be emphasized for those individuals who drink even small amounts of alcohol. Physicians can apply the research evidence describing the known risks and benefits of alcohol consumption when counseling their patients regarding alcohol consumption.

Key Words: alcohol, benefit, recommendations, risk

 One drink is too many and a thousand is not enough.
 --Alcoholics Anonymous aphorism

For a person with a substance abuse disorder, alcohol consumption is likely to serve as a trigger for the compulsive behavior associated with the disease. For other individuals a decision matrix can be applied to inform choices concerning responsible consumption of alcohol. Physicians can apply the research evidence describing the known risks and benefits associated with alcohol consumption when counseling with their patients regarding alcohol-related decisions and behaviors.

Of the 113 million Americans classified as "current drinkers," (1,2) perhaps as many as 23.8% of men and 4.7% of women meet DSM-IV criteria for dependence. (1-5) Males and whites dominate these categories, (1) particularly at higher-volume consumption levels. (6) Alcohol-related social, legal, and health problems (4) result in annual economic costs to society totaling more than $166 billion. (2)

Demographers have long noted an unexpected low incidence of cardiovascular disease in the French population despite an unfavorable exposure to cardiovascular risk factors; namely, a high-fat cuisine combined with heavy tobacco use patterns. A beneficial effect of regular wine consumption has been advanced as a possible explanation of this "French Paradox." Numerous scientific articles have been published in the last few decades that describe beneficial alcohol-related outcome data and beneficial changes in biochemical and metabolic markers for cardiovascular disease. These data support the initial assumptions of the "French Paradox."

Health Benefits of Alcohol

The published health benefits of regular light-to-moderate alcohol consumption define a lower incidence of cardiovascular, metabolic, and dementing illnesses. Other data define the metabolic and biochemical influences of alcohol that, in turn, explain the mechanisms by which mild to moderate alcohol consumption improves these health outcomes.

Lower Myocardial Infarction Rates

Data collected on 87,938 men in the Physicians' Health Survey revealed benefit of alcohol consumption in reducing coronary heart disease (CHD) in both diabetic and nondiabetic populations. A 5.5-year follow-up revealed more dramatic risk reduction in the diabetic cohort. The relative CHD risk was 1.02 for nondiabetic men who drank monthly, 0.82 for those who drank weekly, and 0.61 for daily drinkers. In diabetic men the corresponding relative risks (RR) were 1.11, 0.67, and 0.42. (7) In the Nurses' Health Survey involving 30,092 person-years, the CHD risk for diabetic women was 0.74 for women consuming 0.1 to 4.9 g/d alcohol (a standard drink contains 11 g alcohol) and 0.48 for those consuming 5 g/d or more, relative to those reporting no alcohol intake. (8) Women consuming 5 to 9 g/d alcohol were at higher risk than those consuming 10 g/d or more (9) (Fig. 1).

A 12-year study of 38,077 male health professionals revealed a 0.68 relative risk of myocardial infarction in those who drank alcohol 3 to 4 days per week compared with nondrinkers. There was a 0.63 relative risk of myocardial infarction in men who drank alcohol 5 to 7 days per week. The amount of alcohol consumed per drinking day (less than 10 g versus 30 g or more) did not affect the level of risk; neither did type of alcohol, nor consumption with meals. The key factor was daily intake. A 12.5-g increase in daily alcohol consumption over a 4-year follow-up was associated with an additional decreased risk of myocardial infarction (RR 0.78). (10)

A polymorphism exists in the gene for alcohol dehydrogenase Type 3 (ADH3). This in turn alters the rate of alcohol metabolism among individuals. The homozygosity for the allele associated with a slow rate of ethanol oxidation ([[gamma].sub.2]) conveyed a reduced risk of myocardial infarction (RR 0.65) relative to homozygosity for the allele associated with more rapid oxidation of alcohol ([[gamma].sub.1]). Men who consumed at least one drink per day and were homozygous for the less advantageous [[gamma].sub.1] allele had a relative risk for myocardial infarction of 0.62, as compared with men who drank less than one drink per week. However, men who consumed at least one drink per day and were homozygous for the [[gamma].sub.2] allele had a relative risk for myocardial infarction of 0.14, as compared with men who drank less than one drink per week (Fig. 2). This group of men also had significantly higher HDL-cholesterol levels. The interactions of ADH3 genotype, levels of alcohol consumption, and HDL levels described in these data were mirrored in an independent study of postmenopausal women. (11)


Reduced Myocardial Infarction Mortality

Compared with nondrinkers, patients who consume moderate amounts of alcohol during the year before an acute myocardial infarction (AMI) have significantly reduced mortality rates. Data collected on 1,931 AMI patients over 4 years revealed a 32% lower risk of dying. This all-cause mortality benefit occurred irrespective of the type of alcohol: beer, wine, or spirits. (12)

Reduced Heart Failure Rates

In a study of 2,235 men and women, mean age 73.7 years, moderate alcohol consumption was associated with a reduced rate of heart failure compared with alcohol abstinence. During a maximum follow-up of 14 years, the greatest reduction of heart failure risk, 47%, occurred in individuals who consumed one and one-half to four drinks per day. (13)

Participants in the Framingham Heart Study who were free of congestive heart failure (CHF) and coronary heart disease were studied to determine the relation between alcohol consumption and risk for congestive heart failure. The risk ratio was lowest among men who consumed 8 to 14 drinks per week (RR 0.41) compared with those who drank less than one drink per week. Among women the nadir of benefit occurred in those who consumed 3 to 7 drinks per week (RR 0.49) compared with those who drank less than one drink per week. (14)

Data collected as part of the Studies of Left Ventricular Dysfunction (SOL VD) trials compared 2,594 patients who consumed 1 to 14 alcoholic beverages per week to 3,719 patients who abstained from alcohol. Researchers determined that consumption of up to two drinks per day was safe for established heart failure patients and, in fact, reduced the risk of death with the most dramatic reduction occurring in myocardial infarction rates. (15)

Reduced Risk of Ischemic Stroke

Sacco et al (16) demonstrated that moderate alcohol consumption was significantly protective for ischemic stroke. For consumption of up to two drinks per day, the protective odds ratio (OR) was profound at 0.51. The protective effect was detected in younger and older populations, in men and women, and in all racial and ethnic groups. A J-shaped relationship between alcohol consumption and stroke risk was observed with reduced risk noted at up to two drinks per day and a significantly increased risk (OR 2.96) at volumes of seven or more drinks per day. No differences were noted among the types of alcoholic beverages (16) (Fig. 3).

A study involving more than 13,000 men and women during a 16-year period revealed the relative risk of stroke for those who drank wine daily or weekly to be 0.68 and 0.66, respectively. (17) A meta-analysis of 19 cohort studies and 16 case-control studies revealed a reduced relative risk of ischemic stroke of 0.80 in those consuming <12 g/d, and 0.72 in drinkers consuming 12 to 24 g/d. Increased relative risks of 1.69 and 2.18 for ischemic stroke and hemorrhagic strokes, respectively, were demonstrated for those consuming >60 g/d of alcohol. (18)

In a case-controlled study of more than of 600 women, aged 15 to 44, wine consumption at moderate levels (up to 24 g/d, or one to two glasses per day) produced a 40 to 60% reduction in risk of ischemic stroke (OR 0.38). Alcohol in the form of beer or liquor was less effective for decreasing the risk of stroke. The authors speculated that the high levels of antioxidant flavonoids in wine might provide additional protective benefits. Additional speculation involved inhibition of platelet function and beneficial effects on the fibrinolytic system. (19) Light drinking, but not heavy drinking, has been shown to have preventive effects on atherosclerotic progression in individuals with diabetes mellitus type 2. (20)

Decreased Risk of Dementia

In a 6-year study involving 5,395 individuals aged 55 years or older who were without dementia at the onset, persons who consumed one to three drinks daily had significantly lower risk for dementia (RR 0.58). Vascular dementia, as a subtype, occurred only 29% as frequently in persons who consumed one to three drinks daily as compared with nondrinkers. The type of alcohol consumed (beer, wine, liquor, or fortified wine) did not influence the results (21) (Fig. 4).

Decreased Risk of Developing Diabetes

A 17-year study from England examined the relation between alcohol and type 2 diabetes in 5,221 men aged 40 to 59 years with no history of coronary heart disease, diabetes, or stroke. Moderate drinkers showed significantly lower risk than occasional drinkers (RR = 0.66) for developing type 2 diabetes, after adjustment for physical activity, smoking, and undiagnosed pre-existing coronary heart disease. Reductions in serum insulin and elevations in HDL-cholesterol explained a small amount (20%) of the reduction in risk of type 2 diabetes associated with moderate drinking. (22)

Reduced Risk of Osteoporosis

The prospective Nurses' Health Study determined that women who consumed 75 g or more of alcohol per week had significantly higher bone densities at the lumbar spine compared with nondrinking women (0.951 versus 0.849 g/c[m.sup.2], P = 0.002). This positive association was observed among both current users and never users of postmenopausal estrogens. (23)


A United Kingdom study to determine the relationship between frequency of alcohol consumption and the risk of vertebral deformity investigated 14,237 individuals from 19 European countries. Stratification by age showed that women 65 years and over who drank alcohol more than 5 days per week had a reduced risk of vertebral deformity compared with those drinking alcohol less than once per week. This protection was most obvious after adjusting for age, body mass index, smoking, current level of physical activity and previous fractures (OR 0.65). (24)

All Cause Mortality Reduction

Data compiled from the prospective study of 85,709 women, aged 34 to 59 years, in the Nurses' Health Study revealed a reduced mortality due largely to reduced risk of coronary heart disease among light to moderate drinkers. Heavier alcohol consumption was associated with increased risk of cirrhosis and breast cancer. The overall survival benefit was more prominent in women at greater risk for coronary heart disease. Adjusted relative risk for women who consumed 1.5 to 4.9 g per day of alcohol was 0.76, and was 0.80 for those consuming 5 to 29.9 g/d. There was a nonsignificant trend toward more protection with wine than with beer or spirits. Benefits increased significantly with cohort age. (25)

In the comparable Physicians' Health Study the relative risk reduction for total mortality reached its nadir of 0.73 at 2 to 4 drinks per week. After adjusting for age and other coronary risk factors, the relative risk for total mortality is still reduced 18% for men drinking one standard drink per day. (26) Other studies, one in Danish adults and another in British male physicians, described the nadir of benefit at consumption patterns between 1 to 6 drinks per week and 5 to 9 drinks per week, respectively. (27,28) A meta-analysis of relative risks of alcohol from 16 cohort studies and selected conditions from a further 132 epidemiologic studies suggested that a relative risk of 0.84 at 1.0 to 1.9 drinks/d for men is returned to 1.01 by 3.0 to 3.9 drinks/d. For women, a relative risk of 0.88 at 0 to 0.9 drinks/d is raised to 1.13 at 2.0 to 2.9 drinks/d. The biologically effective dose of alcohol that impacts mortality in women is approximately two standard drinks per day less than in men. (29) These data from the meta-analysis along with data from the Nurses' Health Study and the Physicians' Health Study are reflected in the J-curve shown in Figure 5.

Metabolic Effects of Moderate Alcohol Consumption

Metabolic influences and biologic markers that explain the beneficial effects of moderate alcohol consumption include an increase in HDL-cholesterol, an increase in tissue plasminogen activator (t-PA) without a compensatory increase in plasminogen activator inhibitor type 1 (PAI-1), a decrease in fibrinogen levels, and decreased platelet aggregation. Additional beneficial changes in biologic markers include decreases in insulin levels and resistance, C-reactive protein, and endothelin-1 synthesis, as well as activation of sirtuins.


Increased High-density Lipoprotein Cholesterol

Increased high-density lipoprotein cholesterol (HDL-C) levels promote a reverse transport of lipids that stabilizes atherosclerotic plaque. Approximately half of cardiovascular benefits from moderate alcohol consumption derive from increased levels of high-density lipoprotein cholesterol (HDL-C), decreased levels of low-density lipoprotein cholesterol (LDL-C), and a lowering of plasma apolipoprotein(a) concentration. (30) In addition, alcohol consumption may alter the activities of plasma proteins and enzymes involved in lipoprotein metabolism. Alcohol intake also results in modifications of lipoprotein particles; specifically, low sialic acid content in apolipoprotein components of lipoprotein particles and acetaldehyde modification of apolipoproteins. The effects of alcohol on lipoproteins in cholesterol transport, as well as the novel effects of lipoproteins on vascular wall cells, comprise a complex mechanism through which alcohol is cardioprotective. (31)

Red wine drinking, at 47 g/d, is associated with a 27% increase in HDL cholesterol. Regular wine consumption is associated with 30 to 90% higher levels of polyunsaturated lipids in HDL and with a 27% increase in the cholesterol esterification rate. (32) During three weeks of moderate alcohol consumption, an increase in apo A-I is followed by an increase in HDL cholesterol, then by an increase in paraoxonase (PON) activity. The kinetics and sequence of these increases may be an additional mechanism of action underlying the reduced coronary heart disease risk in moderate drinkers. (33)

Decreased Coagulation Factors

Moderate alcohol intake decreases clot formation by multiple additive mechanisms. Reduction of platelet aggregation occurs. (30) Moderate alcohol consumption decreases fibrinogen levels, (34) plasma viscosity, von Willebrand factor, and factor VII. (35) Regular moderate alcohol consumption has no significant effect on fibrinolysis, as opposed to higher levels of consumption. (35,36) Alcohol consumption up to 14.9 g/d is not associated with increased PAI-1, whereas greater amounts of alcohol intake do result in increased PAI-1. (37) Polyphenolics (ie, catechin, epicatechin, quercetin, resveratrol) found in red wine upregulate both tissue-type plasminogen activator (t-PA) and urokinase-type PA (u-PA) gene transcription. Wine phenolics increase fibrinolytic activity independent of alcohol. (38) Red wine supplementation, in both the Mediterranean-type diet (MD) and high-fat diet (HFD), resulted in decreased plasma fibrinogen and factor VIIc, and increased tPA antigen and PAI-1 antigen. A MD and moderate consumption of red wine has complementary, mostly beneficial effects on hemostatic cardiovascular risk factors. (39)

Decreased Insulin Levels and Insulin Resistance

Among nondrinkers, the age-adjusted incidence of hypertension significantly increases with elevating insulin terciles in both genders, but not among drinkers. The insulin levels and insulin resistance index, adjusted for age and gender, decreases with elevating alcohol intake, while fasting glucose levels remain unchanged. Alcohol modifies and reduces the otherwise close association between insulin resistance and the incidence of hypertension and improves insulin sensitivity. (40)

In a study of severely obese individuals (average body mass index of 45.3 [+ or -] 7), alcohol consumers showed a marked reduction in the adjusted odds ratio of diabetes mellitus type 2 (odds ratio = 0.29; 95% confidence interval, 0.16-0.55) compared with rare or nonconsumers. A "U-shaped" relationship was demonstrated between the amount and frequency of alcohol consumption and fasting triglyceride, fasting glucose, hemoglobin Alc, and index of insulin resistance measurements. (41)

Diet controlled studies have been done to address the effects of daily moderate alcohol consumption on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women. Consumption of 30 g/d of alcohol compared with abstinence reduced fasting insulin concentration by 19.2% (P = 0.004), reduced triglyceride concentration by 10.3% (P = 0.001), and increased insulin sensitivity by 7.2% (P = 0.002). Normal-weight, overweight, and obese individuals had similar results. The researchers speculated that moderate drinking might "reduce the risk of developing type 2 diabetes and cardiovascular disease in this population of women." (42)

Decreased C-reactive Protein

To evaluate the association of alcohol consumption with C-reactive protein, researchers analyzed findings of the Third National Health and Nutrition Examination involving 11,572 individuals. The main outcome measures were C-reactive protein measurements greater than 0.30 mg/dl (corresponding to the 75th percentile for the population) stratified by categories of alcohol consumption. Among nondrinkers 31% had elevated C-reactive protein levels, compared with 21% of low-to-moderate-frequency drinkers and 18% of high-frequency drinkers. Those individuals who drank 1 to 10 times per month (OR 0.83), 11 to 30 times (OR 0.74), and more than 60 times per month (OR 0.67) were less likely than nondrinkers to have elevated C-reactive protein levels. This association supports an anti-inflammatory mechanism by which moderate alcohol use might protect against cardiovascular death. (43) Other studies have supported this finding with plasma C-reactive protein levels decreased by 35% (P = 0.02) after 3 weeks of alcohol consumption as compared with no alcohol consumption. (44)

Increased Activity of Sirtuins

In diverse organisms, calorie restriction slows the pace of aging and increases maximum lifespan by increasing the activity of members of the sirtuin family of NA[D.sup.+]-dependent protein deacetylases. Included in this family are Sir2, SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumor suppressor. Resveratrol, a polyphenol found in red wine, is a potent activator of sirtuins that increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. (44)

Decreased Endothelin-1 Synthesis

Researchers have demonstrated that red wines strongly inhibit the synthesis of endothelin-1, a vasoactive peptide that is crucial in the development of coronary atherosclerosis. Their findings indicate that components specific to red wine may be crucial to this event. (45)

Adverse Medical Consequences of Alcohol Consumption

Heavy alcohol consumption can adversely affect essentially every organ system (See Table 1). (46) There is evidence that chronic consumption of as little as two drinks per day increases the risk for upper respiratory and upper digestive tract malignancies and breast cancer. (47) The relative risk of oral and pharyngeal cancer associated with two drinks per day is 1.75; the same level of alcohol consumption is associated with a relative risk of 1.51 for esophageal cancer. (48) The relative risk of colon cancer associated with two drinks per day is 1.08. In a meta-analysis of 53 studies including over 100,000 women, the relative risk of breast cancer was 1.32 for an average intake of 35 to 44 g of alcohol per day, and 1.46 for those consuming more than 44 g/d. The concurrent use of alcohol and tobacco conferred no additional risk of breast cancer. (49) In the Nurse's Health Study, the use of postmenopausal hormone replacement therapy for 5 or more years together with consumption of 20 or more grams of alcohol daily resulted in a relative risk of breast cancer of 1.99 compared with nondrinking nonusers of estrogen. For comparison, the relative risk of breast cancer for nondrinking users of hormone replacement was 1.32. (50) The American Cancer Society Cancer Prevention Study demonstrated that even less than one drink per day was associated with a 30% higher death rate from breast cancer in postmenopausal women. This association did not hold true for pre- or perimenopausal women. (51)

There is evidence that moderate drinking by patients infected with hepatitis C is associated with a poorer response to therapy and worsened outcomes. (52) This is in contrast to a study correlating liver histology with alcohol consumption in patients with chronic hepatitis C, which seemed to indicate a threshold level of 80 g of alcohol per day for at least 5 years was required to demonstrate an increased degree of hepatic fibrosis. (53)

Binge drinking is a significant problem even among moderate drinkers. In a recent study, 30% of male moderate drinkers (defined as two or less drinks per day) admitted to binge drinking (five or more drinks) within the past 30 days. Binge drinking is associated with especially high social and economic costs: interpersonal violence, fetal alcohol syndrome, unintended pregnancy, child neglect, and lost productivity. (54)

A Deeper and More Sharply Defined "J" Curve

Since its description in 1989, (55) the "U"- or "J"- shaped curve that describes the mortality variance contrasting low levels of consumption with higher, abusive levels has changed. The nadir of benefit is deeper as dramatic data reflect decreases in cardiovascular disease, dementia, metabolic diseases, and all-cause mortality. As daily intake increases, health risks increase (Fig. 5).

The Debate

An American Heart Association Position Statement cautions: "If you drink alcohol, do so in moderation. This means an average of one to two drinks per day for men and one drink per day for women." They further caution people "NOT to start drinking ... if you do not already drink alcohol," and to "consult your doctor on the benefits and risks of consuming alcohol in moderation." (56)

The popularity of the topic of the health benefits of moderate alcohol intake in both medical journals and the lay press gives rise to increased discussion of the topic. A recent column by a popular wine journalist reported on medical studies that "moderate drinking can help prevent strokes, amputated limbs, and dementia.... The cardiac benefits of low-dose alcohol are evident in study after study." He quoted Abigail Zuger's New York Times article titled, "The Case for Drinking," which describes the growing body of evidence that people who consume wine in moderation tend to be healthier and live longer. (57) He further decried the "political correctness" of institutions and authorities that at worst "cover up the results" of the Framingham study and at best are too timid to go so far as to recommend wine in moderation. He concludes by advising his readers to discuss the topic with their family physicians. (58)

Counseling Regarding Drinking Behavior

Individuals who are currently abstinent and comfortable with that lifestyle should not be encouraged to start drinking solely for the potential health benefits. Although convincing data do not currently exist, it is our belief that the risks of developing abusive drinking patterns and the associated detrimental health effects potentially outweigh the advantage of light to moderate drinking. (59,60) Exceptions to this conservative stance may be considered for the patient who is 1) well known to the physician, 2) has no apparent abuse liability, and 3) whose cardiovascular risks demand aggressive intervention.

Recent reports on the potential health benefits of alcohol (57,61) may encourage some individuals to start using alcohol. A cautious approach is warranted. Theoretically, individuals who would benefit the most from such a lifestyle change include older individuals (25,62) and those with a family history or other risk factors for premature cardiovascular disease. (25) For those choosing to initiate alcohol consumption, a conservative prescription-like recommendation of a precise amount at a given time (eg, one glass of wine with the evening meal) would seem indicated. Careful monitoring for escalating usage and/or adverse health consequences is appropriate.

For individuals who have established an adaptive and enjoyable pattern of appropriate alcohol use, and have no identified health problems that could be adversely affected by alcohol use, there appears to be no compelling reason to encourage them to abstain, (63-65) although continued monitoring is indicated. After assessing for contraindications, individuals who do not have a history of alcohol abuse can be counseled regarding the health benefits of light to moderate consumption. (66) While some studies show no difference in the beneficial effects of different forms of alcohol, (67) others have found wine to be most beneficial. (68)

Recommendations regarding alcohol intake should be individualized based on age and gender as well as physical and mental health status. (69) Pregnant women, individuals with medical, psychiatric, or pharmacologic contraindications, and those with personal and/or family histories of substance abuse should be encouraged not to drink at all, while lower limits may be appropriate for those with hypertension or diabetes. (26,70) Everyone should be cautioned regarding the effect of even moderate drinking on motor skill activities such as driving. (69) Individuals for whom alcohol is causing social problems and/or for whom alcohol use poses significant health risks should be counseled to decrease their use or abstain from using alcohol altogether. (59,65,71)


Alcohol is accurately viewed as beneficial nutrition that prolongs life and enhances a gracious and joyful lifestyle for some; and is equally and accurately recognized as a life-destroying multi-system toxin for others. Nowhere in medicine is the double-edged sword so sharp on both sides. The life extending benefits of moderate alcohol intake are similar to HMG Co-A reductase pharmacotherapy and of greater magnitude than that provided by [beta]-blocker therapy following a myocardial infarction. (72) Although it is appropriate to recommend [beta]-blocker therapy following a myocardial infarction due to its demonstrated 23% reduction in mortality, in the authors' opinion physicians should not feel compelled to recommend low-dose alcohol, which provides a 27% mortality reduction. The reason for the authors' hesitation is due to the difference in the magnitude of the risk should patterns of abuse develop. The ancient dictum is Primum non nocere ("First, do no harm"). A well-informed and astute personal physician, who knows his or her patient as well as he or she knows medicine, must still be humbled by the task of advising patients on this subject. We have much knowledge, some insight, but no prescience. Presenting both the pros and cons of moderate alcohol consumption, along with the particular beneficial and risky attributes for a given individual, shouldenhance the ability of each patient to make a truly individualized, informed decision.
Life appears to me too short to be spent in nursing animosity or
registering wrongs.
--Charlotte Bronte

Variation In Relative Risk of MI by ADH3 Allele

 Nondrinker At least 1 drink/d

gamma 1 allele 1 0.65
gamma 2 allele 0.62 0.14

Fig. 2 Bar graph showing the variation in relative risk for myocardial
infarction by ADH3 allele.

Note: Table made from bar graph.

J-Curve Effect of Alcohol and Stroke

 All populations

Nondrinker 1
2 or less/d 0.51
7 or more/d 296

Fig. 3 Graph showing the J-curve effect of alcohol and stroke.

Note: Table made from line graph.

Table 1. Diseases and disorders associated with heavy alcohol

Neurologic disorders
 Withdrawal syndrome
 Delirium tremens
 Wernicke-Korsakoff syndrome
 Alcoholic cerebellar degeneration
 Peripheral neuropathy
 Ischemic stroke
 Intracranial hemorrhage
Cardiac disorders
Hepatic dysfunction
 Alcoholic hepatitis
Gastrointestinal disorders
 Peptic ulcer disease
 Alcoholic myopathy
 Falls and fractures
 Oral and pharyngeal
Hematologic disorders
 Bone marrow suppression
 Nutritional and blood loss anemia
Immune system disorders
 Impaired immune system
 More frequent infections and complications thereof
 Psychiatric comorbidities are exacerbated
 Suicide risk increases
 Sleep disturbance
 Sexual dysfunction
 Obstructive sleep apnea
 Periodic limb movement disorders
 Accidents and injury (to self and others)

Accepted June 9, 2003.

Copyright [c] 2004 by The Southern Medical Association



1. Grant BF. Alcohol consumption, alcohol abuse and alcohol dependence: The United States as an example. Addiction 1994;89:1357-1365.

2. Robert Wood Johnson Foundation. Substance Abuse: The Nation's Number One Health Problem. Princeton, NJ, Robert Wood Johnson Foundation, February 2001.

3. Crum RM. The epidemiology of addictive disorders, in Graham AW, Schultz TK, Mayo-Smith MF, et al (eds): Principles of Addiction Medicine. Chevy Chase, MD, American Society of Addiction Medicine, 2003, ed 3, pp 17-32.

4. Caetano R, Cunradi C. Alcohol dependence: A public health perspective. Addiction 2002;97:633-645.

5. Dawson DA, Archer LD. Relative frequency of heavy drinking and the risk of alcohol dependence. Addiction 1993;88:1509-1518.

6. Greenfield TK, Rogers JD. Who drinks most of the alcohol in the US? The policy implications. J Stud Alcohol 1999;60:78-89.

7. Ajani UA, Gaziano JM, Lotufo PA, et al. Alcohol consumption and risk of coronary heart disease by diabetes status. Circulation 2000;102:500-505.

8. Solomon CG, Hu FB, Stampfer MJ, et al. Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus. Circulation 2000;102:494-499.

9. Stampfer MJ, Hu FB, Manson JE, et al. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 2000;343:16-22.

10. Mukamal KJ, Conigrave KM, Mittleman MA, et al. Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N Engl J Med 2003;348:109-118.

11. Hines LM, Stampfer MJ, Ma J, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001;344:549-555.

12. Mukamal KJ, Maclure M, Muller JE, et al. Prior alcohol consumption and mortality following acute myocardial infarction. JAMA 2001;285:1965-1970.

13. Abramson JL, Williams SA, Krumholz HM, et al. Moderate alcohol consumption and risk of heart failure among older persons. JAMA 2001;285:1971-1977.

14. Walsh CR, Larson MG, Evans JC, et al. Alcohol consumption and risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med 2002;136:181-191.

15. Cooper HA, Exner DV, Domanski MJ. Light-to-moderate alcohol consumption and prognosis in patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000;35:1753-1759.

16. Sacco RL, Elkind M, Boden-Albala B, et al. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA 1999;281:53-60.

17. Truelsen T, Gronbaek M, Schnohr P, et al. Intake of beer, wine, and spirits and risk of stroke: The Copenhagen City Heart Study. Stroke 1998;29:2467-2472.

18. Reynolds K, Lewis B, Nolen JD, et al. Alcohol consumption and risk of stroke: A meta-analysis. JAMA 2003;289:579-588.

19. Malarcher AM. Giles WH, Croft JB, et al. Alcohol intake, type of beverage, and the risk of cerebral infarction in young women. Stroke 2001;32:77-83.

20. Wakabayashi I, Kobaba-Wakabayashi R, Masuda H. Relation of drinking alcohol to atherosclerotic risk in type 2 diabetes. Diabetes Care 2002;25:1223-1228.

21. Ruitenberg A, van Swieten JC, Witteman JC, et al. Alcohol consumption and risk of dementia: The Rotterdam Study. Lancet 2002;359:281-286.

22. Wannamethee SG, Shaper AG, Perry IJ, et al. Alcohol consumption and the incidence of type II diabetes. J Epidemiol Community Health 2002;56:542-548.

23. Feskanich D, Korrick SA. Greenspan SL, et al. Moderate alcohol consumption and bone density among postmenopausal women. J Womens Health 1999;8:65-73.

24. Naves Diaz M, O'Neill TW, Silman AJ. The influence of alcohol consumption on the risk of vertebral deformity. European Vertebral Osteoporosis Study Group. Osteoporos Int 1997;7:65-71.

25. Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med 1995;332:1245-1250.

26. Gaziano JM, Gaziano TA, Glynn RJ, et al. Light-to-moderate alcohol consumption and mortality in the Physicians' Health Study enrollment cohort. J Am Coll Cardiol 2000;35:96-105.

27. Gronbaek M, Deis A. Sorensen TI, et al. Influence of sex, age, body mass index, and smoking on alcohol intake and mortality. BMJ 1994;308:302-306.

28. Doll R, Peto R, Hall E, et al. Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors. BMJ 1994;309:911-918.

29. Holman CD, English DR, Milne E, et al. Meta-analysis of alcohol and all-cause mortality: A validation of NHMRC recommendations. Med J Aust 1996;164:141-145.

30. Agarwal DP. Cardioprotective effects of light-moderate consumption of alcohol: A review of putative mechanisms. Alcohol Alcohol 2002;37:409-415.

31. Hannuksela ML, Liisanantt MK, Savolainen MJ. Effect of alcohol on lipids and lipoproteins in relation to atherosclerosis. Crit Rev Clin Lab Sci 2002;39:225-283.

32. Perret B, Ruidavets JB, Vieu C, et al. Alcohol consumption is associated with enrichment of high-density lipoprotein particles in polyunsaturated lipids and increased cholesterol esterification rate. Alcohol Clin Exp Res 2002;26:1134-1140.

33. Sierksma A, van der Gaag MS, van Tol A, et al. Kinetics of HDL cholesterol and paraoxonase activity in moderate alcohol consumers. Alcohol Clin Exp Res 2002;26:1430-1435.

34. Sierksma A, van der Gaag MS, Kluft C, et al. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels: A randomized, diet-controlled intervention study. Eur J Clin Nutr 2002;56:1130-1136.

35. Mukamal KJ, Jadhav PP, D'Agostino RB, et al. Alcohol consumption and hemostatic factors: Analysis of the Framingham Offspring cohort. Circulation 2001;104:1367-1373.

36. van Golde PM, Hart HC, Kraaijenhagen RJ, et al. Regular alcohol intake and fibrinolysis. Neth J Med 2002;60:285-288.

37. Djousse L, Pankow JS, Arnett DK, et al. Alcohol consumption and plasminogen activator inhibitor type 1: The National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J 2000;139:704-709.

38. Abou-Agag LH, Aikens ML, Tabengwa EM, et al. Polyphenolics increase t-PA and U-PA gene transcription in cultured human endothelial cells. Alcohol Clin Exp Res 2001;25:155-162.

39. Mezzano D, Leighton F, Martinez C, et al. Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic risk factors. Eur J Clin Nutr 2001;55:444-451.

40. Arima H, Kiyohara Y, Kato I, et al. Alcohol reduces insulin-hypertension relationship in a general population: The Hisayama study. J Clin Epidemiol 2002;55:863-869.

41. Dixon JB, Dixon ME, O'Brien PE. Alcohol consumption in the severely obese: Relationship with the metabolic syndrome. Obes Res 2002;10:245-252.

42. Davies MJ, Baer DJ, Judd JT, et al. Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: A randomized controlled trial. JAMA 2002;287:2559-2562.

43. Stewart SH, Mainous AG III, Gilbert G. Relation between alcohol consumption and C-reactive protein levels in the adult US population. J Am Board Fam Pract 2002;15:437-442.

44. Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003 Aug 24 [Epub ahead of print; PMID: 12939617]. Available at: Accessed September 2, 2003.

45. Corder R, Douthwaite JA, Lees DM, et al. Endothelin-1 synthesis reduced by red wine. Nature 2001;414:863-864.

46. Saitz R. Overview of medical and surgical complications, in Graham AW, Schultz TK, Mayo-Smith MF, et al (eds): Principles of Addiction Medicine. Chevy Chase, MD, American Society of Addiction Medicine, 2003, ed 3, pp 1027-1052.

47. Corrao G, Bagnardi V, Zambon A, et al. Exploring the dose-response relationship between alcohol consumption and the risk of several alcohol-related conditions: A meta-analysis. Addiction 1999;94:1551-1573.

48. Bagnardi V, Blangiardo M, La Vecchia C, et al. A meta-analysis of alcohol drinking and cancer risk. Br J Cancer 2001;85:1700-1705.

49. Hamajima N, Hirose K, Tajima K, et al; Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol, tobacco and breast cancer: Collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 2002;87:1234-1245.

50. Chen WY, Colditz GA, Rosner B, et al. Use of postmenopausal hormones, alcohol, and risk for invasive breast cancer. Ann Intern Med 2002;137:798-804.

51. Feigelson HS, Calle EE, Robertson AS, et al. Alcohol consumption increases the risk of fatal breast cancer (United States). Cancer Causes Control 2001;12:895-902.

52. Barder TF. Viral Hepatitis: Practical Evaluation and Treatment. Seattle, WA, Hogrefe & Huber, 2000, ed 3.

53. Khan MH, Thomas L, Byth K, et al. How much does alcohol contribute to the variability of hepatic fibrosis in chronic hepatitis C? J Gastroenterol Hepatol 1998;13:419-426.

54. Naimi TS, Brewer RD, Mokdad A, et al. Binge drinking among US adults. JAMA 2003;289:70-75.

55. Shaper AG, Wannamethee G, Walker M. Alcohol and the U-shaped curve. Lancet 1989;1:336 (letter).

56. American Heart Association. Alcohol, Wine and Cardivascular Disease, Dallas, TX, American Heart Association, 2002. Available at Accessed June 24, 2003.

57. Zuger A. The case for drinking. N Y Times December 31, 2002, p F1.

58. Garr R. Wine, health and political correctness. The Signal Mountain Post 2003 Jan 9;10(1):17.

59. Dawson DA. Alcohol and mortality from external causes. J Stud Alcohol 2001;62:790-797.

60. Cherpitel CJ, Tam T, Midanik L, et al. Alcohol and non-fatal injury in the U.S. general population: A risk function analysis. Accid Anal Prev 1995;27:651-661.

61. Warner M. Here's to your health (transcript). PBS Online NewsHour, 21 Jan 2003. Available at: Accessed June 24, 2003.

62. Klatsky AL, Armstrong MA, Friedman GD. Alcohol and mortality. Ann Intern Med 1992;117:646-654.

63. de Labry LO, Glynn RJ, Levenson MR, et al. Alcohol consumption and mortality in an American male population: Recovering the U-shaped curve--Findings from the Normative Aging Study. J Stud Alcohol 1992; 53:25-32.

64. Fillmore KM, Golding JM, Graves KL, et al. Alcohol consumption and mortality: Part III--Studies of female populations. Addiction 1998;93:219-229.

65. Rehm J, Greenfield TK, Rogers JD. Average volume of alcohol consumption, patterns of drinking, and all-cause mortality: Results from the US National Alcohol Survey. Am J Epidemiol 2001;153:64-71.

66. Ellison RC. Balancing the risks and benefits of moderate drinking. Ann N Y Acad Sci 2002;957:1-6.

67. Gaziano JM, Hennekens CH, Godfried SL, et al. Type of alcoholic beverage and risk of myocardial infarction. Am J Cardiol 1999;83:52-57.

68. Gronbaek M, Becker U, Johansen D, et al. Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Ann Intern Med 2000;133:411-419.

69. Drory Y. Is drinking alcohol good for your health? [in Hebrew]. Harefuah 2001;140:1032-1037, 1117.

70. Meister KA, Whelan EM, Kava R. The health effects of moderate alcohol intake in humans: An epidemiologic review. Crit Rev Clin Lab Sci 2000;37:261-296.

71. Murray RP, Connett JE, Tyas SL, et al. Alcohol volume, drinking pattern, and cardiovascular disease morbidity and mortality: Is there a U-shaped function? Am J Epidemiol 2002;155:242-248.

72. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial. Lancet 2001;357:1385-1390.


* The benefit of alcohol is at its maximum with consumption of as little as 1/2 standard drink/d.

* Benefits are lost and risk increases at a lower volume of consumption for women than for men.

* The risk of abuse and/or addiction may prohibit the safe recommendation for initiating alcohol use solely for health benefits.

* There is no compelling reason to recommend cessation of alcohol consumption in individuals who have demonstrated a pattern of moderate and nonabusive consumption.

John B. Standridge, MD, Robert G. Zylstra, EDD, LCSW, and Stephen M. Adams, MD

From the Department of Family Medicine, University of Tennessee College of Medicine, Chattanooga Unit, Chattanooga, TN.

No grants or external funding sources were used to support the development of this manuscript. None of the authors have any commercial or proprietary conflicts related to this manuscript.

Reprint requests to John B. Standridge, MD, c/o UT Family Practice Center, 1100 E. Third Street, Chattanooga, TN 37403. Email:
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Title Annotation:Review Article
Author:Adams, Stephen M.
Publication:Southern Medical Journal
Date:Jul 1, 2004
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