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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 myocardial infarction: see under 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 biochemical changes (bī·ō·keˈmik·  have been identified that explain the beneficial effects of moderate alcohol consumption. Heavy alcohol consumption, however, can negatively affect neurologic, cardiac, gastrointestinal, hematologic hematological, hematologic

pertaining to or emanating from blood cells.


hematological tests
total and differential white cell counts, hematocrit estimation, erythrocyte count.
, immune, psychiatric and musculoskeletal musculoskeletal /mus·cu·lo·skel·e·tal/ (-skel´e-t'l) pertaining to or comprising the skeleton and muscles.

mus·cu·lo·skel·e·tal
adj.
Relating to or involving the muscles and the skeleton.
 organ systems. Binge drinking binge drinking An early phase of chronic alcoholism, characterized by episodic 'flirtation' with the bottle by binges of drinking to the point of stupor, followed by periods of abstinence; BD is accompanied by alcoholic ketoacidosis–accelerated lipolysis and  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 substance abuse disorder
n.
Any of a category of disorders in which pathological behavioral changes are associated with the regular use of substances that affect the central nervous system.
, 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 DSM-IV
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This reference book, published by the American Psychiatric Association, is the diagnostic standard for most mental health professionals in the United States.
 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 Cardiovascular disease
Disease that affects the heart and blood vessels.

Mentioned in: Lipoproteins Test

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 coronary heart disease: see coronary artery disease.
coronary heart disease
 or ischemic heart disease

Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis).
 (CHD CHD coronary heart disease.

ChD
abbr.
Latin Chirurgiae Doctor (Doctor of Surgery)


CHD,
n.pr See disease, coronary heart.


CHD

canine hip dysplasia.
) 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 alcohol dehydrogenase /al·co·hol de·hy·dro·gen·ase/ (ADH) (de-hi´dro-jen-as) an enzyme that catalyzes the reversible oxidation of primary or secondary alcohols to aldehydes; the reaction is the first step in the metabolism of alcohols by  Type 3 (ADH ADH: see antidiuretic hormone. 3). This in turn alters the rate of alcohol metabolism among individuals. The homozygosity ho·mo·zy·gos·i·ty
n.
The condition of having identical genes at one or more loci in homologous chromosome segments.



homozygosity

the state of having identical alleles in regard to a given character or characters.
 for the allele allele (əlēl`): see genetics.
allele

Any one of two or more alternative forms of a gene that may occur alternatively at a given site on a chromosome.
 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 ho·mo·zy·gous
adj.
Having the same alleles at one or more gene loci on homologous chromosome segments.


Homozygous
Identical genes controlling a specified inherited trait.
 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 (Hardware Description Language) A language used to describe the functions of an electronic circuit for documentation, simulation or logic synthesis (or all three). Although many proprietary HDLs have been developed, Verilog and VHDL are the major standards.  levels described in these data were mirrored in an independent study of postmenopausal post·men·o·paus·al
adj.
Of or occurring in the time following menopause.


postmenopausal Change of life Gynecology adjective Referring to the time in ♀ when menstrual periods stop for ≥ 1 yr
 women. (11)

[FIGURE 1 OMITTED]

Reduced Myocardial Infarction Mortality

Compared with nondrinkers, patients who consume moderate amounts of alcohol during the year before an acute myocardial infarction acute myocardial infarction (·kyōōtˑ mī·ō·karˑ·dē·  (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 The Framingham Heart Study is a cardiovascular study based in Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants.  who were free of congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time.  (CHF CHF

In currencies, this is the abbreviation for the Swiss Franc.

Notes:
The currency market, also known as the Foreign Exchange market, is the largest financial market in the world, with a daily average volume of over US $1 trillion.
) 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 ventricular dysfunction,
n an abnormality in contraction and wall motion within the ventricles.
 (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 antioxidant, substance that prevents or slows the breakdown of another substance by oxygen. Synthetic and natural antioxidants are used to slow the deterioration of gasoline and rubber, and such antioxidants as vitamin C (ascorbic acid), butylated hydroxytoluene  flavonoids flavonoids,
n.pl common plant pigment compounds that act as antioxidants, enhance the effects of vitamin C, and strengthen connective tissue around capillaries.
 in wine might provide additional protective benefits. Additional speculation involved inhibition of platelet function and beneficial effects on the fibrinolytic fibrinolytic

pertaining to or emanating from fibrinolysis.


fibrinolytic agent
substances that stimulate or inhibit fibrinolysis.

fibrinolytic inhibitors
include e-aminocaproic acid and antiplasmin-a1.
 system. (19) Light drinking, but not heavy drinking, has been shown to have preventive effects on atherosclerotic progression in individuals with diabetes mellitus diabetes mellitus

Disorder of insufficient production of or reduced sensitivity to insulin. Insulin, synthesized in the islets of Langerhans (see Langerhans, islets of), is necessary to metabolize glucose. In diabetes, blood sugar levels increase (hyperglycemia).
 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 vascular dementia
n.
A steplike deterioration in intellectual functions that result from multiple infarctions of the cerebral hemispheres. Also called multi-infarct dementia.
, as a subtype (programming) subtype - If S is a subtype of T then an expression of type S may be used anywhere that one of type T can and an implicit type conversion will be applied to convert it to type T. , 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 type 2 diabetes
n.
See diabetes mellitus.
 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 Nurses' Health Study Cardiology A large cohort study that evaluated the effect of exogenous HRT on the risk of cardiovascular disease. See Estrogen replacement therapy, Osteoporosis.  determined that women who consumed 75 g or more of alcohol per week had significantly higher bone densities at the lumbar spine Lumbar spine
The segment of the human spine above the pelvis that is involved in low back pain. There are five vertebrae, or bones, in the lumbar spine.

Mentioned in: Low Back Pain
 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 Estrogens
Hormones produced by the ovaries, the female sex glands.

Mentioned in: Acne, Polycystic Ovary Syndrome

estrogens (es´trōjenz),
n.
. (23)

[FIGURE 4 OMITTED]

A United Kingdom study to determine the relationship between frequency of alcohol consumption and the risk of vertebral ver·te·bral
adj.
1. Of, relating to, or of the nature of a vertebra.

2. Having or consisting of vertebrae.

3. Having a spinal column.
 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 non·sig·nif·i·cant  
adj.
1. Not significant.

2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence.
 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 tissue plasminogen activator
n. Abbr. TPA
1. An enzyme that catalyzes the conversion of plasminogen to plasmin, used to dissolve blood clots rapidly and selectively, especially in the treatment of heart attacks.

2.
 (t-PA) without a compensatory increase in plasminogen activator plasminogen activator /plas·min·o·gen ac·ti·va·tor/ (ak´ti-va?tor) see under activator.

plasminogen activator
n.
See urokinase.
 inhibitor type 1 (PAI-1), a decrease in fibrinogen Fibrinogen

The major clot-forming substrate in the blood plasma of vertebrates. Though fibrinogen represents a small fraction of plasma proteins (normal human plasma has a fibrinogen content of 2–4 mg/ml of a total of 70 mg protein/ml), its conversion
 levels, and decreased platelet aggregation Platelet aggregation
The clumping together of blood cells, possibly forming a clot.

Mentioned in: Herbalism, Traditional Chinese
. 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.

[FIGURE 5 OMITTED]

Increased High-density Lipoprotein Cholesterol high-density lipoprotein cholesterol See HDL-cholesterol.  

Increased high-density lipoprotein cholesterol (HDL-C HDL-C high-density-lipoprotein cholesterol. ) 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 low-density lipoprotein cholesterol (lōˈ-denˑ·s  (LDL-C LDL-C low-density-lipoprotein cholesterol ), and a lowering of plasma apolipoprotein apolipoprotein /apo·lipo·pro·tein/ (ap?o-lip?o-pro´ten) any of the protein constituents of lipoproteins, grouped by function in four classes, A, B, C, and E.

ap·o·lip·o·pro·tein
n.
(a) concentration. (30) In addition, alcohol consumption may alter the activities of plasma proteins and enzymes involved in lipoprotein lipoprotein (lĭp'əprō`tēn), any organic compound that is composed of both protein and the various fatty substances classed as lipids, including fatty acids and steroids such as cholesterol.  metabolism. Alcohol intake also results in modifications of lipoprotein particles; specifically, low sialic acid content in apolipoprotein components of lipoprotein particles and acetaldehyde acetaldehyde (ăs'ĭtăl`dəhīd) or ethanal (ĕth`ənăl'), CH3CHO, colorless liquid aldehyde, sometimes simply called aldehyde. It melts at −123°C;, boils at 20.  modification of apolipoproteins. The effects of alcohol on lipoproteins Lipoproteins
The packages in which cholesterol and triglycerides travel throughout the body.

Mentioned in: Lipoproteins Test

lipoproteins
(lip´ōprō´tēns),
n.
 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 polyunsaturated /poly·un·sat·u·rat·ed/ (-un-sach´er-at-ed) denoting a chemical compound, particularly a fatty acid, having two or more double or triple bonds in its hydrocarbon chain.  lipids in HDL and with a 27% increase in the cholesterol esterification es·ter·i·fi·ca·tion
n.
A chemical reaction resulting in the formation of at least one ester product.



es·teri·fied adj.
 rate. (32) During three weeks of moderate alcohol consumption, an increase in apo A-I A-I General Audiences (Catholic movie rating)  is followed by an increase in HDL cholesterol, then by an increase in paraoxonase (PON (Passive Optical Network) An optical point-to-multipoint access network. There are no optical repeaters or other active devices in a PON, hence the name "passive. ) 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 von Willebrand factor (vWF)
A protein found in the blood that is involved in the process of blood clotting.

Mentioned in: Von Willebrand Disease


von Willebrand factor
, and factor VII. (35) Regular moderate alcohol consumption has no significant effect on fibrinolysis fibrinolysis /fi·bri·nol·y·sis/ (fi?brin-ol´i-sis) dissolution of fibrin by enzymatic action.fibrinolyt´ic

fi·bri·nol·y·sis
n. pl.
, 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 catechin /cat·e·chin/ (kat´e-kin) an astringent principle from the heartwood of Acacia catechu (catechu) and Uncaria gambier (gambir). , epicatechin, quercetin quer·ce·tin
n.
A yellow powdered crystalline compound produced synthetically or occurring as a glycoside in the rind and bark of numerous plants, used medicinally to treat abnormal capillary fragility. Also called meletin.
, resveratrol res·ver·a·trol
n.
A natural compound found in grapes, mulberries, peanuts, and other plants or food products, especially red wine, that may protect against cancer and cardiovascular disease by acting as an antioxidant, antimutagen, and
) 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 HFD Hulbert Financial Digest (newsletter)
HFD Honolulu Fire Department (Honolulu, HI)
HFD Houston Fire Department
HFD Half Duplex
HFD Hrvatsko Farmaceutsko Društvo
), 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 hemostatic /he·mo·stat·ic/ (he?mo-stat´ik)
1. causing hemostasis, or an agent that so acts.

2. due to or characterized by stasis of the blood.


he·mo·stat·ic
adj.
 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 stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers.

strat·i·fied
adj.
Arranged in the form of layers or strata.
 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 polyphenol  

Any of various alcohols containing two or more benzene rings that each have at least one hydroxyl group (OH) attached. Many polyphenols occur naturally in plants and some kinds, such as the flavonoids and tannins, are believed to be beneficial
 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 DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 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 vasoactive /vaso·ac·tive/ (va?zo-) (vas?o-ak´tiv) exerting an effect upon the caliber of blood vessels.

va·so·ac·tive
adj.
 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 pharyngeal /pha·ryn·ge·al/ (fah-rin´je-al) pertaining to the pharynx.

pha·ryn·geal or pha·ryn·gal
adj.
Of, relating to, located in, or coming from the pharynx.
 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 Hormone Replacement Therapy Definition

Hormone replacement therapy (HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced in a woman's body.
 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 American Cancer Society,
n.pr established in 1913, this national volunteer-based health organization is committed to the elimination of cancer through prevention and treatment and to diminishing cancer suffering through advocacy, scholarship, research,
 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 perimenopausal adjective Referring to a period of a ♀'s life–age 45 to 55-ish–in which menstrual periods become irregular; perimenopause is immediately before, during and after menopause. See Menopause.  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 fetal alcohol syndrome (FAS), pattern of physical, developmental, and psychological abnormalities seen in babies born to mothers who consumed alcohol during pregnancy. , 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 American Heart Association (AHA),
n.pr a national voluntary health agency that has the goal of increasing public and medical awareness of cardiovascular diseases and stroke, and thereby reducing the number of associated deaths and disabilities.
 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)

Conclusion

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 hMG menotropins (human menopausal gonadotropin).

HMG
abbr.
human menopausal gonadotropin
 Co-A reductase reductase /re·duc·tase/ (-tas) a term used in the names of some of the oxidoreductases, usually specifically those catalyzing reactions important solely for reduction of a metabolite.  pharmacotherapy pharmacotherapy /phar·ma·co·ther·a·py/ (-ther´ah-pe) treatment of disease with medicines.

phar·ma·co·ther·a·py
n.
Treatment of disease through the use of drugs.
 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 primum non nocere (prēˈ·mum nōnˈ n  ("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 pre·science  
n.
Knowledge of actions or events before they occur; foresight.


prescience
Noun

Formal knowledge of events before they happen [Latin praescire to know beforehand]
. Presenting both the pros and cons pros and cons
Noun, pl

the advantages and disadvantages of a situation [Latin pro for + con(tra) against]
 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
consumption

Neurologic disorders
  Intoxication
  Addiction
  Withdrawal syndrome
  Seizures
  Delirium tremens
  Wernicke-Korsakoff syndrome
  Alcoholic cerebellar degeneration
  Peripheral neuropathy
  Ischemic stroke
  Intracranial hemorrhage
Cardiac disorders
  Hypertension
  Cardiomyopathy
  Arrythmias
Hepatic dysfunction
  Cirrhosis
  Alcoholic hepatitis
Gastrointestinal disorders
  Gastritis
  Esophagitis
  Duodenitis
  Peptic ulcer disease
  Pancreatitis
Musculoskeletal
  Alcoholic myopathy
  Osteoporosis
  Falls and fractures
Malignancy
  Oral and pharyngeal
  Laryngeal
  Esophageal
  Stomach
  Breast
  Liver
  Colon
Hematologic disorders
  Bone marrow suppression
  Nutritional and blood loss anemia
Immune system disorders
  Impaired immune system
  More frequent infections and complications thereof
Psychiatric
  Psychiatric comorbidities are exacerbated
  Suicide risk increases
Other
  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

0038-4348/04/9707-0664

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RELATED ARTICLE: Key Points

* 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 Noun 1. EdD - a doctor's degree in education
DEd, Doctor of Education

doctor's degree, doctorate - one of the highest earned academic degrees conferred by a university
, LCSW LCSW Licensed Clinical Social Worker , and Stephen M. Adams, MD

From the Department of Family Medicine, University of Tennessee The University of Tennessee (UT), sometimes called the University of Tennessee at Knoxville (UT Knoxville or UTK), is the flagship institution of the statewide land-grant University of Tennessee public university system in the American state 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: standrjb@erlanger.org
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