Alcoholic Beverages

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Summary

  • Observational studies have consistently found that moderate alcohol consumption (no more than two alcoholic drinks/day for men and no more than one alcoholic drink/day for women) is associated with a decreased risk of cardiovascular and all-cause mortality. (More information)
  • Moderate alcohol consumption is associated with lowered risks of coronary heart disease (CHD) and ischemic stroke. (More information)
  • Evidence from observational studies suggests that moderate alcohol intake may be associated with reduced risk of type 2 diabetes, dementia, and gallstones, as well as with improved bone mineral density. (More information)
  • Even moderate alcohol consumption may increase the risk of female breast cancer, alcohol-related birth defects, and progression to heavy alcohol consumption in some people. (More information)
  • Heavy alcohol consumption is associated with increased risks of hypertension, stroke, heart rhythm disturbances, dementia, accidents, injury, violence, and damage to the heart, liver, and pancreas. (More information)
  • Heavy alcohol consumption is associated with increased risk of many cancers, including cancers of the mouth, pharynx, larynx, esophagus, liver, breast, colon and rectum. The combined use of alcohol and tobacco greatly increases the risk of oral and esophageal cancers. (More information)
  • Those who consume more than minimal amounts of alcohol should make sure they also consume adequate folate by taking a daily multivitamin that provides 400 μg of folic acid. (More information)
  • There is consensus that the health risks of moderate alcohol consumption outweigh the health benefits for some people. People who should abstain from alcohol include (1, 2): children and adolescents; pregnant women and women who may become pregnant; anyone who has trouble limiting his or her alcohol consumption to moderate levels, particularly recovering alcoholics and those with a family history of alcoholism or alcohol problems; and anyone with chronic liver disease or alcohol-related disease or organ damage. 
  • Anyone planning to drive, operate heavy machinery, or perform other potentially hazardous activities requiring coordination and skill should not consume alcohol.
  • People who would benefit from individualized advice regarding potential health risks and benefits of moderate alcohol consumption include: anyone taking medications (over-the-counter or prescription) with the potential for adverse interactions with alcohol; and anyone with a personal or family history (e.g., parent or sibling) of breast cancer, coronary heart disease, or other conditions related positively or inversely to moderate drinking.

Introduction

While excessive alcohol consumption has been linked to a number of serious health and social problems, observational studies have associated moderate alcohol consumption with some important health benefits. The relationship between alcohol consumption and mortality is often described as J-shaped, meaning that when graphed from alcohol abstinence on the left to heavy drinking on the right, light-to-moderate alcohol consumption (≤2 drinks/day) is associated with lower rates of mortality — mostly from cardiovascular disease — than abstention, while heavy alcohol consumption (>3-4 drinks/day) is associated with higher rates of mortality from a number of causes (3-5). Because the consumption of alcohol can be viewed as a “double-edged sword,” individual decisions regarding alcohol use should take into consideration scientific evidence regarding potential health benefits and risks, as well as personal and family histories of health problems and addictions.

It is important to note the data on alcohol-disease relationships come from only observational studies, not randomized controlled trials, and observational data cannot establish causation. In observational research, potential confounding variables should be adequately adjusted for using statistical techniques. For instance, nondrinkers have been shown to differ from those who consume alcohol in ways that might affect the disease outcome of interest (6). Even when controlling for many potential confounders, residual confounding may still occur.

Definitions (7)

Standard alcoholic drink (8)

A standard alcoholic drink contains approximately 14 grams of alcohol, which is equivalent to 12 ounces of beer (~5% alcohol), 8.5 ounces of malt liquor (~9% alcohol), 5 ounces of wine (~12% alcohol), 3.5 ounces of fortified wine (e.g., sherry or port), or 1.5 ounces of liquor (distilled spirits; ~40% alcohol).

Moderate alcohol consumption

  • Men: No more than two standard alcoholic drinks/day (9)
  • Women: No more than one standard alcoholic drink/day* (9)
  • There is consensus that distributing total weekly alcohol intake evenly to most days is the healthiest drinking pattern. 

Heavy alcohol consumption (8)

  • Men: More than 14 standard alcoholic drinks/week or more than 4 standard alcoholic drinks in a day
  • Women: More than 7 standard alcoholic drinks/week or more than 3 standard alcoholic drinks in a day*

*In addition to weighing less, on average, women absorb and metabolize alcohol differently than men. In general, women have less body water than men of similar body weight, so women achieve higher blood alcohol concentrations after drinking equivalent amounts of alcohol (10). Women also appear to be more vulnerable to adverse health effects of heavy drinking than men. Thus, most definitions of “moderate” or “heavy” drinking offer a lower threshold for women.
 

Potential Health Benefits of Moderate Alcohol Consumption

Mortality

Data from observational studies have shown that light-to-moderate alcohol consumption (≤1 drink/day for women and ≤2 drinks/day for men) is protective against all-cause mortality (4, 11-15). As mentioned above, a J-shaped relationship is apparent when all-cause mortality is plotted against alcohol consumption (alcohol abstinence on the left and heavy drinking on the right of the x-axis) (4, 16). In other words, those who drink moderately have the lowest risk of total mortality when compared to nondrinkers and heavy drinkers, and heavy drinkers have the highest risk of mortality.

The association of reduced mortality with moderate alcohol consumption is largely attributed to a decrease in cardiovascular mortality (14, 16-18), especially from coronary heart disease (see Cardiovascular disease below). However, concern has been raised that some earlier observational studies have misclassified former drinkers in the lifetime abstention group (i.e., the referent group), but most recent studies have not supported such a ‘misclassification hypothesis’ (15, 16, 19).

Cardiovascular disease

Coronary heart disease

Over the past four decades, the most consistent evidence of a health benefit associated with moderate alcohol consumption has been a significant reduction in the risk of coronary heart disease (CHD) — a finding confirmed by a large number of epidemiological studies. When the results of 28 prospective cohort studies were combined in a meta-analysis, adults who consumed an average of 25 grams/day of alcohol (the amount in two standard alcoholic drinks) had a risk of CHD that was 20% lower than adults who did not consume alcohol (20). More recent data from two large prospective cohort studies conducted in the US suggest that the magnitude of CHD risk reduction associated with moderate alcohol consumption may be closer to 30%. In a 12-year study of more than 38,000 male health professionals, those who consumed alcohol at least 3-4 times weekly had a risk of myocardial infarction (heart attack) that was 32% lower than men who drank alcohol less than once weekly (21). Similarly, in a 20-year study of more than 120,000 men and women, those who reported consuming 1-2 alcoholic drinks daily had a risk of death from CHD that was 30% lower than those who did not drink alcohol (22). A 2011 systematic review and meta-analysis of 29 studies found that alcohol consumption was associated with a 29% reduced risk of CHD compared to abstention; intakes of 2.5 to 60.0 grams/day of alcohol were associated with a lower risk of CHD (16).

How does alcohol consumption reduce CHD risk? The development of CHD is characterized by the formation of cholesterol-laden plaque in the arteries (atherosclerosis), vascular inflammation, and clot formation (23). Numerous small, randomized trials have examined the effect of daily alcohol consumption on markers of CHD risk, consistently finding that moderate alcohol consumption significantly increases concentrations of high-density lipoprotein (HDL)-cholesterol — the ‘good cholesterol’ (24, 25). HDLs transport cholesterol from tissues, including arterial walls, back to the liver for elimination or recycling. In addition to increasing HDL levels, moderate alcohol consumption has been shown to increase apolipoprotein A1, a major component of circulating HDL (25). Higher levels of high-density lipoprotein (HDL)-cholesterol have been associated with reductions in CHD risk (26).

Alcohol may also have anti-thrombotic properties. Clot formation is the result of complex interactions between factors that promote coagulation and factors that inhibit coagulation or promote the dissolution of clots. Several randomized trials have found that moderate alcohol consumption decreases serum levels of fibrinogen, a protein that promotes clot formation (25) and increases serum levels of an enzyme that helps dissolve clots (tissue type plasminogen activator) (24).

Further, moderate alcohol consumption may have an anti-inflammatory effect since serum levels of C-reactive protein (CRP), a marker of systemic inflammation and sensitive predictor of CHD risk, are lower in people who drink moderately than those who abstain from alcohol (27-32). Moderate alcohol consumption has also been associated with improvements in adiponectin levels (25), insulin sensitivity (see Type 2 diabetes mellitus below), abdominal obesity (33), and endothelial function (34)

Does the type of alcohol consumed (wine, beer, or liquor) affect CHD risk? Significant reductions in CHD risk have been associated with moderate consumption of wine, beer, and liquor. However, the “French Paradox” — the observation that mortality from CHD is relatively low in France despite relatively high levels of dietary saturated fat and cigarette smoking — led to the idea that regular consumption of red wine might provide additional protection from CHD (35, 36). Red wine contains the phenolic compound resveratrol — although usually at variable and low concentrations (see the article on Resveratrol) — as well as flavonoids like procyanidins; these compounds could provide additional cardiovascular benefits beyond those associated with ethanol. Beer also contains polyphenolic compounds that might confer some cardioprotection (37).

Some large prospective cohort studies have found wine drinkers to be at lower risk of CHD than beer or liquor drinkers (22, 38-40), but others have found no difference (21, 41, 42). Moreover, some studies have observed a decreased risk of myocardial infarction or CHD in predominantly beer-drinking populations in the Czech Republic (43), in Germany (44), and in Japanese men residing in Hawaii (45). A 2011 meta-analysis of prospective cohort and case-control studies found that moderate consumption of wine or beer was associated with a decreased risk of non-fatal vascular events (46). This analysis did not associate drinking liquor with cardiovascular benefit, although the authors noted that binge drinking — which is known to increase CHD risk — was apparent in several of the included studies (46).

Socioeconomic status and lifestyle characteristics (e.g., tobacco use, exercise habits) may differ among people who prefer wine, beer, or liquor, and this may in part explain any additional benefit of one beverage type observed in some studies. For example, several early studies found that people who prefer wine tend to have higher incomes, have more formal education, smoke less, and eat more fruit and vegetables and less saturated fat than people who prefer other alcoholic beverages (47-49). These potential confounders should be controlled or adjusted for in the analysis of observational data.

Thus, although moderate alcohol consumption has been consistently associated with 20%-30% reductions in CHD risk, it is not yet clear whether drinking a specific type of alcoholic beverage might confer additional cardiovascular benefit.

Stroke

Ischemic strokes, which represent 87% of all strokes, are the result of insufficient blood flow to an area of the brain, which may occur when an artery supplying the brain becomes blocked by a blood clot (50). Hemorrhagic strokes occur when a blood vessel ruptures and bleeds into the brain. Although they are less prevalent than ischemic strokes, hemorrhagic strokes are generally more severe and contribute disproportionately to overall stroke mortality (51). Light or moderate alcohol consumption has been associated with a reduced risk of ischemic stroke, but not hemorrhagic stroke, in a number of observational studies (52-58). When the results of 19 prospective cohort and 16 case-control studies of alcohol consumption and the risk of stroke were combined in a meta-analysis, moderate alcohol consumption was associated with a significant reduction in the risk of ischemic stroke (59). Overall, those who consumed one or two drinks daily had a 28% lower risk of ischemic stroke than those who did not consume alcohol. Another meta-analysis of more recent studies (1980-2009) confirmed that moderate alcohol consumption was protective against only ischemic stroke in both men and women (60). A more recent meta-analysis of 27 prospective cohort studies found that light-to-moderate alcohol consumption (<15 grams/day) in women was associated with a reduced risk of ischemic (RR, 0.72) but not hemorrhagic stroke; moderate alcohol consumption (15-30 grams/day) was not linked to either type of stroke in men in this analysis (61).

Thus, light-to-moderate alcohol consumption appears to decrease risk of ischemic stroke, but not hemorrhagic stroke, likely due to the anti-thrombotic effect of alcohol.

Peripheral arterial disease

Just as atherosclerosis of the arteries supplying the heart muscle leads to coronary heart disease, atherosclerosis of the arteries of the extremities leads to peripheral arterial disease (PAD). When atherosclerosis is severe enough to diminish blood flow to the legs, even walking may result in leg or hip pain known as intermittent claudication (62). Impaired vascular endothelial function is also characteristic of the disease and may contribute to the clinical symptoms (63).

Although much less consistent than the evidence for heart disease and stroke, there is limited evidence that moderate alcohol consumption is associated with decreased risk of PAD. Four prospective cohort studies have found moderate alcohol consumption to be associated with significant decreases in several different indicators of PAD (64-67). One of these studies found that the inverse association between alcohol intake and PAD risk was significant in nonsmokers but not smokers, suggesting that the adverse effects of cigarette smoking on PAD risk may outweigh any protective effects of alcohol consumption (64).

Heart failure

Coronary heart disease is a major cause of heart failure. A prospective study in a cohort of 21,601 men and another in a cohort of 126,236 men and women found that moderate alcohol intake was inversely associated with heart failure, especially heart disease related to CHD (68, 69). More recently, in a cohort of 4,490 older adults (65 years or older at baseline) followed for more than 20 years (1,380 cases of heart failure), drinking one or more alcoholic drink per week was associated with a 26% lower risk of heart failure compared to abstainers (70).

Sudden cardiac death

While several studies have found that heavy alcohol consumption increases risk of sudden cardiac death (SCD; see below), the association of light-to-moderate alcohol consumption and SCD is less clear. Studies on this association have reported mixed results, but the two largest prospective cohort studies to date have found a lower risk of SCD with light-to-moderate alcohol consumption (71, 72).

Type 2 diabetes mellitus

Three meta-analyses have found a U-shaped relationship between alcohol consumption and incidence of type 2 diabetes mellitus, with greater protection being observed for women (73-75). The most recent meta-analysis included 20 prospective cohort studies and associated moderate alcohol consumption (22-25 grams of alcohol daily or 1.6-1.8 drinks/day) with a 40% risk reduction for women and a 13% risk reduction for men compared to lifetime alcohol abstainers (74). Heavy alcohol consumption (62 grams/day or 4.4. drinks/day for men and 51 grams/day or 3.6 drinks/day for women) was associated with an increased risk for type 2 diabetes (74).

Increased insulin secretion by the pancreas and decreased insulin sensitivity are important factors leading to the development of type 2 diabetes. Research suggests that moderate alcohol intake may decrease serum insulin levels, increase adiponectin (an adipocyte hormone inversely associated with type 2 diabetes) levels (25), and improve insulin sensitivity (76-79). On the other hand, heavy alcohol consumption may increase the risk of type 2 diabetes by contributing to obesity, especially abdominal obesity, disturbing carbohydrate metabolism, and/or impairing pancreatic or liver function (80).

Osteoporosis

Osteoporosis, a condition common among the elderly, results from progressive loss of bone mineral density (BMD). Several observational studies have associated light or moderate alcohol consumption with higher BMD in older adults compared to abstainers (81-91). Some studies have found stronger protective relationships among wine (89) or beer drinkers (89, 90) in comparison to those who consume liquor, suggesting that non-alcohol components (e.g., silicon in beer) might help explain the association. The effects of alcohol on bone health may also be dependent on age, gender, and hormonal status (reviewed in 92).

It is important to note that the available data come from observational studies, and the observed associations may be confounded, e.g., individuals who consume alcohol in moderation may have an overall healthier lifestyle than those who drink heavily or abstain. However, a recent study in perimenopausal women found that moderate alcohol intake was associated with improved BMD independent of various lifestyle factors, including smoking status, fruit and vegetable intake, and physical activity level (90).

Cognitive decline, dementia, and Alzheimer’s disease

Although alcoholism and heavy alcohol consumption (>3-4 drinks/day) is known to increase the risk of cognitive impairment and dementia (93-95), recent meta-analyses and reviews have reported that light-to-moderate alcohol consumption in older adults is associated with a decreased risk of dementia and Alzheimer’s disease when compared to abstention (93, 96, 97). Some meta-analyses have not found a significant reduced risk for vascular type dementia (96, 98) or for cognitive decline (93, 96, 98, 99). A few studies have suggested that consumption of wine may be especially protective against dementia, although inconsistent findings have been observed, and many studies have not distinguished among the various types of alcohol.

At least three epidemiological studies have used magnetic resonance imaging (MRI) to examine relationships between alcohol intake and subclinical abnormalities in the brains of healthy middle-aged or older adults. Two studies found that infarctions (areas of dead tissue) were less frequent in the brains of those reporting light or moderate alcohol intake compared to those who abstained from alcohol (100, 101). However, another study found no relationship between alcohol intake and the presence of infarction (102). Two of the studies measuring brain atrophy, a characteristic of Alzheimer’s disease and alcoholic dementia, found brain atrophy to be lower in those who abstained from alcohol compared to alcohol consumers (100, 102). The other study found less brain atrophy with light-to-moderate alcohol consumption but only in carriers of the apolipoprotein E (APOE) ε4 allele, who are at increased risk for Alzheimer’s disease (101). Because of the complex nature of alcohol’s effects on the brain, further research is needed to determine the risks and benefits of alcohol consumption with respect to cognitive function and dementia.

Gallstones

The majority of prospective cohort studies (103-107) and case-control studies (108, 109) have found that men and women with moderate alcohol intakes have lower risks of gallstones or gallbladder surgery (cholecystectomy) than those who do not consume alcohol. Although the reasons for the consistent inverse association between moderate alcohol consumption and gallstone incidence are not entirely clear, regular alcohol intake may result in bile that is less likely to crystallize into gallstones or stimulate gallbladder emptying (106).
 

Health Risks of Moderate Alcohol Consumption

Pregnancy

Fetal alcohol spectrum disorders (FASD) is a continuum of developmental abnormalities resulting from gestational alcohol exposure; FASD may affect as many as 1%-2% of US children (110, 111). Fetal alcohol syndrome (FAS) — a severe FASD — is a cluster of physical and mental birth defects associated with heavy alcohol consumption during pregnancy. Some characteristics of FAS include facial abnormalities, mental retardation, and growth impairment. More moderate alcohol consumption during pregnancy (7-14 drinks/week) has been associated with more subtle effects on cognitive and behavioral development (112, 113). Children of mothers who drank moderately during pregnancy have been found to have problems with memory, attention and learning, and behavior (114). Overall, studies on the association of low-to-moderate drinking during pregnancy and mental health of offspring have reported mixed results (reviewed in 115). However, it is important to note that these studies are observational in nature and may have not adequately controlled for potential confounding factors (e.g., lifestyle differences [in women who drank alcohol during pregnancy versus those who abstained] that influence mental development) (115).

Since no safe level of alcohol consumption has been established at any stage of pregnancy, pregnant women and women who are planning a pregnancy should abstain from alcohol (116, 117).

Breast cancer

More than 100 observational studies have been completed on the association between alcohol consumption and female breast cancer, with most finding an increased risk (118-121). Even though the available data come from observational studies, many consider the association to be causal. Regular alcohol consumption as low as one or two drinks per day has been associated with modest but significant increases in breast cancer risk. A threshold for harm, however, is difficult to define due to potential underreporting of alcohol intake by heavy drinkers, which could result in heavy drinkers being misclassified as ‘moderate alcohol consumers’ (122).

A linear dose-dependent relationship between alcohol consumption and breast cancer risk has been observed for premenopausal and postmenopausal breast cancer regardless of the type of alcoholic beverage consumed. Pooled and meta-analyses have found that each 10-gram increase in daily alcohol consumption (slightly less than one drink) is associated with a 7%-10% increased risk of breast cancer in women (123-125). Studies of alcohol consumption and breast cancer-specific mortality have reported mixed results, with a recent meta-analysis of 25 prospective cohort studies finding an increased risk only with alcohol consumption in excess of 20 grams (1.4 drinks)/day (126). Moderate alcohol consumption has been consistently associated with reduced risk of all-cause mortality (see Mortality above).  

Although the mechanisms for the consistent association between alcohol intake and breast cancer incidence have not been clearly identified, proposed mechanisms include acetaldehyde formation, induction of CYP2E1 metabolism and increased oxidative stress, increased circulating estrogen or androgen levels, and enhanced invasiveness of breast cancer cells (119, 127). Current estimates are that about one in eight women (12.4%) in the US will develop breast cancer at some point in her lifetime (128). Although there are many risk factors for breast cancer, alcohol consumption is one of only a few modifiable risk factors. 

Folate and breast cancer

Alcohol interferes with the absorption, transport, and metabolism of folate, which is required for DNA methylation and DNA repair (see the article on Folate). Alterations in these processes may result in mutations or altered gene expression, which increase the risk of cancer (118). Several (129-134), but not all (135-139), studies have found that sufficient folate intake may modify the association between alcohol intake and breast cancer risk. Although the interactions between folate, alcohol, and breast cancer risk remain to be clarified, it makes sense for women who drink alcohol to take a daily multivitamin containing 400 μg of folic acid.

Progression to heavy or hazardous drinking

Some people, such as recovering alcoholics and those with family histories of alcohol abuse or alcoholism, may not be able to maintain moderate drinking habits. Susceptibility to alcoholism is affected by genetic, psychosocial, and environmental factors. Children of an alcoholic parent have been found to be at significantly higher risk of developing alcoholism than those without an alcoholic parent (140). This increase in risk is likely related to interactions between genetic factors and factors related to the family environment. The National Institute on Alcohol Abuse and Alcoholism recommends that people with a family history of alcoholism, especially in a parent, approach moderate drinking carefully (141).

Medication interactions

In the liver, alcohol is metabolized by the same enzymes as many medications. Therefore, alcohol consumption can affect the activation or breakdown of a number of medications. The consumption of alcohol may also increase sedation, drowsiness, and hypotensive effects caused by numerous prescription and over-the-counter medications. Although serious interactions between alcohol and medications are more common in the presence of heavy alcohol consumption, even moderate alcohol consumption may hypothetically increase the risk of some adverse reactions in susceptible people (142). Women and older adults are particularly at risk for interactions between alcohol and medications (143, 144).

Many different classes of prescription medication may interact adversely with alcohol, including antibiotics, anticonvulsants, anticoagulants (e.g., Coumadin), antidepressants, antidiabetic agents, antihypertensive agents, vasodilators (e.g., nitrates and calcium channel blockers), barbiturates, benzodiazepines (sedatives), histamine H2-receptor blockers, muscle relaxants, and narcotic and non-narcotic pain relievers. Over-the-counter medications and herbal preparations may also interact with alcohol, including pain medications like aspirin, acetaminophen (Tylenol), ibuprofen (Advil, Motrin), and naproxen sodium (Aleve); cold and allergy medications like diphenhydramine (Benadryl) and chlorpheniramine; heartburn medications like cimetidine (Tagamet) and ranitidine (Zantac); and herbal preparations like chamomile, valerian, and kava.

To help avoid potentially serious interactions between alcohol and medications, make sure your health care provider is aware of your alcohol intake. Before taking prescription or over-the-counter medications, read the product warning labels or consult a pharmacist or health care provider to determine whether alcohol consumption increases the risk of adverse effects. It may, in general, be advisable to separate taking any medication and drinking alcohol by two to three hours. For more information on potentially serious interactions between alcohol and medications, see the National Institute on Alcohol Abuse and Alcoholism website.
 

Health Benefits of Heavy Alcohol Consumption

None
 

Health Risks of Heavy Alcohol Consumption

Pregnancy

Heavy consumption of alcohol during pregnancy causes fetal alcohol syndrome (FAS). See above.

Cardiovascular disease

Hypertension

Heavy alcohol consumption has been consistently associated with an increased risk of high blood pressure (hypertension) in prospective cohort and case-control studies (145-147). A 2009 systematic review and meta-analysis of 12 prospective cohort studies found consuming 50 grams (3.6 drinks)/day of alcohol was associated with a 1.6-fold and 1.8-fold higher risk of hypertension in men and women, respectively; alcohol intake at twice that level (100 grams (~7 drinks)/day) was associated with a relative risk of 2.5 for men and 2.8 for women (148).

The results of numerous clinical trials indicate that reducing alcohol intake lowers blood pressure in hypertensive and normotensive individuals. A meta-analysis that combined the results of 15 randomized controlled trials found that reducing alcohol consumption resulted in significant decreases in both systolic and diastolic blood pressure (149).

Stroke

Ischemic strokes are the result of insufficient blood flow to an area of the brain, which may occur when an artery supplying the brain becomes blocked by a blood clot. Hemorrhagic strokes occur when a blood vessel ruptures and bleeds into the brain. Although regular, moderate alcohol consumption has been associated with decreased risk of ischemic stroke in some studies, heavy alcohol consumption has been associated with increased risk of both ischemic stroke and hemorrhagic stroke. A meta-analysis that combined the results of 19 prospective cohort and 16 case-control studies found that heavy drinking more than doubled the risk of hemorrhagic stroke and increased the risk of ischemic stroke by 70% (59). A meta-analysis of recent studies (1980-2009) confirmed that heavy drinking is associated with increased risks of ischemic and hemorrhagic stroke in both men and women (60). Heavy alcohol consumption may increase the risk of stroke by contributing to hypertension, cardiomyopathy (heart muscle damage), cardiac rhythm disturbances, and coagulation (clotting) disorders and impaired hemostasis.

Cardiac arrhythmias and sudden cardiac death

The long-recognized association between bouts of heavy alcohol consumption and cardiac rhythm disturbances (arrhythmias) was called “holiday heart syndrome” because it was first described in people who were admitted to hospitals after holidays or weekends (150). Atrial fibrillation is the cardiac arrhythmia most commonly associated with heavy alcohol use (151, 152). A 2010 systematic review and meta-analysis found a dose-dependent association between daily alcohol consumption and risk of this type of cardiac arrhythmia, with an increased risk being found with consumption greater than 24 grams/day (1.7 drinks/day) for women and 36 grams/day (2.6 drinks/day) for men (153). A 2014 meta-analysis of seven prospective studies found that consumption of more than two drinks per day was associated with increased risk of atrial fibrillation in men and women, and the risk increased by 8% with each additional daily drink (154, 155). Additionally, several studies have found that heavy alcohol consumption (>5 drinks per day) increases risk of sudden cardiac death (SCD) (156, 157).

The ways by which alcohol may trigger arrhythmias and SCD are not fully known. Alcohol may interfere with the contractility of heart muscle cells, change the shape and structure of heart muscle cells, contribute to electrolyte imbalance, and/or induce oxidative stress (158).

Alcoholic cardiomyopathy

Alcoholic cardiomyopathy is a heart muscle disease caused by long-term, heavy alcohol consumption (159); this disease likely occurs in only a small proportion (<10%) of heavy drinkers (160). Alcoholic cardiomyopathy occurs in two stages: (1) an early asymptomatic stage, when the damage to the heart muscle has no obvious symptoms; and (2) a symptomatic stage, when the heart muscle is too weak to pump effectively. Although the level of alcohol consumption resulting in alcoholic cardiomyopathy has not been clearly established, people consuming at least seven alcoholic drinks daily for more than five years are thought to be at risk of developing asymptomatic alcoholic cardiomyopathy. Those who continue to drink heavily ultimately develop heart failure. Research suggests that women may be more susceptible to alcohol’s toxic effects on the heart muscle than men (161, 162).

Alcoholic liver disease

Chronic excessive alcohol use is a major cause of illness and death from liver disease (163). Alcoholic liver disease is characterized by a spectrum of liver injury, including steatosis (fatty liver), hepatitis (a potentially fatal inflammation of the liver), fibrosis, and cirrhosis — the most advanced form of alcoholic liver disease. In cirrhosis, the formation of fibrotic scar tissue results in progressive deterioration of liver function. Complications of advanced liver disease include severe bleeding from distended veins in the esophagus (esophageal varices), brain damage (hepatic encephalopathy), fluid accumulation in the abdomen (ascites), and kidney failure.

A 2004 meta-analysis of nine studies found a dose-responsive increase in risk for liver cirrhosis with increasing amounts of alcohol consumed: relative risks (RR) of 2.9 for 25 grams (1.8 drinks)/day, 7.1 for 50 grams (3.6 drinks)/day, 26.5 for 100 grams (7.1 drinks)/day (164). Another meta-analysis found a higher RR for liver cirrhosis with increasing doses but also suggested a threshold response for morbidity from liver cirrhosis (higher risk in women with consumption >24 g (1.7 drinks)/day of alcohol, and higher risk in men with consumption >36 g (2.6 drinks)/day of alcohol) (165). Risk of mortality from liver cirrhosis was increased with any alcohol consumption in women and with consumption of >12 g (0.9 drinks)/day in men; a stronger relationship between alcohol consumption and mortality from liver cirrhosis versus morbidity might be expected because alcohol consumption is known to exacerbate any existing liver disease (165).

Serious liver disease has been found to develop in approximately 10% of those who consume more than 60 grams per day of alcohol (4.3 drinks/day). Women are more susceptible to serious alcoholic liver disease than men (165, 166), and individuals with hepatitis C infection have an increased risk of alcoholic liver disease (167).

Cancer

Heavy alcohol consumption has been found to increase the risk of cancer at a number of sites (168). Heavy alcohol consumption is consistently and dose-dependently associated with increases in risk of cancers of the mouth, pharynx, larynx, esophagus, liver, colon, rectum, and breast (165). Moreover, the combination of smoking and alcohol results in even more dramatic increases in cancer risks (169). Increased risk of liver cancer with long-term heavy alcohol consumption may be related to alcoholic cirrhosis of the liver or increased susceptibility to cancer caused by viral hepatitis.

Alcohol-related brain disorders

Chronic heavy alcohol use and alcohol dependence are associated with detrimental effects on the brain and its function, especially memory and executive functions (170). Alcoholics have been observed to suffer from cerebral atrophy (shrinkage of brain tissue), which likely contributes to alcohol-associated dementia and cognitive impairment (94). In contrast to the progressive cerebral atrophy observed in Alzheimer’s disease, alcohol-related cerebral atrophy may decrease after a period of abstinence. Alcohol-related brain disorders may be associated with nutritional deficiencies like thiamin (171) or niacin (172)

Pancreatitis

Pancreatitis is a painful inflammation of the pancreas. Acute pancreatitis is characterized by the sudden onset of severe upper abdominal pain, often accompanied by nausea and vomiting (173). Although most attacks of acute pancreatitis require only supportive care, a small percentage of people may experience serious or life-threatening complications. Studies estimate that 19%-32% of acute pancreatitis cases have an alcoholic etiology (reviewed in 174).

Chronic pancreatitis results in progressive destruction of the pancreas, leading to loss of pancreatic function (175). An estimated 60%-72% of chronic pancreatitis cases have an alcoholic etiology. The risk of developing chronic pancreatitis increases with the quantity and duration of alcohol consumed: an increased risk of chronic pancreatitis is observed with long-term consumption of five or more alcoholic drinks per day (174). Only a small percentage (<10%) of alcoholics develop clinical pancreatitis; thus, hereditary and environmental factors are also thought to play a role. The disease is more common in men than in women, in Blacks compared to Whites, and in smokers versus nonsmokers (176, 177).

Bone health

Chronic alcoholism has deleterious effects on bone health, including decreased bone mineral density and increased risk of fracture. Consumption of large quantities of alcohol (100-200 grams/day) directly impairs activity of osteoblasts — the bone-forming cells. Negative effects on bone health are also indirectly caused by the malnutrition experienced by alcoholics (92).

Accidents, injury, and violence

Alcohol use is associated with an increased risk of injury in a number of circumstances, including motor vehicle accidents, falls, and fires (178). Data from hospital emergency departments indicate that consuming as little as one or two alcoholic drinks in the previous six hours significantly increases the risk of injury (179). Thirty-one percent of all traffic fatalities in the US are alcohol-related (180). Although the legal blood alcohol concentration (BAC) limit for drivers is 0.08 (grams of alcohol/deciliter of blood) in the US, most scientific studies have found significant impairment of driving-related skills at a BAC of 0.05 (181). For reference, a BAC of 0.05 might be achieved by a 175-pound male consuming three standard alcoholic drinks in one hour or a 120-pound female consuming two drinks in one hour (182).

Excessive alcohol use is associated with all forms of violence, including suicide, homicide, domestic violence, sexual assault, and gang violence. Although the reasons for alcohol-associated violence are complex, alcohol use appears to increase the risk of violent behavior in some populations (183).

Mortality

Heavy alcohol consumption increases the risk of mortality (4, 16). As mentioned above, the relationship between alcohol consumption and mortality is often described as J-shaped, meaning those with high intakes of alcohol have a higher risk of mortality than nondrinkers. A 2011 meta-analysis of eight prospective cohort studies found that consumption of >60 grams/day of alcohol was associated with a 30% increase in mortality from all causes (16).


Authors and Reviewers

Originally written in 2004 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in December 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in August 2015 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in August 2015 by:
Arthur L. Klatsky, M.D.
Senior Consultant in Cardiology
Adjunct Investigator, Division of Research
Kaiser Permanente Medical Care Program
Oakland, CA

Copyright 2004-2024  Linus Pauling Institute


References

1.  Ecker RR, Klatsky AL. Doctor, should I have a drink? An algorithm for health professionals. Ann N Y Acad Sci. 2002;957:317-320.  (PubMed)

2.  US Department of Health and Human Services, US Department of Agriculture. Nutrition and your health: Dietary Guidelines for Americans [Website]. Available at: http://www.health.gov/dietaryguidelines/dga2000/document/choose.htm#alcohol. Accessed 11/4/03.

3.  Klatsky AL. Drink to your health? Sci Am. 2003;288(2):74-81.  (PubMed)

4.  Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med. 2006;166(22):2437-2445.  (PubMed)

5.  Krenz M, Korthuis RJ. Moderate ethanol ingestion and cardiovascular protection: from epidemiologic associations to cellular mechanisms. J Mol Cell Cardiol. 2012;52(1):93-104.  (PubMed)

6.  Naimi TS, Brown DW, Brewer RD, et al. Cardiovascular risk factors and confounders among nondrinking and moderate-drinking U.S. adults. Am J Prev Med. 2005;28(4):369-373.  (PubMed)

7.  National Institute on Alcohol Abuse and Alcoholism. Helping patients who drink too much: a clinician's guide [Web page]. January 2007. Available at: http://pubs.niaaa.nih.gov/publications/Practitioner/CliniciansGuide2005/clinicians_guide.htm. Accessed 10/3/07.

8.  National Institute on Alcohol Abuse and Alcoholism. Helping patients who drink too much: a clinician's guide: NIH Publication No. 07-3769; 2005. 

9.  US Department of Agriculture and US Department of Health and Human Services. Dietary Guidelines for Americans, 2010. Washington, D.C.: US Government Printing Office, December 2010.

10.  National Institute on Alcohol Abuse and Alcoholism. Women and alcohol. Available at: http://pubs.niaaa.nih.gov/publications/womensfact/womensfact.htm. Accessed 7/29/15.

11.  Thun MJ, Peto R, Lopez AD, et al. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med. 1997;337(24):1705-1714.  (PubMed)

12.  Poikolainen K. Alcohol and mortality: a review. J Clin Epidemiol. 1995;48(4):455-465.  (PubMed)

13.  Lee SJ, Sudore RL, Williams BA, Lindquist K, Chen HL, Covinsky KE. Functional limitations, socioeconomic status, and all-cause mortality in moderate alcohol drinkers. J Am Geriatr Soc. 2009;57(6):955-962.  (PubMed)

14.  Djousse L, Lee IM, Buring JE, Gaziano JM. Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms. Circulation. 2009;120(3):237-244.  (PubMed)

15.  Fuller TD. Moderate alcohol consumption and the risk of mortality. Demography. 2011;48(3):1105-1125.  (PubMed)

16.  Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011;342:d671.  (PubMed)

17.  Mukamal KJ, Chen CM, Rao SR, Breslow RA. Alcohol consumption and cardiovascular mortality among U.S. adults, 1987 to 2002. J Am Coll Cardiol. 2010;55(13):1328-1335.  (PubMed)

18.  Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med. 1995;332(19):1245-1250.  (PubMed)

19.  Roerecke M, Rehm J. The cardioprotective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis. Addiction. 2012;107(7):1246-1260.  (PubMed)

20.  Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction. 2000;95(10):1505-1523.  (PubMed)

21.  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(2):109-118.  (PubMed)

22.  Klatsky AL, Friedman GD, Armstrong MA, Kipp H. Wine, liquor, beer, and mortality. Am J Epidemiol. 2003;158(6):585-595.  (PubMed)

23.  Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340(2):115-126.  (PubMed)

24.  Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ. 1999;319(7224):1523-1528.  (PubMed)

25.  Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ. 2011;342:d636.  (PubMed)

26.  Rader DJ. Regulation of reverse cholesterol transport and clinical implications. Am J Cardiol. 2003;92(4A):42J-49J.  (PubMed)

27.  Albert MA, Glynn RJ, Ridker PM. Alcohol consumption and plasma concentration of C-reactive protein. Circulation. 2003;107(3):443-447.  (PubMed)

28.  Stewart SH, Mainous AG, 3rd, Gilbert G. Relation between alcohol consumption and C-reactive protein levels in the adult US population. J Am Board Fam Pract. 2002;15(6):437-442.  (PubMed)

29.  Imhof A, Froehlich M, Brenner H, Boeing H, Pepys MB, Koenig W. Effect of alcohol consumption on systemic markers of inflammation. Lancet. 2001;357(9258):763-767.  (PubMed)

30.  Sierksma A, van der Gaag MS, Kluft C, Hendriks HF. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study. Eur J Clin Nutr. 2002;56(11):1130-1136.  (PubMed)

31.  Whitfield JB, Heath AC, Madden PA, Pergadia ML, Montgomery GW, Martin NG. Metabolic and biochemical effects of low-to-moderate alcohol consumption. Alcohol Clin Exp Res. 2013;37(4):575-586.  (PubMed)

32.  Wang JJ, Tung TH, Yin WH, et al. Effects of moderate alcohol consumption on inflammatory biomarkers. Acta Cardiol. 2008;63(1):65-72.  (PubMed)

33.  O'Keefe JH, Bybee KA, Lavie CJ. Alcohol and cardiovascular health: the razor-sharp double-edged sword. J Am Coll Cardiol. 2007;50(11):1009-1014.  (PubMed)

34.  Suzuki K, Elkind MS, Boden-Albala B, et al. Moderate alcohol consumption is associated with better endothelial function: a cross sectional study. BMC Cardiovasc Disord. 2009;9:8.  (PubMed)

35.  St Leger AS, Cochrane AL, Moore F. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet. 1979;1(8124):1017-1020.  (PubMed)

36.  Criqui MH, Ringel BL. Does diet or alcohol explain the French paradox? Lancet. 1994;344(8939-8940):1719-1723.  (PubMed)

37.  Arranz S, Chiva-Blanch G, Valderas-Martinez P, Medina-Remon A, Lamuela-Raventos RM, Estruch R. Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer. Nutrients. 2012;4(7):759-781.  (PubMed)

38.  Renaud SC, Gueguen R, Siest G, Salamon R. Wine, beer, and mortality in middle-aged men from eastern France. Arch Intern Med. 1999;159(16):1865-1870.  (PubMed)

39.  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(6):411-419.  (PubMed)

40.  Streppel MT, Ocke MC, Boshuizen HC, Kok FJ, Kromhout D. Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study. J Epidemiol Community Health. 2009;63(7):534-540.  (PubMed)

41.  Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. BMJ. 1996;312(7033):731-736.  (PubMed)

42.  Wannamethee SG, Shaper AG. Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality. Am J Public Health. 1999;89(5):685-690.  (PubMed)

43.  Bobak M, Skodova Z, Marmot M. Effect of beer drinking on risk of myocardial infarction: population based case-control study. BMJ. 2000;320(7246):1378-1379.  (PubMed)

44.  Keil U, Chambless LE, Doring A, Filipiak B, Stieber J. The relation of alcohol intake to coronary heart disease and all-cause mortality in a beer-drinking population. Epidemiology. 1997;8(2):150-156.  (PubMed)

45.  Yano K, Rhoads GG, Kagan A. Coffee, alcohol and risk of coronary heart disease among Japanese men living in Hawaii. N Engl J Med. 1977;297(8):405-409.  (PubMed)

46.  Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G. Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis. Eur J Epidemiol. 2011;26(11):833-850.  (PubMed)

47.  Mortensen EL, Jensen HH, Sanders SA, Reinisch JM. Better psychological functioning and higher social status may largely explain the apparent health benefits of wine: a study of wine and beer drinking in young Danish adults. Arch Intern Med. 2001;161(15):1844-1848.  (PubMed)

48.  Barefoot JC, Gronbaek M, Feaganes JR, McPherson RS, Williams RB, Siegler IC. Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study. Am J Clin Nutr. 2002;76(2):466-472.  (PubMed)

49.  McCann SE, Sempos C, Freudenheim JL, et al. Alcoholic beverage preference and characteristics of drinkers and nondrinkers in western New York (United States). Nutr Metab Cardiovasc Dis. 2003;13(1):2-11.  (PubMed)

50.  American Stroke Association. Ischemic strokes (clots) [Web page]. Available at: http://www.strokeassociation.org/STROKEORG/AboutStroke/TypesofStroke/IschemicClots/Ischemic-Strokes-Clots_UCM_310939_Article.jsp. Accessed 9/24/14.

51.  Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin. 2008;26(4):871-895, vii.  (PubMed)

52.  Berger K, Ajani UA, Kase CS, et al. Light-to-moderate alcohol consumption and risk of stroke among U.S. male physicians. N Engl J Med. 1999;341(21):1557-1564.  (PubMed)

53.  Sacco RL, Elkind M, Boden-Albala B, et al. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA. 1999;281(1):53-60.  (PubMed)

54.  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(1):77-83.  (PubMed)

55.  Mukamal KJ, Chung H, Jenny NS, et al. Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study. Stroke. 2005;36(9):1830-1834.  (PubMed)

56.  Jimenez M, Chiuve SE, Glynn RJ, et al. Alcohol consumption and risk of stroke in women. Stroke. 2012;43(4):939-945.  (PubMed)

57.  Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. Lifestyle factors on the risks of ischemic and hemorrhagic stroke. Arch Intern Med. 2011;171(20):1811-1818.  (PubMed)

58.  Iso H, Baba S, Mannami T, et al. Alcohol consumption and risk of stroke among middle-aged men: the JPHC Study Cohort I. Stroke. 2004;35(5):1124-1129.  (PubMed)

59.  Reynolds K, Lewis B, Nolen JD, Kinney GL, Sathya B, He J. Alcohol consumption and risk of stroke: a meta-analysis. JAMA. 2003;289(5):579-588.  (PubMed)

60.  Patra J, Taylor B, Irving H, et al. Alcohol consumption and the risk of morbidity and mortality for different stroke types--a systematic review and meta-analysis. BMC Public Health. 2010;10:258.  (PubMed)

61.  Zhang C, Qin YY, Chen Q, et al. Alcohol intake and risk of stroke: a dose-response meta-analysis of prospective studies. Int J Cardiol. 2014;174(3):669-677.  (PubMed)

62.  Mills JL. Peripheral arterial disease. In: Rakel RE, Bope ET, eds. Rakel: Conn's Current Therapy 2002. New York: W.B. Saunders Company; 2002:340-343.

63.  Kiani S, Aasen JG, Holbrook M, et al. Peripheral artery disease is associated with severe impairment of vascular function. Vasc Med. 2013;18(2):72-78.  (PubMed)

64.  Vliegenthart R, Geleijnse JM, Hofman A, et al. Alcohol consumption and risk of peripheral arterial disease: the Rotterdam study. Am J Epidemiol. 2002;155(4):332-338.  (PubMed)

65.  Camargo CA, Jr., Hennekens CH, Gaziano JM, Glynn RJ, Manson JE, Stampfer MJ. Prospective study of moderate alcohol consumption and mortality in US male physicians. Arch Intern Med. 1997;157(1):79-85.  (PubMed)

66.  Djousse L, Levy D, Murabito JM, Cupples LA, Ellison RC. Alcohol consumption and risk of intermittent claudication in the Framingham Heart Study. Circulation. 2000;102(25):3092-3097.  (PubMed)

67.  Mukamal KJ, Kennedy M, Cushman M, et al. Alcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study. Am J Epidemiol. 2008;167(1):34-41.  (PubMed)

68.  Klatsky AL, Chartier D, Udaltsova N, et al. Alcohol drinking and risk of hospitalization for heart failure with and without associated coronary artery disease. Am J Cardiol. 2005;96(3):346-351.  (PubMed)

69.  Djousse L, Gaziano JM. Alcohol consumption and risk of heart failure in the Physicians' Health Study I. Circulation. 2007;115(1):34-39.  (PubMed)

70.  Del Gobbo LC, Kalantarian S, Imamura F, et al. Contribution of major lifestyle risk Factors for incident heart failure in older adults: the Cardiovascular Health Study. JACC Heart Fail. 2015;3(7):520-528.  (PubMed)

71.  Albert CM, Manson JE, Cook NR, Ajani UA, Gaziano JM, Hennekens CH. Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians. Circulation. 1999;100(9):944-950.  (PubMed)

72.  Chiuve SE, Rimm EB, Mukamal KJ, et al. Light-to-moderate alcohol consumption and risk of sudden cardiac death in women. Heart Rhythm. 2010;7(10):1374-1380.  (PubMed)

73.  Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ. Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care. 2005;28(3):719-725.  (PubMed)

74.  Baliunas DO, Taylor BJ, Irving H, et al. Alcohol as a risk factor for type 2 diabetes: A systematic review and meta-analysis. Diabetes Care. 2009;32(11):2123-2132.  (PubMed)

75.  Carlsson S, Hammar N, Grill V. Alcohol consumption and type 2 diabetes Meta-analysis of epidemiological studies indicates a U-shaped relationship. Diabetologia. 2005;48(6):1051-1054.  (PubMed)

76.  Meyer KA, Conigrave KM, Chu NF, et al. Alcohol consumption patterns and HbA1c, C-peptide and insulin concentrations in men. J Am Coll Nutr. 2003;22(3):185-194.  (PubMed)

77.  Kenkre PV, Lindeman RD, Lillian Yau C, Baumgartner RN, Garry PJ. Serum insulin concentrations in daily drinkers compared with abstainers in the New Mexico elder health survey. J Gerontol A Biol Sci Med Sci. 2003;58(10):M960-963.  (PubMed)

78.  Greenfield JR, Samaras K, Jenkins AB, Kelly PJ, Spector TD, Campbell LV. Moderate alcohol consumption, estrogen replacement therapy, and physical activity are associated with increased insulin sensitivity: is abdominal adiposity the mediator? Diabetes Care. 2003;26(10):2734-2740.  (PubMed)

79.  Bantle AE, Thomas W, Bantle JP. Metabolic effects of alcohol in the form of wine in persons with type 2 diabetes mellitus. Metabolism. 2008;57(2):241-245.  (PubMed)

80.  Kao WH, Puddey IB, Boland LL, Watson RL, Brancati FL. Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study. Am J Epidemiol. 2001;154(8):748-757.  (PubMed)

81.  Laitinen K, Valimaki M, Keto P. Bone mineral density measured by dual-energy X-ray absorptiometry in healthy Finnish women. Calcif Tissue Int. 1991;48(4):224-231.  (PubMed)

82.  Holbrook TL, Barrett-Connor E. A prospective study of alcohol consumption and bone mineral density. BMJ. 1993;306(6891):1506-1509.  (PubMed)

83.  Felson DT, Zhang Y, Hannan MT, Kannel WB, Kiel DP. Alcohol intake and bone mineral density in elderly men and women. The Framingham Study. Am J Epidemiol. 1995;142(5):485-492.  (PubMed)

84.  New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr. 1997;65(6):1831-1839.  (PubMed)

85.  Kroger H, Tuppurainen M, Honkanen R, Alhava E, Saarikoski S. Bone mineral density and risk factors for osteoporosis--a population-based study of 1600 perimenopausal women. Calcif Tissue Int. 1994;55(1):1-7.  (PubMed)

86.  Hansen MA, Overgaard K, Riis BJ, Christiansen C. Potential risk factors for development of postmenopausal osteoporosis--examined over a 12-year period. Osteoporos Int. 1991;1(2):95-102.  (PubMed)

87.  Rapuri PB, Gallagher JC, Balhorn KE, Ryschon KL. Alcohol intake and bone metabolism in elderly women. Am J Clin Nutr. 2000;72(5):1206-1213.  (PubMed)

88.  Ganry O, Baudoin C, Fardellone P. Effect of alcohol intake on bone mineral density in elderly women: The EPIDOS Study. Epidemiologie de l'Osteoporose. Am J Epidemiol. 2000;151(8):773-780.  (PubMed)

89.  Tucker KL, Jugdaohsingh R, Powell JJ, et al. Effects of beer, wine, and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr. 2009;89(4):1188-1196.  (PubMed)

90.  McLernon DJ, Powell JJ, Jugdaohsingh R, Macdonald HM. Do lifestyle choices explain the effect of alcohol on bone mineral density in women around menopause? Am J Clin Nutr. 2012;95(5):1261-1269.  (PubMed)

91.  Wosje KS, Kalkwarf HJ. Bone density in relation to alcohol intake among men and women in the United States. Osteoporos Int. 2007;18(3):391-400.  (PubMed)

92.  Maurel DB, Boisseau N, Benhamou CL, Jaffre C. Alcohol and bone: review of dose effects and mechanisms. Osteoporos Int. 2012;23(1):1-16.  (PubMed)

93.  Neafsey EJ, Collins MA. Moderate alcohol consumption and cognitive risk. Neuropsychiatr Dis Treat. 2011;7:465-484.  (PubMed)

94.  Tyas SL. Alcohol use and the risk of developing Alzheimer's disease. Alcohol Res Health. 2001;25(4):299-306.  (PubMed)

95.  Stavro K, Pelletier J, Potvin S. Widespread and sustained cognitive deficits in alcoholism: a meta-analysis. Addict Biol. 2013;18(2):203-213.  (PubMed)

96.  Peters R, Peters J, Warner J, Beckett N, Bulpitt C. Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 2008;37(5):505-512.  (PubMed)

97.  Panza F, Frisardi V, Seripa D, et al. Alcohol consumption in mild cognitive impairment and dementia: harmful or neuroprotective? Int J Geriatr Psychiatry. 2012;27(12):1218-1238.  (PubMed)

98.  Panza F, Capurso C, D'Introno A, et al. Alcohol drinking, cognitive functions in older age, predementia, and dementia syndromes. J Alzheimers Dis. 2009;17(1):7-31.  (PubMed)

99.  Anstey KJ, Mack HA, Cherbuin N. Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatry. 2009;17(7):542-555.  (PubMed)

100.  Mukamal KJ, Longstreth WT, Jr., Mittleman MA, Crum RM, Siscovick DS. Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study. Stroke. 2001;32(9):1939-1946.  (PubMed)

101.  den Heijer T, Vermeer SE, van Dijk EJ, et al. Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia. Am J Clin Nutr. 2004;80(4):992-997.  (PubMed)

102.  Ding J, Eigenbrodt ML, Mosley TH, Jr., et al. Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a community-based population of middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2004;35(1):16-21.  (PubMed)

103.  Kato I, Nomura A, Stemmermann GN, Chyou PH. Prospective study of clinical gallbladder disease and its association with obesity, physical activity, and other factors. Dig Dis Sci. 1992;37(5):784-790.  (PubMed)

104.  Misciagna G, Leoci C, Guerra V, et al. Epidemiology of cholelithiasis in southern Italy. Part II: Risk factors. Eur J Gastroenterol Hepatol. 1996;8(6):585-593.  (PubMed)

105.  Leitzmann MF, Giovannucci EL, Stampfer MJ, et al. Prospective study of alcohol consumption patterns in relation to symptomatic gallstone disease in men. Alcohol Clin Exp Res. 1999;23(5):835-841.  (PubMed)

106.  Leitzmann MF, Tsai CJ, Stampfer MJ, et al. Alcohol consumption in relation to risk of cholecystectomy in women. Am J Clin Nutr. 2003;78(2):339-347.  (PubMed)

107.  Maclure KM, Hayes KC, Colditz GA, Stampfer MJ, Speizer FE, Willett WC. Weight, diet, and the risk of symptomatic gallstones in middle-aged women. N Engl J Med. 1989;321(9):563-569.  (PubMed)

108.  Tseng M, Everhart JE, Sandler RS. Dietary intake and gallbladder disease: a review. Public Health Nutr. 1999;2(2):161-172.  (PubMed)

109.  Scragg RK, McMichael AJ, Baghurst PA. Diet, alcohol, and relative weight in gall stone disease: a case-control study. Br Med J (Clin Res Ed). 1984;288(6424):1113-1119.  (PubMed)

110.  Riley EP, Infante MA, Warren KR. Fetal alcohol spectrum disorders: an overview. Neuropsychol Rev. 2011;21(2):73-80.  (PubMed)

111.  Waterman EH, Pruett D, Caughey AB. Reducing fetal alcohol exposure in the United States. Obstet Gynecol Surv. 2013;68(5):367-378.  (PubMed)

112.  Jacobson JL, Jacobson SW. Drinking moderately and pregnancy. Effects on child development. Alcohol Res Health. 1999;23(1):25-30.  (PubMed)

113.  Jacobson JL, Dodge NC, Burden MJ, Klorman R, Jacobson SW. Number processing in adolescents with prenatal alcohol exposure and ADHD: differences in the neurobehavioral phenotype. Alcohol Clin Exp Res. 2011;35(3):431-442.  (PubMed)

114.  Jacobson JL, Jacobson SW. Effects of prenatal alcohol exposure on child development. Alcohol Res Health. 2002;26(4):282-286.  (PubMed)

115.  Niclasen J. Drinking or not drinking in pregnancy: the multiplicity of confounding influences. Alcohol Alcohol. 2014;49(3):349-355.  (PubMed)

116.  Centers for Disease Control and Prevention. Fetal Alcohol Spectrum Disorders (FASDs). Alcohol use in pregnancy. April 2014. Available at: http://www.cdc.gov/ncbddd/fasd/alcohol-use.html. Accessed 8/6/15.

117.  American Academy of Pediatrics. Committee on Substance Abuse and Committee on Children With Disabilities. Fetal alcohol syndrome and alcohol-related neurodevelopmental disorders. Pediatrics. 2000;106(2 Pt 1):358-361.  (PubMed)

118.  Singletary KW, Gapstur SM. Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA. 2001;286(17):2143-2151.  (PubMed)

119.  Seitz HK, Pelucchi C, Bagnardi V, La Vecchia C. Epidemiology and pathophysiology of alcohol and breast cancer: Update 2012. Alcohol Alcohol. 2012;47(3):204-212.  (PubMed)

120.  International Agency for Research on Cancer WHO. IARC monographs on the evaluation of carcingenic risks to humans. Vol 96; 2010. Available at: http://monographs.iarc.fr/ENG/Monographs/vol96/index.php. Accessed 8/24/15.

121.  Scoccianti C, Lauby-Secretan B, Bello PY, Chajes V, Romieu I. Female breast cancer and alcohol consumption: a review of the literature. Am J Prev Med. 2014;46(3 Suppl 1):S16-25.  (PubMed)

122.  Klatsky AL, Udaltsova N, Li Y, Baer D, Nicole Tran H, Friedman GD. Moderate alcohol intake and cancer: the role of underreporting. Cancer Causes Control. 2014;25(6):693-699.  (PubMed)

123.  Smith-Warner SA, Spiegelman D, Yaun SS, et al. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA. 1998;279(7):535-540.  (PubMed)

124.  Hamajima N, Hirose K, Tajima K, et al. 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(11):1234-1245.  (PubMed)

125.  Key J, Hodgson S, Omar RZ, et al. Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes Control. 2006;17(6):759-770.  (PubMed)

126.  Gou YJ, Xie DX, Yang KH, et al. Alcohol consumption and breast cancer survival: a meta-analysis of cohort studies. Asian Pac J Cancer Prev. 2013;14(8):4785-4790.  (PubMed)

127.  Brooks PJ, Zakhari S. Moderate alcohol consumption and breast cancer in women: from epidemiology to mechanisms and interventions. Alcohol Clin Exp Res. 2013;37(1):23-30.  (PubMed)

128.  National Cancer Institute. Breast Cancer Risk in American Women. [Web page]. Available at: http://www.cancer.gov/types/breast/risk-fact-sheet. Accessed 12/15/15.

129.  Baglietto L, English DR, Gertig DM, Hopper JL, Giles GG. Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study. BMJ. 2005;331(7520):807.  (PubMed)

130.  Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst. 2000;92(3):266-269.  (PubMed)

131.  Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001;12(4):420-428.  (PubMed)

132.  Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281(17):1632-1637.  (PubMed)

133.  Zhang SM, Willett WC, Selhub J, et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst. 2003;95(5):373-380.  (PubMed)

134.  Sellers TA, Vierkant RA, Cerhan JR, et al. Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2002;11(10 Pt 1):1104-1107.  (PubMed)

135.  Feigelson HS, Jonas CR, Robertson AS, McCullough ML, Thun MJ, Calle EE. Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev. 2003;12(2):161-164.  (PubMed)

136.  Tjonneland A, Christensen J, Olsen A, et al. Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark. Eur J Clin Nutr. 2006;60(2):280-286.  (PubMed)

137.  Duffy CM, Assaf A, Cyr M, et al. Alcohol and folate intake and breast cancer risk in the WHI Observational Study. Breast Cancer Res Treat. 2009;116(3):551-562.  (PubMed)

138.  Suzuki R, Iwasaki M, Inoue M, et al. Alcohol consumption-associated breast cancer incidence and potential effect modifiers: the Japan Public Health Center-based Prospective Study. Int J Cancer. 2010;127(3):685-695.  (PubMed)

139.  Larsson SC, Bergkvist L, Wolk A. Folate intake and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3444-3449.  (PubMed)

140.  Lieberman DZ. Children of alcoholics: an update. Curr Opin Pediatr. 2000;12(4):336-340.  (PubMed)

141.  National Institute on Alcohol Abuse and Alcoholism. A family history of alcoholism: are you at risk? [Web page]. June 2012. Available at: http://pubs.niaaa.nih.gov/publications/FamilyHistory/famhist.htm. Accessed 9/9/14.

142.  Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54.  (PubMed)

143.  National Institute on Alcohol Abuse and Alcoholism. Older adults and alcohol. Available at: http://pubs.niaaa.nih.gov/publications/olderAdults/olderAdults.htm#toc03. Accessed 9/9/14.

144.  National Institute on Alcohol Abuse and Alcoholism. Alcohol: a women's health issue. 2008. Available at: http://pubs.niaaa.nih.gov/publications/brochurewomen/women.htm. Accessed 8/24/15.

145.  Klatsky AL. Alcohol and cardiovascular disease--more than one paradox to consider. Alcohol and hypertension: does it matter? Yes. J Cardiovasc Risk. 2003;10(1):21-24.  (PubMed)

146.  Cushman WC. Alcohol consumption and hypertension. J Clin Hypertens (Greenwich). 2001;3(3):166-170.  (PubMed)

147.  Briasoulis A, Agarwal V, Messerli FH. Alcohol consumption and the risk of hypertension in men and women: a systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2012;14(11):792-798.  (PubMed)

148.  Taylor B, Irving HM, Baliunas D, et al. Alcohol and hypertension: gender differences in dose-response relationships determined through systematic review and meta-analysis. Addiction. 2009;104(12):1981-1990.  (PubMed)

149.  Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2001;38(5):1112-1117.  (PubMed)

150.  Klatsky AL. Alcohol and cardiovascular diseases: a historical overview. Novartis Found Symp. 1998;216:2-12; discussion 12-18, 152-158.  (PubMed)

151.  Koskinen P, Kupari M, Leinonen H. Role of alcohol in recurrences of atrial fibrillation in persons less than 65 years of age. Am J Cardiol. 1990;66(12):954-958.  (PubMed)

152.  Ruigomez A, Johansson S, Wallander MA, Rodriguez LA. Incidence of chronic atrial fibrillation in general practice and its treatment pattern. J Clin Epidemiol. 2002;55(4):358-363.  (PubMed)

153.  Samokhvalov AV, Irving HM, Rehm J. Alcohol consumption as a risk factor for atrial fibrillation: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil. 2010;17(6):706-712.  (PubMed)

154.  Larsson SC, Drca N, Wolk A. Alcohol consumption and risk of atrial fibrillation: a prospective study and dose-response meta-analysis. J Am Coll Cardiol. 2014;64(3):281-289.  (PubMed)

155.  Conen D, Albert CM. Alcohol consumption and risk of atrial fibrillation: how much is too much? J Am Coll Cardiol. 2014;64(3):290-292.  (PubMed)

156.  Wannamethee G, Shaper AG. Alcohol and sudden cardiac death. Br Heart J. 1992;68(5):443-448.  (PubMed)

157.  Dyer AR, Stamler J, Paul O, et al. Alcohol consumption, cardiovascular risk factors, and mortality in two Chicago epidemiologic studies. Circulation. 1977;56(6):1067-1074.  (PubMed)

158.  Balbao CE, de Paola AA, Fenelon G. Effects of alcohol on atrial fibrillation: myths and truths. Ther Adv Cardiovasc Dis. 2009;3(1):53-63.  (PubMed)

159.  Piano MR, Phillips SA. Alcoholic cardiomyopathy: pathophysiologic insights. Cardiovasc Toxicol. 2014;14(4):291-308.  (PubMed)

160.  Klatsky AL. Alcohol and cardiovascular diseases: where do we stand today? J Intern Med. 2015;278(3):238-250.  (PubMed)

161.  Fernandez-Sola J, Nicolas-Arfelis JM. Gender differences in alcoholic cardiomyopathy. J Gend Specif Med. 2002;5(1):41-47.  (PubMed)

162.  Urbano-Marquez A, Estruch R, Fernandez-Sola J, Nicolas JM, Pare JC, Rubin E. The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men. JAMA. 1995;274(2):149-154.  (PubMed)

163.  Louvet A, Mathurin P. Alcoholic liver disease: mechanisms of injury and targeted treatment. Nat Rev Gastroenterol Hepatol. 2015;12(4):231-242.  (PubMed)

164.  Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med. 2004;38(5):613-619.  (PubMed)

165.  Rehm J, Baliunas D, Borges GL, et al. The relation between different dimensions of alcohol consumption and burden of disease: an overview. Addiction. 2010;105(5):817-843.  (PubMed)

166.  Maher JJ. Alcoholic liver disease. In: Feldman M, Friedman LS, Sleisenger LH, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. 7th ed. St. Louis: W.B. Saunders; 2002:1375-1387.

167.  Lieber CS. Alcohol and hepatitis C. Alcohol Res Health. 2001;25(4):245-254.  (PubMed)

168.  Bagnardi V, Blangiardo M, La Vecchia C, Corrao G. Alcohol consumption and the risk of cancer: a meta-analysis. Alcohol Res Health. 2001;25(4):263-270.  (PubMed)

169.  Doll R, Forman D, La Vecchia C, Woutersen R. Alcoholic beverages and cancers of the digestive tract and larynx. In: MacDonald I, ed. Health Issues Related to Alcohol Consumption. Oxford: Blackwell Science Ltd; 1999:351-394.

170.  Bernardin F, Maheut-Bosser A, Paille F. Cognitive impairments in alcohol-dependent subjects. Front Psychiatry. 2014;5:78.  (PubMed)

171.  Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol Suppl. 2000;35(1):2-7.  (PubMed)

172.  Greenberg DM, Lee JW. Psychotic manifestations of alcoholism. Curr Psychiatry Rep. 2001;3(4):314-318.  (PubMed)

173.  DiMagno EP, Chari S. Acute Pancreatitis. In: Feldman M, Friedman LS, Sleisenger LH, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. St. Louis: W.B. Saunders; 2002:913-942.

174.  Yadav D, Whitcomb DC. The role of alcohol and smoking in pancreatitis. Nat Rev Gastroenterol Hepatol. 2010;7(3):131-145.  (PubMed)

175.  Forsmark CE. Chronic Pancreatitis. In: Feldman M, Friedman LS, Sleisenger LH, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. St. Louis: W.B. Saunders; 2002.

176.  Yadav D, Papachristou GI, Whitcomb DC. Alcohol-associated pancreatitis. Gastroenterol Clin North Am. 2007;36(2):219-238, vii.  (PubMed)

177.  Pandol SJ, Lugea A, Mareninova OA, et al. Investigating the pathobiology of alcoholic pancreatitis. Alcohol Clin Exp Res. 2011;35(5):830-837.  (PubMed)

178.  Health risks and benefits of alcohol consumption. Alcohol Res Health. 2000;24(1):5-11.  (PubMed)

179.  Vinson DC, Maclure M, Reidinger C, Smith GS. A population-based case-crossover and case-control study of alcohol and the risk of injury. J Stud Alcohol. 2003;64(3):358-366.  (PubMed)

180.  US National Highway Traffic Safety Admininstration's National Center for Statistics and Analysis. Traffic safety facts. 2013 data: Alcohol-impaired driving. December 2014. Available at: http://www-nrd.nhtsa.dot.gov/Pubs/812102.pdf. Accessed 8/6/15.

181.  Moskowitz H, Fiorentino DA. Review of the literature on the effects of low doses of alcohol on driving-related skills. Washington D.C.: National Highway Traffic Safety Administration; 2000.

182.  Fisher HR, Simpson RI, Kapur BM. Calculation of blood alcohol concentration (BAC) by sex, weight, number of drinks and time. Can J Public Health. 1987;78(5):300-304.  (PubMed)

183.  National Institute on Alcohol Abuse and Alcoholism. Alcohol alert: alcohol, violence, and aggression [Web page]. October 2000. Available at: http://pubs.niaaa.nih.gov/publications/aa38.htm. Accessed 10/3/07.