Long-term effects of alcohol: Difference between revisions

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The relationship between alcohol consumption and health is somewhat ambiguous. Regular light-to-moderate alcohol intake has been shown to have positive effects on health,^[1] chiefly because of its cardiovascular effects.^[2]^[3]^[4]^[5] Conversely, frequent heavy drinking can increase the risk of developing alcoholism, alcoholic liver disease, and cancer. A single episode of "binge drinking" can have immediate negative consequences, including death.

Alcohol consumption during pregnancy, especially drinking heavily or during early stages of prenatal development, has been shown to cause fetal alcohol syndrome. For a small subset of the population genetically sensitive to its effects, even light consumption &ndash for some, as little as a single drink &ndash causes severe headache or nausea.

Scientific Study

History

The relationship between alcohol consumption and health has been the subject of formal scientific research since at least 1926, when Dr. Raymond Pearl published his book, Alcohol and Longevity, in which he reported his finding that drinking alcohol in moderation was associated with greater longevity than either abstaining or drinking heavily.^[6] Since that time data have come in from all over the world. Studies have focused on both men and women, various age groups, and people of many ethnic groups. Published papers now total in the many hundreds. Much evidence is not simply correlational or time sequence in nature. Some of the many specific ways by which alcohol leads to improved cardiovascular health are now understood, often in great detail. ^[7]

Modern Understanding

Research in various countries has found the all-cause mortality rates range from 16 to 28% lower among moderate drinkers than among abstainers^[8]^[9]^[10]^[11] (Yuan).

The medical studies establishing this relationship are large (some include over 200,000 people), cross-cultural (have been conducted in countries around the world), and are sometimes long-term (the longest beginning in 1948 and continuing to this day).^[12]

Quantity Recommended

The U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA) has completed an extensive review of current scientific knowledge about the health effects of moderate alcohol consumption. It found that the lowest death rate from all causes occurs at the level of one to two drinks per day. That is, moderate drinkers have the greatest longevity.^[13]^[14]

A 23-year prospective study of 12,000 male British physicians aged 48–78, found that overall mortality was significantly lower in the group consuming an average of 2–3 "units" (British unit = 8g) per day than in the non-alcohol-drinking group (relative risk 0.81, confidence interval 0.76-0.87, P = 0.001).^[15] The authors noted that the causes of death that are already known to be augmentable by alcohol accounted for only 5% of the deaths (1% liver disease, 2% cancer of the mouth, pharynx, larynx, or oesophagus, and 2% external causes of death) and were significantly elevated only among men consuming >2 units/day.

In a 1996 American Heart Association scientific statement, Thomas A. Pearson, MD, Ph. D noted, "A large number of observational studies have consistently demonstrated a U-shaped relation between alcohol consumption and total mortality. This relation appears to hold in men and women who are middle aged or older. The lowest mortality occurs in those who consume one or two drinks per day. In teetotalers or occasional drinkers, the rates are higher than in those consuming one or two drinks per day. In persons who consume three or more drinks per day, total mortality climbs rapidly with increasing numbers of drinks per day."

Cardiovascular System

The cardiovascular effects of consistent, moderate alcohol intake are perhaps the most studied and the most widely-accepted. The World Health Organization Technical Committee on Cardiovascular Disease asserted that the relationship between moderate alcohol consumption and reduced death from heart disease could no longer be doubted.^[16] Consumption of red wine may be particularly favourable, since red wines contain certain polyphenol antioxidants associated with cardiovascular health. One study determined that the potential long-term benefits of moderate alcohol consumption on cardiovascular health surpassed all other factors except the cessation of smoking.^[17]

Alcohol appears to be hormetic.^[18] Medical research demonstrates that, consumed in moderation, alcohol increases HDL (“good cholesterol”), decreases thrombosis (blood clotting), reduces fibrinogen (a blood clotter), increases fibrinolysis (clot dissolving), reduces artery spasm from stress, increases coronary blood flow and increases insulin sensitivity -- all good for heart health^[19]^[20] (Rimm; Zhang). Additionally, Thrombosis is lower among moderate drinkers than teetotalers. ^[21]

Cardiovascular Disease

Coronary Heart Disease

Pearson reviewed the evidence supporting the effect of alcohol consumption on coronary heart disease (CHD): "More than a dozen prospective studies have demonstrated a consistent, strong, dose-response relation between increasing alcohol consumption and decreasing incidence of CHD. The data are similar in men and women in a number of different geographic and ethnic groups. Consumption of one or two drinks per day is associated with a reduction in risk of approximately 30% to 50%. Studies of coronary narrowings defined by cardiac catheterization or autopsy show a reduction in atherosclerosis in persons who consume moderate amounts of alcohol. In general, the inverse association is independent of potential confounders, such as diet and cigarette smoking. Concerns that the association could be an artifact due to cessation of alcohol consumption in persons who already have CHD have largely been disproved."^[22]

Another study found that when men increased their alcohol intake from very low to moderate, they significantly reduced their risk of coronary heart disease. The study monitored the health of 18,455 males for a period of seven years. ^[23]

Coronary Vascular Disease

Moderate drinking has been found to reduce the risk of angina pectoris.^[24] In heart attack patients who are treated with alcohol, the tissues affected by low blood flow are healthier and stronger than those who receive no alcohol because of alcohol's positive effects on artery walls.^[25] Similarly, drinking alcoholic beverages in moderation may help patients recover from coronary stenting. Healing appears to be promoted by the inflammation inhibiting effects of alcohol. ^[26]

Peripheral Vascular Disease

"Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men.".^[27] "In this large population-based study, moderate alcohol consumption was inversely associated with peripheral arterial disease in women but not in men. Residual confounding by smoking may have influenced the results. Among nonsmokers an inverse association was found between alcohol consumption and peripheral arterial disease in both men and women."^[28]^[29]

Heart Attack and Stroke

Drinking in moderation has been found to help those who have suffered a heart attack survive it. ^[30]^[31] To determine if moderate drinkers have fewer heart attacks because they might lead more healthful lifestyles than do abstainers or heavy drinkers, Harvard scientists recently reported their study of only healthy men who led healthful lifestyles. For up to 16 years the doctors monitored the health of 8,867 men who didn't smoke, were of normal weight, exercised at least 30-60 minutes per day, and ate a balanced healthful diet. Among these healthy men with healthy lifestyles, those who consumed anywhere from 1/2 to two alcoholic drinks of beer, wine or liquor per day had significantly decreased risk of heart attacks. Those who averaged slightly more (one to two drinks per day) had the lowest risk.^[32] Other research also addresses this question.

Compared to abstaining, drinking in moderation is associated with a reduced risk of stroke, whereas abusing alcohol is associated with an increased risk of stroke.^[33] A study of over 22,000 male physicians aged 40-84 years old over an average of 12 years, concluded, "Light-to-moderate alcohol consumption reduces the overall risk of stroke and the risk of ischemic stroke in men. The benefit is apparent with as little as one drink per week. Greater consumption, up to one drink per day, does not increase the observed benefit."^[34]

Cardiomyopathy

The cardiovascular effects of alcohol are not all beneficial, however; studies show that large-quantity consumption of alcohol can lead to alcoholic cardiomyopathy, commonly known as "holiday heart syndrome." Alcoholic cardiomyopathy presents in a manner clinically identical to idiopathic dilated cardiomyopathy, involving hypertrophy of the musculature of the heart that can lead to a form of cardiac arrythmia. These electrical anomales, represented on an EKG, often vary in nature, but range from nominal changes of the PR, QRS, or QT intervals to paroxsysmal episodes of ventricular tachycardia. The pathophysiology of "holiday heart syndrome" has not been firmly identified, but certain hypotheses cite an increased secretion of epinephrine and norepinephrine, increased sympathetic output, or a rise in the level of plasma free fatty acids as possible mechanisms.^[35]

Hematologic diseases

Alcoholics may have anemia from several causes;^[36] they may also develop thrombocytopenia from direct toxic effect on megakaryocytes, or from hypersplenism.

Nervous System

A meta-analysis of 35 previous studies of the effect of alcohol consumption on stroke risk found that "compared with abstainers, consumption of more than 60 g of alcohol per day (i.e., over four standard drinks -- heavy drinking) was associated with an increased relative risk of total stroke, 1.64 (95% confidence interval [CI], 1.39-1.93); ischemic stroke, 1.69 (95% CI, 1.34-2.15); and hemorrhagic stroke, 2.18 (95% CI, 1.48-3.20), while consumption of less than 12 g/d was associated with a reduced relative risk of total stroke, 0.83 (95%, CI, 0.75-0.91) and ischemic stroke, 0.80 (95% CI, 0.67-0.96), and consumption of 12 to 24 g/d was associated with a reduced relative risk of ischemic stroke, 0.72 (95%, CI, 0.57-0.91). The meta-regression analysis revealed a significant nonlinear relationship between alcohol consumption and total and ischemic stroke and a linear relationship between alcohol consumption and hemorrhagic stroke."^[37]

These findings have been disputed; A 2003 John Hopkins study has linked moderate alcohol use to brain shrinkage and did not find any reduced risk of stroke among moderate drinkers.^[38]

Brain development

Consuming large amounts of alcohol over a period of time can impair normal brain development in humans.^[39]^[40] Deficits in retrieval of verbal and nonverbal information and in visuospatial functioning were evident in youths with histories of heavy drinking during early and middle adolescence.^[41]

The other way around, abstinence from chronic heavy alcohol consumption encourages new brain cell development.^[42]

Nearly half of chronic alcoholics may have myopathy.^[43] Proximal muscle groups are especially affected. Twenty-five percent of alcoholics may have peripheral neuropathy, including autonomic.^[44]

Cognition

Research has demonstrated a positive association between moderate drinking and cognition or thinking ability. A study of 6,033 British civil servants who were followed an average of 11 years found that those who consumed at least one drink in the previous week, compared with those who did not, were significantly less likely to have poor cognitive function. The beneficial effect extended to those drinking more than 240 g per week (approximately 30 drinks). Higher levels of consumption were not investigated. ^[45] A three-year longitudinal study of several hundred men in the Netherlands found that low-to-moderate alcohol drinking was associated with a significantly lower risk for poor cognitive function than abstaining. ^[46] A large prospective study that examined the effects of alcohol consumption on men 18 years later found that non-drinkers and heavy drinkers had the poorest cognitive ability. Moderate alcohol consumption was associated with the highest cognitive performance later in life.(82) ^[47] A longitudinal study in France found that, among the women studied, moderate alcohol consumption was associated with higher cognitive function. Moderate drinkers were 2.5 times more likely to receive the highest cognitive ability scores than were abstainers. ^[48]

Two recent studies have added to the evidence that drinking in moderation is associated with better cognitive ability. Researchers in Australia studied 7,485 people age 20 to 64. They found that moderate drinkers performed better than abstainers on all, measures of cognitive ability. ^[49]

Dementia and Alzheimer’s Disease

Research has found moderate drinking to be associated with lower risk of dementia, including Alzheimer’s disease. A study of about 6,000 people age 65 and older found that moderate drinkers had a 54% lower chance of developing dementia than did abstainers. ^[50] A study in the Netherlands of 7,983 people age 55 or older over a period averaging six years found that those who consumed one to three drinks per day had a significantly lower risk of dementia (including Alzheimer’s) than did non-drinkers. ^[51] Over one thousand persons age 65 and older were studied over a period of seven years. Researchers found, that overall, light and moderate drinkers suffered less mental decline than did teetotalers. ^[52] A study of 1,018 men and women age 65-79 whose mental health was monitored for an average of 23 years found that “drinking no alcohol, or too much, increases risk of cognitive impairment.” ^[53] In Italy researchers examined 15,807 people 65 years of age and older. Among the drinkers only 19% showed signs of mental impairment compared to 29% of the abstainers. ^[54] In a study of 402 people at least 75 years of age who were followed almost six years found that light to moderate drinking was significantly associated with a decreased risk of dementia and Alzheimer's disease compared with non-drinkers. ^[55] The results of a study of 12,480 women age 70-81 beginning in 1980 found that women who consumed alcohol moderately on a daily basis were about 20% less likely than non-drinkers to experience poor memory and decreased thinking abilities. ^[56] A study of 7,469 women age 65 and older found that those who consumed up to three drinks per day scored significantly better than non-drinkers on global cognitive function, including such things as concentration, memory, abstract reasoning, and language. ^[57] A study of over 9,000 women age 70-79 over a four-year period. After adjusting for other factors that might effect mental function, the researchers found that the women who drank in moderation performed significantly on five of seven tests. They also performed significantly better on a global score that combined all seven tests ^[58] A study of older women found that moderate drinkers (those who consumed up to two drinks per day) demonstrated better memory abilities than abstainers. The performance memory tests included such things as remembering a story, a route, hidden objects, future intentions and connecting random numbers and letters. In all cases, the group who drank scored better than those who did not drink. They also performed better on concentration, verbal-associative capacities and oral fluency. ^[59]

In people with mild cognitive impairment, consuming up to a drink of alcohol per day reduced the development of dementia by 85% compared to teetotalers. The Italian study participants, age 65 to 84, were studied over a period of three and one-half years. ^[60]

Studies have found the risks of Alzheimer's disease to be as much as 75% lower among drinkers than among teetotalers. A study of found that those who drank regularly, including those who consumed in excess of U.S. recommend levels (one drink per day for women and two for men) had a significantly lower risk of Alzheimer’s disease than did non-drinkers. ^[61] A French study of 2,273 subjects over a period of three years found that moderate drinkers were significantly less likely than non-drinkers to develop either dementia or Alzheimer’s disease. ^[62]

A review of existing research to identify how dementia can be reduced found that that both abstaining from alcohol and abusing it are risk factors for cognitive decline and dementia. ^[63]

Essential tremor

Essential tremors can be temporarily and dramatically relieved in up to two-thirds of patients by drinking small amounts of alcohol, thus avoiding the serious side effects of the most effective and expensive medications or the dangers of surgery. ^[64]

Digestive System and Weight Gain

Except from pancreatitis and liver disease, there is uncertainty whether alcohol is devastating or beneficial on the gastrointestinal system. Its impact on weight-gain is contentious: some studies find no effect, ^[65] others find decreased^[66] or increased effect on weight gain.

Alcohol use increases the risk of chronic gastritis (stomach inflammation);^[67]^[68] it is one cause of cirrhosis, hepatitis, and pancreatitis in both its chronic and acute forms.

Gallbladder disease

Consumption of alcohol is unrelated to gallbladder disease.^[69] However one study suggested that drinkers who take Vitamin C (ascorbic acid) might reduce their risk. "After adjustment for potential confounding variables, use of ascorbic acid supplements among drinkers was associated with a decreased prevalence of gallbladder disease … and cholecystectomy …. Use of ascorbic acid supplements among non-drinkers was not significantly associated with either prevalence of gallbladder disease or cholecystectomy. Further study is necessary to confirm our findings and, specifically, to examine the combined effects of ascorbic acid and alcohol on cholesterol metabolism."^[70]

Gallstones

Research has found that drinking reduces the risk of developing gallstones. Compared with alcohol abstainers, the relative risk of gallstone disease, controlling for age, sex, education, smoking, and body mass index, is 0.83 for occasional and regular moderate drinkers (< 25 ml of ethanol per day), 0.67 … for intermediate drinkers (25-50 ml per day), and 0.58 … for heavy drinkers. This inverse association was consistent across strata of age, sex, and body mass index."^[71] Frequency of drinking also appears to be a factor. "An increase in frequency of alcohol consumption also was related to decreased risk. Combining the reports of quantity and frequency of alcohol intake, a consumption pattern that reflected frequent intake (5-7 days/week) of any given amount of alcohol was associated with a decreased risk, as compared with nondrinkers. In contrast, infrequent alcohol intake (1-2 days/week) showed no significant association with risk.”^[72]

Other Systems

Urinary System: Kidney stones

Research indicates that drinking alcohol is associated with a lower risk of developing kidney stones. One study concludes, "Beer consumption was inversely associated with risk of kidney stones; each bottle of beer consumed per day was estimated to reduce risk by 40% …. Since beer seemed to be protective against kidney stones, the physiologic effects of other substances besides ethanol, especially those of hops, should also be examined."^[73] "…consumption of coffee, alcohol, and vitamin C supplements were negatively associated with stones."^[74] "After mutually adjusting for the intake of other beverages, the risk of stone formation decreased by the following amount for each 240-ml (8-oz) serving consumed daily: caffeinated coffee, 10%; decaffeinated coffee, 10%; tea, 14%; beer, 21%; and wine, 39%."^[75] "…stone formation decreased by the following amount for each 240-mL (8-oz) serving consumed daily: 10% for caffeinated coffee, 9% for decaffeinated coffee, 8% for tea, and 59% for wine." (CI data excised from last two quotes.).^[76]

Endocrine System: Diabetes

Moderate drinkers may have a lower risk of diabetes than non-drinkers. "Alcohol intake increases insulin sensitivity and may partly explain both the J-shaped relationship between the prevalence of diabetes and the amount of alcohol consumption and the decreased mortality for myocardial infarction."^[77] "Compared with abstainers men who drank 30.0-49.9 g of alcohol daily had a relative risk of diabetes of 0.61."^[78] "Consumption of 30 g/d of alcohol (2 drinks per day) has beneficial effects on insulin and triglyceride concentrations and insulin sensitivity in nondiabetic postmenopausal women."^[79] After adjustment for age, randomized treatment assignment, smoking, physical activity, and body mass index, the relative risk estimates of diabetes for those reporting alcohol use of rarely/never were 1.00 (referent), 1 to 3 drinks per month 1.03, 1 drink per week 0.89, 2 to 4 drinks per week 0.74, 5 to 6 drinks per week 0.67, and 1 or more drinks per day 0.57.^[80] "The results of this study suggested that moderate alcohol consumption may reduce the risk of type 2 diabetes. On the other hand, binge drinking and high alcohol consumption may increase the risk of type 2 diabetes in women."^[81]

Skeletal System

Light to moderate alcohol consumption appears to reduce the risk of developing rheumatoid arthritis, according to research. ^[82]

Moderate alcohol consumption is associated with higher bone mineral density in postmenopausal women. "…alcohol consumption significantly decreased the likelihood [of osteoporosis]."^[83] "Moderate alcohol intake was associated with higher BMD [bone mineral density] in postmenopausal elderly women."^[84] "Social drinking is associated with higher bone mineral density in men and women [over 45]."^[85]

Immune System, Bacterial Contamination, and Cancer

Bacterial Infection

Drinking strong alcoholic beverages with a meal may offer some protection against bacterial contamination. The antibacterial activity of red and white wine against enteropathogens, (e.g. Shigella or Salmonella^[86]) may protect against bacterial diarrhoea in a similar way to bismuth salicylate.^[87].

There is a protective effect of alcohol consumption against active infection with H pylori^[88] In contrast, alcohol intake (comparing those who drink > 30 gm of alcohol per day to nondrinkers) is not associated with higher risk of duodenal ulcer ^[89]

Cancer

The NIAAA states that "Although epidemiologic studies have found a clear association between alcohol consumption and development of certain types of cancer, study findings are often inconsistent and may vary by country and by type of cancer."^[90] The U.S. Department of Health & Human Services’ National Toxicology Program listed alcohol as a known carcinogen in 2000 .^[91]

Others are more cautious in their evaluation. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) reports that "Although there is no evidence that alcohol itself is a carcinogen, alcohol may act as a cocarcinogen by enhancing the carcinogenic effects of other chemicals. For example, studies indicate that alcohol enhances tobacco's ability to stimulate tumor formation in rats (Garro & Lieber). In humans, the risk for mouth, tracheal, and esophageal cancer is 35 times greater for people who both smoke and drink than for people who neither smoke nor drink (Blot et al.), implying a cocarcinogenic interaction between alcohol and tobacco-related carcinogens (Garro & Lieber)."^[90] One study determined that "3.6% of all cancer cases worldwide are related to alcohol drinking, resulting in 3.5% of all cancer deaths."^[92] The NiAAA suggests that "considerable evidence suggests a connection between heavy alcohol consumption and increased risk for cancer, with an estimated 2 to 4 percent of all cancer cases thought to be caused either directly or indirectly by alcohol."^[90]

Specific Demographics

Research is lacking on the possible brain effects of light or moderate alcohol consumption among young humans.^[93]

Fetal alcohol syndrome or FAS is a disorder of permanent birth defects that occurs in the offspring of women who drink alcohol during pregnancy. Drinking heavily or during the early stages of prenatal development has been conclusively linked to FAS; the impact of light or moderate consumption is not yet fully understood.

Notes

References

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^ Antilla, Tiia, et al. Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study. British Medical Journal, 2004, 329, 538-539.
^ Zuccala, G. , et al. Dose-related impact of alcohol consumption on cognitive function in advanced age: Results of a multicenter study. Alcoholism: Clinical and Experimental Research, 2001, 25, 1743-1748.
^ Huang W, Qiu C, Winblad B, Fratiglioni L. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. Journal of Clinical Epidemiology, 2002, 55(10), 959-64.
^ Stampfer, M.J., et al. Effects of moderate alcohol consumption on cognitive function in women. New England Journal of Medicine, 2005, 352, 245-253.
^ Espeland, M., et al. Association between alcohol intake and domain-specific cognitive function in older women. Neuroepidemiology, 2006, 1(27), 1-12.
^ Harrison, P.G. Moderate Drinking Helps Preserve Women's Brains. Reuters Health, June 15, 2001. See also Reuters, Associated Press, ABCNEWS, and HealthSCOUT of same date.
^ McDougall, Graham. Older Women’s Cognitive and Affective Response to Moderate Drinking. Paper presented at the meetings of the National Congress on the State of Science in Nursing Research. Washington, DC, October 7-8, 2004.
^ Solfrizzi, V. et al. Alcohol consumption, mild cognitive impairment, and progression to dementia. Neurology, 2007, 68(2)
^ Cupples, LA; Weinberg, J; Beiser, A; Auerbach, SH; Volicer, L; Cipolloni, PB; Wells, J; Growdon, JH; DAgostino, RB; Wolf, PA; Farrer, LA Effects of smoking, alcohol and APOE genotype on Alzheimer disease: The MIRAGE study Alzheimer Report, 2000, 3, 105-114.
^ Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area Revue neurologique (Paris). 1997 Apr;153(3):185-92.
^ Andel, R., Hughes, T.F., & Crowe, M.G. (2005). Strategies to reduce the risk of cognitive decline and dementia. Aging Health, 1(1),107-116.
^ Charles P. D., et al. Classification of tremor and update on treatment. American Family Physician, 1999, 59(6), 565-72; Bain, P. G., et al. A study of hereditary essential tremor. Brain, 1994, 117 (Pt 4), 805-24 ; Lou, J.S., & Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology, 1991, 41 (2 Pt 1), 234-8; Singer C, et al. Gait abnormality in essential tremor. Movement Disorders, 1994, 9(2), 193-6; Wasielewski PG, et al. Pharmacologic treatment of tremor. Movement Disorders, 1998, 13 (Suppl 3), 90-100; Boecker, H., et al. The effect of ethanol on alcoholic-responsive essential tremors: a positron emission tomography study. Annals of Neurology, 1996, 39, 650-658, 1996; Setting a steady course for benign essential tremor. The Johns Hopkins Medical Letter, 1999 (December), 11(10).
^ Cordain, L;, Bryan, E D; Melby, C L; Smith, M J Influence of moderate daily wine consumption on body weight regulation and metabolism in healthy free-living males Journal of the American College of Nutrition 1997, Vol 16, Issue 2 134-139.
^ (Arif, A. A. & Rohrer, J. E. Patterns of Alcohol Drinking and its Association with Obesity: Data from the Third National Health and Nutrition Examination Survey, 1988-1994 BMC Public Health, 2005 5 December), (5), 126.)
^ National Institute on Alcohol Abuse and Alcoholism (NIAAA) Alcohol Research & Health Vol. 24, No. 1, 2000 Health Risks and Benefits of Alcohol Consumption (PDF)
^ Bode, Christiane; Bode, J. Christiane Alcohol’s Role in Gastrointestinal Tract Disorders Alcohol Health & Research World Vol. 21, No. 1, 1997
^ Sahi T, Paffenbarger RS Jr, Hsieh CC, Lee IM Body mass index, cigarette smoking, and other characteristics as predictors of self-reported, physician-diagnosed gallbladder disease in male college alumni American Journal of Epidemiology 1998 Apr 1;147(7):644-51
^ Simon JA, Grady D, Snabes MC, Fong J, Hunninghake DB Ascorbic acid supplement use and the prevalence of gallbladder disease. Heart & Estrogen-Progestin Replacement Study (HERS) Research Group Journal of Clinical Epidemiology 1998 Mar;51(3):257-65
^ La Vecchia C, Decarli A, Ferraroni M, Negri E Alcohol drinking and prevalence of self-reported gallstone disease in the 1983 Italian National Health Survey Epidemiology 1994 Sep;5(5):533-6
^ Leitzmann MF, Giovannucci EL, Stampfer MJ, Spiegelman D, Colditz GA, Willett WC, Rimm EB Prospective study of alcohol consumption patterns in relation to symptomatic gallstone disease in men Alcohol: Clinical and Experimental Research 1999 May;23(5):835-41
^ Hirvonen, Tero; Pietinen, Pirjo; Virtanen, Mikko; Albanes, Demetrius; Virtamo, Jarmo Nutrient Intake and Use of Beverages and the Risk of Kidney Stones among Male Smokers American Journal of Epidemiology Vol. 150, No. 2: 187-194
^ Soucie, J. Michael; Coates, Ralph J; McClellan, William; Austin, Harland; Michael Thun Relation between Geographic Variability in Kidney Stones Prevalence and Risk Factors for Stones American Journal of Epidemiology Vol. 143, No. 5: 487-495
^ Curhan GC, Willett WC, Rimm EB, Spiegelman D, Stampfer MJ Prospective study of beverage use and the risk of kidney stones American Journal of Epidemiology 1996 Feb 1;143(3):240-7
^ Curhan GC, Willett WC, Speizer FE, Stampfer MJ Beverage use and risk for kidney stones in women Annals of Internal Medicine 1998 Apr 1;128(7):534-40
^ Avogaro A, Watanabe RM, Dall'Arche A, De Kreutzenberg SV, Tiengo A, Pacini G. Acute alcohol consumption improves insulin action without affecting insulin secretion in type 2 diabetic subjects Diabetes Care, 2004 (June 6), 27(6), 1369-1374
^ Rimm EB, Chan J, Stampfer MJ, Colditz GA, Willett WC Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men British Medical Journal 1995 Mar 4;310(6979):555-9
^ Davies, Michael J; Baer, David J; Judd, Joseph T; Brown, Ellen D; Campbell, William S; Taylor, Philip R Effects of Moderate Alcohol Intake on Fasting Insulin and Glucose Concentrations and Insulin Sensitivity in Postmenopausal Women: A Randomized Controlled Trial Journal of the American Medical Association, 2002, 287(19), 2559-2562.
^ Ajani, Umed A; Hennekens, Charles H; Spelsberg, Angela; Manson, JoAnn E Alcohol Consumption and Risk of Type 2 Diabetes Mellitus Among US Male Physicians Archives of Internal Medicine, 2000, 160, 1025-1050
^ Sofia Carlsson, Niklas Hammar, Valdemar Grill, and Jaakko Kaprio Alcohol consumption and the incidence of type 2 diabetes: a 20-year follow-up of the Finnish Twin Cohort Study Diabetes Care, 2003, 26(10), 2785-2786.
^ Turesson, Carl. Increased Alcohol Intake Associated with Decreased Risk of Developing Rheumatoid Arthritis. (Abstract) Paper presented at the annual European Congress of Rheumatology. Barcelona, Spain. June 13-16, 2007. European League Against Rheumatism, June 15, 2007; Myllykangas-Lusojarvi, R., Aho, K., Kautiainen, H., and Hakala, M. Reduced incidence of alcohol related deaths in subjects with rheumatoid arthritis. Annals of Rheumatoid Diseases, 2000, 59, 75-76; Voight, L., et al. Smoking, obesity, alcohol consumption and the risk of rheumatoid arthritis. Epidemiology, 1994, 5, 525-532.
^ Siris, Ethel S; Miller, Paul D; Barrett-Connor, Elizabeth; Faulkner, Kenneth G; Wehren, Lois E; Abbott, Thomas A; Berger, Marc L; Santora, Arthur C; Sherwood, Louis M Identification and Fracture Outcomes of Undiagnosed Low Bone Mineral Density in Postmenopausal Women Journal of the American Medical Association, 2001;286:2815-2822
^ Rapuri, Prema B; Gallagher, J Christopher; Balhorn, Kurt E; Ryschon, Kay L Alcohol intake and bone metabolism in elderly women American Journal of Clinical Nursing Vol. 72, No. 5, 1206-1213, November 2000
^ Holbrook TL, Barrett-Connor E A prospective study of alcohol consumption and bone mineral density British Medical Journal 1993 Jun 5;306(6891):1506-9
^ Desenclos JA, Klontz KC, Wilder MH, Gunn RA The protective effect of alcohol on the occurrence of epidemic oyster-borne hepatitis A Epidemiology 1992 Jul;3(4):371-4
^ Weisse, Martin E; Eberly, Bardwell; Person, Donald A Wine as a digestive aid: comparative antimicrobial effects of bismuth salicylate and red and white wine British Medical Journal 1995;311:1657-1660 (23 December)
^ Brenner, Hermann; Rothenbacher, Dietrich; Bode, Günter; Adler, Guido Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study British Medical Journal 1997;315:1489-1492 (6 December)
^ Aldoori WH, Giovannucci EL, Stampfer MJ, Rimm EB, Wing AL, Willett WC A prospective study of alcohol, smoking, caffeine, and the risk of duodenal ulcer in men Epidemiology 1997 Jul;8(4):420-4.
^ ^a ^b ^c National Institute on Alcohol Abuse and Alcoholism Alcohol Alert No. 21 PH 345 July 1993
^ National Toxicology Program Alcoholic Beverage Consumption: Known to be a human carcinogen First listed in the Ninth Report on Carcinogens (2000)(PDF)
^ Burden of alcohol-related cancer substantial
^ http://www2.potsdam.edu/hansondj/HealthIssues/references/1127400726.html

Trevisan, M., et al. Drinking pattern and mortality: a longitudinal study; Gaziano, J. M., et al. A prospective cohort study of moderate alcohol consumption and sudden death in the Physicians' Health Study. Abstract . The Canadian Journal of Cardiology, June, 1997, volume 13, Supplement B.

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[4] National Institute on Alcohol Abuse and Alcoholism. Alcohol Alert, No. 45, October, 1999; Blackwelder, W. C., et al. Alcohol and mortality. The Honolulu Heart Study. American Journal of Medicine, 1980, 68(2), 164-169.

[5] Rimm et al., Trevisan et al.

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[10] Fuchs CS, Stampfer MJ, Colditz GA, Giovannucci EL, Manson JE, Kawachi I, Hunter DJ, Hankinson SE, Hennekens CH, Rosner B Alcohol consumption and mortality among women New England Journal of Medicine 1995 May 11;332(19):1245-50

[11] Klatsky AL, Friedman GD, Siegelaub AB Alcohol and mortality. A ten-year Kaiser-Permanente experience Annals of Internal Medicine 1981 Aug;95(2):139-45

[12] Alcohol and Longevity Facts & Information

[13] U.S. Government: Moderate Drinking Benefits Health

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[20] Paassilta Marita; Kervinen, Kari; Rantala, Asko O; Savolainen, Markku J; Lilja, Mauno; Reunanen, Antti; Kesäniemi, Y Antero Social alcohol consumption and low Lp(a) lipoprotein concentrations in middle aged Finnish men: population based study British Medical Journal 1998 February 14; 316(7131): 594–595

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[24] Camargo CA Jr, Stampfer MJ, Glynn RJ, Grodstein F, Gaziano JM, Manson JE, Buring JE, Hennekens CH Moderate alcohol consumption and risk for angina pectoris or myocardial infarction in U.S. male physicians Archives of Internal Medicine 1997 Mar 1;126(5):372-5

[25] Alcohol Helps Reduce Damage After Heart Attack

[26] Zairis, M.N., et al. C Reactive protein, moderate alcohol consumption, and long term prognosis after successful coronary stenting: four year results from the GENERATION study. Heart, 2004, 90, 419-424

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[29] Mingardi, R; Avogaro, A; Noventa, F; Strazzabosco, M; Stocchiero, C; Tiengo, A; Anderle, G "Alcohol intake is associated with a lower prevalence of peripheral vascular disease in non-insulin dependent diabetic women" Nutrition Metabolism and Cardiovascular Disease 7(4): 301– 308, 1997. (No abstract found online.)

[30] Gaziano, J. et al. Potential mortality benefits for drinkers with previous heart attacks. The Lancet, 1998, 332, 1882-1885; Mulkamal, K.J. et al. Prior alcohol consumption and mortality following acute myocardial infarction. Journal of the American Medical Association, 2001, 285(15), 1965-1970

[31] Alcohol helps reduce damage after heart attacks

[32] Mulkamal, K.J., et al. Alcohol consumption and risk of coronary heart disease in men with healthy lifestyles. Archives of Internal Medicine, 2006 (October), 166(19), 2145-2150

[33] Rodgers, H. et al. Alcohol and stroke. A case-control study of drinking habits past and present Stroke, 1993. 24(10), 1473-1477.

[34] Berger et al Light-to-Moderate Alcohol Consumption and the Risk of Stroke among U.S. Male Physicians New England Journal of Medicine 341(21):1557-1564, November 18, 1999

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[40] Tapert SF, Brown GG, Kindermann SS, Cheung EH, Frank LR, Brown SA fMRI measurement of brain dysfunction in alcohol-dependent young women Alcoholism: Clinical & Experimental Research 2001 Feb;25(2):236-45

[41] Brown SA, Tapert SF, Granholm E, Delis DC Neurocognitive functioning of adolescents: effects of protracted alcohol use Alcoholism: Clinical and Experimental Research 2000 Feb;24(2):164-71

[42] American Association for the Advancement of Science New brain cells develop during alcohol abstinence, UNC study shows

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[45] Britton, A., Singh-Manoux, A., Marmot, M. Alcohol consumption and cognitive function in the Whitehall II Study. American Journal of Epidemiology,2004 Aug 1;160(3):240-7.

[46] Launer LJ, Feskens EJ, Kalmijn S, Kromhout D Smoking, drinking, and thinking. The Zutphen Elderly Study American Journal of Epidemiology 1996 Feb 1;143(3):219-27

[47] Galanis, DJ; Joseph C, Masaki KH, Petrovitch H, Ross GW, White L A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia Aging Study American Journal of Public Health Vol 90, Issue 8 1254-1259

[48] Dufouil, Carole; Ducimetière, Pierre; Ducimetière, Pierre Sex Differences in the Association between Alcohol Consumption and Cognitive Performance American Journal of Epidemiology Vol. 146, No. 5: 405-412

[49] Rodgers, B., et al. Non-linear relationships between cognitive function and alcohol consumption in young, middle-aged and older adults: The PATH Through Life Project. Addiction, 2005, 100(9), 1280-1290; Anstey, K. J., et al. Lower cognitive test scores observed in alcohol are associated with demographic, personality, and biological factors: The PATH Through Life Project. Addiction, 2005, 100(9), 1291-1301.

[50] Mulkamal, K. J. et al. Prospective study of alcohol consumption and risk of dementia in older adults. Journal of the American Medical Association, 2003 (March 19), 289, 1405-1413.

[51] Ruitenberg, A., et al. Alcohol consumption and risk of demewntia: the Rotterdam Study. Lancet, 2002, 359(9303), 281-286.

[52] Ganguli, M., et al. Alcohol consumption and cognitive function in late life: A longitudinal community study. Neurology, 2005, 65, 1210-12-17.

[53] Antilla, Tiia, et al. Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study. British Medical Journal, 2004, 329, 538-539.

[54] Zuccala, G. , et al. Dose-related impact of alcohol consumption on cognitive function in advanced age: Results of a multicenter study. Alcoholism: Clinical and Experimental Research, 2001, 25, 1743-1748.

[55] Huang W, Qiu C, Winblad B, Fratiglioni L. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. Journal of Clinical Epidemiology, 2002, 55(10), 959-64.

[56] Stampfer, M.J., et al. Effects of moderate alcohol consumption on cognitive function in women. New England Journal of Medicine, 2005, 352, 245-253.

[57] Espeland, M., et al. Association between alcohol intake and domain-specific cognitive function in older women. Neuroepidemiology, 2006, 1(27), 1-12.

[58] Harrison, P.G. Moderate Drinking Helps Preserve Women's Brains. Reuters Health, June 15, 2001. See also Reuters, Associated Press, ABCNEWS, and HealthSCOUT of same date.

[59] McDougall, Graham. Older Women’s Cognitive and Affective Response to Moderate Drinking. Paper presented at the meetings of the National Congress on the State of Science in Nursing Research. Washington, DC, October 7-8, 2004.

[60] Solfrizzi, V. et al. Alcohol consumption, mild cognitive impairment, and progression to dementia. Neurology, 2007, 68(2)

[61] Cupples, LA; Weinberg, J; Beiser, A; Auerbach, SH; Volicer, L; Cipolloni, PB; Wells, J; Growdon, JH; DAgostino, RB; Wolf, PA; Farrer, LA Effects of smoking, alcohol and APOE genotype on Alzheimer disease: The MIRAGE study Alzheimer Report, 2000, 3, 105-114.

[62] Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area Revue neurologique (Paris). 1997 Apr;153(3):185-92.

[63] Andel, R., Hughes, T.F., & Crowe, M.G. (2005). Strategies to reduce the risk of cognitive decline and dementia. Aging Health, 1(1),107-116.

[64] Charles P. D., et al. Classification of tremor and update on treatment. American Family Physician, 1999, 59(6), 565-72; Bain, P. G., et al. A study of hereditary essential tremor. Brain, 1994, 117 (Pt 4), 805-24 ; Lou, J.S., & Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology, 1991, 41 (2 Pt 1), 234-8; Singer C, et al. Gait abnormality in essential tremor. Movement Disorders, 1994, 9(2), 193-6; Wasielewski PG, et al. Pharmacologic treatment of tremor. Movement Disorders, 1998, 13 (Suppl 3), 90-100; Boecker, H., et al. The effect of ethanol on alcoholic-responsive essential tremors: a positron emission tomography study. Annals of Neurology, 1996, 39, 650-658, 1996; Setting a steady course for benign essential tremor. The Johns Hopkins Medical Letter, 1999 (December), 11(10).

[65] Cordain, L;, Bryan, E D; Melby, C L; Smith, M J Influence of moderate daily wine consumption on body weight regulation and metabolism in healthy free-living males Journal of the American College of Nutrition 1997, Vol 16, Issue 2 134-139.

[66] (Arif, A. A. & Rohrer, J. E. Patterns of Alcohol Drinking and its Association with Obesity: Data from the Third National Health and Nutrition Examination Survey, 1988-1994 BMC Public Health, 2005 5 December), (5), 126.)

[67] National Institute on Alcohol Abuse and Alcoholism (NIAAA) Alcohol Research & Health Vol. 24, No. 1, 2000 Health Risks and Benefits of Alcohol Consumption (PDF)

[bode1-68] Bode, Christiane; Bode, J. Christiane Alcohol’s Role in Gastrointestinal Tract Disorders Alcohol Health & Research World Vol. 21, No. 1, 1997

[69] Sahi T, Paffenbarger RS Jr, Hsieh CC, Lee IM Body mass index, cigarette smoking, and other characteristics as predictors of self-reported, physician-diagnosed gallbladder disease in male college alumni American Journal of Epidemiology 1998 Apr 1;147(7):644-51

[70] Simon JA, Grady D, Snabes MC, Fong J, Hunninghake DB Ascorbic acid supplement use and the prevalence of gallbladder disease. Heart & Estrogen-Progestin Replacement Study (HERS) Research Group Journal of Clinical Epidemiology 1998 Mar;51(3):257-65

[71] La Vecchia C, Decarli A, Ferraroni M, Negri E Alcohol drinking and prevalence of self-reported gallstone disease in the 1983 Italian National Health Survey Epidemiology 1994 Sep;5(5):533-6

[72] Leitzmann MF, Giovannucci EL, Stampfer MJ, Spiegelman D, Colditz GA, Willett WC, Rimm EB Prospective study of alcohol consumption patterns in relation to symptomatic gallstone disease in men Alcohol: Clinical and Experimental Research 1999 May;23(5):835-41

[73] Hirvonen, Tero; Pietinen, Pirjo; Virtanen, Mikko; Albanes, Demetrius; Virtamo, Jarmo Nutrient Intake and Use of Beverages and the Risk of Kidney Stones among Male Smokers American Journal of Epidemiology Vol. 150, No. 2: 187-194

[74] Soucie, J. Michael; Coates, Ralph J; McClellan, William; Austin, Harland; Michael Thun Relation between Geographic Variability in Kidney Stones Prevalence and Risk Factors for Stones American Journal of Epidemiology Vol. 143, No. 5: 487-495

[75] Curhan GC, Willett WC, Rimm EB, Spiegelman D, Stampfer MJ Prospective study of beverage use and the risk of kidney stones American Journal of Epidemiology 1996 Feb 1;143(3):240-7

[76] Curhan GC, Willett WC, Speizer FE, Stampfer MJ Beverage use and risk for kidney stones in women Annals of Internal Medicine 1998 Apr 1;128(7):534-40

[77] Avogaro A, Watanabe RM, Dall'Arche A, De Kreutzenberg SV, Tiengo A, Pacini G. Acute alcohol consumption improves insulin action without affecting insulin secretion in type 2 diabetic subjects Diabetes Care, 2004 (June 6), 27(6), 1369-1374

[78] Rimm EB, Chan J, Stampfer MJ, Colditz GA, Willett WC Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men British Medical Journal 1995 Mar 4;310(6979):555-9

[79] Davies, Michael J; Baer, David J; Judd, Joseph T; Brown, Ellen D; Campbell, William S; Taylor, Philip R Effects of Moderate Alcohol Intake on Fasting Insulin and Glucose Concentrations and Insulin Sensitivity in Postmenopausal Women: A Randomized Controlled Trial Journal of the American Medical Association, 2002, 287(19), 2559-2562.

[80] Ajani, Umed A; Hennekens, Charles H; Spelsberg, Angela; Manson, JoAnn E Alcohol Consumption and Risk of Type 2 Diabetes Mellitus Among US Male Physicians Archives of Internal Medicine, 2000, 160, 1025-1050

[81] Sofia Carlsson, Niklas Hammar, Valdemar Grill, and Jaakko Kaprio Alcohol consumption and the incidence of type 2 diabetes: a 20-year follow-up of the Finnish Twin Cohort Study Diabetes Care, 2003, 26(10), 2785-2786.

[82] Turesson, Carl. Increased Alcohol Intake Associated with Decreased Risk of Developing Rheumatoid Arthritis. (Abstract) Paper presented at the annual European Congress of Rheumatology. Barcelona, Spain. June 13-16, 2007. European League Against Rheumatism, June 15, 2007; Myllykangas-Lusojarvi, R., Aho, K., Kautiainen, H., and Hakala, M. Reduced incidence of alcohol related deaths in subjects with rheumatoid arthritis. Annals of Rheumatoid Diseases, 2000, 59, 75-76; Voight, L., et al. Smoking, obesity, alcohol consumption and the risk of rheumatoid arthritis. Epidemiology, 1994, 5, 525-532.

[83] Siris, Ethel S; Miller, Paul D; Barrett-Connor, Elizabeth; Faulkner, Kenneth G; Wehren, Lois E; Abbott, Thomas A; Berger, Marc L; Santora, Arthur C; Sherwood, Louis M Identification and Fracture Outcomes of Undiagnosed Low Bone Mineral Density in Postmenopausal Women Journal of the American Medical Association, 2001;286:2815-2822

[84] Rapuri, Prema B; Gallagher, J Christopher; Balhorn, Kurt E; Ryschon, Kay L Alcohol intake and bone metabolism in elderly women American Journal of Clinical Nursing Vol. 72, No. 5, 1206-1213, November 2000

[85] Holbrook TL, Barrett-Connor E A prospective study of alcohol consumption and bone mineral density British Medical Journal 1993 Jun 5;306(6891):1506-9

[86] Desenclos JA, Klontz KC, Wilder MH, Gunn RA The protective effect of alcohol on the occurrence of epidemic oyster-borne hepatitis A Epidemiology 1992 Jul;3(4):371-4

[87] Weisse, Martin E; Eberly, Bardwell; Person, Donald A Wine as a digestive aid: comparative antimicrobial effects of bismuth salicylate and red and white wine British Medical Journal 1995;311:1657-1660 (23 December)

[88] Brenner, Hermann; Rothenbacher, Dietrich; Bode, Günter; Adler, Guido Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study British Medical Journal 1997;315:1489-1492 (6 December)

[89] Aldoori WH, Giovannucci EL, Stampfer MJ, Rimm EB, Wing AL, Willett WC A prospective study of alcohol, smoking, caffeine, and the risk of duodenal ulcer in men Epidemiology 1997 Jul;8(4):420-4.

[alert21-90] National Institute on Alcohol Abuse and Alcoholism Alcohol Alert No. 21 PH 345 July 1993

[91] National Toxicology Program Alcoholic Beverage Consumption: Known to be a human carcinogen First listed in the Ninth Report on Carcinogens (2000)(PDF)

[92] Burden of alcohol-related cancer substantial

[93] ttp://www2.potsdam.edu/hansondj/HealthIssues/references/1127400726.html

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