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CORK Bibliography: Alcohol, Beneficial Effects

100 citations. January 2003 to present

Prepared: March 2008

Arif AA; Rohrer JE. Patterns of alcohol drinking and its association with obesity: data from the third national health and nutrition examination survey, 1988-1994. BMC Public Health 5: article 126, 2005. (26 refs.)

Background: Recent reports suggest that alcohol use may have a protective effect on obesity. This study explores association between obesity and alcohol consumption in the non-smoking U.S. adult population. Methods: We analyzed data on a total of 8,236 respondents who participated in the Third National Health and Nutrition Examination Survey. Body mass index (weight-kg/height-m(2)) was derived from measured height and weight data and categorized into: normal weight, overweight, and obese. Alcohol consumption was measured using following measures: history of drinking, binge drinking, quantity of drinks/day, frequency of drinking, and average volume of drinks/week. Results: Mean body mass index in this sample of non-smokers was 26.4 (95% CI: 26.1, 26.7). Approximately 46% of respondents were classified as current drinkers. Current drinkers had lower odds of obesity (Adjusted odds ratio = 0.73, 95% CI: 0.55, 0.97) as compared to non-drinkers. The odds of overweight and obesity were significantly greater among binge drinkers and those consuming four or more drinks/day. However, those who reported drinking one or two drinks per day had 0.46 (95% CI: 0.34, 0.62) and 0.59 (95% CI: 0.41, 0.86) times the odds of obesity, respectively. Similarly, the odds of obesity were significantly lower among those who reported drinking frequently and consuming less than five drinks per week. The association between overweight and other alcohol measures was less pronounced. Conclusion: The results suggest further exploring the possible role of moderate alcohol drinking in controlling body weight in adults.

Austin GL; Galanko JA; Martin CF; Sandler RS. Moderate alcohol consumption protects against colorectal adenomas in smokers. Digestive Diseases and Sciences 53(1): 116-122, 2008. (27 refs.)

Background: Although some studies have shown an association between alcohol consumption and colorectal adenomas, the effect of moderate alcohol consumption is not well defined, nor is the interaction between alcohol and smoking. Aim: To investigate the relationship between different levels of alcohol consumption and colorectal adenomas and to determine whether smoking modifies this relationship. Methods Eligible patients who underwent a complete colonoscopy were included (179 cases and 466 controls). Alcohol consumption was obtained from a lifestyle questionnaire. Patients were divided into three groups: (1) Abstainers: 0 drinks/week; (2) Moderate drinkers: > 0 to < 7 drinks/week; (3) Heavy drinkers: > 7 drinks/week. Odds ratios (OR) were calculated using logistic regression, controlling for gender, age, body mass index, use of non-steroidal anti-inflammatory medications. Results were stratified by the number of years smoked. Results: The proportion of patients with adenomas was 29.6% in abstainers, 22.1% in moderate drinkers, and 36.7% in heavy drinkers. The relationship between alcohol consumption and colorectal adenomas varied significantly by smoking history. For individuals who had never smoked, heavy drinkers were at significantly increased odds of having an adenoma compared to moderate drinkers (OR 3.08; 95% CI: 1.50-6.32), while no difference was seen for abstainers (OR 0.99; 95% CI: 0.52-1.89). Similarly, among individuals who had smoked 1-14 years, heavy drinkers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.61; 95% CI: 1.04-6.51), and no difference was seen for abstainers (OR 1.02; 95% CI: 0.33-3.10). Somewhat unexpectedly, among individuals who had smoked for 15 or more years, abstainers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.04; 95% CI: 0.91-4.59), while heavy drinkers were not at increased odds of having an adenoma (OR 0.73; 95% CI: 0.27-1.97). Conclusions: Consumption of less than seven alcohol drinks per week does not increase the risk of having a colorectal adenoma. We found evidence in this study that moderate alcohol consumption among long-term smokers may potentially decrease the risk of an adenoma compared to abstainers.

Badia E; Sacanella E; Fernandez-Sola J; Nicolas JM; Antunez E; Rotilio D et al. Decreased tumor necrosis factor-induced adhesion of human monocytes to endothelial cells after moderate alcohol consumption. American Journal of Clinical Nutrition 80(1): 225-230, 2004. (31 refs.)

Background: Moderate alcohol consumption protects against ischemic heart disease, possibly through an antiinflammatory effect. However, little is known about the mechanisms by which alcohol may interfere in the development of atherosclerosis. Objective: We analyzed the effects of 2 alcoholic beverages with high (red wine) or low (gin) polyphenolic content on human monocyte adhesion to an endothelial cell line (Ea.hy926). Design: This was a randomized, crossover trial with 8 healthy men. After a washout period, the subjects received 30 g ethanol/d as red wine or gin for 28 d. Before and after each intervention, a dietary survey and laboratory analysis were performed. Adhesion of human monocytes to endothelial cells was measured in basal and stimulated [by tumor necrosis factor alpha (TNF-alpha)] conditions. Adhesion molecules involved in monocyte-endothelium interactions were determined on the cell surface. Results: The mean expression of very late activation antigen 4 on monocytes significantly decreased after red wine intake [by 18% (95% Cl: 33%, 3%); P = 0.022]. Monocyte adhesion significantly increased after TNF-alpha stimulation of endothelial cells. This increase, however, was 39% less (95% CI: 48%,35%; P = 0.049) after gin intake than after the respective washout period and was nearly abolished by red wine intake [96% less than after the respective washout period (95% Cl: 142%, 76%); P < 0.001]. The reduction after red wine intake was significantly different from that after gin intake (P = 0.014). Conclusions: TNF-alpha-induced adhesion of monocytes to endothelial cells was virtually abolished after red wine consumption but was only partially reduced after gin consumption. This effect may be due to the down-regulation of adhesion molecules on the monocyte surface.

Baglietto L; English DR; Hopper JL; Powles J; Giles GG. Average volume of alcohol consumed, type of beverage, drinking pattern and the risk of death from all causes. Alcohol and Alcoholism 41(6): 664-671, 2006. (38 refs.)

Background: The objective was to investigate associations between average volume of alcohol consumption, type of beverage and drinking pattern and all-cause mortality in the Melbourne Collaborative Cohort Study. Methods: Average consumption, including type of beverage, was estimated from beverage-specific questions on quantity and frequency of consumption. Pattern of consumption was estimated from a 7-day diary. During an average of 10.5 years of follow-up of 36 984 participants, 1971 deaths occurred. Results: For both men and women, mortality curves were J-shaped (nadir at 9-12 g/day of alcohol consumption; upper protective dose of 42-76 g/day). Wine consumption was associated with lower mortality (for men, minimum hazard ratio (HR) at 20-39 g/day of wine consumption: 0.69; 95% confidence interval (CI): 0.54-0.87; for women, minimum HR at 1-19 g/day: 0.82; 95% CI: 0.70-0.98). Beer was associated with an increased risk for men (test for trend, P = 0.05), but not for women. After adjustment for total amount of alcohol consumed, the number of drinking-days was inversely associated with the risk of dying in men (P-trend = 0.04). Conclusions: These results confirm previous findings about the effect of average volume of alcohol and type of beverage and suggest that drinking pattern is an independent risk factor for all-cause mortality.

2006, Medical Council on Alcohol

Bassus S; Mahnel R; Scholz T; Wegert W; Westrup D; Kirchmaier CM. Effect of dealcoholized beer (Bitburger Drive (R)) consumption on hemostasis in humans. Alcoholism: Clinical and Experimental Research 28(5): 786-791, 2004. (33 refs.)

Background: The beneficial effect of moderate alcohol consumption in lowering the risk of cardiovascular disease has been shown in several epidemiologic studies. Such studies have also shown, however, that the protective effect of alcoholic beverages like wine and beer is not only due to the ethanol content but also to the presence of nonalcoholic constituents. The positive effect of alcoholic beverages has been attributed to changes in lipoprotein metabolism, but there is substantial evidence that effects on hemostasis play an important role. Whether the effects of alcoholic beverages on hemostasis are due exclusively to ethanol or are due, in part, to nonalcoholic components, is still under debate.Methods: We have examined the hemostatic effects of 3 liters of beer, dealcoholized beer, and ethanol/water (v/v 4%), consumed over a period of 3 hr, in 12 young healthy volunteers. Platelet parameters CD62, PAC-1, and monocyte platelet aggregates were analyzed using flow cytometric measurements. The activity of factor VII was determined with a prothrombin time (PT) assay and plasminogen activator inhibitor activity using a chromogenic substrate. Thrombin generation was determined according to the method of Hemker. Results: All three fluids administered, dealcoholized beer, beer, and ethanol, reduced the expression of activated fibrinogen receptor, the platelet activation marker CD62, and the formation of monocyte-platelet-aggregate. In addition, dealcoholized beer also showed significant inhibitory effects on thrombin generation, whereas beer and ethanol showed procoagulatory effects.Conclusions: This study has shown that the acute consumption of dealcoholized beer inhibits thrombogenic activity in young adults. This action could have a beneficial effect on the development of coronary artery disease. Thus, the consumption of dealcoholized beer could provide cardiovascular benefit without the negative effects of alcohol.

Bau PFD; Bau CHD; Rosito GA; Manfroi WC; Fuchs FD. Alcohol consumption, cardiovascular health, and endothelial function markers. (review). Alcohol 41(7): 479-488, 2007. (108 refs.)

Cardiovascular diseases are among the worldwide leading causes of shorter life expectancy and loss of quality of life. Thus, any influence of diet or life habits on the cardiovascular system may have important implications for public health. Most world populations consume alcoholic beverages. Since alcohol may have both protective and harmful effects on cardiovascular health, the identification of biochemical mechanisms that could explain such paradoxical effects is warranted. The vascular endothelium is the target of important mediating pathways of differential ethanol concentrations, such as oxidative stress, lipoproteins, and insulin resistance. Alcohol-induced endothelial damage or protection may be related to the synthesis or action of several markers, such as nitric oxide, cortisol, endothelin-1, adhesion molecules, tumor necrosis factor alpha, interleukin-6, C-reactive protein, and haemostatic factors. The expression of these markers is consistent with the J-shaped curve between alcohol consumption and cardiovascular health. However, there is genetic and phenotypic heterogeneity in alcohol response, and despite the apparent beneficial biochemical effects of low doses of ethanol, there is not enough clinical and epidemiological evidence to allow the recommendation to consume alcoholic beverages for abstemious individuals. Considering the potential for addiction of alcoholic beverage consumption and other negative consequences of alcohol, it would be worthwhile to identify substances able to mimic the beneficial effects of low doses of ethanol without its adverse effects.

Beilin LJ; Puddey IB. Alcohol and cardiovascular disease: More than one paradox to consider. (editorial). Journal of Cardiovascular Risk 10(1): 1-3, 2003. (10 refs.)

Berridge V. Why alcohol is legal and other drugs are not: An examination of the relevance of past experiences to current policy-making. History Today 54(5): 18-20, 2004. (0 refs.)

All drugs, of whatever sort, have been legal or illegal at some stage in some societies, and forms of legal and regulatory control have varied. In England you could buy opiates over the counter until the 1860s, just as alcohol was available. Laudanum (opium dissolved in alcohol) was a semi-medical/ semi-recreational pick-me-up. This essay considers two questions: How can we make sense of these changes? Do they stem from the relative harmfulness of the substances concerned? And how can understanding of historical variety feed into current policy-making? There is discussion of two different, and at times divergent or convergent, perspectives, those of medicine and those involving legal controls.

Beutelspacher SC; Serbecic N; Tan PH; Mehrabi M; Nielsen P; Yamane Y. Low dose-ethanol modulates toxic effect of iron-overloading in the liver. Journal of Nutritional Science and Vitaminology 50(2): 78-86, 2004. (38 refs.)

The oxidant properties of iron-overload and simultaneous ethanol consumption have received much interest, due to evidence reporting from hereditary hemochromatosis (HC). The full form of this disease is often associated with chronic alcoholism. An additive effect of toxicity of iron and ethanol was assumed. In this study, we examined nutritively iron-loaded Wistar rats (n = 5 9) (TMH-Ferrocene) additionally fed with ethanol up to 8 % in drinking water for 3 6 wk. Methods: By reverse-phase HPLC we measured the concentration of ascorbic acid, tocopherole and retinol in serum and liver homogenates as well as transaminases in the serum. Lipid peroxidation was assessed utilizing the ethane-exhalation method. Iron concentration in the liver was measured with the Bathophenanthrolin-method. Liver histology was performed to investigate the iron deposits and the organ damage (H.E., Azan and Berlin-blue-stainings). Results: 1. Vitamin C: A linear decrease of the concentration of vitamin C in serum and liver was found independent of alcohol and iron uptake. 2. Vitamin E: Animals fed iron and alcohol showed elevated vitamin E concentrations in the serum but not in the liver. 3. Vitamin A: Elevated levels in serum but strongly decreasing levels in liver could be measured. 4. Histology: All iron-fed animals showed massive deposits of iron in the liver. Iron diet caused liver cirrhosis, while an additional administration of ethanol Could prevent this. 5. Lipid peroxidation increased in animals fed ethanol and iron, but was significantly lower in animals only receiving an iron diet. Conclusion: Evidence indicates that the additional exposition to ethanol in iron-loaded animals could modulate the organ damage and oxidative stress. The biochemical findings are positively correlated to the histology.

Beyer S. Cardiovascular disease in alcohol abusers. Journal of Addictions Nursing 15(2): 75-79, 2004. (20 refs.)

Moderate alcohol use (two or fewer drinks daily) may offer some degree of protection from coronary artery disease and stroke. Any potential benefit must be weighed against an individual's risk profile for alcohol abuse or dependence and the associated health and social consequences. Health costs of alcohol abuse are well into the billions. Heavy alcohol consumption is associated with cardiomyopathy, arrhythmias, hypertension, stroke, and sudden death. Alcohol is the major cause of nonischemic cardiomyopathy in the Western world. In any health care setting, education about the potential risks and benefits of alcohol use must be provided with health promotion and maintenance strategies tailored to the individual.

Bobak M; Marmot M. Wine and heart disease: A statistical approach. IN: Sandler M; Pinder R, eds. Wine: A Scientific Exploration. London: Taylor and Francis, Inc., 2003. pp. 92-107. (49 refs.)

That wine is protective against heart disease has become part of the conventional wisdom. the beneficial effect is seen as a property of the wine than from the ethanol per se. This chapter review the evidence linking the consumption of wine, and of alcohol in general, with a reduced risk of coronary heart disease. The discussion is confronted by the issue of the pattern of drinking. Recent studies have begun to question whether regular or episodic drinking has differential effects, and this is taken into account. The chapter considers alcohol use and all cause mortality; the relationship of alcohol and cardiovascular disease; and whether wine is more cardioprotective than ethanol.

Britton A. How much and how often should we drink? Interpret with caution new evidence on frequency and amount of men's drinking. (editorial). British Medical Journal 332(7552): 1224-1225, 2006. (4 refs.)

Britton A; Marmot M. Different measures of alcohol consumption and risk of coronary heart disease and all-cause mortality: 11-year follow-up of the Whitehall II Cohort. Addiction 99(1): 109-116, 2004. (29 refs.)

Aims: To investigate the relationship between three measures of alcohol consumption obtained simultaneously in a large cohort and the validated risk of coronary heart disease and all-cause mortality during follow-up. Design: Prospective cohort study with median follow-up of 11 years. Setting: The Whitehall II Cohort Study: London-based civil service. Participants: A total of 10 308 (33% female) civil servants aged 35-55 years at baseline (1985-88). Measurements: Self-reported volume of alcohol consumed during past week, frequency of drinking over past year, usual amount consumed per drinking session. Main outcome measures: Coronary heart disease and all-cause mortality until 1999. Findings: A U-shaped relationship was found between volume of alcohol consumed per week and outcome. Compared to those who drank moderately (10-80 g alcohol per week), non-drinkers and those drinking more than 248 g per week had approximately a twofold increased risk of mortality. The optimal frequency of drinking was between once or twice a week and daily, after adjustment for average volume consumed per week. Those drinking twice a day or more had an increased risk of mortality (male hazard ratio 2.44 95% CI 1.31-4.52) compared to those drinking once or twice a week. Drinking only once a month or only on special occasions had a 50% increased risk of mortality. The usual amount consumed per drinking session was not indicative of increased health risk in this cohort. Conclusions: Epidemiological studies should collect information on frequency of drinking in addition to average volume consumed in order to inform sensible drinking advice.

Britton A; Singh-Manoux A; Marmot M. Alcohol consumption and cognitive function in the Whitehall II study. American Journal of Epidemiology 160(3): 240-247, 2004. (36 refs.)

The authors investigated the relation between alcohol consumption and cognitive function in a United Kingdom cohort study (4,272 men, 1,761 women) with median follow-up of 11 years. Measures of alcohol consumption were obtained at baseline (1985-1988) and four subsequent phases of data collection. Cognitive function (memory test, AH4, Mill-Hill, phonemic and semantic fluency) was assessed at phase 5 (1997-1999), when participants were aged 46-68 years. Of people who reported drinking alcohol in the past year, those who consumed at least one drink in the past 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). The effect was stronger for women than men and was not confined to those with evidence of vascular disease. Similar associations were found in cross-sectional and longitudinal analyses. The relations were not explained by confounding by smoking and by physical and mental health and, to a large extent, were not mediated by cholesterol or blood pressure. However, the relations were weakened when social position was added to the model. The authors concluded that for middle-aged subjects, increasing levels of alcohol consumption were associated with better function regarding some aspects of cognition. Nonetheless, it is not proposed that these findings be used to encourage increased alcohol consumption.

Bulpitt CJ. How many alcoholic drinks might benefit an older person with hypertension? (review). Journal of Hypertension 23(11): 1947-1951, 2005. (29 refs.)

Lowering alcohol intake reduces blood pressure and hence cardiovascular risk. However, abstainers have an increase in cardiovascular risk and the advice to reduce intake to low levels may not be sound. This review examines the effects of lowering alcohol consumption in terms of blood pressure and coronary heart disease (CHD). The relationship between both CHD and stroke and alcohol consumption, and the benefits and disadvantages of alcohol consumption in the general population, are discussed. Where available, the results of large meta-analyses are reported. It is concluded that the hypertensive patient over the age of 60 who drinks over 16 drinks per week should be advised to reduce his or her alcohol intake but a daily drink may be advisable and the patient should not stop drinking entirely. It is not suggested that the non-drinker should start drinking, but most hypertensives are over the age of 60 when community studies suggest that drinking alcohol does more good than harm.

Burger M; Bronstrup A; Pietrzik K. Derivation of tolerable upper alcohol intake levels in Germany: A systematic review of risks and benefits of moderate alcohol consumption. Preventive Medicine 39(1): 111-127, 2004. (292 refs.)

Background. The objective of this study is to weigh the risks of moderate alcohol consumption against its benefits and, as a result, to derive tolerable upper alcohol intake levels (TUALs) for the German adult population. Methods. Human studies assessing the effects of moderate alcohol consumption (less than or equal to40 g/day) on coronary heart disease, stroke, blood pressure, diseases of the liver, gallbladder, bile duct, and pancreas, cancer of the mouth/pharynx/larynx/oesophagus, stomach, colon/rectum, and breast, foetal alcohol syndrome/foetal alcohol effects, as well as all-cause mortality, published in the 10-15 years before 1999, have been systematically reviewed. The quality of studies has been evaluated using a self-constructed evaluation scheme. As a result of comparing the critical endpoints of alcohol intake related to morbidity and mortality, the TUALs have been derived. Results. The TUALs have been set at 10-12 g/day for healthy women and 20-24 g/day for healthy men of the adult population (18 years and older). Additional guidelines on alcohol use have been defined, taking into account further important aspects like alcohol consumption patterns and high-risk groups. Conclusions. The TUALs are not intended to be recommended intake levels. However, if the TUALs and the additional guidelines are followed, a relation of alcohol consumption to an increased risk of alcohol-associated diseases is unlikely for the majority of the population.

Connor J. The life and times of the J-shaped curve. (editorial). Alcohol and Alcoholism 41(6): 583-584, 2006. (15 refs.)

Cooper KA; Chopra M; Thurnham DI. Wine polyphenols and promotion of cardiac health. (review). Nutrition Research Reviews 17(1): 111-129, 2004. (139 refs.)

Wine polyphenols are considered to have beneficial effects on CHD and atherosclerosis. The consumption of red wine is high in Italy and France, approximately four times greater than that in the UK. This disparity in red wine consumption is thought to be the reason for the 'French paradox', where France was shown to have a coronary mortality rate close to that of China or Japan despite saturated fat intakes and cholesterol levels similar to the UK and USA. In the present review, we discuss the effects of wine and some of its polyphenol constituents on early pathological indicators of CHD such as plasma lipids, the endothelium and vasculature, platelets and serum antioxidant activity. The review also examines whether the polyphenols or the alcohol in wine is responsible for the effects on markers of heart disease. The present review concludes that red wine polyphenols have little effect on plasma lipid concentrations but wine consumption appears to reduce the susceptibility of LDL to oxidation and increase serum antioxidant capacity. However, these effects do depend on the amount of wine and period of supplementation. Authors who have examined specific polyphenols suggest that some phenolics appear to have endothelium-dependent vaso-relaxing abilities and some a positive effect on NO concentrations. Red wine phenolics also have an inhibitory effect on platelet aggregation, and individual phenolics also have a similar effect in vitro, although it should be noted that there are often discrepancies as large as ten-fold between the concentrations of polyphenolics tested in vitro and their measured levels in vivo. Evidence suggests that alcohol has a positive synergistic effect with wine polyphenols on some atherosclerotic risk factors. Thus evidence that wine drinking is beneficial for cardiac health continues to accumulate but more research is required to understand fully and exactly the functions of red wine polyphenols.

De La Zerda DJ; Cohen O; Beygui RE; Kobashigawa J; Hekmat D; Laks H. Alcohol use in donors is a protective factor on recipients' outcome after heart transplantation. Transplantation 83(9): 1214-1218, 2007. (15 refs.)

Objective. The outcome of heart transplantation is highly influenced by good donor selection. Because a history of alcoholism is prevalent among potential heart donors, we sought to explore the effect of alcohol use in donors on the outcome of heart transplantation in the recipient. Method. A total of 437 consecutive patients underwent heart transplantation from January 2002 through September 2005. Patients' files were retrospectively studied. Mean follow-up period was 3.14-+/- 1.9 years (range, 3 days to 6.5 yrs). The cohort was divided into two subgroups. The alcoholic donor group (ADG) included 98 of 421 patients and the nonalcoholic donor group (NADG) included 323 of 421 patients. Mean age was 35.3 +/- 11.4 yrs (range, 18-66) for the ADG and 33 +/- 12.2 yrs (range, 18-62) for the NADG. Results. Mortality among the ADG was 7 of 98 (7.1%) and for NADG was 55 of 323 (17.1%) (P=0.015). The mean interval time between transplant and mortality was, for ADG, 27.7 +/- 20.6 months (range, 0.07-51) and for NADG, 16.4 +/- 19.6 months (range, 0.14-73) (P=0.031). Survival rate was significantly higher among the ADG at 72.8 +/- 1.9 months compared with NADG at 66.2 +/- 1.5 months (P=0.019). Overall rejection rate was 22 of 421 (5.2%); rejection rate was 17 of 323 (5.2%) in NADG and 5 of 98 (5.1%) in ADG. Rejection free survival was 74.6 +/- 0.85 with no significant difference between the two groups (P=0.85). Conclusion. The chronic alcoholism of donors was found to be a protective factor regarding the outcome after heart transplantation. Significant differences were found in mortality rate and survival after heart transplantation between the ADG and NADG. These data support the fact that it is safe to use donors' hearts regardless of a history of alcoholism.

de Lorgeril M; Salen P; Martin JL; Boucher F; de Leiris J. Interactions of wine drinking with omega-3 fatty acids in patients with coronary heart disease: A fish-like effect of moderate wine drinking. American Heart Journal 155(1): 175-181, 2008. (27 refs.)

Background: Moderate alcohol drinking and marine omega-3 fatty acids (omega 3) have both been associated with low mortality from coronary heart disease (CHD). However, there is little data evaluating the interactions of wine ethanol drinking with omega 3 in CHD patients. Methods The relationships between wine drinking and marine omega 3 were evaluated in a cross-sectional study in patients with CHD participating in a randomized trial testing the effect of a high alpha-linolenic acid (ALA, the main plant omega 3) diet. Daily ethanol intake was calculated as energy and expressed as a percentage of total energy. Plant and marine omega 3 in the diet were carefully evaluated in each patient in both groups. Results: Patients were classified according to their habitual consumption of ethanol. Patients in the "high ALA group" and controls ("low ALA group") were analyzed separately. Within each group, there was a progressive increase in marine omega 3 levels with increased alcohol intake, with a level of eicosapentanoic acid (EPA) that increased by 50% (P < .005) and 37% (P < .05) in the low and high ALA groups, respectively. After controlling for potential confounders (including dietary EPA) in a multivariate linear model, the association between wine ethanol and EPA remained significant in the low (P < .001) and high (P < .05) ALA groups. Conclusion: In these patients with CHD, moderate wine drinking was associated with higher marine omega 3 concentrations than no alcohol use. Although the data have to be confirmed in large groups, this effect of wine comparable to that of fish may partly explain the protective effects of wine drinking against CHD.

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. (review). Archives of Internal Medicine 166(22): 2437-2445, 2006. (58 refs.)

Background: Moderate consumption of alcohol is inversely related with coronary disease, but its association with mortality is controversial. We performed a meta-analysis of prospective studies on alcohol dosing and total mortality. Methods: We searched PubMed for articles available until December 2005, supplemented by references from the selected articles. Thirty-four studies on men and women, for a total of 1,015 835 subjects and 94,533 deaths, were selected. Data were pooled with a weighed regression analysis of fractional polynomials. Results: AJ-shaped relationship between alcohol and total mortality was confirmed in adjusted studies, in both men and women. Consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was inversely associated with total mortality, maximum protection being 18% in women (99% confidence interval, 13%-22%) and 17% in men (99% confidence interval, 15%-19%). Higher doses of alcohol were associated with increased mortality. The inverse association in women disappeared at doses lower than in men. When adjusted and unadjusted data were compared, the maximum protection was only reduced from 19% to 16%. The degree of association in men was lower in the United States than in Europe. Conclusions: Low levels of alcohol intake (1-2 drinks per day for women and 2-4 drinks per day for men) are inversely associated with total mortality in both men and women. Our findings, while confirming the hazards of excess drinking, indicate potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival.

2006, American Medical Association

Djousse L; Gaziano JM. Alcohol consumption and risk of heart failure in the Physicians' Health Study I. Circulation 115(1): 34-39, 2007. (31 refs.)

Background - Heart failure is the leading cause of hospitalization among the elderly, and 1 in 5 adults aged 40 years will develop heart failure in their lifetime. Data on the effects of moderate alcohol consumption on the risk of heart failure have been sparse and inconsistent. This study sought to evaluate the association between moderate alcohol consumption and incident heart failure. Methods and Results - A total of 21,601 participants of the Physicians' Health Study I who were free of heart failure and provided data on alcohol intake at baseline were prospectively followed up from 1982 to 2005. Incident heart failure cases were ascertained through annual follow-up questionnaires and validated with the use of Framingham criteria. During an average follow-up of 18.4 years, 904 incident cases of heart failure occurred. The crude incidence rates of heart failure were 25.0, 20.0, 24.3, and 20.6 cases per 10,000 person-years for alcohol categories of < 1, 1 to 4, 5 to 7, and > 7 drinks per week, respectively. Corresponding hazard ratios ( 95% CI) were 1.0 (reference), 0.90 (0.76 to 1.07), 0.84 (0.71 to 0.99), and 0.62 (0.41 to 0.96), respectively, with P for trend = 0.012 adjusted for age, body mass index, smoking, and history of valvular heart disease. There was no evidence for a strong association between moderate alcohol consumption and heart failure without antecedent coronary artery disease. Conclusions: Although heavy drinking should be discouraged, our data indicate that moderate drinking may lower the risk of heart failure. The lack of an association between moderate alcohol intake and heart failure without antecedent coronary artery disease suggests that possible benefits of moderate drinking on heart failure may be mediated through beneficial effects of alcohol on coronary artery disease.

2007, Lippincott, Williams & Wilkins

Donaldson IM. Bon sante: is wine good for your health? (editorial). Internal Medicine Journal 34(5): 221-223, 2004. (55 refs.)

Evans A; Marques-Vidal P; Ducimetiere P; Montaye M; Arveiler D; Bingham A et al. Patterns of alcohol consumption and cardiovascular risk in northern Ireland and France. Annals of Epidemiology 17(5, Supplement S): S75-S80, 2007. (27 refs.)

The PRIME Study was begun in 1991 and recruited 10,600 men aged 50 to 59 years in the WHO MONICA Project centers of Belfast, Lille, Strasbourg and Toulouse. Although drinkers in France and Northern Ireland consumed almost identical amounts, the pattern of consumption was different. In Northern Ireland beer and spirits were the staple beverages, whereas in France it was predominantly red wine; in France, 90% of men drank at least one unit per week versus 61% in Northern Ireland. Frenchmen drank evenly throughout the week, whereas in Northern Ireland two thirds of the consumption took place on Friday and Saturday nights. In the 5-year follow up of PRIME in France, the usual cardiovascular protective effect of increasing consumption (up to 45 units per week) was shown and the level of significance for trend in consumption was highly significant (p = 0.006); in Northern Ireland, this pattern was less consistent and did not attain significance. It remains a matter of conjecture whether in Northern Ireland the beneficial effects of alcohol consumption were annulled by a pattern of drinking that increases blood pressure, a well-established risk factor for heart disease, or whether the protection in France resulted from the consumption of wine along with food.

Femia R; Natali A; L'Abbate A; Ferrannini E. Coronary atherosclerosis and alcohol consumption: Angiographic and mortality data. Arteriosclerosis, Thrombosis, and Vascular Biology 26(7): 1607-1612, 2006. (34 refs.)

Objective - Moderate alcohol consumption is associated with reduced cardiovascular disease (CVD) risk. Whether this protection is based on a lesser degree of coronary atherosclerosis has not been established. Methods and Results - We studied 1676 men and 465 women consecutively undergoing coronary angiography. A score (ATS) was calculated by summing the percent lumen narrowing of all main vessels; alcohol consumption was quantitated by questionnaire. In univariate analysis, ATS was significantly (P <= 0.001) associated with male sex, age, familial CVD, smoking, diabetes, hypertension, and serum cholesterol levels; alcohol consumption was associated with less frequent diabetes (P < 0.001) and lower ATS (P=0.02). By multivariate analysis, alcohol intake was associated with lower ATS (P < 0.01) independently of the other risk factors; the estimated effect size was comparable to that associated with a 1-mmol decrement in serum cholesterol. Over a median follow-up of 93 months, 37 women and 194 men died from a cardiac cause. By Cox analysis, positive predictors for cardiac mortality were male sex (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1 to 2.6]), age (HR, 2.1; 95% CI, 1.8 to 2.5 per decade) and diabetes (HR, 1.7; 95% CI, 1.2 to 2.4), whereas alcohol consumption was the only negative predictor (HR, 0.84; 95% CI, 0.71 to 1.00). Conclusions - In a selected high-risk population, moderate alcohol consumption was independently associated with less coronary atherosclerosis and lower risk for cardiac mortality.

2006, Lippincott, Williams & Wilkins

Ferreira I; Twisk JWR; van; Mechelen W; Kemper HCG; Stehouwer CDA. Development of fatness, fitness, and litestyle from adolescence to the age of 36 years - Determinants of the metabolic syndrome in young adults: The Amsterdam growth and health longitudinal study. Archives of Internal Medicine 165(1): 42-48, 2005. (47 refs.)

Background: Among young adults, the metabolic syndrome is an increasingly frequent risk factor for cardiovascular disease. Its determinants are, however, incompletely understood. We investigated the time course, from adolescence (age, 13 years) to young adulthood (age, 36 years), of important potential determinants (body fatness and fat distribution, cardiopulmonary fitness, and lifestyle) in 364 individuals (189 women). Methods: Data were derived from the Amsterdam Growth and Health Longitudinal Study and analyzed with the use of generalized estimating equations. Results: The prevalence of the metabolic syndrome at the age of 36 years, as identified with a modified National Cholesterol Education Program definition of the syndrome, was 10.4%. Subjects with the metabolic syndrome at the age of 36 years, compared with those without the syndrome, had (from adolescence to the age of 36 years) the following: (1) a more marked increase in total body fatness and in subcutaneous trunk fat; (2) a more marked decrease in cardiopulmonary fitness levels; (3) a more marked increase inphysical activities of light-to-moderate intensity, but a more marked decrease in hard physical activities; (4) a trend toward a higher energy intake throughout the years; and (5) a decreased likelihood of drinking alcoholic beverages. Conclusions: Fatness, fitness, and lifestyle are important determinants of the metabolic syndrome in young adults. More important, these associations were independent of each other and, therefore, represent separate potential targets for the prevention of the metabolic syndrome. Our study further suggests that intervening early in life (eg, in the period of transition from adolescence to adulthood) may be a fruitful area for prevention of the metabolic syndrome.

Fuchs FD; Chambless LE. Is the cardioprotective effect of alcohol real? (review). Alcohol 41(6): 399-402, 2007. (43 refs.)

A large number of investigations in experimental, clinical, and epidemiological settings have given support to the idea that consumption of moderate amounts of alcoholic beverages, particularly wine, protects against coronary heart disease (CHD). Biological effects of other components of wine in human beings, however, have been hardly demonstrated, and alcohol itself has several potential adverse effects on the cardiovascular system. Not all epidemiological surveys have found protection from alcoholic beverages and in African-Americans, alcohol consumption was a risk factor for the incidence of CHD. The possibility that the lower risk of drinkers of moderate amounts of wine or other beverages is secondary to a health cohort effect in whites is not negligible, and could be discarded only in a clinical trial. In view of the potential risks of alcohol, a more cautious view about the beneficial effects of alcoholic beverages is warranted.

Fuchs FD; Chambless LE; Folsom AR; Eigenbrodt ML; Duncan BB; Gilbert A et al. Association between alcoholic beverage consumption and incidence of coronary heart disease in whites and blacks: The Atherosclerosis Risk in Communities Study. American Journal of Epidemiology 160(5): 466-474, 2004. (57 refs.)

The authors evaluated the relation between consumption of alcoholic beverages and incidence of coronary heart disease in White and African-American participants in the Atherosclerosis Risk in Communities Study. The average duration of follow-up was 9.8 years between 1987 and 1998. The association was analyzed by means of Cox proportional hazards regression models. The authors found a positive association between ethanol consumption and incident coronary heart disease for Black men (for a 13-g/day increment in ethanol consumption, adjusted hazard ratio (HR) = 1.13, 95% confidence interval (CI): 1.01, 1.28) and an inverse association for White men (HR = 0.88, 95% CI: 0.79, 0.99). There was an inverse association of coronary heart disease with rare drinking (HR = 0.47, 95% CI: 0.28, 0.80) and with consumption of greater than or equal to70 g of ethanol per week (HR = 0.49, 95% CI: 0.24, 0.98) in White women and with consumption of greater than or equal to210 g/week (HR = 0.56, 95% CI: 0.33, 0.95) in White men. In Black men, the association was positive for consumption of 140-<210 g/week (HR = 2.61, 95% CI: 1.11, 6.17). The contrasting findings in Whites and Black men in this cohort raise the question of whether the cardioprotective effect of alcohol is real or may be confounded by lifestyle characteristics of drinkers.

Ganguli M; Bilt JV; Saxton JA; Shen C; Dodge HH. Alcohol consumption and cognitive function in late life: A longitudinal community study. Neurology 65(8): 1210-1217, 2005. (75 refs.)

Objective: To examine the association between alcohol use and cognitive decline in a longitudinal study of a representative elderly community sample free of dementia at baseline. Methods: Cognitive functions and self-reported drinking habits were assessed at 2-year intervals over an average of 7 years of follow-up. Cognitive measures, grouped into composites, were examined in association with alcohol consumption. Trajectory analyses identified latent homogeneous groups with respect to alcohol use frequency over time, and their association with average decline over the same period in each cognitive domain. Models controlled for age, sex, education, depression, smoking, general mental status (Mini-Mental State Examination [MMSE]), performance on the given test at baseline, and subsequent new-onset dementia during follow-up. Results: The authors found three homogeneous trajectories that they characterized as no drinking, minimal drinking, and moderate drinking. Few heavy drinkers were identified in this elderly cohort. Compared to no drinking, both minimal and moderate drinking were associated with lesser decline on the MMSE and Trailmaking tests. Minimal drinking was also associated with lesser decline on tests of learning and naming. These associations were more pronounced when comparing current drinkers to former drinkers (quitters) than to lifelong abstainers. Conclusion: In a representative elderly cohort over an average of 7 years, a pattern of mild-to-moderate drinking, compared to not drinking, was associated with lesser average decline in cognitive domains over the same period.

Gerhauser C. Beer constituents as potential cancer chemopreventive agents. (review). European Journal of Cancer 41(13): 1941-1954, 2005. (116 refs.)

Beer is a complex alcoholic beverage made from barley (malt), hop, water and yeast. Phenolic constituents of beer are derived from malt (70-80%) and hop (20-30%). Structural classes include simple phenols, benzoic- and cinnamic acid derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins, (prenylated) chalcones and flavonoids as well as alpha- and iso-alphaacids derived from hop. Compounds belonging to different structural classes have distinct profiles of biological activity in in vitro test systems, and in combination might lead to enhanced effects. Scientific evidence has accumulated over the past 10 years pointing to the cancer preventive potential of selected hop-derived beer constituents, i.e., prenylflavonoids including xanthohumol and isoxanthohumol, and hop bitter acids. Chemopreventive activities observed with these compounds relevant to inhibition of carcinogenesis at the initiation, promotion and progression phases, as well as results from in vivo studies on metabolism, bioavailability and efficacy are summarised in this review.

Gmel G; Gutjahr E; Rehm J. How stable is the risk curve between alcohol and all-cause mortality and what factors influence the shape? A precision-weighted hierarchical meta-analysis. European Journal of Epidemiology 18(7): 631-642, 2003. (86 refs.)

Objective: To determine the influence of six determining variables on the shape of the risk curve between alcohol and all-cause mortality. Methods: Data: Based on a systematic search with clear inclusion criteria, all articles on alcohol and all-cause mortality until 2000 were included. Statistical methods: Precision-weighted pooling of relative risks (RRs); precision-weighted hierarchical analysis. Variables: For pooling: RRs for different categories of average volume of drinking, lifetime abstainers and ex-drinkers. For hierarchical analysis: on first level: consumption in grams of pure alcohol per day; on second level: length of follow-up time in months; per capita consumption; average age, proportion of abstainers, average volume of drinking, and variability of average volume of drinking at baseline. Outcomes measures: RR of former and current drinkers for all-cause mortality compared to abstainers. Results: The main hypotheses could be confirmed for males: Ex-drinkers had a higher mortality risk than lifetime abstainers; the higher and the more diverse the average volume of alcohol consumption, the wider the dip of the curve; the older the persons at baseline, the more pronounced the protective effect; and the longer the follow-up time, the less pronounced the protective effect. Except for average volume of drinking effects for females went in the same direction but with one exception did not reach significance. Conclusions: There are systematic influences on the shape of the risk curve between alcohol and all-cause mortality. The overall beneficial effect of light to moderate drinking remained under all scenarios, indicating a high validity of the overall shape despite the heterogeneity between studies.

Goldberg DM; Soleas GJ. Resveratrol: Biochemistry, cell biology and the potential role in disease prevention. IN: Sandler M; Pinder R, eds. Wine: A Scientific Exploration. London: Taylor and Francis, Inc., 2003. pp. 160-198. (189 refs.)

Resveratrol, a recently identified constituent of wine (1992), was hypothesized as in large measure responsibly for the putative health benefits of red wine. However, early studies seemed not to support the initial enthusiasm. This article is a literature review. It covers inflammation and atherosclerosis; cell growth, proliferation and cancer; antioxidant activity; vascular relaxation and nitric oxide production; oestorgenic activity; as well as bioavailability and absorption. In conclusion, the authors are of the opinion that it is unlikely wine can provide sufficient amounts to be present in biologically useful concentrations, due to the rapid excretion. However, it is possible that large-scale production of resvertatrol may be possible for pharmaceutical purposes.

Gorinstein S; Trakhtenberg S. Alcohol beverages and biochemical changes in blood. (review). Addiction Biology 8(4): 445-454, 2003. (101 refs.)

Coronary atherosclerosis is the major cause of death in western civilization: one of every three in men as well as in women. It was shown that diets supplemented with moderate quantities of alcoholic beverages could lead to positive biochemical changes in blood of the consumers, which are regarded widely as indicators of improved prevention of atherosclerosis. This review summarizes the recent epidemiological, experimental and clinical investigations concerning mainly the plasma biochemical changes in lipid levels, anticoagulant and antioxidant activities.

Gronbaek M. Confounders of the relation between type of alcohol and cardiovascular disease. Annals of Epidemiology 17(5, Supplement S): S13-S15, 2007. (20 refs.)

There have been numerous reports from epidemiologic studies showing that moderate drinkers have lower rates of cardiovascular disease (CVD) than do those who drink heavily or not at all. A number of scientific reports from scientists around the world suggest confounding may play a role in the reported beneficial health effects associated with moderate drinking. Among potentially confounding variables for these reported associations are the frequency of alcohol consumption, drinking pattern (steady or binge drinking), type of beverage, and differences in the pattern of drinking associated with different types of beverages. In some papers, individuals who report primarily wine consumption have been shown to be at lower risk of CVD and total mortality, and there is evidence for greater beneficial effects from more frequent, regular drinking. However, other potential confounders include better cognitive function, higher socioeconomic status, better subjective health, and a healthier diet, including food purchases, all of which are more common in regular drinkers and wine drinkers. Thus, the question of whether the beneficial effects of beverage types differ, with additional benefits for wine, remains unresolved.

Gunzerath L; Faden V; Zakhari S; Warren K. National Institute on Alcohol Abuse and Alcoholism Report on Moderate Drinking. (editorial). Alcoholism: Clinical and Experimental Research 28(6): 829-847, 2004. (223 refs.)

In support of the 2005 update of the U.S. Department of Agriculture/U.S. Department of Health and Human Services Dietary Guidelines, the National Institute on Alcohol Abuse and Alcoholism was asked to assess the strength of the evidence related to health risks and potential benefits of moderate alcohol consumption, with particular focus on the areas of cardiovascular disease, breast cancer, obesity, birth defects, breastfeeding, and aging. The findings were reviewed by external researchers with extensive research backgrounds on the consequences and benefits of alcohol consumption. This report now serves as the National Institutes of Health's formal position paper on the health risks and potential benefits of moderate alcohol use.

Harding R; Stockley CS. Communicating through government agencies. Annals of Epidemiology 17(5, Supplement S): S98-S102, 2007. (38 refs.)

A comparison of worldwide recommendations on alcohol consumption reveals wide disparity among countries. This could imply that many of the recommendations do not adequately accommodate the science, given that the science is equally valid worldwide. Such a view, however, would be an oversimplification of the problem that those who formulate such guidelines face. The objective of guidelines is to influence and change behavior among target populations. It follows, therefore, that several factors then become relevant: behavior that is thought to be in need of change, the culture and mindset of the target populations, and the kind of message that is likely to be effective. There are some tensions between advice intended only to reduce the prevalence of misuse and that which also seeks to reflect the evidence on the beneficial health effects of moderate consumption.

Heath DB. Why we don't know more about the social benefits of moderate drinking. Annals of Epidemiology 17(5, Supplement S): S71-S74, 2007. (23 refs.)

The scientific literature about drinking shows that a preoccupation with the harms that occasionally befall those who drink too much or too fast is coupled with a virtual ignorance (in both senses of that term) about the benefits that more often accrue to the vast majority who are moderate drinkers. It is ironic that reviews of the subject that appear under the World Health Organization (WHO) imprint have paid almost no attention to two thirds of WHO's definition of health: "...mental and social well-being...," while focusing overwhelmingly on the physical aspects. This imbalance is so striking that in a recent WHO-affiliated publication the authors suggested that social consequences may be "the forgotten dimension." This, despite the fact that drinking plays very important roles in many societies with respect to such widely recognized and appreciated benefits as celebration, relaxation, sociability, enhancement of food, concretization of the social order, and time out, in addition to medical and therapeutic benefits. The time is ripe for increasing collaboration to investigate such social benefits in ways that would be of greater interest and of use to those who heretofore have neglected them.

Hendriks HFJ. Moderate alcohol consumption and insulin sensitivity: Observations and possible mechanisms. Annals of Epidemiology 17(5, Supplement S): S40-S42, 2007. (13 refs.)

Light to moderate alcohol consumption is associated with a reduced risk for cardiovascular diseases. Epidemiologic studies, like our analysis of the European Prospective Investigation into Cancer and Nutrition study, suggest that moderate alcohol consumption is also associated with a reduced risk of type 2 diabetes, reported for various populations. This risk reduction may be explained by an increase in insulin sensitivity after moderate alcohol consumption. Indeed, a positive association between alcohol consumption and insulin sensitivity is consistently reported in cross-sectional studies. Mechanisms for the effect of alcohol on insulin sensitivity may include modulation of changes in the endocrine functioning of fat tissue, modulation of the inflammatory status of several organs, and/or modulation of glucose and fatty acid metabolism.

Heng K; Hargarten S; LAyde P; Craven A; Zhu S. Moderate alcohol intake and motor vehicle crashes: The conflict between health advantage and at-risk use. Alcohol and Alcoholism 41(4): 451-454, 2006. (43 refs.)

Aims: To review the evidence on moderate alcohol intake and motor vehicle crash (MVC) risk, and discuss the possible public health tension in balancing risk reduction and increment with respect to moderate alcohol intake. Method: A Medline review was conducted on moderate alcohol intake, MVC, and cardiovascular disease (CVD) risks. Result: Moderate alcohol intake (24 g ethanol, two US standard drinks, or less a day) is associated with 20% reduction in risk of CVD. Public awareness of this may contribute to why rates of driving with blood alcohol content (BAC) <0.08 g/dl in the United States are static. Studies show 3- to 17-fold increased risk of a fatal MVC with BAC < 0.08 g/dl compared to sober drivers. The United States has 0.08 g/dl BAC laws, higher than that reached by a driver drinking two drinks per day or less. Conclusion: The public should be educated that although moderate alcohol drinking may not violate BAC laws, it still carries significant risk of MVC. Current BAC laws in some countries needs re-evaluation.

2006, Medical Council on Alcohol

Hijmering ML; de Lange DW; Lorsheyd A; Kraaijenhagen RJ; de Wiel AV. Binge drinking causes endothelial dysfunction, which is not prevented by wine polyphenols: a small trial in healthy volunteers. Netherlands Journal of Medicine 65(1): 29-35, 2007. (27 refs.)

Background: Binge drinking (the consumption of large quantities (> 5 units) of alcohol in a short period) is associated with increased cardiovascular mortality. Wine polyphenols are considered to be protective against cardiovascular diseases. We conducted an experimental study to evaluate the acute effects of alcohol consumption on flow-mediated vasodilation and general cardiovascular parameters, using beverages with high polyphenolic content (HPC) and low polyphenolic content (LPC). Methods: Two groups of ten volunteers were asked to drink two different kinds of beverages. In 45 minutes, three units of red wine or an alcoholic beverage with a low polyphenolic count were consumed. Then 45 minutes were allowed for complete uptake of the alcohol or polyphenolic compounds. Next, all volunteers underwent blood pressure readings, ECG and flow-mediated vasodilation. Blood samples were taken at the same time for routine chemistry, inflammation parameters and lipids. Then the entire cycle was repeated once (in total six units of alcohol in 180 minutes). Results: No differences were found between the two drinks. Alcohol itself dose-dependently increased forearm blood flow by vasodilation of both arterioles and distribution arteries. However, flow-mediated vasodilation (FMD) for the LPC group (n=10) decreased from 7-31 +/- 4-78 (% +/- SD) to 2.82 +/- 2.9 after three drinks and 1.21 +/- 3.25 after six drinks. The FMD values for the HPC group (n=10) decreased from 8.61 +/- 1.78 to 1.78 +/- 3.71 and 1.19 +/- 2.6. There were no significant changes between the LPC and the HPC group at the three time points. Conclusion: Although ethanol produces vasodilation at the level of the distribution artery as well as at an arteriolar level, it causes a decrease in flow-mediated vasodilation. This endothelial dysfunction is not corrected by the polyphenols present in wine.

Hines LM. Genetic modification of the effect of alcohol consumption on CHD. Proceedings of the Nutrition Society 63(1): 73-79, 2004. (61 refs.)

The deleterious health effects of high alcohol consumption are numerous and well recognized; however, the effect of moderate alcohol consumption on overall health continues to be a debated issue. Among the more prevalent diseases in Westernized countries, epidemiological research suggests that alcohol in moderation substantially reduces the risk of CHD, while it modestly increases the risk for certain cancers, such as breast and colon cancer. Despite the overwhelming data supporting the beneficial effect of moderate alcohol consumption on the cardiovascular system, some researchers are not convinced. Sceptics argue that the reduction in risk is attributed to a favourable lifestyle factor associated with moderate alcohol consumption, or that it may be attributed to constituents of alcoholic beverages other than ethanol, such as the antioxidants in the grapes. In order to promote overall health for the general public, it is necessary to elucidate these issues. One approach is to study population differences in alcohol metabolic efficiency, which is likely to contribute to an individual's susceptibility to alcohol-associated diseases. Among the population there is substantial variability in the efficiency to metabolize alcohol. Genetic variation among the alcohol-metabolizing genes is known to produce isoenzymes with distinct kinetic properties. Studying genetic differences that potentially influence disease susceptibility among populations may provide insight into the mechanism(s) for the relationship between risk factor and disease, such as alcohol and CHD.

Karatzi K; Papamichael C; Aznaouridis K; Karatzis E; Lekakis J; Matsouka C et al. Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease. Coronary Artery Disease 15(8): 485-490, 2004. (35 refs.)

Background: Several studies suggest that red wine is beneficial in coronary artery disease (CAD). Although the long-term effect of moderate red wine consumption on endothelial function is currently under investigation, there is little knowledge about its effect on postprandial endothelial function and haemostatic factors. The aim of the present study was to investigate the postprandial effects of alcohol content and the antioxidants of red wine on endothelial function and fibrinogen levels in CAD patients. Methods Fifteen males with angiographically documented CAD were recruited for the study. All volunteers ingested 250 ml of either red wine or de-alcoholized red wine on two different days. Blood samples (for analysis of fibrinogen and blood lipids) were collected and flow-mediated dilatation (FMD) was determined before and 30, 60 and 90 min following consumption of each beverage Results: FMD was higher following the consumption of de-alcoholized red wine [type of wine effect, P = 0.05 repeated measures analysis of variance (ANOVA)]. Furthermore, the pattern of the response was different between the two beverages, as FMD increased following the ingestion of de-alcoholized red wine, but it decreased after consumption of regular red wine (type of wine by time interaction effect, P = 0.006 repeated measures ANOVA Fibrinogen concentrations were unaltered Conclusions: Acute ingestion of red wine without alcohol led to higher FMD than ingestion of regular red wine in CAD patients. The acute effect of red wine on endothelial function may be different than its long-term effect and it could be attributed to its constituents other than alcohol.

Kasuda S; Sakurai Y; Shima M; Morimura Y; Kudo R; Takeda T et al. Inhibition of PAR4 signaling mediates ethanol-induced attenuation of platelet function in vitro. Alcoholism: Clinical and Experimental Research 30(9): 1608-1614, 2006. (36 refs.)

Background: Reduction in coronary heart disease morbidity in response to moderate consumption of alcoholic beverages may be partly mediated by ethanol-induced inhibition of platelet function. However, the precise mechanisms by which ethanol modulates platelet activation induced by thrombin, which plays a central role in hemostasis, remain unclear. The goal of this study was to investigate ethanol-induced changes in platelet function and clarify the underlying mechanisms including PAR1 and PAR4 activity and [Ca2+](i) dynamics in vitro. Methods: Platelet aggregation, increase in intracellular calcium ([Ca2+](i)), and release of platelet factor 4 and beta-thromboglobulin induced by alpha-thrombin, PAR1-agonist peptide (AP), or PAR4-AP were assessed in the presence or absence of ethanol. Results: Ethanol exposure inhibited low-dose thrombin (0.5 nM)-induced aggregation but not an increase in [Ca2+](i). In contrast, ethanol had no effect on high-dose thrombin (10 nM)-induced aggregation or the [Ca2+](i) increase. Ethanol did not significantly inhibit thrombin-induced release of platelet factor 4 and beta-thromboglobulin. Ethanol reduced PAR1-AP-induced aggregation, but did not affect the spike form of [Ca2+](i) increase. In contrast, ethanol inhibited the increase in [Ca2+](i) as well as the aggregation in response to PAR4-AP and resulted in delayed [Ca2+](i) peak time. Furthermore, ethanol inhibited both PAR1-AP- and PAR4-AP-induced platelet factor 4 and beta-thromboglobulin release. Conclusions: These data suggest that ethanol inhibits platelet aggregation via inhibition of PAR4 signaling and subsequent inhibition of Ca2+ influx and granule release. This phenomenon may contribute to the reduction in coronary heart disease morbidity in response to consumption of alcoholic beverages.

Klatsky A. Wine, alcohol and cardiovascular diseases. IN: Sandler M; Pinder R, eds. Wine: A Scientific Exploration. London: Taylor and Francis, Inc., 2003. pp. 108-139. (212 refs.)

This chapter reviews the adverse and beneficial relations of both light-moderate and heavy alcohol drinking to several non-atherothrombotic cardiovascular conditions. It then proves an overview of the relationship to coronary heart disease, stroke and peripheral arterial disease. Based on the evidence that there are beneficial effects to alcohol use, nonetheless in terms of the general populations the author poses the following as guidelines for the general population: (1) the overall health risk of a heavy drinker will be reduced by reduction of drinking or abstinence; (2) because of the unknown risk of progression to heavier drinking, abstainers should not be indiscriminately advised to drink for cardiovascular health benefit; (3) Light to moderate drinkers, who constitute the majority of people need no change in drinking habits for health reasons, except in special circumstances.

Klatsky AL; Udaltsova N. Alcohol drinking and total mortality risk. Annals of Epidemiology 17(5, Supplement S): S63-S67, 2007. (19 refs.)

To evaluate further the relation between alcohol consumption and total mortality, we have carried out new Cox proportional hazards model analyses of 21,535 deaths through 2002 in the Kaiser Permanente study. This follow-up includes 2,618,523 person-years of observation, with a mean follow-up of 20.6 years. We adjusted for age, sex, ethnicity, body mass index, marital status, education, and smoking. New methodology was used to stratify light-moderate drinkers into groups felt more or less likely to include under-reporters. The analysis reconfirms that the relation of alcohol drinking to total mortality is J-shaped, with reduced risk (mainly because of less cardiovascular disease) for lighter drinkers and increased risk for persons reporting more than 3 drinks per day. Infrequent (occasional) drinkers have risk similar to that of lifelong abstainers, while former drinkers are at increased risk, especially for noncardiac death. The general shape of the relation of alcohol to mortality is similar for men and women. Age differences are substantial, with the apparent benefit from light-moderate drinking not seen before middle life. Our data indicate further that the apparent magnitude of benefit of lighter drinking is probably reduced by systematic underreporting.

Kolovou GD; Salpea KD; Anagnostopoulou KK; Mikhailidis DP. Alcohol use, vascular disease, and lipid-lowering drugs. Journal of Pharmacology and Experimental Therapeutics 318(1): 1-7, 2006. (68 refs.)

Many epidemiological and clinical studies have shown that light-to-moderate alcohol (Alc) consumption is associated with reduced risk of coronary heart disease (CHD) and total mortality in middle-aged and elderly men and women. The plausible mechanisms for the putative cardioprotective effects include increased levels of high-density lipoprotein cholesterol, prevention of clot formation, reduced platelet aggregation, promotion of blood clot dissolution, and lowering of plasma lipoprotein ( a) concentration. Individuals who need to be treated with lipid-lowering drugs, such as dyslipidemic or CHD patients, may benefit from these effects of Alc. Because hypolipidemic treatment is usually continued for life, an important issue is the suitability of Alc consumption in these patients. In the present review, the beneficial effects of Alc consumption on CHD risk, its side effects, and its safety and suitability when coadministered with hypolipidemic drugs are discussed.

Kondo K. Beer and health: Preventive effects of beer components on lifestyle-related diseases. Biofactors 22(1-4 Special Issue): 303-310, 2004. (42 refs.)

It has been demonstrated that the light-to-moderate consumption of alcoholic beverages is associated with significant reductions in all-cause and particularly cardiovascular mortality. While the inverse association between red-wine consumption and cardiovascular risk is globally recognized as the French paradox, many epidemiological studies have concluded that beer and red wine are equally beneficial. Moderate alcohol intake improves lipoprotein metabolism and lowers cardiovascular mortality risk. The question now is whether additional health benefits associated with the non-alcohol components in beer may be expected. This article summarizes the results of the latest studies on the health benefits of beer while referring to our recent results, which demonstrate the preventive effects of beer and its components on lifestyle-related diseases. A series of studies using animal models have shown that beer may prevent carcinogenesis and osteoporosis; beer provides plasma with significant protection from oxidative stress; and isobumulones, the bitter substances derived from hops, may prevent and improve obesity and type-2 diabetes, improve lipid metabolism, and suppress atherosclerosis. Further studies are needed to clarify the components in addition to isohumulones that are responsible for these beneficial effects of beer, and the underlying mechanisms must be addressed.

Kroenke CH; Chu NF; Rifai N; Spiegelman D; Hankinson SE; Manson JE; Rimm EB. A cross-sectional study of alcohol consumption patterns and biologic markers of glycemic control among 459 women. Diabetes Care 26(7): 1971-1978, 2003. (42 refs.)

OBJECTIVE - Little research has explored associations of drinking patterns with glycemic control, especially among women. Our objective was to determine the relationship of patterns of alcohol consumption-including average daily consumption, weekly frequency of consumption, drinking with meals, and beverage type-with biologic markers of insulin resistance m young women. RESEARCH DESIGN AND METHODS - This study was cross-sectional in design. The subjects consisted of a stratified random subpopulation of 459 U.S. normal-weight and over-weight female nurses, 33-50 years of age, drawn from the Nurses' Health Study 11 and sampled for distinct drinking patterns. Women provided blood samples and detailed information on dietary and lifestyle factors between 1995 and 1999. The main outcome measures were fasting insulin, C-peptide, and HbA, c. RESULTS - Adjusting for age, smoking, physical activity, television watching, BMI, and several dietary factors, average alcohol intake was inversely associated with HbA,c (units in percentage of HbA,,): 0 g/day (reference = 5.36%), 0.1 to <5.0 g/day (-0.04%), 5.0 to <15.0 g/day (-0.09%), 15.0 to <25.0 g/day (-0.10%), and greater than or equal to25.0 g/day (-0.17%) (P value, test for trend <0.001). We found an inverse association of alcohol intake and insulin, but only for women with a BMI greater than or equal to25 kg/m(2). Specifically, insulin levels were lowest for episodic drinkers consuming greater than or equal to2 drinks per day on 0-3 days per week. Consumption with meals and type of alcoholic beverage did not further influence these results. CONCLUSIONS - Moderate alcohol consumption of 1-2 drinks per day on a few to several days of the week may have a beneficial glycemic effect, particularly among over-weight women.

Kuepper-Nybelen J; Thefeld W; Rothenbacher D; Brenner H. Patterns of alcohol consumption and Helicobacter pylori infection: Results of a population-based study from Germany among 6545 adults. Alimentary Pharmacology & Therapeutics 21(1): 57-64, 2005. (22 refs.)

Background: Moderate alcohol consumption has been suggested to facilitate elimination of Helicobacter pylori infection. Aim: To investigate the relationship between alcohol consumption and infection with H. pylori, with particular consideration of the role of age, different alcoholic beverages and specific drinking habits. Methods: These issues were addressed in the German National Health Survey, conducted in a representative population sample between October 1997 and March 1999. Overall, 6545 subjects provided data on frequency and average amount of different alcoholic beverages consumed. H. pylori infection status was measured by serum immunoglobulin G antibodies. Results: Seroprevalence of the infection was highest among subjects who reported drinking no alcohol (49.3%) and lowest among subjects consuming 25-50 g alcohol/day (35.2%, adjusted odds ratio = 0.60, 95% confidence interval: 0.48-0.75). This inverse association was consistently seen for different alcoholic beverages and in all age groups and it was particularly pronounced among women and among regular but moderate drinkers. There was also an inverse dose-response relationship between the frequency of alcohol consumption and H. pylori infection. Conclusions: This analysis supports suggestions that regular but moderate consumption of alcohol from various sources may facilitate elimination of H. pylori infection.

Lee CM. Positive and negative consequences of alcohol use among college students. (meeting abstract). Alcoholism: Clinical and Experimental Research 28(5 Supplement): 103A-103A, 2004. (0 refs.)

Leighton F; Urquiaga I. Changes in cardiovascular risk factors associated with wine consumption in intervention studies in humans. Annals of Epidemiology 17(5, Supplement S): S32-S36, 2007. (34 refs.)

Evidence that links moderate wine consumption to cardiovascular health corresponds mostly to ecological observations. Intervention studies using moderate wine consumption with ischemic heart disease as the end point will probably not be available soon because they require long-term follow-up and adequately randomized experimental groups. In contrast, short-term studies focused on risk factors are feasible and should provide evidence suitable for a critical assessment of the apparent beneficial role of moderate drinking, as well as other lifestyle measures, on cardiovascular health. Our intervention studies suggest an increase in HDL-cholesterol, decrease in the omega-6/omega-3 ratio, and in some cases a slight increase in triglyceride levels from moderate drinking. Observed changes in hemostasis include reduced coagulation and increased fibrinolysis; effects on blood pressure have been inconsistent. There is a reduction in inflammatory markers and an increase in endothelial function. Effects of wine are greater for subjects on a Mediterranean diet than those on an occidental diet. Several key biochemical or physiological processes related to atherogenesis are positively modified by wine consumption. From our observations, we conclude that wine in moderation and as part of the diet is directly responsible for changes that may help decrease the risk of cardiovascular disease.

Letenneur L. Moderate alcohol consumption and risk of developing dementia in the elderly: The contribution of prospective studies. Annals of Epidemiology 17(5, Supplement S): S43-S45, 2007. (8 refs.)

Moderate alcohol consumption, after controlling for potential confounding factors, has been found to be associated with a lower risk of developing dementia in several prospective epidemiological studies from Europe, the United States, and China. When the type of alcoholic beverage consumed is analyzed, moderate wine intake has been systematically associated with lower risk. However, moderate consumption has very different definitions across studies, ranging from monthly or weekly drinking to 3 to 4 drinks per day. In addition, different results have been observed according to sex; some studies found the same effect in men and women, while others found either no association or a stronger association in women. All of these results lead to the conclusion that the observed association is fragile and needs further confirmation.

Maraldi C; Volpato S; Kritchevsky SB; Cesari M; Andresen E; Leeuwenburgh C et al. Impact of inflammation on the relationship among alcohol consumption, mortality, and cardiac events -- The Health, Aging, and Body Composition Study. Archives of Internal Medicine 166(14): 1490-1497, 2006. (29 refs.)

Background: Uncertainty remains about the overall survival benefit of alcohol consumption and the mechanisms underlying the cardioprotective effect of light to moderate alcohol intake. Recent evidence suggests an anti-inflammatory effect of light to moderate alcohol consumption. We investigated the relationship of alcohol intake with all-cause mortality and cardiac events and evaluated whether this relationship is mediated or modified by inflammatory markers. Methods: The analysis included 2487 subjects, aged 70 to 79 years, without baseline coronary heart disease (CHD) or heart failure (HF), participating in the Health, Aging, and Body Composition study. All-cause mortality and incident cardiac events ( CHD and HF) were detected during a mean follow-up of 5.6 years. Alcohol consumption and serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed at baseline. Results: A total of 397 participants died, and 383 experienced an incident cardiac event. Compared with never or occasional drinkers, subjects drinking 1 to 7 drinks per week had lower age-, sex-, and race- adjusted incidences of death (27.4 vs 20.1 per 1000 person-years, respectively) and cardiac events (28.9 vs 20.8 per 1000 person-years). After adjustment for confounders, compared with never or occasional drinkers, light to moderate drinkers (1-7 drinks per week) showed a decreased risk of death (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.56-1.00) andcardiac events (HR, 0.72; CI, 0.54- 0.97). Adjustment for potential mediators, and particularly inflammatory marker levels, did not affect the strength of this association. Conclusion: Light to moderate alcohol consumption was associated with significantly lower rates of cardiac events and longer survival, independent of its antiinflammatory effect.

Marchand A; Demers A; Durand P; Simard M. The moderating effect of alcohol intake on the relationship between work strains and psychological distress. Journal of Studies on Alcohol 64(3): 419-427, 2003. (70 refs.)

Objective: This study investigated the extent to which alcohol intake modified the associations between psychological distress and work strains. Method: The data were obtained from a sample of 10,387 employees nested in 422 occupations. Four types of alcohol drinkers were defined according to drinker status measured by alcohol intake over the last week: (1) abstainers, (2) drinkers who abstained from drinking in the last seven days, (3) low-risk drinkers (according to the Canadian guidelines), (4) high-risk drinkers. The Ilfeld scale was used to measure the level of psychological distress (referencing the last week). Work strains were measured according to Karasek's skills utilization, decision authority and psychological demands, as well as by regularity of work schedule, number of working hours per week, exposure to physical and chemical risks, job status and type of remuneration. Multilevel logistic regressions were conducted with adjustments for gender and age. Results: 6.1% of the logit variance of psychological distress was between occupations. Alcohol intake showed a U-shaped relationship with psychological distress, and it was a moderator of skills utilization and exposure to physical risks. Decision authority, psychological demands, work schedule, gender and age were linked to psychological distress. Conclusions: Moderate alcohol intake is not associated with psychological distress and does not intensify the effect of work strains. The results give some support to the positive effect of moderate alcohol consumption on stress reduction and mental health.

Masters JA. Moderate drinking and cardiovascular disease. Annual Review of Nursing Research 23: 65-97, 2005

The adverse consequences of heavy alcohol use are well known. However, recent media reports of a possible cardiovascular benefit associated with moderate drinking have revived public interest in the use of alcohol for "medicinal purposes." Knowledge development regarding guidelines for moderate alcohol use has lagged behind public interest in the possible health benefits of moderate alcohol use. At this time, evidence-based primary health promotion interventions related to the risks and benefits of moderate alcohol use are lacking in the health care literature. This chapter reviews 22 reports describing the relationship between moderate drinking and cardiovascular disease. The reports are classified by the level of evidence and critiqued on seven aspects of method. Conclusions: related to the strength of the evidence that moderate drinking is a useful primary health promotion intervention are presented.

Mattace-Raso F; vander Cammen TJM; vanden Elzen APM; Schalekamp MADH; Asmar R; Reneman RS et al. Moderate alcohol consumption is associated with reduced arterial stiffness in older adults: the Rotterdam study. Journal of Gerontology Series A. Biological Sciences and Medical Sciences 60(11): 1479-1483, 2005. (35 refs.)

BACKGROUND: Light-to-moderate alcohol consumption has been associated with a lower risk of cardiovascular disease. The protective effect of alcohol could involve arterial properties as arterial stiffness and distensibility. METHODS: The relationship between alcohol and arterial stiffness was studied within the framework of the Rotterdam Study, a population-based study in individuals aged 55 and older. The present study included 3178 participants in the third examination phase. Arterial stiffness was measured by two different methods, i.e., the carotid-femoral pulse wave velocity and the DC of the common carotid artery. Categories of alcohol consumption were defined as follows: < or =3 glasses of alcohol per week, 4-10 glasses per week, 11-20 glasses per week, and > or =21 glasses per week. Linear regression analysis was used to investigate the association between alcohol consumption and measures of arterial stiffness. RESULTS: In multivariate-adjusted models, women drinking 4-10, 11-20, and > or =21 glasses of alcoholic beverage per week had a -0.07 (0.22 to -0.38), -0.18 (0.12 to -0.49), and 0.12 (0.19 to -0.43) m/s difference in mean pulse wave velocity compared to those drinking 0-3 glasses per week (reference group). Corresponding differences in the carotid DC were 0.68 (1.21 to 0.15), 0.28 (0.82 to -0.25), and 0.36 (0.91 to -0.18) 10(-3)/kPa. In men, the estimates were not statistically significant, although a similar trend was observed. CONCLUSIONS: Moderate alcohol consumption is associated with lower arterial stiffness in women independently of cardiovascular risk factors and atherosclerosis.

McGregor D; Murray RP; Barnes GE. Personality differences between users of wine, beer and spirits in a community sample: The Winnipeg Health and Drinking Survey. Journal of Studies on Alcohol 64(5): 634-640, 2003. (41 refs.)

Objective: To date there are many studies describing the protective and risk factors associated with alcohol consumption and cardiovascular health (the U- or J-shaped curve). These studies have only accounted for part of the effects. One hypothesis is that personality differences may account for some of the unexplained variance. It is also unclear if wine, beer and distilled spirits have equivalent effects on health. The purpose of this study is to describe the differences in personality among users of wine, beer and spirits. Method: Data were from a community sample of 1,257 men and women in Winnipeg, Manitoba, Canada, that was first enrolled in 1989-90. We examined and compared the demographic and personality characteristics of wine, beer and spirits drinkers in this sample. Results: The groups differed significantly on the dimensions of extraversion, psychoticism and reducer-augmenter in univariate tests. In multivariate models, for the total sample and for females, predominant drinking of wine was associated with low scores on the Vando scale (augmenters). Higher consumption of beer among males was associated with higher levels of neuroticism. Conclusions: In these instances, personality does contribute to the characterization of groups.

Mukamal K. Alcohol intake and noncoronary cardiovascular diseases. Annals of Epidemiology 17(5, Supplement S): S8-S12, 2007. (63 refs.)

Moderate drinking has complex associations with cardiovascular diseases other than coronary heart disease. Recent cohort studies examining the relationship between alcohol use and ischemic stroke have shown a modest association, with risk ratios approximating 0.8 and the lowest risk among those who drink less than daily. In contrast, alcohol use is generally associated with an approximate dose-dependent risk for hemorrhagic stroke throughout the full range of intake. Several prospective studies of alcohol intake and congestive heart failure have found lower risk with moderate drinking. This risk is also dose dependent through the moderate range, but its underlying mechanism remains uncertain. Accounting for the lower risk of myocardial infarction associated with moderate intake does not eliminate the observed association. Cohort studies have found no association of long-term alcohol intake with risk of atrial fibrillation below levels of at least 3 standard drinks per day. Finally, two prospective studies have found lower risks of claudication or clinically more severe peripheral arterial disease among moderate drinkers, an association also supported by cross-sectional studies of alcohol intake and ankle-brachial index.

Mukamal KJ; Chung HJ; Jenny NS; Kuller LH; Longstreth WT; Mittleman MA et al. Alcohol consumption and risk of coronary heart disease in older adults: The Cardiovascular Health Study. Journal of the American Geriatrics Society 54(1): 30-37, 2006. (50 refs.)

OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome. DESIGN: Prospective cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline. MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly. RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95% confidence interval (CI)=0.71-1.14), 0.93 (95% CI=0.73-1.20), 0.76 (95% CI=0.53-1.10), and 0.58 (95% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9% to 10% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele. CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.

Mukamal KJ; Kennedy M; Cushman M; Kuller LH; Newman AB; Polak J et al. Alcohol consumption and lower extremity arterial disease among older adults - The cardiovascular Health Study. American Journal of Epidemiology 167(1): 34-41, 2008. (40 refs.)

Few studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95% confidence interval (CI): 0.71, 1.71) for < 1 alcoholic drink per week, 0.56 (95% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95% CI: 0.53, 1.97) for >= 14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.

Mukamal KJ; Kuller LH; Fitzpatrick AL; Longstreth WT; Mittleman MA; Siscovick DS. Prospective-study of alcohol consumption and risk of dementia in older adults. Journal of the American Medical Association 289(11): 1405-1413, 2003. (289 refs.)

Context: Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear. Objective To determine the prospective relationship of alcohol consumption and risk of dementia among older adults. Design, Setting, and Participants Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999. Main Outcome Measures: Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI. Results: Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term=.001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia. Conclusions: Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.

Mumenthaler MS; Yesavage JA; Taylor JL; O'Hara R; Friedman L; Lee H et al. Psychoactive drugs and pilot performance: A comparison of nicotine, donepezil, and alcohol effects. Neuropsychopharmacology 28(7): 1366-1373, 2003. (41 refs.)

The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing 1: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the FS of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine) = 0.80; ES (donepezil) = 1.02; ES (alcohol acute) = -3.66; ES (alcohol 8 h) = -0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention, Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

Ngandu T; Helkala EL; Soininen H; Winblad B; Tuomilehto J; Nissinen A et al. Alcohol drinking and cognitive functions: Findings from the Cardiovascular Risk Factors Aging and Dementia (CAIDE) study. Dementia and Geriatric Cognitive Disorders 23(3): 140-149, 2007. (48 refs.)

Background: Moderate alcohol drinking is suggested to be beneficial for cognitive functions, but the results of previous studies have varied greatly. Little is known about the effects of midlife alcohol drinking on the cognitive functions later in life. Methods: Participants were derived from random, population-based samples studied in Eastern Finland in 1972, 1977, 1982, or 1987. A total of 1,341 participants were reexamined in 1998, after an average follow-up period of 21 years, at ages 65-79 years. Results: The participants who did not drink alcohol at midlife had a poorer performance in episodic memory, psychomotor speed, and executive function in late life as compared with infrequent and frequent drinkers, adjusted for sociodemographic and vascular factors. Also late-life nondrinkers had poorer psychomotor speed and executive function. These findings were evident especially among nonsmokers. Further, no interactions between apolipoprotein E4 and alcohol or sex and alcohol were found. Conclusions: Alcohol drinking both at midlife and later is favorably related to the function in several cognitive domains, including episodic memory, psychomotor speed, and executive function, in late life. However, it is not clear whether the association is causal, what is the possible mechanism, and what would be a safe limit of drinking for the best cognitive function.

Nieters A; Deeg E; Becker N. Tobacco and alcohol consumption and risk of lymphoma: Results of a population-based case-control study in Germany. International Journal of Cancer 118(2): 422-430, 2006. (65 refs.)

Changing trends in lifestyle exposures are suggested to be contributing factors to the increasing incidence rates for lymphoma. We investigated the relationship between smoking and alcohol consumption and the risk of lymphoma among adult participants of a population-based case-control study recently conducted in Germany. In 710 case-control pairs, an increased risk of lymphoma was associated with a long duration of smoking (p for trend = 0.01 for men) and smoking of > 20 cigarettes per day (OR = 2.7; 95% CI = 1.4-5.2 for women). Elevated odds ratios were seen for most lymphoma subentities, albeit mostly without reaching statistical significance. A strong association was evident between smoking and multiple myeloma (OR = 2.4, 95% CI = 0.98-5.74 for men; OR = 2.9, 95% CI = 1.1-7.4 for women) and Hodgkin's lymphoma among men (OR = 3.6; 95% CI = 1.7-7.5). Alcohol consumption 10 years prior to the date of interview appeared to decrease the risk of lymphoma. Odds ratios for men who reported alcohol consumption were 53% lower (95% CI = 0.31-0.71) compared to men who drank very little or no alcohol. The same tendency was evident for women, although the association was less pronounced. The inverse relationship was also seen for low amounts of alcohol and did not appear to be restricted to specific types of beverages. Although biologic rationale for a protective effect of alcohol consumption may be given, a more in-depth analysis involving genetic markers is indicated to clarify if ethanol, other components in alcoholic beverages, or factors associated with moderate drinking reduce lymphoma risk among adults. In conclusion, this investigation suggests a positive association between tobacco smoking and lymphoma risk and finds decreased odds ratios among consumers of alcohol.

Nolte E; Britton A; McKee M. Trends in mortality attributable to current alcohol consumption in east and west Germany. Social Science & Medicine 56(7): 1385-1395, 2003. (49 refs.)

There is emerging awareness of alcohol as a cause of the persisting health divide between east and west Germany. This study quantifies the burden of alcohol attributable mortality in the two parts of Germany in the 1990s, taking account of both adverse and beneficial effects of alcohol. We used an epidemiological approach that applies cause-specific alcohol attributable fractions derived from published relative risks and data on the distribution of alcohol consumption in east and west Germany in 1990/1992 and 1998 to mortality data for the two regions in 1992 and 1997, thus producing an estimate of the number of alcohol attributable deaths 'caused' or 'prevented'. Including the cardio-protective effect of alcohol, there were about 1.4% more deaths among men aged 20 + in 1992 in Germany than would have been expected in a non-drinking population, while there were 0.1% fewer deaths among women. By 1997, this had increased to 1.8% excess male deaths and 0.1% excess female deaths. In 1997, alcohol 'caused' 9.0% of all deaths in east German men compared with 5.6% in the west (women east: 2.5%; women west: 2.2%). At the same time, alcohol 'prevented' 5.2% deaths in east German men compared with 4.3% in the west, while there were 2.9% and 2.0% fewer deaths in women. This resulted in a net excess of deaths due to alcohol, except east German women, where 0.3% deaths were estimated to have been averted by alcohol. Although by 1997 net deaths 'caused' by alcohol had increased in the west and declined in the east, the burden of mortality due to alcohol among men remained highest in the east whereas in women the order had reversed. Mortality attributable to alcohol contributes considerably to overall mortality and to the east-west gap in Germany. This study points to the need for comprehensive policies on alcohol in Germany to close the persisting east-west health gap.

Obisesan TO. Wine: Protective in macular degeneration. IN: Sandler M; Pinder R, eds. Wine: A Scientific Exploration. London: Taylor and Francis, 2003. pp. 285-298. (52 refs.)

The protective effects of consumption of wine against macular degeneration are discussed. It is noted that age-related macular degeneration (ARMD), which is a bilateral progressive disease, is the leading cause of blindness in older adults, with approximately 30% of people over the age of 65 years going on to suffer from this disorder. The definition of ARMD is broad, encompassing both mild degrees of atrophy and severe hemorrhagic disease. Research evidence suggests that moderate wine consumption is associated with reduced rates of ARMD. The combination of the antioxidant effect of wine, its effect on platelet aggregability, intracellular calcium and its anti-inflammatory property may all be involved. Section headings in this book chapter include: (1) the influence of wine consumption on age-related macular degeneration; (2) mechanism of the influence of wine on age-related macular degeneration; (3) platelet aggregability and fibrinolytic activity, and cardiovascular disease risk for age-related macular degeneration; (4) antioxidation effect of wine and age-related macular degeneration; (5) anti-inflammatory effect of wine and age-related macular degeneration; (6) wine consumption, nutrition and age-related macular degeneration; (7) how much alcohol is protective; and (8) other disagreements between studies.

Pai JK; Hankinson SE; Thadhani R; Rifai N; Pischon T; Rimm EB. Moderate alcohol consumption and lower levels of inflammatory markers in US men and women. Atherosclerosis 186(1): 113-120, 2006. (36 refs.)

Objective: Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect. Methods and results: From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake. Markers of inflammation were soluble tumor necrosis factor-alpha receptors I and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), and interleukin-6 (IL-6). We found significant inverse linear trends for sTNF-R1 (P-trend < 0.001 men; 0.03 women) and sTNF-R2 (p-trend = 0.002 men; 0.08 women) with increasing alcohol intake. Compared to non-drinkers, men who consumed on average 1-2 drinks/day had 26% lower CRP (-0.66 mg/L, p = 0.13), and 36% lower IL-6 (-1.12 pg/ml, p = 0.02) levels. Among women, a similar though stronger association was observed at half drink per day. Compared to non-drinkers, both men and women who consumed 1-2 drinks/drinking day had significantly lower sTNF-R1 (-9% in men, -6% in women) and sTNTF-R2 (-7% in men, -6% in women) levels as well as lower CRP (-10% in men, -32% in women) and IL-6 (-45% in men, -27% in women) levels. Conclusions: Alcohol in moderation is associated with lower levels of inflammatory markers and may lower risk of CVD through these mechanisms.

Papamichael C; Karatzi K; Karatzis E; Papaioannou TG; Katsichti P; Zampelas A et al. Combined acute effects of red wine consumption and cigarette smoking on haemodynamics of young smokers. Journal of Hypertension 24(7): 1287-1292, 2006. (30 refs.)

OBJECTIVE: Red wine seems to improve haemodynamic variables, while smoking provokes adverse effects. The haemodynamic effects of their combined use is unknown. The purpose of the present study was to examine the acute effects of red wine and its constituents, in combination with the smoking of one cigarette, on haemodynamic parameters, such as blood pressure and wave reflections, in a group of smokers. METHODS: Twenty smokers (12 males, eight females) participated in a double-blind, crossover study comprised of 3 study days. All subjects either smoked one cigarette, or smoked and drank 250 ml of red wine, or 250 ml of de-alcoholized red wine (containing the same type and similar concentration of antioxidants). Applanation tonometry and generalized transfer functions were used to estimate aortic pressure waveforms at baseline and 30, 60 and 90 min after each trial. The augmentation index (AIx) was used to express wave reflections. RESULTS: Smoking increased peripheral systolic blood pressure (P < 0.005) 30 min later, but simultaneous consumption of either type of red wine caused no such effect. Additionally, smoking caused no overall effect on AIx, while smoking and drinking either regular or de-alcoholized red wine reduced AIx (P < 0.001). The reduction of AIx after red wine consumption was significantly greater than the respective reduction after de-alcoholized red wine (P = 0.004). CONCLUSION: Antioxidant substances in red wine counteracted the smoking-induced increase in peripheral systolic blood pressure. Both alcohol and antioxidants in red wine decrease wave reflections in uncomplicated habitual smokers postprandially, indicating an additional favourable effect of red wine.

Piriyawat P; Labiche LA; Burgin WS; Aronowski JA; Grotta JC. Pilot dose-escalation study of caffeine plus ethanol (caffeinol) in acute ischemic stroke. Stroke 34(5): 1242-1245, 2003. (13 refs.)

Background and Purpose-In animal models, the combination of caffeine and ethanol (caffeinol) provides robust neuroprotection at blood levels that should be easily and safely achieved in humans. This study was designed to determine the safety and tolerability of ascending doses of this combination in stroke patients. Methods-This Food and Drug Administration-approved open-label, single-arm, dose-escalation study had 3 original dose groups: group 1, caffeine 6 mg/kg plus ethanol 0.2 g/kg; groups 2 and 3, incremental increases of caffeine and ethanol by 2 mg/kg and 0.2 g/kg, respectively. Intravenous thrombolysis was encouraged if patients qualified. Drug was started within 6 hours of stroke onset, and blood levels of caffeine and ethanol were drawn at baseline and end of infusion. The target blood caffeine and ethanol ranges were 8 to 10 mug/mL and 30 to 50 mg/dL, respectively. Clinical outcome measurements included the National Institutes of Health Stroke Scale at the end of infusion, at 24 hours, and at discharge. Potential complications from caffeine and ethanol were recorded. Cases were reviewed by an independent stroke neurologist for safety. Results-A total of 23 patients were recruited. Target blood caffeine and ethanol levels were reached in 0 of the 4 patients in the first group. The second dose group (caffeine 8 mg/kg plus ethanol 0.4 g/kg) included 8 patients. The median end-of-infusion caffeine and ethanol levels were within the desired target ranges. Two days after infusion, 1 patient in this group with preexisting cardiac disease and end-of-infusion caffeine and ethanol levels of 10.7 mug/mL and 69 mg/dL developed reversible congestive heart failure and required transfer to an intensive care unit. The original third dose group was canceled given achievement of target blood caffeine and ethanol levels in group 2. However, 3 new dose groups were created in an attempt to minimize the dose of ethanol. Although blood levels were proportional to dose, none of these new dose groups provided optimal blood levels. Congestive heart failure occurred in 1 other patient with previously asymptomatic cardiomyopathy. No other side effects were noted. Concomitant thrombolytic therapy was given in 8 patients, 1 of whom died of intracerebral hemorrhage. Conclusions-Caffeinol alone or combined with intravenous tissue plasminogen activator can be administered safely. Caffeine 8 mg/kg plus ethanol 0.4 g/kg produces target caffeine and ethanol levels of 8 to 10 mug/mL and 30 to 50 mg/dL, respectively. A randomized, placebo-controlled trial is needed to determine the neuroprotective effect of this combination.

Pool-Zobel BL; Dornacher I; Lambertz R; Knoll M; Seitz HK. Genetic damage and repair in human rectal cells for biomonitoring: Sex differences, effects of alcohol exposure, and susceptibilities in comparison to peripheral blood lymphocytes. Mutation Research 551(1-2): 127-134, 2004. (35 refs.)

Introduction: Cells other than lymphocytes may be preferable as surrogate biomarkers during exposure monitoring. In nutritional toxicology, cells from colorectal tissues are particularly relevant for studying associations between food and cancer. Thus, we have previously shown that colonic cells of males have higher levels of DNA damage than females, which (among other factors) could be due to a higher consumption of alcoholic beverages by males. To test this hypothesis, we have performed a first exploratory study to compare DNA damage in rectal cells from biopsies of male patients with alcohol abuse and of male and female controls. Peripheral blood lymphocytes were additionally monitored to assess systemic exposure loads. Methods: Cells were isolated and subjected to microgelelectrophoresis +/- endonuclease III to measure DNA breaks and oxidized pyrimidine bases ("comet-assay"). Cell aliquots were treated with H2O2 for 5 min in suspension culture and processed immediately or after 60 min to determine induced damage and its persistence. Results: Pooled data from subjects of all groups revealed that oxidative DNA damage in rectal cells directly correlated to damage in lymphocytes. Female controls had lower levels of DNA damage than male controls, confirming the previous studies. An unexpected result was that male alcohol abusers had significantly less genetic damage than male controls. Also, repair was detected in lymphocytes of male alcohol abusers and female controls, but not in male controls. Conclusion: This is the first time the comet-assay has been used to detect genotoxicity in human rectal cells as a biomonitoring tool. Our pilot study confirms earlier reports on sex differences and indicates a good correlation between damage in rectal cells and damage in lymphocytes and implies that alcohol exposure enhances endogenous defence.

Puddey IB; Beilin LJ. Alcohol is bad for blood pressure. Clinical and Experimental Pharmacology & Physiology 33(9): 847-852, 2006. (63 refs.)

The regular consumption of alcohol elevates blood pressure, with global estimates that the attributable risk for hypertensive disease from alcohol is 16%. The increase in blood pressure is approximately 1 mmHg for each 10 g alcohol consumed and is largely reversible within 2-4 weeks of abstinence or a substantial reduction in alcohol intake. This increase in blood pressure occurs irrespective of the type of alcoholic beverage. In particular, the postulated effects of vasodilator flavonoid components of red wine to lessen or reverse alcohol-related hypertension have not been borne out in intervention studies. Heavy drinking, especially a binge pattern of drinking, is linked to a higher incidence of cerebral thrombosis, cerebral haemorrhage and coronary artery disease deaths, although a role for alcohol-related hypertension in the causal pathway is not well defined. In contrast, the light to moderate intake of alcohol has been consistently linked to a reduced risk of atherosclerotic vascular disease end-points. Such a protective effect may also extend to hypertensive subjects. However, the magnitude of any protective effect appears to have been exaggerated because of unmeasured confounders, especially diet, lifestyle and patterns of drinking. Furthermore, a decrease in overall mortality with drinking appears confined to older subjects and to populations with a high background cardiovascular risk profile. Any putative cardiovascular benefits from drinking need to be carefully considered against the effects of alcohol to elevate blood pressure, together with many other adverse health consequences from drinking. Maximum cardiovascular benefit occurs at relatively low levels of consumption (i.e. one to two standard drinks a day in men (10-20 g alcohol) and up to one a day in women (10 g alcohol). In hypertensive subjects, consumption beyond these levels would be unwise.

Ramstedt M. Is alcohol good or bad for Canadian hearts? A time-series analysis of the link between alcohol consumption and IHD mortality. Drug and Alcohol Review 25(4): 315-320, 2006. (30 refs.)

The objective of this study was to analyse the population level association between alcohol consumption and ischaemic heart disease (IHD) mortality in Canada. Yearly changes in IHD mortality rates from 1950 to 1998 were analysed in relation to yearly changes in alcohol consumption, employing the Box & Jenkins technique for time-series analyses. All models controlled for cigarette smoking and one analysis with focus on men also included female IHD mortality as an indicator of other risk factors for IHD. A 1-litre increase in per capita alcohol consumption was associated with an increase in overall IHD mortality as well as among men and women with fully 1%, but no estimate reached statistical significance. A positive and significant relationship between smoking and IHD mortality was demonstrated in all models. According to the model with focus on male IHD mortality, an increase in per capita consumption by 1 litre was related significantly to a 1% increase in male IHD mortality. No significant effects were found in different male age groups. The idea that alcohol saves more IHD deaths than it causes in Canada is not in accordance with these findings. An increase in overall alcohol consumption is more likely to cause an increase in IHD mortality than to lower the number of IHD deaths, at least among men.

Rehm J; Patra J; Taylor B. Harm, benefits, and net effects on mortality of moderate drinking of alcohol among adults in Canada in 2002. Annals of Epidemiology 17(5, Supplement S): S81-S86, 2007. (28 refs.)

Alcohol is an important risk factor contributing to the burden of chronic diseases and injuries, but is also associated with some health benefits. This study estimates risks and benefits associated with moderate consumption of alcohol in terms of mortality for Canada in 2002 by age and sex. Distribution of exposure was taken from a Canadian survey and corrected for per capita consumption from production and sales data; risk relationships were taken from published literature to calculate alcohol-attributable fractions for moderate consumption. If moderate consumption is based on average volume alone, 866 net deaths in 2002 among those younger than 70 years of age were due to moderate consumption of alcohol (1.3% of all the deaths in this age group, consisting of 1653 deaths caused and 787 deaths prevented). When heavy drinking episodes were excluded, the net effect was beneficial (55 prevented deaths, 0.09% of all deaths); the net burden was higher for younger ages and the net benefits for older ages. The net impact of average moderate alcohol consumption on mortality depends on patterns of drinking. Beneficial net effects are seen only when heavy drinking occasions are excluded. Policies should strive to reduce the burden of moderate alcohol consumption while preserving the beneficial impacts.

Rehm J; Sempos CT; Trevisan M. Average volume of alcohol consumption, patterns of drinking and risk of coronary heart disease: A review. Journal of Cardiovascular Risk 10(1): 15-20, 2003. (10 refs.)

The effect of average volume of alcohol on coronary heart disease (CHD) is J-shaped in established market economies. Light to moderate drinkers have less risk than abstainers, with heavy drinkers displaying the highest level of risk. This relationship between average volume of alcohol consumption and CHD is modified by different patterns of drinking. Heavy drinking occasions as well as drinking outside meals are related to increased CHD risk, independently of volume of drinking. Beverage type does not seem to have much impact, even though there are some indications that wine is more protective than other forms of alcohol. Physiological mechanisms have been identified to explain this complex relationship between alcohol and CHD. Since patterns of drinking are important in determining CHD risk, they should be included in future epidemiologic studies, together with biomarkers further to test hypotheses about pathways.

Reid MC; van Ness PH; Hawkins KA; Towle V; Concato J; Guo ZC. Light to moderate alcohol consumption is associated with better cognitive function among older male veterans receiving primary care. Journal of Geriatric Psychiatry and Neurology 19(2): 98-105, 2006. (49 refs.)

Among older persons, the effects of light to moderate alcohol consumption on cognitive function remain inadequately defined. The authors sought to determine whether light to moderate drinking is associated with better cognitive function among older men. Participants included men aged 65 years or older enrolled in a Veteran's Administration (VA) primary care clinic. Current (past 1 year) and lifetime use, cognitive functioning (as determined by the Trail Making Part B, Symbol Digit, FAS, and Hopkins Verbal Learning tests), and demographic, psychosocial, and medical status were obtained using standardized methods. Participants (N = 760) had a mean age of 74 (range, 65-89) years. Current drinkers (n = 509) as compared with never (n = 31) and former (n = 220) drinkers demonstrated significantly better cognitive performance on 3 (Trails B, Symbol Digit, and Hopkins Verbal Learning) of the 4 tests (P < .01 for all comparisons). In multiple linear regression models, current light to moderate drinking (ie, 7 or fewer drinks per week), as compared to a reference group of never and former drinkers, was associated with better performance on the Trails B, Symbol Digit, and Hopkins Verbal Learning tests (P < .01 for all comparisons). The number of years drinking 7 or fewer drinks per week also was independently associated with better cognitive performance. Current consumption of 7 or fewer drinks per week and the number of years drinking at this level are both associated with better cognitive performance in older male veterans receiving primary care. These findings are consistent with the hypothesis that light to moderate drinking confers cognitive benefits to older persons.

Rimm EB; Moats C. Alcohol and coronary heart disease: Drinking patterns and mediators of effect. Annals of Epidemiology 17(5, Supplement S): S3-S7, 2007. (41 refs.)

An inverse association between alcohol consumption and coronary heart disease (CHD) has been shown in epidemiologic studies for more than 30 years; beneficial changes in high-density lipoprotein (HDL) cholesterol, clotting factors, insulin sensitivity, and inflammation provide biological plausibility. Recently, the importance of including drinking patterns in defining "moderate drinking" has been appreciated. A recent meta-analysis raised questions about systematic misclassification error in observational studies because of inclusion among "nondrinkers" of ex-drinkers and/or occasional drinkers. However, misclassification among a small percentage of nondrinkers cannot fully explain the inverse relation, and there is substantial evidence to refute the "sick Centre" hypothesis. Furthermore, it has been shown that moderate alcohol consumption reduces CHD and mortality in individuals with hypertension, diabetes, and existing CHD. To address the issue of residual confounding by healthy lifestyle in drinkers, in a large prospective study we restricted analysis to only "healthy" men (who did not smoke, exercised, ate a good diet, and were not obese). Within this group, men who drank moderately had a relative risk for CHD of 0.38 (95% Cl, 0.16-0.89) compared with abstainers, providing further evidence to support the hypothesis that the inverse association of alcohol to CHD is causal, and not confounded by healthy lifestyle behaviors.

Romeo J; Warnberg J; Nova E; Diaz LE; Gomez-Martinez S; Marcos A. Moderate alcohol consumption and the immune system: A review. British Journal of Nutrition 98(Supplement 1): S111-S115, 2007. (46 refs.)

Increasing evidence suggests that light to moderate amounts of polyphenol-rich alcoholic beverages like wine or beer could have health benefits. Scientists have long debated the effects of alcohol on immune function, showing on the one hand, that high doses of alcohol consumption can directly suppress a wide range of immune responses, and that alcohol abuse is associated with an increased incidence of a number of infectious diseases. On the other hand, moderate alcohol consumption seems to have a beneficial impact on the immune system compared to alcohol abuse or abstinence. Therefore, the link between alcohol consumption, immune response, as well as infectious and inflammatory processes remains not completely understood. With this in mind, it is important to realise that other factors, unrelated or indirectly related to immune function, like drinking patterns, beverage type, amount of alcohol, or gender differences, will affect the influence that alcohol consumption may have on the immune system. This review summarises published data describing the effects that light to moderate amounts of polyphenol-rich beverages like wine or beer seem to have on immunity in healthy adults.

Rouillier P; Boutron-Ruault MC; Bertrais S; Arnault N; Daudin JJ; Bacro JN et al. Alcohol and atherosclerotic vascular disease risk factors in French men: Relationships are linear, J-shaped, and U-shaped. Alcoholism: Clinical and Experimental Research 29(1): 84-88, 2005. (24 refs.)

Background: Although it is well admitted that alcohol displays a U-shaped relationship with atherosclerotic vascular disease, individual relationships between alcohol and atherosclerosis risk factors may be different and have not been determined precisely for several of them. Methods: A cross-sectional study within the SU.VI.MAX French cohort study was performed to assess the curve of potential relationships between alcohol and atherosclerosis risk factors in 2126 healthy men. Mean daily alcohol intake was derived from 37 alcoholic beverages in twelve 24-hr dietary recalls. Logistic models were adjusted for age. Results: Apolipoprotein B (ApoB), fasting glucose, body mass index, waist-to-hip ratio, and waist circumference displayed a linear relationship with alcohol. The odds ratios and 95% confidence intervals associated