Co-Occurrence of IgA Antibodies Against Ethanol Metabolites and Tissue Transglutaminase in Alcohol Consumers: Correlation with Proinflammatory Cytokines and Markers of Fibrogenesis

IgA antibodies to tissue transglutaminase have been suggested to be specific indicators of celiac disease. However, no studies have addressed the relationships between such antibodies and alcohol abuse, which is also a common cause of IgA-isotype immune responses and tissue injury in the gastrointestinal tract and liver. Here, measurements of specific IgAs against tissue transglutaminase and proteins modified by acetaldehyde, the first metabolite of ethanol, showed significantly higher levels of both antibodies in alcoholic liver disease patients than in healthy controls or heavy drinkers without liver disease. These antibodies also significantly co-occurred in heavy drinkers without liver disease, moderate drinkers, and abstainers, and correlated with biomarkers of alcohol consumption, proinflammatory cytokines and markers of fibrogenesis. The data suggests a link between such immune responses, perturbations in cytokine profiles and fibrogenesis, which should be implicated in studies on the pathogenesis and diagnosis of ethanol-induced tissue injury and celiac disease.     

Immune Responses to Ethanol Metabolites and Cytokine Profiles Differentiate Alcoholics with or without Liver Disease

OBJECTIVES: Excessive alcohol consumption is associated with the generation of antibodies against neoantigens induced by ethanol metabolism. However, the associations between such immune responses, ethanol consumption, and liver injury remain unclear. METHODS: Eight-six male alcoholics with (n=54) or without (n=32) liver disease, and 20 male volunteers (6 abstainers, 14 moderate drinkers) underwent clinical, morphological, and biochemical assessments of liver status and ethanol consumption. RESULTS: Antiacetaldehyde adduct IgAs in both groups of alcoholics were significantly higher than those in the controls. Elevated IgGs occurred in patients with liver disease, whereas IgMs were high in the heavy drinkers without apparent liver disease. Liver disease patients had high levels of both proinflammatory (IL-2, IL-6, IL-8, TNF-alpha) and antiinflammatory (IL-10) cytokines, whereas those without liver disease showed elevated IL-6, IL-8, and IL-10 only. Ethanol consumption correlated significantly with antiadduct IgA and IL-6 levels, which also showed parallel changes upon abstinence. CONCLUSIONS: Alcoholic liver disease is associated with the generation of IgAs and IgGs against acetaldehyde-derived antigens and enhanced levels of both pro- and antiinflammatory cytokines, whereas elevated IgA, IL-6, and IL-10 characterize alcoholics without liver disease. These data suggest that immunological mechanisms may play a role in the sequence of events leading to liver disease in some patients with excessive drinking.     

IgA Immune Responses Against Acetaldehyde Adducts and Biomarkers of Alcohol Consumption in Patients with IgA Glomerulonephritis

Background: The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo‐antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined. Methods: A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self‐reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate‐deficient transferrin (CDT), glutamyl transferase, γ‐CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde–protein adducts. Results: In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and γ ‐CDT, p < 0.05. In the reference population, all biomarkers and anti‐adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti‐adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self‐reported ethanol intake. Conclusions: These data indicate high levels of IgA antibodies against acetaldehyde‐derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti‐adduct immune responses in IgAGN patients are warranted.     

Alcohol intake and diet in France, the prominent role of lifestyle.

AIM: Moderate alcohol intake is related to a decrease of coronary heart disease. This protective effect may be attributed to ethanol but may also depend on the type of alcoholic beverages. However, these differences may be confounded by lifestyle and diet. We investigated the relationships between alcohol consumption, beverage type preference and socio-economic status, diet and lifestyle. METHODS AND RESULTS: A cross-sectional survey on cardiovascular risk factors and nutrition was carried out from 1995 to 1997 by the French MONICA Centres. A sample of 1110 middle-aged men (45-64 years) was randomly recruited; 12.8% of men were abstainers and 16.3% reported a consumption of #10878;60 g/d alcohol. Smoking, waist-to-hip ratio and hypertension increased along with the amount of alcohol intake. Physical activity (from 40.9% in abstainers to 23.8% in heavy drinkers, p=0.0025), educational level (from 11.9+/-4.4 to 11.1+/-3.8 years, p=0.01), socio-economic status and diet quality index (from 7.1+/-2.3 to 6.3+/-2.0, p<0.0001 after multivariate adjustment) decreased along with the increase of alcohol consumption and were higher among wine drinkers than among beer or mixed drinkers. Diet quality index was 7.1+/-1.9, 6.4+/-1.8 and 6.6+/-1.9 among wine, beer and mixed drinkers, respectively (p=0.007 after multivariate adjustment). CONCLUSION: Moderate alcohol drinkers or wine drinkers have healthy diet and behaviours compared to other drinkers or abstainers. The living area plays a significant role in the dieting behaviours.     

Alcohol consumption, alcohol dependence, and all-cause mortality

BACKGROUND: This study examined the effects of alcohol consumption and DSM-IV alcohol dependence on the risk of mortality. METHODS: Data from the 1988 National Health Interview Survey Alcohol Supplement were matched to the National Death Index for the years 1988 to 1995 (baseline n = 37,682 U.S. adults age > or =25 linked to 3,586 deaths). All mortality analyses were based on proportional hazards models that adjusted for age, sex, race/ethnicity, marital status, education, income, labor force status, body mass index, smoking status, and poor health indicators at baseline. RESULTS: When dependence was not considered and all past-year abstainers were used as the reference group, both light and moderate drinkers exhibited a reduced risk of mortality, with hazards ratios of 0.76 (0.68-0.84) and 0.84 (0.74-0.96). Heavy drinkers had about the same risk of dying as did past-year abstainers, and very heavy drinkers had an increased risk that was not significant (OR = 1.17, CI = 0.93-1.47). When lifetime abstainers were used as the reference category, the protective effect of moderate drinking fell short of significance, and there were nearly significant increased risks among former drinkers and very heavy drinkers. When dependence was considered, light and moderate drinkers without dependence had a reduced mortality risk regardless of reference group, and there was no significant effect among heavy or very heavy drinkers without dependence. Among dependent drinkers, there was no protective effect of light or moderate drinking, and very heavy drinkers had a significantly increased risk (OR = 1.56 relative to past-year abstainers and 1.65 relative to lifetime abstainers). CONCLUSIONS: Because alcohol dependence nullifies the protective effect of light and moderate drinking, it is important to understand its role as an independent risk factor for mortality. Differences between dependent and nondependent drinkers who drank comparable amounts suggest that this risk may result from longer and heavier drinking histories before baseline, more severe health problems at baseline, more heavy episodic drinking, and, possibly, differences in beverage preference.     

Heavy alcohol intake, homocysteine and Type 2 diabetes.

Although moderate alcohol intake is associated with reduced risk of atherosclerotic disease in both the general population and in diabetic patients, a recent report suggests that heavy alcohol intake facilitates the development of atherosclerosis exclusively in diabetic individuals. We studied cross-sectionally the effects of the interaction between ethanol consumption category and the prevalence of diabetes on plasma total homocysteine (tHcy), a risk factor for atherosclerotic disease, in middle-aged men. Heavy drinking was associated with elevated tHcy levels only in diabetic subjects but not in non-diabetic subjects. Plasma tHcy of heavy drinkers (average ethanol consumption > 30 ml/day) was higher than that of abstainers in the diabetic subgroup (10.25 +/- 3.39 vs. 8.88 +/- 1.94 micromol/l, P < 0.05), whereas tHcy levels in heavy drinkers were comparable with that of abstainers in the non-diabetic subgroup (9.36 +/- 2.52 vs. 9.12 +/- 2.10 micromol/l, NS). In a two-factor anova, significant interaction was observed on the effects of ethanol consumption category and diabetes prevalence on tHcy levels (P < 0.01). Confounding factors including folate, vitamin B(12), creatinine, age or cigarette smoking did not contribute to the interaction. These findings may partly explain the reported association between heavy drinking and atherosclerosis in diabetic subjects.     

Alcohol use, alcohol disorders, and the use of health services: results from a population survey.

Data from a population survey were used to explore relationships among drinking levels/patterns, alcohol dependence or abuse, and the use of emergency services, hospital admissions, and frequent visits to general practitioners in the past year. For both males and females, self-reported hospital admissions were less common among daily moderate drinkers than among lifetime abstainers. Among males, drinkers with no history of alcohol dependence or abuse were less likely to report being in hospital in the last year than lifetime abstainers. For females, some groups defined by drinking patterns/levels and current drinkers without symptoms of alcohol abuse or dependence were more likely to report using emergency services than lifetime abstainers.     

Alcohol consumption and mortality in Alameda County

The association between level of alcohol consumption and 15-year mortality, focusing particularly on the possible protective effect of light drinking compared to abstention, was studied in a representative population sample of 6928 residents of Alameda County, California. Because abstainers differ from light, moderate and heavy drinkers on a number of demographic, physical, and psychosocial characteristics, the role of these as confounders of the alcohol/mortality association was examined. Using multiple logistic models, the mortality experience of abstainers, moderate drinkers, heavy drinkers and very heavy drinkers was compared with that of light drinkers. Among men only, very heavy drinkers were at significantly greater risk of death from all causes than were light drinkers (OR = 2.5, p less than 0.01). Neither abstainers nor other drinkers were at significantly higher risk of death from ischemic heart disease than were light drinkers. This pattern of results persisted with adjustment for 11 covariates of alcohol consumption in addition to age.     

Oxidative stress and a thrombophilic condition in alcoholics without severe liver disease

BACKGROUND AND OBJECTIVES: The degree of oxidative stress and its association with a thrombophilic condition, if any, were investigated in alcoholics before the onset of severe liver disease. DESIGN AND METHODS: Reactive oxygen species and total antioxidant capacity were evaluated using two new kinetic spectrophotometric methods in a selected group of 45 consecutive chronic alcohol abusers and 42 apparently healthy moderate drinkers, used as controls. The hemostatic system was explored by detecting the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT) with enzyme-linked immunosorbent assays, while D-dimer plasma levels were measured with a turbidimetric immunoassay. RESULTS: Reactive oxygen species were significantly higher (p<0.001) in heavy drinkers than in controls: 328.1 (143.4-847.2) U.CARR vs 250 (200.7-366.8) U.CARR, respectively. The total antioxidant capacity was similar in chronic alcohol abusers and in moderate drinkers: 360.2 (336.8-374.4) microMol HClO/mL vs 369 (362-378.4) microMol HClO/mL, respectively. All molecular markers of hemostatic system activation were significantly increased in chronic alcohol abusers in comparison with those in moderate drinkers, as follows: TAT: 2.5 (1.4-13) microg/L vs 1.5 (1-4.1) mocrog/L, respectively (p<0.001); F1+2: 1.7 (0.5-5.2) nMol/L vs 0.9 (0.4-1.1) nMol/L, respectively (p<0.01); D-dimer: 235.5 (208-462) ng/mL vs 163.5 (71-233) ng/mL, respectively (p<0.001). INTERPRETATION AND CONCLUSIONS: Our results suggest that oxidative stress and a thrombophilic condition can be observed in heavy drinkers without severe liver disease. The new test available for measuring reactive oxygen species in serum proved to be reliable and useful as an early marker of tissue damage.     

Carbohydrate-Deficient Transferrin as an Alcohol Marker among Female Heavy Drinkers: A Population-Based Study

Carbohydrate-deficient transferrin (CDT) has previously been reported to be an excellent marker of male alcoholics. Less is known of its efficiency among women and especially of early-phase alcohol abuse in nonselected populations. The present population-based study examined the diagnostic value of CDT among consecutive women, including 13 teetotallers, 135 social drinkers (mean alcohol consumption 45 ± 34 g/week), and 57 nonalcoholic heavy drinkers (197 ± 97 g/week). Sixty-two women with a well-documented history of chronic alcoholism (942 ± 191 g/week) were also studied, as well as 36 pregnant women used as a reference group. Two weeks of abstinence among 11 alcoholics was followed. The CDT (containing part of isotransferrin with pl = 5.7, 5.8, and 5.9) was separated by anion exchange chromatography and assayed by radioimmunoassay. In the whole material, CDT correlated significantly with alcohol consumption (r= 0.43, p < 0.001) but not with conventional markers (γ-glutamyltransferase, AST, ALT, and mean corpuscular volume). The CDT values of alcoholics (34 ± 20 units/liter) were significantly (p < 0.001) higher than those of teetotallers (19 ± 6 units/liter), social drinkers (20 ± 6 units/liter), or pregnant women (16 ± 13 units/ liter). Heavy drinkers also had higher values (25 ± 13 units/liter), but the difference did not reach statistic significance. The specificity of CDT was on the level of conventional markers when the cut-off value was increased from 26 to 29 units/liter. At a specificity of 95%, CDT found 19% of the heavy drinkers and 52% of the alcoholics; the best traditional marker, AST, with a specificity of 97%, found 7% and 56%, respectively. CDT was useful for follow-up of alcohol withdrawal when its initial value was elevated. In general, CDT (as well as conventional laboratory markers) does not seem to be sensitive enough in the detection of alcohol abuse in the female population. This is especially clear among nonalcoholic female heavy drinkers. CDT gives, however, additional information about alcohol abuse, and it may be recommended for parallel use with conventional markers in clinical use.     

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C

The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hydroxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated as markers of oxidative stress in 145 CHC patients with different alcohol consumption, 20 HCV-free heavy drinkers (HD) without liver disease, and 50 healthy controls. Anti-MDA IgG was increased in CHC patients irrespective of alcohol intake as well as in the HD group. CHC patients with moderate alcohol intake (<50 g ethanol/d), but not HD, also had significantly higher values of anti-AAHP-HSA, anti-HNE-HSA, and anti-Ox-CL IgG (P <.05) than controls. A further elevation (P <.001) of these antibodies was evident in CHC patients with heavy alcohol intake (>50 g ethanol/d). Anti-AAHP and anti-Ox-CL IgG above the 95th percentile in the controls were observed in 24% to 26% of moderate and 58% to 63% of heavy drinkers but only in 6% to 9% of the abstainers. The risk of developing oxidative stress during CHC was increased 3-fold by moderate and 13- to 24-fold by heavy alcohol consumption. Heavy drinking CHC patients had significantly more piecemeal necrosis and fibrosis than abstainers. Diffuse piecemeal necrosis was 4-fold more frequent among alcohol-consuming patients with lipid peroxidation-related antibodies than among those without these antibodies. In conclusion, even moderate alcohol consumption promotes oxidative stress in CHC patients, suggesting a role for oxidative injury in the worsening of CHC evolution by alcohol.     

CDT by Anion-Exchange Chromatography Followed by RIA as a Marker of Heavy Drinking Among Men

Carbohydrate-deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population-based study examined the diagnostic value of CDT among consecutive middle-aged males including 122 social drinkers (mean alcohol consumption 88 ± 79 g per week) and 77 non-alcoholic heavy drinkers (301 ± 195 g/wk). Ninety-six men with a well-documented history of chronic alcoholism (≥1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pl = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean ± SD = 14 ± 5 U/I) were significantly lower than those of heavy drinkers (19 ± 13 U/I, p < 0.01) and alcoholics (34 ± 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption ( r = 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non-alcoholic heavy drinkers.     

Relative Versus Absolute Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

BACKGROUND: Carbohydrate-deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate-deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis. METHODS: Absolute concentrations (U/I) and relative values (%) of carbohydrate-deficient transferrin determined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionnaire) in patients with acute alcoholic hepatitis (n = 19), alcoholic liver cirrhosis (n = 37), and nonalcoholic liver diseases (n = 16). RESULTS: The concentration of carbohydrate-deficient transferrin was increased (p < 0.001) in nonabstaining patients (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 +/- 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 +/- 7.8 U/l) despite higher alcohol consumption (median 130 g/d), nor in abstainers with alcoholic liver cirrhosis (19.4 +/- 6.0 U/l) or nonalcoholic liver disease (18.5 +/- 6.7 U/l). However, the relative values of carbohydrate-deficient transferrin were increased both in acute alcoholic hepatitis (7.9 +/- 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 +/- 2.8%), but not in abstainers with alcoholic liver cirrhosis (4.6 +/- 3.5%) or nonalcoholic liver disease (3.8 +/- 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, respectively, but 79% and 97% for relative values of carbohydrate-deficient transferrin. The concentrations of carbohydrate-deficient and total transferrin in serum were strongly correlated (r = 0.60; p = 0.008). CONCLUSIONS: The relative value (% of total), but not the absolute concentration, of carbohydrate-deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.     

High Diastolic Blood Pressure: Common Among Women Who Are Heavy Drinkers

The present study evaluates the relationship of different alcohol consumption levels to blood pressure among women. Blood pressure values were compared between four groups of women consuming different amounts of alcohol. Three groups were formed from the middle-aged female population participating in a health survey ( n = 219): 15 consecutive alcohol abstainers, 136 consecutive moderate drinkers, and 68 consecutive heavy drinkers. Also, 78 consecutive female alcoholics reporting for treatment were included, forming the fourth group. The prevalence of systolic blood pressure ≥160 mm Hg did not increase in relation to alcohol consumption. In contrast, the percentage of women showing diastolic blood pressure ≥90 mm Hg clearly increased ( p = 0.004) from abstainers (7%) to moderate drinkers (18%), to heavy drinkers (32%), and to alcoholics (37%). The highest blood pressure values were found among heavy drinkers. Compared with abstainers, the mean difference in systolic blood pressure was –12 mm Hg, with a 95% confidence interval from –2 to –23 mm Hg. For diastolic blood pressure, the difference was –6 mm Hg with a 95% confidence interval from 1 to –13 mm Hg. Among alcoholics, the blood pressure values had returned essentially to normal after 4 days of abstinence. It is concluded that alcohol consumption increases both systolic and diastolic blood pressure values among women. However, only diastolic blood pressure values increase enough to be clinically significant. Moderately elevated diastolic blood pressure, combined with normal systolic blood pressure, might thus be a possible sign of alcohol abuse among women. Abstinence should be emphasized as an inexpensive and rapidly effective treatment for mild hypertension among female alcohol abusers.     

Drinking and spouse abuse among U.S. Army soldiers

BACKGROUND: This study examines the relationship between typical weekly drinking and perpetration of spouse abuse as well as the relationship between the perpetrator's typical weekly drinking and alcohol use during the abuse event among U.S. Army male soldiers. METHODS: Cases include all active duty, male, enlisted Army spouse abusers identified in the Army's Central Registry who had also completed an Army Health Risk Appraisal Survey (HRA) between 1991 and 1998 (N = 9534). Cases were matched on sex, rank, and marital status with 21,786 control subjects who had also completed an HRA. RESULTS: In multivariate logistic regression models, heavy drinkers (22 or more drinks per week) were 66% more likely to be spouse abusers than were abstainers (odds ratio 1.66; 95% confidence interval 1.40-1.96). In addition, self-reported moderate and heavy drinkers were three times as likely and light drinkers (1-7 drinks per week) were twice as likely as nondrinkers to be drinking during the time of the abuse event. CONCLUSION: Self-reported heavy drinking is an independent risk factor for perpetration of spouse abuse among male, enlisted Army soldiers. Even 5 years or more after ascertainment of typical drinking habits, there is a significant association between self-reported heavy drinking and alcohol involvement at the time of the spouse abuse event. Personnel who work with perpetrators and victims of spouse abuse should be trained carefully to query about current and typical drinking patterns.     

Alcohol use and cardiovascular disease preventive services

BACKGROUND: Moderate drinking is associated with decreased cardiovascular mortality. Biological effects may mediate this association, but differences in utilization of preventive services may be important. DESIGN AND METHODS: Cross-sectional analysis of adults participating in the Third National Health and Nutrition Examination Survey with data on alcohol use and prior use of services for the detection and treatment of hypertension and hypercholesterolaemia. Regression models were analysed to provide age-, sex- and race-adjusted risk estimates for outcomes related to these services for several patterns of alcohol use relative to regular light drinkers. RESULTS: Hypertension was more common in most alcohol use strata compared with regular light drinkers (adjusted prevalence ratios 1.22 for lifelong abstainers, 1.33 for nonlifelong abstainers, 1.35 for infrequent moderate drinkers, 2.01 for frequent moderate drinkers, 1.73 for infrequent heavy drinkers and 1.98 for regular heavy drinkers, P-values < 0.05). Having had blood pressure measured was similar in all drinking strata. The prevalence of hypercholesterolaemia was similar in drinking strata, but most drinking patterns were associated with lower use of services to detect high cholesterol (prevalence ratios 0.7 for lifelong abstainers, 0.8 for nonlifelong abstainers, infrequent moderate and regular moderate drinkers, 0.6 for infrequent heavy drinkers, and 0.7 for regular heavy drinkers, P-values < 0.05). CONCLUSIONS: The utilization of cardiovascular disease preventive services may contribute to the beneficial association of moderate drinking with cardiovascular mortality. Additional research is needed to estimate the influence of differences in health services utilization on the association of alcohol use with cardiovascular disease outcomes.     

Longitudinal analysis of alcohol consumption and health of middle-aged women in Australia

Aims To assess the prospective association between alcohol consumption and self‐rated health: in particular whether there is a relationship between stable alcohol intake and health; whether health is affected by changes in alcohol consumption; whether having a chronic condition alters the relationships between stable and changing alcohol intake and health; and whether the health of longer‐term abstainers is different from more recent and intermittent abstainers. Design Longitudinal analysis of a prospective, population‐based study. Setting Australia. Participants A total of 13 585 randomly selected 45–50‐year‐old women surveyed in 1996, of whom 9396 (69%) were resurveyed in 1998, 2001 and 2004. Measurements Estimates for the General Health subscale of the SF‐36 for different levels of alcohol intake adjusted for having a chronic condition, depression, smoking and other factors. Findings Longitudinal models of consistent alcohol intake showed mean scores for general health of moderate drinkers were significantly better than that of non‐drinkers [mean difference = 4.3, standard error (SE) = 0.61], occasional drinkers (mean difference = 3.1, SE = 0.52) and heavy drinkers (mean difference = 2.1, SE = 1.00). Among moderate drinkers, a decrease or variation in alcohol consumption was associated with a significant decline of three to four points in general health. Similar results were obtained when women with an existing chronic condition were excluded from these models. The health of recent abstainers and intermittent drinkers was the same as longer‐term abstainers. Conclusions Consistent moderate drinkers had the best health even after adjustment for having a chronic condition, depression and life‐style factors. Poorer health was associated with decreased alcohol intake among occasional and moderate drinkers.     

Relationship Between Alcohol Intake and Immunoglobulin A Immunoreactivity with Acetaldehyde-Modified Bovine Serum Albumin

Acetaldehyde, the main metabolite of ethanol, is a highly reactive species that reacts with macromolecules to produce unstable and stable adducts. Acetaldehyde-modifled proteins are immunogenic and have been detected in the liver and blood of alcoholics. Furthermore, antibodies reactive with acetaldehyde-modified proteins have been detected in the plasma of social drinkers and alcoholics. However, the class distribution of immunoglobulins reactive with modified proteins was different in the two groups, being predominantly immunoglobulin (Ig)M in social drinkers, but IgM and IgA in alcoholics. In this study, we demonstrate that heavy drinkers (alcohol intake > 130 g/week for females and 150 g/week for males) also exhibit IgA reactivity with acetaldehyde-modified proteins. The IgA adduct-spe-cific reactivity (IgA reactivity with acetaldehyde-modified bovine serum albumin-reactivity with native bovine serum albumin) showed a moderate correlation with self-reported alcohol intake, but did not correlate with markers such as plasma transaminase, γ-glutamyl-transferase activity, or mean corpuscular volume. IgA adduct-spe-cific reactivity had similar specificity to the conventional tests of alcohol abuse, but had higher sensitivity than the other tests, especially with heavy drinkers. Data presented herein demonstrate that elevated IgA reactivity with acetaldehyde-modified epitopes is associated with heavy drinking and is a potential marker for high alcohol intake.     

Moderate Alcohol Consumption Protects Against Colorectal Adenomas in Smokers

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.     

Effects of alcohol consumption on cardiovascular events in male patients with healed myocardial infarction.

BACKGROUND: In Western countries, many studies have shown that among healthy people moderate drinkers have a lower incidence of cardiovascular events than abstainers and heavy drinkers. However, it is not clear whether this is true in patients with a healed myocardial infarction (MI). METHODS AND RESULTS: In the present study cardiovascular events were defined as cardiac events or strokes. Male patients only were included because the incidence of cardiovascular events is low in females. In patients younger than 65 years, the incidence of cardiovascular events was 34.6 persons per year (54 cases: 3.9%) of abstainers, 17.4 persons per year (20 cases: 1.9%) of moderate drinkers (p<0.01 vs abstainers) and 30.3 s persons per year (18 cases: 3.2%) of heavy drinkers. However, in those aged 65 years or older, the incidence was 47.8 persons per year (24 cases: 4.5%) of abstainers, 58.4 persons per year (14 cases: 5.6%) of moderate drinkers, and 314.8 persons per year (12 cases: 19.7%) of heavy drinkers. In this age group, cardiovascular events were significantly higher in heavy drinkers than in the other 2 groups (p<0.01), and the incidence was not lower in the moderate drinkers than in abstainers as shown in the younger group. CONCLUSIONS: In patients younger than 65 years with a healed MI, drinking limited less than 30 ml/day (moderate intake) reduces the incidence of cardiovascular events, but not in those aged 65 years or older.