5: Cancer Lett 2000 Sep 29;158(1):85-91 Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Schneider Y, Vincent F, Duranton B, Badolo L, Gosse F, Bergmann C, Seiler N, Raul F. ULP/CJF INSERM 95-09, Laboratory of Metabolic and Nutritional Control in Digestive Oncology, IRCAD, 1 Place de l'Hopital, 67091, Strasbourg, France. Resveratrol, a natural polyphenolic phytoalexine present in grapes and wines, has been reported to exert a variety of important pharmacological effects. We investigated the effects of resveratrol on the growth and polyamine metabolism of CaCo-2 human colon cancer cells. Treatment of the CaCo-2 cells with 25 microM resveratrol caused a 70% growth inhibition. The cells accumulated at the S/G2 phase transition of the cell cycle. No signs of cytotoxicity or apoptosis were detected. Resveratrol caused a significant decrease of ornithine decarboxylase (ODC) activity, a key enzyme of polyamine biosynthesis, which is enhanced in cancer growth. ODC inhibition resulted in the reduction of the intracellular putrescine content, indicating that polyamines might represent one of several targets involved in the anti-proliferative effects of resveratrol. PMID: 10940513 [PubMed - indexed for MEDLINE]
1: N Engl J Med 2001 Feb 22;344(8):549-55 Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. Hines LM, Stampfer MJ, Ma J, Gaziano JM, Ridker PM, Hankinson SE, Sacks F, Rimm EB, Hunter DJ. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. lhines@hsph.harvard.edu BACKGROUND: A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3) alters the rate of alcohol metabolism. We investigated the relation among the ADH3 polymorphism, the level of alcohol consumption, and the risk of myocardial infarction in a nested case-control study based on data from the prospective Physicians' Health Study. METHODS: We identified 396 patients with eligible newly diagnosed cases of myocardial infarction among men in the Physicians' Health Study. Of these patients, 374 were matched with 2 randomly selected control subjects each and the remaining 22 with 1 control each (total, 770 controls). The ADH3 genotype (gamma1gamma1, gamma1gamma2, or gamma2gamma2) was determined in all subjects. We examined the relations among the level of alcohol intake, the ADH3 genotype, and plasma high-density lipoprotein (HDL) levels in this study population and in a similar cohort of women. RESULTS: As compared with homozygosity for the allele associated with a fast rate of ethanol oxidation (gamma1), homozygosity for the allele associated with a slow rate of ethanol oxidation (gamma2) was associated with a reduced risk of myocardial infarction (relative risk, 0.65; 95 percent confidence interval, 0.43 to 0.99). Moderate alcohol consumption was associated with a decreased risk of myocardial infarction in all three genotype groups (gamma1gamma1, gamma1gamma2, and gamma2gamma2); however, the ADH3 genotype significantly modified this association (P=0.01 for the interaction). Among men who were homozygous for the gamma1 allele, those who consumed at least one drink per day had a relative risk of myocardial infarction of 0.62 (95 percent confidence interval, 0.34 to 1.13), as compared with the risk among men who consumed less than one drink per week. Men who consumed at least one drink per day and were homozygous for the gamma2 allele had the greatest reduction in risk (relative risk, 0.14; 95 percent confidence interval, 0.04 to 0.45). Such men also had the highest plasma HDL levels (P for interaction = 0.05). We confirmed the interaction among the ADH3 genotype, the level of alcohol consumption, and the HDL level in an independent study of postmenopausal women (P=0.02). CONCLUSIONS: Moderate drinkers who are homozygous for the slow-oxidizing ADH3 allele have higher HDL levels and a substantially decreased risk of myocardial infarction. PMID: 11207350 [PubMed - indexed for MEDLINE]
2: BMJ 1999 Dec 11;319(7224):1523-8 Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. eric.rimm@channing.harvard.edu OBJECTIVE: To summarise quantitatively the association between moderate alcohol intake and biological markers of risk of coronary heart disease and to predict how these changes would lower the risk. DESIGN: Meta-analysis of all experimental studies that assessed the effects of moderate alcohol intake on concentrations of high density lipoprotein cholesterol, apolipoprotein A I, fibrinogen, triglycerides, and other biological markers previously found to be associated with risk of coronary heart disease. PARTICIPANTS: Men and women free of previous chronic disease and who were not dependent on alcohol. Studies were included in which biomarkers were assessed before and after participants consumed up to 100 g of alcohol a day. INTERVENTIONS: Alcohol as ethanol, beer, wine, or spirits. MAIN OUTCOME MEASURES: Changes in concentrations of high density lipoprotein cholesterol, apolipoprotein A I, Lp(a) lipoprotein, triglycerides, tissue type plasminogen activator activity, tissue type plasminogen activator antigen, insulin, and glucose after consuming an experimental dose of alcohol for 1 to 9 weeks; a shorter period was accepted for studies of change in concentrations of fibrinogen, factor VII, von Willebrand factor, tissue type plasminogen activator activity, and tissue type plasminogen activator antigen. RESULTS: 61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol. On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease. CONCLUSIONS: Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors. Publication Types: Meta-analysis PMID: 10591709 [PubMed - indexed for MEDLINE]
3: Am Heart J 1991 Jun;121(6 Pt 1):1854-6 Bashing booze: the danger of losing the benefits of moderate alcohol consumption. Kaplan NM. Publication Types: Editorial PMID: 2035417 [PubMed - indexed for MEDLINE]
4: Atherosclerosis 2000 Nov;153(1):107-17 Catechin in the Mediterranean diet: vegetable, fruit or wine? Ruidavets J, Teissedre P, Ferrieres J, Carando S, Bougard G, Cabanis J. INSERM U 518, Departement d'epidemiologie, Faculte de medecine, 37 Allees Jules Guesde, 31073 Cedex, Toulouse, France. ruidavet@cict.fr The aim of this study was to determine which type of diet contributes most to plasma concentration of (+)-catechin, a naturally occurring antioxidant flavonoid. Consecutive subjects (n=180) were screened. A blood sample was collected after a fasting period and (+)-catechin measurement in plasma was performed by high-performance liquid chromatography (HPLC) method using fluorescence detection. Dietary consumption of the last evening meal was assessed by a dietary recall method. Taking fruit, vegetable and wine consumption into account, four types of diet were identified. After adjustment for confounding factors, concentration of (+)-catechin in plasma was three-fold higher in diet with fruit and vegetable but without wine (449.5 microg/l), and four-fold higher in diet with wine but without vegetable and fruit (598.5 microg/l) in comparison to diet without fruit, vegetable and wine (131.6 microg/l). When the consumption of vegetable, fruit and wine was combined, the concentration was the highest (637.1 microg/l) (P<0. 001). Vegetable, fruit and wine were the major determinants of plasma (+)-catechin concentration (P<0.001). This study demonstrates that the highest plasma concentration of (+)-catechin was observed in subjects consuming fruit, vegetable and wine, and its antioxidant and antiaggregant activity could partly explain the relative protection against coronary heart disease (CHD). PMID: 11058705 [PubMed - indexed for MEDLINE]
6: Eur J Clin Nutr 2000 Apr;54(4):321-8 Patterns of alcohol consumption in middle-aged men from France and Northern Ireland. The PRIME study. Marques-Vidal P, Arveiler D, Evans A, Montaye M, Bingham A, Ruidavets JB, McMaster D, Haas B, Amouyel P, Ducimetiere P. INSERM U518, Faculte de Medecine Purpan, Toulouse, France. OBJECTIVE: To assess the patterns of alcohol consumption in France and Northern Ireland. DESIGN: Four cross-sectional studies. SETTING: Sample of 50-59 y old men living in France and Northern Ireland, consuming at least one unit of alcoholic beverage per week. SUBJECTS: 5363 subjects from France and 1367 from Northern Ireland. INTERVENTIONS: None. RESULTS: Consumption of wine was higher in France whereas consumption of beer and spirits was higher in Northern Ireland. Alcohol drinking was rather homogeneous throughout the week in France, whereas Fridays and Saturdays accounted for 60% of total alcohol consumption in Northern Ireland. In both countries, current smokers had a higher consumption of all types of alcoholic beverages than non-smokers. Similarly, obese and hypertensive subjects had a higher total alcohol consumption than non-obese or normotensive subjects, but the type of alcoholic beverages differed between countries. In Northern Ireland, subjects which reported some physical activity consumed significantly less alcoholic beverages than sedentary subjects, whereas no differences were found in France. Conversely, subjects with dyslipidemia consumed more alcoholic beverages than normolipidemic subjects in France, whereas no differences were found in Northern Ireland. In France, total alcohol, wine and beer consumption was negatively related to socioeconomic status and educational level. In Northern Ireland, total alcohol, beer and spirits consumption was negatively related whereas wine consumption was positively related to socioeconomic status and educational level. CONCLUSIONS: Alcohol drinking patterns differ between France and Northern Ireland, and also according to cardiovascular risk factors, socioeconomic and educational levels. SPONSORSHIP: Merck, Sharp & Dohme-Chibret (France), the NICHSA and the Department of Health and Social Service (Northern Ireland). PMID: 10745283 [PubMed - indexed for MEDLINE]
7: Eur J Clin Invest 1999 May;29(5):387-94 Moderate red wine consumption in healthy volunteers reduced plasma clearance of apolipoprotein AII. Gottrand F, Beghin L, Duhal N, Lacroix B, Bonte JP, Fruchart JC, Luc G. Department of Atherosclerosis, INSERM U325, Institut Pasteur de Lille, France. BACKGROUND: The mechanisms of the positive relationship between alcohol intake and plasma concentration of high-density lipoprotein (HDL) are still unclear. The present study shows the metabolism modifications of apolipoprotein (apo) AI and apoAII in normolipidaemic healthy volunteers after a period of moderate red wine consumption. DESIGN: Five non-smoking male subjects were studied at the end of two consecutive 4-week periods, one without alcohol and the other with an intake of 50 g per day of alcohol, in random order. The metabolic parameters of apoAI and apoAII in HDL were determined after endogenous labelling using amino acid labelled with stable isotope. Cholesterol, triacylglycerols, HDL-cholesterol, apoAI, apoAII, LpAI, LpAI:AII were determined in plasma at the end of the two study periods. RESULTS: Cholesterol and triacylglycerols did not vary significantly during the two periods, whereas HDL-cholesterol increased from 43.8 to 50.0 mg dL-1 (P < 0.05). ApoAI and apoAII increased significantly (20% and 60% respectively) after the diet was supplemented with alcohol. LpAI:AII increased from 73.8 to 101.6 mg dL-1 (+32%) (P < 0.05), whereas alcohol had no effect on the concentration of LpAI. The alcohol treatment did not significantly alter the metabolism of apoAI. Conversely, the fractional catabolic rate of apoAII decreased significantly by 21% (P < 0.05) with alcohol, whereas the production rate of apoAII tended to increase by 18% (P = 0.08). CONCLUSION: The decrease in the fractional catabolic rate of apoAII could lead to an accumulation of apoAII-containing lipoproteins in plasma and account for the dramatic increase in LpAI:AII observed in the plasma of subjects consuming alcohol. Publication Types: Clinical trial Randomized controlled trial PMID: 10354195 [PubMed - indexed for MEDLINE]
8: Novartis Found Symp 1998;216:208-17; discussion 217-22, 152-8 The French paradox and wine drinking. Renaud S, Gueguen R. INSERM (Institut National pour la Sante et al Recherche Medicale), Unit 330, Universite Bordeaux 2, France. Despite a high level of risk factors such as cholesterol, diabetes, hypertension and a high intake of saturated fat, French males display the lowest mortality rate from ischaemic heart disease and cardiovascular diseases in Western industrialized nations (36% lower than the USA and 39% lower than the UK). By contrast, mortality from all causes is only 8% lower than in the USA and 6% than in the UK, owing to a high level of cancer and violent deaths. In a recent study of 34,000 middle-aged men from Eastern France with a follow-up of 12 years we have observed that for 48 g of alcohol (mostly wine) per day as the mean intake, mortality from cardiovascular diseases was lower by 30%, all-cause mortality was reduced by 20%, but mortality by cancer and violent death was increased compared with abstainers. Thus the so-called 'French Paradox' (a low mortality rate specifically from cardiovascular diseases) may be due mainly to the regular consumption of wine. Publication Types: Review Review, tutorial PMID: 9949795 [PubMed - indexed for MEDLINE]
9: Rev Neurol (Paris) 1997 Apr;153(3):185-92 Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB. Unite de Recherche Epidemiologique, INSERM U 330, Universite de Bordeaux II, France. Alcoholism is a possible cause of dementia, mainly through associated nutritional deficiencies and, rarely, through acute direct toxicity. However alcohol consumption was not found to be a risk factor in previous epidemiologic studies. We prospectively studied 3,777 community residents aged 65 and over, in the districts of Gironde and Dordogne. Average daily alcoholic consumption was recorded at baseline. Incident cases of dementia and Alzheimer's disease were screened at follow-up with explicit criteria. At 3 years, 2,273 subjects not demented at baseline were still available for follow-up. Wine was the only alcoholic beverage reported by more than 95 p. 100 of regular drinkers. In the 318 subjects drinking 3 to 4 standard glasses per day (> 250 and up to 500 ml), categorized as moderate drinkers, the crude odds ratio (OR) was 0.18 for incident dementia (p < 0.01) and 0.25 for Alzheimer's disease (p < 0.03), as compared to the 971 non-drinkers. After adjusting for age, sex, education, occupation, baseline MMSE and other possible confounders, the ORs were respectively 0.19 (p < 0.01) and 0.28 (p < 0.05). In the 922 mild drinkers (< 1 to 2 glasses per day) there was a negative association only with AD, after adjustment (OR = 0.55; p < 0.05). The inverse relationship between moderate wine drinking and incident dementia was explained neither by known predictors of dementia nor by medical, psychological or socio-familial factors. Considering also the well documented negative associations between moderate wine consumption and cardiovascular morbidity and mortality in this age group, it seems that there is no medical rationale to advise people over 65 to quit drinking wine moderately, as this habit carries no specific risk and may even be of some benefit for their health. Advising all elderly people to drink wine regularly for prevention of dementia would be however premature at this stage. PMID: 9296132 [PubMed - indexed for MEDLINE]
10: Clin Chim Acta 1996 Mar 15;246(1-2):77-89 Effects of alcohol on platelet functions. Renaud SC, Ruf JC. INSERM, Unit 330, Bordeaux, France. Recent epidemiologic studies have consistently shown that moderate intake of alcoholic beverages protect against morbidity and mortality from coronary heart disease and ischemic stroke. By contrast, alcohol drinking may also predispose to cerebral hemorrhage. These observations suggest an effect of alcohol similar to that of aspirin. Several studies in humans and animals have shown that the immediate effect of alcohol, either added in vitro to platelets or 10 to 20 min after ingestion, is to decrease platelet aggregation in response to most agonists (thrombin, ADP, epinephrine, collagen). Several hours later, as, in free-living populations deprived of drinking since the previous day it is mostly secondary aggregation to ADP and epinephrine and aggregation to collagen that are still inhibited in alcohol drinkers. By contrast, in binge drinkers or in alcoholics after alcohol withdrawal, response to aggregation, especially that induced by thrombin, is markedly increased. This rebound phenomenon, easily reproduced in rats, may explain ischemic strokes or sudden death known to occur after episodes of drunkenness. The platelet rebound effect of alcohol drinking was not observed with moderate red wine consumption in man. The protection afforded by wine has been recently duplicated in rats by grape tannins added to alcohol. This protection was associated with a decrease in the level of conjugated dienes, the first step in lipid peroxidation. In other words, wine drinking does not seem to be associated with the increased peroxidation usually observed with spirit drinking. Although further studies are required, the platelet rebound effect of alcohol drinking could be associated with an excess of lipid peroxides known to increase platelet reactivity, especially to thrombin. Publication Types: Review Review, tutorial PMID: 8814972 [PubMed - indexed for MEDLINE]
2: Pain 1988 Feb;32(2):159-63 Erratum in: Pain 1991 Sep;46(3):343 Feeling no pain: alcohol as an analgesic. Woodrow KM, Eltherington LG. Department of Psychiatry, Stanford University School of Medicine, CA 94305. Orally administered ethyl alcohol (1 ml/kg of 100% ethyl alcohol + 1 ml/kg tonic water) (the equivalent of two cocktails) produced tolerance to experimentally induced pain comparable to 0.17 mg/kg s.q. morphine (11.6 mg in a 70 kg person) [corrected]. Pain threshold, i.e., the initial awareness of pain, was not modified by either morphine or alcohol. The experiment was run using 18 paid subjects in an experimenter-blinded design. Both a pharmacologically active placebo (atropine) as well as a totally inactive placebo (saline) were employed. Pain induction occurred via mechanical pressure on the Achilles tendon utilizing a device previously standardized in the clinical screening of over 100,000 patients for pain awareness. These results suggest that alcohol, in non-intoxicating quantities, may be an effective adjunct to other analgesic modalities. Publication Types: Clinical trial Controlled clinical trial PMID: 3362554 [PubMed - indexed for MEDLINE]
4: Alcohol Res Health 1999;23(1):15-23 Moderate drinking and reduced risk of heart disease. Klatsky AL. Department of Medicine, Kaiser Permanente Medical Center, Oakland, California, USA. Although heavier drinkers are at increased risk for some heart diseases, moderate drinkers are at lower risk for the most common form of heart disease, coronary artery disease (CAD) than are either heavier drinkers or abstainers. This association has been demonstrated in large-scale epidemiological studies from many countries. Abstainers may share traits potentially related to CAD risk, such as psychological characteristics, dietary habits, and physical exercise patterns. However, evidence supports a direct protective effect of alcohol, even after data have been adjusted for the presence of these factors. The alcohol-CAD relationship is also independent of the hypothetically increased risk status among abstainers who stopped drinking for medical reasons. All alcoholic beverages protect against CAD, although some additional protection may be attributable to personal traits or drinking patterns among people who share some beverage preferences or to nonalcohol ingredients in specific beverages. Alcohol's protective effect may result from favorable alterations in blood chemistry and the prevention of clot formation in arteries that deliver blood to the heart muscle. Because CAD accounts for a large proportion of total mortality, the risk of death from all causes is slightly lower among moderate drinkers than among abstainers, but heavier drinkers are at considerably higher total mortality risk. PMID: 10890794 [PubMed - indexed for MEDLINE]
5: Novartis Found Symp 1998;216:2-12; discussion 12-8, 152-8 Alcohol and cardiovascular diseases: a historical overview. Klatsky AL. Kaiser Permanente Medical Center, Oakland, CA 94611, USA. Evident disparities in relationships make it desirable to consider several disorders separately. (1) Alcoholic cardiomyopathy was perceived 150 years ago, but understanding was clouded by recognition of beriberi and of synergistic toxicity from alcohol with arsenic or cobalt. (2) A report of a link between heavy drinking and hypertension in WWI French soldiers was apparently ignored for > 50 years. Epidemiological and intervention studies have now firmly established this association, but a mechanism remains elusive. (3) The 'holiday heart syndrome', an increased risk of supraventricular tachyarrhythmias in alcoholics, has been widely known to clinicians for 25 years; data remain sparse about the total role of heavier drinking in cardiac rhythm disturbances. (4) Failure of earlier studies to distinguish types of stroke impeded understanding; it now seems probable that alcohol drinking increases risk of haemorrhagic stroke but lowers risk of ischaemic stroke. (5) Heberden reported angina relief by alcohol in 1786, and an inverse alcohol-atherosclerosis association was observed by pathologists early in this century. Recent population studies and plausible mechanisms support a protective effect of alcohol against coronary disease. International comparisons dating back to 1819 suggest beverage choice as a factor, but this issue (the 'French Paradox') remains unresolved. Publication Types: Historical article PMID: 9949784 [PubMed - indexed for MEDLINE]
6: Am J Cardiol 1997 Aug 15;80(4):416-20 Comment in: Am J Cardiol. 1998 Feb 15;81(4):530 Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization. Klatsky AL, Armstrong MA, Friedman GD. Department of Medicine, Kaiser Permanente Medical Center, Oakland, California 94611, USA. International comparison data suggest that wine may be more protective against coronary artery disease than beer or liquor. There are potentially protective antioxidants in wine, especially red wine. However, prospective population studies suggest that each beverage type may reduce coronary risk. The role of alcoholic beverage choice in coronary risk remains unresolved. We performed a prospective study of coronary disease hospitalizations among 128,934 adult members of a Northern California prepaid comprehensive health care program. Alcohol data were supplied at health examinations. Using Cox proportional-hazards models with 9 covariates, analyses were performed of the roles of each major beverage type (wine, beer, and liquor) and of drinking only table wine (red, white, or both). Generally, coronary risk traits were most favorable for wine drinkers and least favorable for liquor drinkers. Among 3,931 persons hospitalized for coronary disease, total alcohol drinking was inversely related to risk in both sexes. Uncontrolled for total alcohol, each beverage type showed evidence for coronary protection, weakest for liquor and strongest for beer in men and wine in women. Controlled for total alcohol, these relations were much reduced, and lost statistical significance except for beer in men and both red and white wine (combined) in all persons. We conclude that (1) drinking ethyl alcohol apparently protects against coronary disease, and (2) there may be minor additional benefits associated with drinking both beer and wine, but not especially red wine. PMID: 9285651 [PubMed - indexed for MEDLINE]
7: BMJ 1996 Mar 23;312(7033):731-6 Comment in: ACP J Club. 1996 Sep-Oct;125(2):50-1 BMJ. 1996 Aug 10;313(7053):365 BMJ. 1996 Aug 10;313(7053):365-6 BMJ. 1996 Dec 14;313(7071):1555; discussion 1555-6 Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. OBJECTIVES: To review the effect of specific types of alcoholic drink on coronary risk. DESIGN: Systematic review of ecological, case-control, and cohort studies in which specific associations were available for consumption of beer, wine, and spirits and risk of coronary heart disease. SUBJECTS: 12 ecological, three case-control, and 10 separate prospective cohort studies. MAIN OUTCOME MEASURES: Alcohol consumption and relative risk of morbidity and mortality from coronary heart disease. RESULTS: Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found an association for beer, and four for spirits. CONCLUSIONS: Results from observational studies, where alcohol consumption can be linked directly to an individual's risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink. Publication Types: Review Review literature PMID: 8605457 [PubMed - indexed for MEDLINE]
8: Clin Chim Acta 1996 Mar 15;246(1-2):91-105 Alcohol and hypertension. Klatsky AL. Department of Cardiology, Kaiser Permanente Medical Care Program, Oakland, CA 94611, USA. Epidemiologic studies in the past two decades have firmly established a relationship between regular, heavier alcohol consumption and hypertension. This association has been demonstrated in both cross-sectional and prospective studies. It is found in both sexes and several races and is independent of the type of alcoholic beverage, adiposity, education, smoking, salt intake, and several other traits. Clinical experiments show that blood pressure falls in days to weeks with abstinence from alcohol and that it rises again within days after resuming drinking. No mechanism has been demonstrated for this alcohol/blood pressure effect. Alcohol withdrawal symptoms have not been seen in the clinical experiments; thus, this is not likely to be the major explanation. Studies of the role of alcohol in hypertension sequelae, such as coronary heart disease and stroke, have been difficult because of the effects of alcohol, independent of blood pressure, in these conditions. Overall, it is likely that this alcohol-hypertension relation is causal. Restriction of intake by heavier drinkers lowers blood pressure in some, and heavy alcohol ingestion should always be considered by clinicians as a possible hypertension risk factor. Publication Types: Review Review, tutorial PMID: 8814973 [PubMed - indexed for MEDLINE]
9: Annu Rev Med 1996;47:149-60 Alcohol, coronary disease, and hypertension. Klatsky AL. Division of Cardiology, Kaiser Permanente Medical Care Program, Oakland, California 94611, USA. Disparities in the relationships between alcohol consumption and various cardiovascular conditions are now evident, with complex interrelationships between conditions. An inverse relationship of alcohol use to coronary heart disease is supported by many population studies. Interpretation of these data as a protective effect of alcohol against coronary disease is strengthened by plausible mechanisms. Although some experimental data suggest the hypothesis that wine, in particular, has additional protective benefit, prospective studies show no consensus on this point. Strong, consistent epidemiologic data support a relationship of heavier drinking to hypertension. Intervention studies show a pressor effect of alcohol, which appears and regresses within several days, but a mechanism has not yet been established. As with most aspects of alcohol and health effects, the data do not suggest monotonic relationships of alcohol with these conditions. Thus, amount of alcohol taken is a crucial consideration. Advice to concerned persons needs to take into account individual factors in drinkers or potential drinkers. Publication Types: Review Review, tutorial PMID: 8712769 [PubMed - indexed for MEDLINE]
12: Prev Med 1988 Nov;17(6):683-5 Alcohol and breast cancer. Hiatt RA, Klatsky A, Armstrong MA. Division of Research, Kaiser Permanente, Piedmont, Oakland, California 94611-5463. We examined breast cancer incidence in a cohort of about 69,000 women who answered detailed questions about alcohol consumption from 1979 to 1984. Among women with no prior cancer, breast cancer had developed in 303 by the end of 1984 for an age-adjusted incidence of 1.3/1,000 person years of follow-up. In analysis controlling only for age there was a progressive increase in breast cancer incidence corresponding to each higher level of reported alcohol consumption. In multivariate analyses controlling for age, race, body mass, and smoking, the relative risk at 1-2 drinks/day was 1.5 (95% confidence interval (CI) 1.0-2.3), at 3-5 drinks/day was 1.5 (95% CI 0.8-2.8), and at 6 or more drinks/day was 3.3 (95% CI 1.2-9.3). Past drinkers tended to have been heavier drinkers than current drinkers and had a relative risk of 2.2 (95% CI 1.2-3.9). Study of wine, beer, and liquor use did not suggest that any particular alcoholic beverage was responsible. Significant associations with heavy alcohol consumption were strongest among white and postmenopausal women. This study adds support to the growing evidence that alcohol may be a risk factor for development of breast cancer. PMID: 3266668 [PubMed - indexed for MEDLINE]
13: Alcohol Alcohol 1987;Suppl 1:117-24 The cardiovascular effects of alcohol. Klatsky AL. Department of Medicine, Kaiser Permanente Medical Center, Oakland, California. The central fact about the relations of alcohol consumption to cardiovascular (CV) conditions is disparity. There is powerful evidence that susceptible persons suffer heart muscle damage from use of large amounts of alcoholic beverages, leading to alcoholic cardiomyopathy. Thiamine deficiency has CV consequences which may interact with heavy drinking in persons with poor nutritional intake. Substantial evidence links alcohol use to hypertension. Intervention studies demonstrate an apparent pressor effect of alcohol, which appears and regresses within several days. Alcohol use is inversely related to coronary heart disease (CAD); possible protective mechanisms have surfaced. The data provide no evidence which justify heavier alcohol intake. Publication Types: Review Review, tutorial PMID: 3322303 [PubMed - indexed for MEDLINE]
14: BMJ 1999 Dec 11;319(7224):1523-8 Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. eric.rimm@channing.harvard.edu OBJECTIVE: To summarise quantitatively the association between moderate alcohol intake and biological markers of risk of coronary heart disease and to predict how these changes would lower the risk. DESIGN: Meta-analysis of all experimental studies that assessed the effects of moderate alcohol intake on concentrations of high density lipoprotein cholesterol, apolipoprotein A I, fibrinogen, triglycerides, and other biological markers previously found to be associated with risk of coronary heart disease. PARTICIPANTS: Men and women free of previous chronic disease and who were not dependent on alcohol. Studies were included in which biomarkers were assessed before and after participants consumed up to 100 g of alcohol a day. INTERVENTIONS: Alcohol as ethanol, beer, wine, or spirits. MAIN OUTCOME MEASURES: Changes in concentrations of high density lipoprotein cholesterol, apolipoprotein A I, Lp(a) lipoprotein, triglycerides, tissue type plasminogen activator activity, tissue type plasminogen activator antigen, insulin, and glucose after consuming an experimental dose of alcohol for 1 to 9 weeks; a shorter period was accepted for studies of change in concentrations of fibrinogen, factor VII, von Willebrand factor, tissue type plasminogen activator activity, and tissue type plasminogen activator antigen. RESULTS: 61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol. On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease. CONCLUSIONS: Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors. Publication Types: Meta-analysis PMID: 10591709 [PubMed - indexed for MEDLINE]