EDITORIAL REVIEW Is Abstinence from Red Wine Hazardous to Your Health?

By Arthur L Klatsky, MD

A Very Public Message and Risk of movement of high-risk persons into Hardly a month goes by without Coronary Disease the nondrinking reference group.4-5 the appearance of a research find- Social and medical harm from This “sick quitter” hypothesis has been ing suggesting that drinking red heavier drinking has been evident refuted by a number of studies,3,6 in- wine is good for you. The media for millennia, but the concept of a cluding KP analyses.7-8 Studies that publicity is never nuanced or subtle, safe drinking limit was also accepted. separate exdrinkers from lifelong ab- so the headlines blare. Here are Perhaps better than “safe” is the word stainers or controlled for baseline CAD several recent ones: “Procyanidin- “sensible,” since no level is absolutely risk also consistently show that drink- rich red wines reduce heart attack safe for all persons. Modern popu- ers have lower CAD risk than life- and mortality,” “, a red- lation cohort studies2 confirm the long abstainers. Although there have wine ingredient, improves health increased risks of heavy drinking, been no randomized, controlled tri- and survival in mice on a high- defined as >3 standard-sized drinks/ als of CAD outcome events, many epi- ,” and “Cabernet sauvignon red day. The same studies show that light demiologists now feel that there is wine reduces the risk of to moderate drinkers have lower little doubt that alcohol exerts a pro- Alzheimer’s disease.” With the hint risks of tective effect against CAD. of greater longevity what non-red (CAD), ischemic stroke, and type 2 Plausible biological mechanisms wine drinker wouldn’t feel pressure diabetes mellitus. Thus, for total mor- for CAD protection by alcohol start to start a red wine habit? What per- tality, the composite is a J-shaped with higher levels of protective high- What person son over age 65 years wouldn’t con- curve, with lowest risk among drink- density-lipoprotein (HDL) choles- over age 65 sider a lifestyle change that prom- ers who take < 3 drinks per day, and terol in drinkers.9 The evidence for years wouldn’t ised a lower chance of Alzheimer’s? highest risk from numerous condi- this effect of alcohol is compelling. consider a The public has heard the implied tions among heavy drinkers. The Several analyses in different cohorts lifestyle change message. A 60 Minutes TV broad- lower mortality risk of lighter drink- show that HDL effect explains about that promised a cast (CBS: 1991 Nov 17) attributed ers is due mostly to less CAD. 50% of the alcohol-CAD benefit. This lower chance of lower heart attack risk in France Light drinkers have about 30% is an effect of alcohol, without speci- Alzheimer’s? partially to red wine. This expla- lower CAD mortality risk and an ap- ficity for wine. Antithrombotic effects, nation of the “French Paradox” proximately 10% lower total mortal- less specifically an alcohol effect, are (low coronary disease death rate ity risk.3 Consistency in studies, rela- also supported by substantial data.10 despite relatively unfavorable life- tive specificity of benefit for CAD and Less established mechanisms for style habits) has become widely plausible biological mechanisms for CAD benefit of alcohol include im- known. Red wine sales in the US protection by alcohol against CAD, proved endothelial function and re- skyrocketed in the 1990s and re- support a causal protective effect. duced insulin resistance. The evi- main high. In a recent Kaiser Some earlier studies were unable to dence that mechanisms of benefit Permanente (KP) survey, 80% of separate exdrinkers from lifelong ab- have to do with ethyl alcohol means those interviewed had heard of stainers or to control for baseline CAD that any nonalcohol-related benefit presumed benefit from alcohol and risk. Skeptics have repeatedly cited from a specific beverage type, such half of these volunteered that this this problem as the explanation of as red wine, would be additional to was true only of red wine.1 spurious benefit really due to prior that from alcohol.

Arthur L Klatsky, MD, is a Senior Consultant in and an Adjunct Investigator at the Division of Research for the Kaiser Permanente Medical Care Program in Oakland, CA. E-mail: [email protected]

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Is Red Wine Better? in Denmark show that wine drink- benefits of red wine for CAD in- Support for the hypothesis that ers have lower risk of total mortal- volves interpretive stretching of the wine may be more beneficial than ity, , and stroke, but the Dan- data. For example, the truly fasci- liquor or beer is of two major types. ish investigators point out that, nating resveratrol—longevity story The first consists of international compared to beer/liquor drinkers, involves up-regulation of a genetic comparisons showing lower CAD wine drinkers have a healthier drink- system (the sirtuin genes) that in- mortality in wine-drinking countries ing amount and pattern.14 The Dan- fluence metabolic processes pro- (eg, France) than in countries where ish wine drinkers smoke less, exer- moting longevity.18 Resveratrol has beer or distilled spirits are the pre- cise more, eat healthier diets, have this effect and has shown the abil- ponderant alcoholic beverages.3,11 higher socioeconomic status, and ity to increase longevity in several Called ecological studies, these score higher on intelligence tests. It species. Extrapolation from the analyses relate mean consumption is well known that in epidemiologic doses used in the mouse study to … our data to aggregate mortality. Since studies “healthy” traits tend to clus- humans indicates that a comparable California traits of individuals are not involved, ter in the same individuals. In ob- human resveratrol dose from drink- wine drinkers these ecological studies are not well servational studies there may be re- ing red wine would involve >1000 had the controlled for confounding expla- sidual confounding by uncontrolled glasses per day, hardly a practical healthiest nations. The second type of evi- or incompletely controlled traits. KP proposition. In the oligomeric lifestyle dence, the type frequently receiv- studies show evidence of CAD ben- procyanidins (OPC) report19 corre- habits. ing media hyperbole, is the efit from each major beverage type, lations were done between OPC presence of potentially beneficial with apparent benefit greatest for content of wines and longevity in nonalcohol compounds in wine.11,12 wine, next for beer, and least for several areas, with the finding that Found usually more concentrated in spirits.8,15 Importantly, the apparent both were highest in certain areas red wine, these substances are effect was the same for white wine of France and Sardinia. Found mostly phenolic compounds with as for red wine. As in Denmark, our largely in seeds, the OPC’s antioxidant and antithrombotic California wine drinkers had the are said by the authors to be the properties. Since oxidation of low- healthiest lifestyle habits. wine polyphenols with the stron- density-lipoprotein (LDL) choles- Wine has been called the “bever- gest endothelial relaxant effect. terol is an integral part of develop- age of moderation.”16 To some ex- These analyses were not controlled ment of atherosclerotic plaques, it tent this seems true in Denmark and for other potential confounders; in follows that antioxidant compounds in California, both of which include the view of this commentator these in the diet represent an appealing substantial numbers of persons that data do not suggest that wine drink- hypothesis for benefit. Diets rich in drink each beverage type. Yet in ers would do well by switching to natural antioxidants seem to be as- countries in which wine drinking pre- Sardinian wines. The Alzheimer’s sociated with better health out- ponderates most heavy drinkers drink report20 was another mouse study. comes, although trials of antioxidant the prevalent, usually inexpensive supplementation have been disap- beverage. Resultant wine-induced Problems When Giving pointing. Many feel that red wine pathologies include liver , Advice could be considered a fermented systemic hypertension, cardiomyopa- In view of the major health prob- food beverage with beneficial anti- thy, and peripheral neuropathy.17 lems of heavier drinking, there are oxidant ingredients. Organ damage from chronic heavy legitimate concerns about any medi- Epidemiologic studies with data drinking is related primarily to life- cal advice that encourages drinking. about specific beverage types are time ethyl alcohol intake, not bever- Although it is likely that few heavy fewer in number than those that age choice. In the appropriate cul- imbibers drink to improve their deal with total alcohol consumption. tural milieu, some wine drinkers health, the concerns are based on They do not consistently and con- readily progress to heavy drinking. the fear that some persons might not vincingly support specific additional In the US, for low cost some alcohol- be able to handle the knowledge of benefit from wine.3,8,11 Important in ics choose wine. The pejorative term benefit responsibly, and deliberately this regard are good studies in beer- “wino” arose because a proportion or inadvertently indulge in heavier drinking populations showing ap- of down-and-out alcoholics drink drinking. Advice to persons already parent substantial CAD protection by cheap fortified wine or jug wine. heavy drinkers needs no risk/ben- that beverage.13 A series of studies The acceptance of the specific efit individualization. Since nothing

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in the medical literature justifies scientific knowledge offers insuffi- Zakhari S, Wassef M. Research heavier drinking and increased risks cient basis for urging the man or Monograph 1997;1:369-91. predominate, all heavier drinkers woman who prefers another bever- 10. Zakhari S. Molecular mechanisms underlying alcohol-induced should reduce intake or abstain. age to switch. Most of the CAD ben- cardioprotection: contribution of The advice problem can be ame- efit derives from ethyl alcohol. If hemostatic components. Alcohol Clin liorated by individualization of ad- small amounts are taken in the opti- Exp Res 1999 Jun;23(6):1108-10. vice to light drinkers and abstainers,21 mal pattern, slowly and with food, it 11. Rimm EB, Klatsky AL, Grobbee D, taking into account risk/benefit fac- is likely that beer, liquor, white wine, Stampfer MJ. Review of moderate tors like age, sex, personal and fam- and red wine would have fairly simi- alcohol consumption and reduced risk of coronary heart disease: is the ily history of problem drinking, and lar benefit. Most moderate drinkers effect due to beer, wine, or spirits? risk of CAD, certain or other are more interested in the sensory BMJ 1996 Mar 23;312(7033):731-6. Most illnesses. Advice to drink must be pleasures and relaxing effect than in 12. Booyse FM, Parks DA. Moderate moderate weighed very carefully for nondrink- health benefit. One hopes that the wine and alcohol consumption: ers. Abstainers usually have a valid number of people who drink red Beneficial effects on cardiovascular drinkers are disease. Thromb Haemost 2001 more reason for abstinence. Alcohol drink- wine when they would prefer some- Aug;86(2):517-28. ❖ interested in ing is not at or near the top of the thing else is not too large. 13. Keil U, Chambless LE, Doring A, the sensory list of ways to reduce CAD risk; it Filipiak B, Stieber J. The relation of pleasures and comes well after smoking avoidance, References alcohol intake to coronary heart relaxing effect proper diet and exercise, and atten- 1. Klatsky AL, Armstrong MA, Landy C, disease and all-cause mortality in a tion to lipids, hypertension, diabe- Udaltsova N. The effect of coronary beer-drinking population. than in health disease on changes in drinking in an 1997 Mar;8(2):150-6. tes and obesity. However, the case benefit. older population. Alcohol Research 14. Gronbaek M. Wine, alcohol and that lighter drinking in a healthy pat- 2003;8:211-3. cardiovascular risk: open issue. Is tern has health benefits has become 2. Corrao G, Bagnardi V, Zambon A, La wine better than alcohol? J Thromb compelling. Thus it is as inappropri- Vecchia C. A meta-analysis of Haemost 2004 Nov;2(11):2041–8. ate for public health officials to pro- alcohol consumption and the risk of 15. Klatsky AL, Armstrong MA, Friedman mote general abstinence as to ad- 15 diseases. Prev Med 2004 GD. Red wine, white wine, liquor, May;38(5):613-9. beer, and risk for coronary artery vise the entire population to drink. 3. Klatsky, AL. Drink to your health? Sci disease hospitalization. Am J Cardiol Most adults already are established Am 2003 Feb;288(2):74-81. 1997 Aug 15; 80(4):416-20. light-moderate drinkers. Except for 4. Shaper AG, Wannamethee G, 16. Stockwell TR, Lang E, Lewis PN. Is special reasons an established light- Walker M. Alcohol and mortality in wine the drink of moderation? Med J moderate drinker at average or British men: explaining the U- Aust 1995;162:578, 580-1. greater than average CAD risk should shaped curve. Lancet 1988 Dec 17. Klatsky AL. Where have all the winos 3;2(8623):1267-73. gone? Epidemiology 2002 not be advised to abstain. Studies 5. Fillmore KM, Kerr WC, Stockwell T, Mar;13(2):120-2. have shown that this applies to those et al. Moderate alcohol use and 18. Baur JA, Pearson KJ, Price NL, et al. with and without pre-existent CAD, reduced mortality risk: systematic Resveratrol improves health and hypertension, and diabetes. Most error in prospective studies. survival of mice on a high-calorie medication-alcohol interactions are Addiction Research and Theory diet. Nature 2006 Nov 2006;14:1-1-132. 16;444(7117):337-42. documented only with heavy alco- 6. Klatsky, AL. Errors in Selection of 19. Corder R, Mullen W, Khan SC, et al. hol intake; this should not be too “Error-Free” Studies. Addiction Oenology: red wine procyanidins readily generalized to a Research and Theory 2007;15:1 (In and vascular health. Nature 2006 of all alcohol for these patients. Press). Nov 30;444(7119):566-72. 7. Klatsky AL, Armstrong MA, Friedman 20. Wang J, Ho L, Zhao Z, et al. Conclusion GD. Alcohol and mortality. Ann Moderate consumption of Cabernet Intern Med 1992;117:646-54. Sauvignon attenuates Abeta But what about the abstinence 8. Klatsky AL, Friedman GD, Armstrong neuropathology in a mouse model of from red wine issue in the title? The MA, Kipp H. Wine, liquor, beer, and Alzheimer’s disease. FASEB J 2006 short answer is that the question of mortality. Am J Epidemiol 2003 Sep Nov;20(13):2313-20. additional benefit from nonalcohol 15;158(6):585-95. 21. Klatsky AL. Should patients with ingredients is unresolved. Red wine 9. Dreon DM, Krauss RM. Alcohol, heart disease drink alcohol? JAMA is obviously fine for the light-mod- lipids and lipoproteins. Chapter 20 in 2001 Apr 18;285(15):2004-06. National Institute of Health. Alcohol erate drinker who prefers it, but the and the cardiovascular system. Eds

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