ALCOHOL AND SPECIAL POPULATIONS : BIOLOGICAL VULNERABILITY

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1 INTERNATIONAL CENTER FOR ALCOHOL POLICIES ICAP REPORTS 10 NOVEMBER 2001 ALCOHOL AND SPECIAL POPULATIONS : BIOLOGICAL VULNERABILITY Alcohol has been consumed in most societies around the world since the dawn of recorded history, and probably longer. Most people who drink responsibly derive pleasure from their drinking and experience few adverse effects. For some, moderate alcohol consumption may even confer health benefits (Chick, 1999; Doll, 1998; English et al., 1995; Zakhari & Gordis, 1999). However, for certain individuals or in certain circumstances, even low or moderate levels of alcohol may be problematic. Due to a number of reasons, these individuals may be particularly vulnerable to adverse effects of alcohol consumption. For a large portion of these special populations, vulnerability is generally not psychological or due to social or economic conditions. Instead, a biological predisposition makes them especially susceptible. Thus, as for those at risk for other reasons, greater attention needs to be given to drinking patterns, to how much or even whether they drink. The term special populations has sometimes been applied to groups that fall into this higher risk category, reflecting the fact that, for the most part, advice on drinking given to populations at large may not apply to them. Because of their vulnerability, these individuals should probably be concerned about the effects alcohol may have on them. It is important to distinguish between those with a biological vulnerability to alcohol, for whom even low amounts of alcohol may result in problems, and those at risk because of their heavy and chronic alcohol consumption. The risk factors for these two groups may be quite different, as are the implications for prevention, although there may also be areas of overlap. The work of Cloninger (Johnson et al., 2000) suggests that those with the highest genetic risk become heavy drinkers quite early in life, continuing as heavy and reckless drinkers well into adulthood. This issue of ICAP Reports examines those special populations with a biological vulnerability to alcohol. Addressed are the factors that make these individuals particularly susceptible, as well as the implications of such vulnerability for policy recommendations. 1

2 BIOLOGICAL VULNERABILITY TO ALCOHOL BBiological vulnerability to alcohol depends on several factors. The genetic makeup of an individual, general health status, or the presence of a particular medical condition may confer vulnerability to alcohol. Variables such as gender, race, and age also play a role, all influencing the way in which ethanol is metabolized by the human body and the way in which it interacts with other biological functions. Genetics TThe genetic makeup of individuals and, in some cases, groups of individuals, is largely responsible for their vulnerability to alcohol. Genetic differences may underlie variation in how alcohol is metabolized, how the brain and its neurotransmitter systems respond to alcohol, or the effects of alcohol on particular organs or conditions. Research such as the ongoing Collaborative Study on the Genetics of Alcoholism (COGA), conducted under the auspices of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in the United States, has contributed greatly to the understanding of the genetic mechanisms involved in biological vulnerability (Begleiter et al., 1995, 1999). The results of these studies suggest that variations in several genes may be involved, including those coding for the enzymes responsible for metabolizing alcohol and those coding for receptors to neurotransmitters responsible for how the brain responds to alcohol (Begleiter,1995; Loh & Ball, 2000). In fact, a genetic component has been identified for a number of neurotransmitter systems (Eckert et al., 1998). For some populations, genetic vulnerability means low tolerance to alcohol and the inability to process it, while for others it is an increased risk for alcohol abuse or dependence. The genetic variations involved may also coincide with phenotype markers that could possibly be used to identify vulnerable individuals. Among these are characteristic electrical brain activity (Porjesz, 1998) and certain personality traits (Soloff, 2000). Research (Schuckit & Smith, 2001) has suggested that high tolerance to alcohol early in life may predict the development of dependence later in life. For individuals whose genetic makeup puts them at increased risk for alcohol abuse and dependence, it seems clear that there is a familial component to vulnerability, transmitted from one generation to the next (Goodwin, 1985; Schuckit et al., 2000). Data from North America and Western Europe suggest that an estimated 5 to 10 % of female relatives of alcoholics and 25% of male relatives will themselves develop alcohol dependence (Goodwin, 1985). Perhaps the best known example of genetic variation in the response to alcohol is the heightened sensitivity to alcohol consumption among some Asians. Here, alcohol metabolism is impaired by a nonfunctional form of the enzyme aldehyde dehydrogenase (ALDH) (Wall & Ehlers, 1995; Wall et al., 2000). In individuals who possess this deficiency (which rarely occurs in those of European or African descent), reactions to even small amounts of alcohol may be severe (Goedde et al., 1992). Among the effects are facial flushing, nausea, heart palpitations, and dizziness (Neumark et al., 1998). Two subgroups exist among those affected those with an inactive form of the enzyme (often referred to as fast flushers ), and those with a moderate inactivation of ALDH ( slow flushers ) (Wall & Ehlers, 1995). Research suggests that roughly half of Chinese, Japanese, Koreans and other Asians are affected by this condition (Smith, 1986; Tsutsumi & Takada, 1997). In Japan, for example, the deficiency characterizes 25 40% of 2

3 the population (Maezawa, 1995). Nearly 25% of Han Chinese appear to possess this deficiency, as do between 15 and 30% of Koreans (Shen et al., 1997). Similar variations in ALDH have been found in other ethnic groups, such as Ashkenzic Jews (Neumark et al., 1998). There is evidence that variation in the ALDH genotype among Native American tribes, as well as among the indigenous populations of South America, may also contribute to vulnerability to alcohol in those individuals (Gill et al., 1999). It has been argued that ALDH deficiency, while making populations vulnerable to certain immediate effects of alcohol, also acts as a protective mechanism, an early warning that may help avoid alcohol abuse (Harada, 1991). It is possible that variations in the levels of enzyme activity may account for some differences in consumption patterns among racial and regional groups. Although no actual protective effect has been established, this may be an explanation for the relatively low incidence of alcohol dependence among certain populations (Chen et al., 1999; Neumark et al., 1998). Health Status While genetic predisposition clearly plays a role in whether or not an individual is vulnerable to alcohol, other biological factors are also involved. One of the main determinants of susceptibility to potential adverse effects of alcohol is health status. General health, nutritional state, and the presence of certain ailments and conditions play an important role. Nutrition is a key factor in how alcohol affects the human body. Individuals who are malnourished are especially vulnerable. For example, thiamine deficiency, most often seen in chronic alcohol abusers, has been linked with neurological impairment and conditions such as Wernicke-Korsakoff syndrome (Charness, 1999). Various health conditions, notably diabetes, also increase vulnerability to alcohol. For diabetics, even moderate alcohol consumption can induce low blood sugar levels (hypoglycemia) (Emanuelle et al., 1998), and the interaction between alcohol and medications for treating diabetes can result in facial flushing, rapid heartbeat, and dangerously low blood pressure (Weathermon & Crabb, 1999). As alcohol has the effect of increasing blood pressure, individuals with hypertension may be adversely affected by drinking (Beilin, 1995). Although moderate alcohol consumption has been shown to reduce the risk of cardiovascular disease, it may have the opposite effect for hypertensive individuals (Klatsky, 1977; Gyntelberg et al., 1974). Finally, for those infected with hepatitis C, alcohol may accelerate the rate of liver damage and increase the risk of cirrhosis (Regev & Jeffers, 1999). Alcohol s interaction with medications can also prove harmful. It may, for example, enhance the sedative effects of tricyclic antidepressants, antihistamines, barbiturates, muscle relaxants, benzodiazepines, and opioids (Weathermon & Crabb, 1999). When combined with large amounts of alcohol, analgesics such as aspirin and ibuprofen may cause internal bleeding and liver damage. The anti-clotting effects of the anticoagulant warfarin may be altered by alcohol, making those taking it particularly vulnerable (Weathermon & Crabb, 1999). 3

4 OGender One of the main influences in vulnerability to alcohol is gender, often addressed in advice on drinking by providing separate recommendations for men and women. By virtue of their physiology, women are more susceptible than men to the effects of alcohol. A smaller blood volume and higher proportion of body fat mean that the effects of alcohol are felt at lower doses in women than they are in men (Thomasson, 1995). Women and men also differ from each other in the way they metabolize alcohol. The activity of alcohol dehydrogenase (ADH), the other key enzyme involved in the breakdown of ethanol, is roughly 70-80% greater in men than it is in women (Frezza et al., 1990; Lieber, 2000). This difference diminishes in older women, especially in postmenopausal women, whose estrogen levels do not fluctuate with the menstrual cycle (Eriksson, 1996). Related to the vulnerability of women to alcohol is the issue of pregnancy. Here, it is not so much the pregnant woman, but the developing fetus that may be placed at risk. The threshold at which vulnerability to alcohol begins has not been established (Allebeck & Olsen, 1998). However, it is clear that above a certain level, the effect of alcohol on fetal development is dose-related, with heavy chronic maternal drinking having effects on growth and development and, in severe cases, potentially resulting in fetal alcohol effects (FAE) and syndrome (FAS). The levels at which alcohol is involved and the implications for policy continue to be debated, often influenced by cultural differences (Abel, 1998). Research suggests that there may be some association between alcohol consumption and the risk for breast cancer, although the extent of this link and the role of other predisposing factors have not been determined (Katsouyanni, 1994). Studies have indicated that a genetic component may be involved in any vulnerability for breast cancer that may be linked to alcohol consumption (Vachon et al., 2000). Age AAnother important factor in biological vulnerability to alcohol is age. It has been shown that the activity of the metabolizing enzyme ADH decreases with age, especially in men, increasing their susceptibility to the effects of ethanol (Seitz et al., 1990). In addition, the elderly are more likely than younger people to suffer poor health and take medications, increasing their vulnerability for reasons addressed earlier. Changes in general metabolism in the elderly may also put them at increased risk (Koehler, 2001). Biological vulnerability to alcohol is not limited to the elderly but may also be an issue for young people. Aside from the psychosocial aspects of alcohol abuse for children and youth, there is evidence that physiological changes occurring in the developing brains of children may affect the way in which responses to alcohol are modulated (Spear, 2000). Much of the research on the effects of alcohol on these processes is derived from animal models and from experiments conducted in vitro. Consequently, some caution is required when extrapolating these data to humans, as the levels of alcohol needed to effect changes in animal models are often significantly different from the conditions created when people drink. 4

5 TPOLICY IMPLICATIONS The biological vulnerability to alcohol in special populations also has implications for policy, particularly in the area of prevention. Measurable markers that identify at -risk individuals may bring about new approaches to both screening and education measures. It is therefore important that physicians be educated in advances in this area and be able to pass such information on to their patients. By providing accurate information and advice on drinking patterns to vulnerable individuals, by teaching them about responsible drinking appropriate to their particular condition, or, in some cases, about not drinking at all, it may be possible to reduce the risk of harm. As a harm reduction measure, the use of targeted information, tailored to the needs of particular groups, has proven effective. Such information is included in the drinking and dietary guidelines published by a number of countries around the world (ICAP 1996, 2001). In addition to such official resources for educating the public, there is also a need for other trusted sources more often relied upon for health advice to be aware of the particular needs of vulnerable populations. The information a physician gives a patient, for example, plays an important role. It is therefore critical that physicians be versed in the biology of vulnerability to alcohol and that they provide their patients with accurate and balanced advice that addresses each one s particular needs. From a harm reduction perspective, certain aspects of biological vulnerability to alcohol allow focused interventions that can help alleviate adverse effects for some individuals. In Australia, for instance, commercially available flour for cooking and baking is enriched with thiamine, a measure aimed directly at mitigating the effects of heavy alcohol consumption among individuals who are also more likely to be malnourished (Harper et al. 1998; Truswell 2000). Research is the final area in which the understanding of vulnerability to alcohol and policy intersect. While research continues to focus on the biological underpinnings of this vulnerability, much still remains uncovered. It is important to encourage research aimed both at identifying the sources of vulnerability and also at devising new strategies for using such findings for the purposes of prevention. SUMMARY T This paper has attempted to provide a brief overview of the biological factors that make some individual more vulnerable than others to the effects of alcohol. Biological vulnerability to alcohol is complex, involving as much the genetic blueprint of an individual as general health and other factors over which they may be little control. A full and detailed discussion is beyond the scope of this paper. However, it is the interaction between these factors and the behaviors in which we, as individuals, engage that determines whether or not such a predisposition will result in harm. At the same time, this interaction offers possible policy approaches to avoiding potential harm through the promotion of responsible drinking patterns and the identification of harmful ones. 5

6 REFERENCES Abel, E Alcohol and Alcoholism, 33: Allebeck, P. & Olsen, J Alcoholism: Clinical and Experimental Research, 22: 329S-332S Begleiter, H. et al Alcohol Health and Research World, 19: Begleiter, H. et al Genetic Epidemiology, 17: S25-S30 Beilin, L Clinical and Experimental Pharmacology and Physiology, 22: Charness, M Alcoholism: Clinical and Experimental Research, 23: Chen, Y. et al Alcoholism: Clinical and Experimental Research, 23: Chick, J European Addiction Research, 5: Doll, R Drug and Alcohol Review, 17: Eckardt, M. et al Alcoholism: Clinical and Experimental Research, 22: Emanuelle, N. et al Alcohol Health and Research World, 22: English, D.R. et al The Quantification of Drug-Caused Morbidity and Mortality in Australia, Canberra : Australian Government Publishing Service. Eriksson, C. et al Alcoholism: Clinical and Experimental Research, 20: Frezza, M. et al New England Journal of Medicine, 322: Gill, K. et al Journal of Studies on Alcohol, 60: Goedde, H. et al Human Genetics, 88: Goodwin, D Archives of General Psychiatry, 42: Gyntelberg, F Acta Medica Scandinavica, 195: Harada, S Journal of the Anthropological Society of Nippon. 99: Harper, C.G et al Medical Journal of Australia, 168: ICAP ICAP Reports 1: Safe Alcohol Consumption. Washington, DC: ICAP. ICAP Invited Opinions: Drinking Guidelines. From: 13 August, 2001 Johnson, B.A. et al American Journal of Addiction, 9: Katsouyanni, K. et al International Journal of Cancer, 58: Klatsky, A. et al New England Journal of Medicine, 296:

7 Koehler, K. et al American Journal of Clinical Nutrition, 73: Lieber, C Alcoholism: Clinical and Experimental Research, 24: Loh, E. & Ball, D Neurochemistry International, 37: Maezawa, Y. et al. Alcoholism: Clinical and Experimental Research, 19: Neumark, Y. et al Journal of Studies on Alcohol, 59: Porjesz, B. et al Alcoholism: Clinical and Experimental Research, 22: Regev, A. & Jeffers, L Alcoholism: Clinical and Experimental Research, 23: Schuckit, M.A. & Smith, T.L Addiction, 96: Schuckit, M. et al Journal of Studies on Alcohol, 57: Schuckit, M. et al Alcohol and Alcoholism, 35: Seitz, H. et al New England Journal of Medicine, 323: Shen, Y. et al Alcoholism: Clinical and Experimental Research, 21: Smith, M In: Advances in Human Genetics Volume 15, New York: Plenum Press, pp Soloff, P. et al Alcoholism: Clinical and Experimental Research, 24: Spear, L Alcohol Research and Health, 24: Thomasson, H In: M. Galanter, Ed., Alcoholism and Women: Recent Developments in Alcoholism Volume 12, New York: Plenum Press, pp Thomasson, H Alcoholism: Clinical and Experimental Research, 24: Truswell, A.S Addiction, 95(6): Tsutsumi, M. & Takada, A In: Rana, S. & Taketa, K., Ed., Liver and Environmental Xenobiotics, New Delhi: Narosa Publishing House, pp Urashima, S. et al Alcohol and Alcoholism, 28: Vachon et al Cancer, 92: Wall, T.L. & Ehlers, C.L Alcohol Health and Research World, 19: Wall, T.L. et al Journal of Studies on Alcohol, 61: Weathermon, R. & Crabb, D Alcohol Research and Health, 23: Yoshida, A. et al European Journal of Biochemistry, 251: Zakhari, S. & Gordis, E Proceedings of the Association of American Physicians, 111:

8 ICAP The International Center for Alcohol Policies (ICAP) is dedicated to helping reduce the abuse of alcohol worldwide and to promoting understanding of the role of alcohol in society through dialogue and partnerships involving the beverage alcohol industry, the public health community and others interested in alcohol policy. ICAP is a not-for-profit organization supported by twelve major international beverage alcohol companies. Other ICAP Reports include: Issue 1: Safe Alcohol Consumption: A Comparison of Nutrition and Your Health: Dietary Guidelines for Americans and Sensible Drinking Issue 2: The Limits of Binge Drinking Issue 3: Health Warning Labels Issue 4: Drinking Age Limits Issue 5: What Is a Standard Drink? Issue 6: Government Policies on Alcohol and Pregnancy Issue 7: Estimating Costs Associated with Alcohol Abuse: Towards a Patterns Approach Issue 8: Who are the Abstainers? Issue 9: Self-Regulation of Beverage Alcohol Advertising International Center for Alcohol Policies 1519 New Hampshire Avenue, NW Washington, DC Phone: Fax: Web site: 8