Panel Discussion II: Net Effects of Moderate Alcohol Consumption on Health
Article Outline
- Abstract
- Moderate Alcohol Consumption and Type 2 Diabetes
- Alcohol Consumption and Cognitive Function
- Alcohol and Cancer
- Moderate Alcohol Consumption, Inflammation, and Liver Disease
- Does Drinking with Meals Modify the Effects of Alcohol?
- Moderate Alcohol Consumption and Mental Health
- Moderate Alcohol Consumption and Total Mortality
- Age to Begin Alcohol Consumption
This discussion focused on the effects of moderate alcohol consumption on conditions other than cardiovascular diseases and on total mortality. The panel was chaired by Richard Smallwood, and the panelists were Henk F.J. Hendriks, Luc Letenneur, Klim McPherson, Gyongyi Szabo, Nady el-Guebaly, and Arthur Klatsky.
Moderate Alcohol Consumption and Type 2 Diabetes
Smallwood initiated the discussion by asking if there is enough evidence to support a causal relationship between alcohol consumption and risk of type 2 diabetes. Hendriks replied that while findings from epidemiologic studies seem to be promising, he did not think that one could draw a definite conclusion and that more research is needed to understand the biological mechanisms. Eric Rimm stated that “sick quitters” may be a concern for investigators when they assess the effect of alcohol intake on the risk of coronary heart disease (CHD) because so-called “sick quitters” may have other diseases, such as hypertension, a risk factor for CHD. Studies that evaluate the relationship between alcohol and type 2 diabetes, however, are unlikely to be influenced by “sick quitter” bias because no data suggest that conditions such as hypertension or gout associated with excessive drinking would necessarily put a subject at higher risk for type 2 diabetes.
Alcohol Consumption and Cognitive Function
Letenneur stated that while he and his colleagues found that moderate alcohol drinkers tend to have lower risk of Alzheimer's disease, because of marked variability among studies he is not convinced that such a reduced risk is attributable to alcohol consumption per se. He suspected that factors other than alcohol may play a role. Kenneth Mukamal commented that there were disparities in findings with regard to a possible interaction between genes and alcohol consumption on the risk of dementia. For example, the Rotterdam Study and the Cardiovascular Health Study (CHS) had different results on the relation of apolipoprotein E to Alzheimer's disease; no one was able to explain why the results differed.
When asked about experimental studies on alcohol and indices of cognition in animals, Letenneur responded that several animal studies have shown that the administration of alcohol improves memory. Some have shown that it works through the retinoic acid pathway, and others found that alcohol increases the survival of neurons of the hippocampus, which is a primary target of Alzheimer's disease.
Jürgen Rehm asked about competing risk factors and death, and how these factors were controlled for when studying alcohol consumption and Alzheimer's disease. Letenneur commented that most studies, in fact, had a short follow-up period; thus attrition should not be a major threat to the validity of such studies. Furthermore, since drinkers tended to have longer survival times, if competing or survival bias exists, it would only reduce the protective effects of alcohol on cognitive function or risk of Alzheimer's disease.
Several participants commented that if light-to-moderate alcohol consumption does have a protective effect on dementia, it should have a stronger effect on vascular dementia via its demonstrated effects on blood vessels. Mukamal stated that their studies had not shown significant differences by type of dementia, and the results from the CHS found a similar U-shaped relationship for vascular dementia and for Alzheimer's disease between alcohol consumption and white matter assessed by magnetic resonance imaging. Since many cerebral pathological changes probably have a vascular component, he speculated that there may be an overlap between these two diseases that could be difficult to tease out perfectly.
Alcohol and Cancer
Rimm stated that, to date, at least five studies have reported that the relation of alcohol consumption to the risk of breast cancer was modified by folate intake. Since animal studies suggest that alcohol does not have direct carcinogenic effect, he was wondering if alcohol has an effect only on selected people in the population who are on a certain diet or exposed to other risk factors.
McPherson commented that the underlying biological mechanisms linking alcohol consumption to the risk of cancer vary depending on the type of cancer. He suspected that the further away the cancer site is from the gastrointestinal tract, the more complicated the mechanisms are. He believed that the current findings of increased risk of breast and colon cancer only suggest an association, rather than prove causation. Mukamal pointed out there was strong evidence to suggest that moderate alcohol consumption is associated with higher levels of sex steroid hormones in women, which explains an association with both higher bone mineral density and with increased risk of breast cancer among moderate alcohol drinkers. Hendriks disagreed, saying that data from his trials did not show any evidence that alcohol intake increases the sex steroid hormones and he suspected that other biological mechanisms rather than the estrogenic effect of alcohol may play a role. Some investigators hypothesized that the risk of certain types of cancers, such as head and neck or esophageal cancer, may be related to the type of beverage consumed. However, McPherson responded that, in his opinion, there is no clear evidence supporting differences in risk of cancer according to beverage type.
Moderate Alcohol Consumption, Inflammation, and Liver Disease
Szabo said that data suggest that there is a linear relationship between amount of fat deposition in the liver and progression of liver disease, as well as cirrhosis; the risk of progression to liver cirrhosis, even after stopping alcohol use, is greater in women than in men. Szabo further commented that distinguishing nonalcoholic steatosis hepatitis (NASH) from alcoholic steatosis hepatitis (ASH) is difficult based on the pathologic findings. She agreed with others that in many early studies, NASH may have been misdiagnosed as ASH. Cofactors, such as hepatitis B or hepatitis C, were not known at the time of many early studies where most cases were attributed only to alcohol consumption.
Rehm commented that both incidence and mortality of liver disease vary greatly among countries. In European countries, there are 5-fold differences in certain age groups and 10-fold lower rates in women in some countries. Alcohol intake alone seemed unable to explain such big differences. He speculated that some other cofactors may interact with alcohol to put certain people at much higher risk. Szabo suggested that genetic factors that may be unique to certain populations could play a role. For example, in certain parts of Europe there is a high frequency of genes leading to hemochromatosis. Subjects with these genes are at higher risk of developing alcohol-induced liver disease and have a low threshold for the amount of alcohol intake that will lead to its clinical manifestations. Likewise, the frequency of hepatitis C infection varies greatly in different part of Europe and tends to be higher than in the United States. Szabo speculated that genetic factors and hepatitis infection may also play roles in the high frequency of NASH in certain parts of Mexico and in the Hispanic population in the United States. Marjana Martinic asked if bacterial contamination of beverages in parts of Mexico may contribute to high rates of cirrhosis. Rehm indicated that the prevalence of liver cirrhosis is still high in those areas, even after the local government tried to eliminate various risk factors, including contaminated home brews.
Klatsky asked why all long-term heavy alcohol drinkers do not develop alcohol-related liver disease. Szabo agreed that was the case, in that only about 20% of heavy drinkers develop liver disease. She added that a few studies have looked at genetic factors that may affect susceptibility to cirrhosis but, as of now, we do not have very good markers or genetic profiles that can serve as biomarkers to test the population for such effects.
Ellison said that heavy drinkers have often been advised to stop drinking completely for 1 or 2 days per week to let the “liver recover,” but most data currently available have shown that the more frequently one drinks, the stronger the protective effects on obesity, CHD, and total mortality. He wondered if there is any evidence suggesting that people should avoid alcohol consumption for a day or two per week to protect their liver. Szabo stated that she was not aware of any clinical data to support this claim. Rehm added that their results from several different data sets all suggest that the more spread out the same amount of alcohol consumption, the lower the risk of morbidity and mortality. He did not believe there is sound empirical evidence to suggest a practice of setting aside one day per week for not drinking, as long as overall drinking is moderate.
Does Drinking with Meals Modify the Effects of Alcohol?
It was stated that if one consumes alcohol with food, it reduces the blood alcohol levels by about one half; does this suggest that drinking alcohol with meals could reduce the toxic effects on the liver and reduce the risk of cirrhosis and cancer by one half? Szabo did not think that studies have carefully studied this issue, but admitted that drinking patterns can certainly influence blood alcohol levels. Morten Grønbæk added that data seem to suggest that the protective effect of alcohol on CHD does not vary by whether one drinks with meals or at other times. Since determination of blood alcohol levels requires blood samples, it is not easy for investigators to distinguish between the first pass metabolism and overall alcohol stimulation. Grønbæk believed that a body exposed to the same amount of alcohol will probably generate the same amount of reactive oxygen radicals. McPherson pointed out that most studies on alcohol and cancer basically looked at consumption, irrespective of when and how alcohol is consumed, and he was not aware of any study that examined alcohol consumption and cancer according to whether alcohol is consumed with or without food.
Moderate Alcohol Consumption and Mental Health
There was a comment about the difficulty of quantifying some aspects of mental health that may result from alcohol, such as relief of anxiety, feeling good, or happiness. El-Guebaly stated that it is a great challenge for studies of alcohol and mental health to get detailed information on mental health status. While some instruments are available and have been used to assess these dimensions, “the devil is in the details.” Investigators should not put a lot of trust into a simple question; one may have to ask numerous questions, say 15 or 20, to obtain the necessary detailed information on mental health.
Moderate Alcohol Consumption and Total Mortality
Smallwood commented on the view among some scientists that the protective effects of alcohol on CHD have been exaggerated and that such protection occurs only at high levels of drinking. This issue has recently been considered by officials in Australia and may prompt changes in policy in that country to make alcohol less accessible. In response to this, Klatsky said that he was not aware of any new evidence suggesting that only heavy drinking is associated with protection against CHD. In fact, almost all studies have consistently shown a U-shaped curve between amount of alcohol intake and CHD mortality, as well as total mortality, with the lowest mortality rate among moderate alcohol drinkers. He added that there are certainly errors in assigning the specific cause of death, but misclassification of total mortality is unlikely to occur. Thus the statement that any protective effect of alcohol on mortality requires high levels of intake is not justified by recent scientific data.
Kaye Fillmore said that since alcohol consumption data are usually based on questionnaires, she was concerned whether investigators were able to get reliable data in studies that included subjects with illiteracy or semiliteracy. Klatsky responded that her question was pertinent, as the way that investigators ask a question can certainly affect the results of a study. However, in his studies almost 90% of subjects could answer the questions, and questionnaires were completed within the clinic; thus literacy could not be a major issue that would affect the findings he presented.
Rehm pointed out that some studies have shown that the protective effects of alcohol consumption on CHD are less apparent among certain ethnic groups, for example, African Americans. He wondered if such a difference could be attributed to different drinking patterns among different racial groups. Klatsky commented that differences in drinking pattern is certainly one explanation, and he asserted that African Americans, in general, tend to drink less than white persons. Alun Evans raised the issue of whether the lack of protective effects on mortality among the Asian population in Klatsky's study could be due to cultural prohibitions against alcohol among Asians, possibly leading to under-reporting bias. Klatsky responded that indices of heavy drinking were also infrequent among Asians, suggesting that under-reporting was not a major problem in that group. He added that bias, if a factor, should be present across all categories of alcohol consumption.
Age to Begin Alcohol Consumption
The question was raised as to the age at which drinking may have potentially beneficial health effects. Rimm believed that there is no beneficial effect among people younger than 50 years of age. He stated, however, that he was not aware of any study that allowed the investigators to test whether people who started drinking alcohol before age 50 years or later would have different risks of heart disease or mortality. Furthermore, the latency period of any effect of alcohol on heart disease is likely to be long, especially if we believe that biological mechanisms of such protective effects are mediated through alcohol's impact on high-density lipoprotein cholesterol and on inflammation. Thus consumption in the 30s or 40s might lead to benefits later in life. Ellison mentioned that he was aware of one study among relatively young people, by Rosenberg and colleagues from 1981, at a time when myocardial infarction (MI) among women was high because of the combination of cigarette smoking and birth control pills containing high levels of sex steroids. That study reported that the risk of MI among women younger than 50 years was 30% lower for drinkers than for abstainers.
PII: S1047-2797(07)00017-8
doi:10.1016/j.annepidem.2007.01.015
