Patterns of alcohol consumption and Helicobacter pylori infection: results of a population-based study from Germany among 6545 adults

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1 Aliment Pharmacol Ther 2005; 21: doi: /j x Patterns of alcohol consumption and Helicobacter pylori infection: results of a population-based study from Germany among 6545 adults J. KUEPPER-NYBELEN*, W. THEFELD, D. ROTHENBACHER* & H. BRENNER* *Department of Epidemiology, German Centre for Research on Ageing, Heidelberg, Germany; Robert Koch-Institute, Berlin, Germany Accepted for publication 3 September 2004 SUMMARY Background: Moderate alcohol consumption has been suggested to facilitate elimination of Helicobacter pylori infection. Aim: To investigate the relationship between alcohol consumption and infection with H. pylori, with particular consideration of the role of age, different alcoholic beverages and specific drinking habits. Methods: These issues were addressed in the German National Health Survey, conducted in a representative population sample between October 1997 and March Overall, 6545 subjects provided data on frequency and average amount of different alcoholic beverages consumed. H. pylori infection status was measured by serum immunoglobulin G antibodies. Results: Seroprevalence of the infection was highest among subjects who reported drinking no alcohol (49.3%) and lowest among subjects consuming g alcohol/day (35.2%, adjusted odds ratio ¼ 0.60, 95% confidence interval: ). This inverse association was consistently seen for different alcoholic beverages and in all age groups and it was particularly pronounced among women and among regular but moderate drinkers. There was also an inverse dose response relationship between the frequency of alcohol consumption and H. pylori infection. Conclusions: This analysis supports suggestions that regular but moderate consumption of alcohol from various sources may facilitate elimination of H. pylori infection. INTRODUCTION Helicobacter pylori infection is a major cause of peptic ulcer disease 1 and an important risk factor for gastric cancer. 2 According to estimates of the International Agency for Research on Cancer, roughly half of the world s population is infected. 3 Childhood appears to be the critical period during which H. pylori is acquired. 4 After childhood, the infection seems to persist in the majority of infected persons throughout life, but there is Correspondence to: Dr D. Rothenbacher, Department of Epidemiology, German Centre for Research on Ageing, Bergheimer Str. 20, Heidelberg, Germany. rothenbacher@dzfa.uni-heidelberg.de evidence that spontaneous elimination of H. pylori may occur. 5 One factor that might be related to suppression or elimination of the infection in adulthood is alcohol consumption because of its antibacterial effect, which has been clearly demonstrated in vitro. 6 Several studies have addressed the relation of alcohol consumption with H. pylori infection. In five recent studies specifically focussing on this issue, 7 11 an inverse relation between moderate alcohol consumption and H. pylori infection was consistently found. However, sample size limitations of previous studies hindered more detailed analyses regarding specific effects of various amounts of alcoholic beverages or the role of specific drinking habits. In this study, we Ó 2005 Blackwell Publishing Ltd 57

2 58 J. KUEPPER-NYBELEN et al. carried out a detailed analysis of the influence of typical drinking habits on H. pylori infection and, furthermore, we evaluated the dose response relationship by type of alcoholic beverage between alcohol consumption and H. pylori infection in a representative population sample of 6545 persons. MATERIALS AND METHODS Study population and study design This analysis is based on the first National Health Interview and Examination Survey conducted in a representative sample of the population from both parts of Germany (East and West) between October 1997 and March A detailed description of the survey methodology has been given elsewhere. 13 Briefly, a twostage stratified probability sample (communities, individuals) was drawn from the non-institutionalized residential population aged years with sufficient knowledge of the German language. Overall, 7124 men and women participated in the study (response rate 61.4%). In each of the 120 communities selected, a research centre was set up. The participants were invited to fill out a questionnaire with respect to medical history and various lifestyle characteristics such as dietary habits, smoking, alcohol consumption and physical activity. In particular, subjects were asked about the frequency and the average amount of different alcoholic beverages consumed in the last 12 months. In addition, subjects were asked whether their current consumption of alcoholic beverages was equal, lower or higher than in the past. Blood samples were collected by venipuncture. Serum samples were stored and analysed for H. pylori immunoglobulin G antibodies by enzymelinked immunosorbent assay (Hoffmann-La Roche, Basel, Switzerland) in a central laboratory at the Robert Koch Institute, Berlin. Levels above 20 U/mL were considered positive. Statistical analyses We first described the study population according to basic socioeconomic characteristics. We then calculated total and beverage-specific alcohol consumption from reported average consumption frequencies and amounts. A relative weight of alcohol of 0.8 g/ml and average alcohol contents of 4.5% for beer, 11% for wine and 40% for spirits was assumed. We classified study participants according to either frequency of drinking (categories: never, one to several times a month, one to several times a week, daily) or the average amount of alcohol consumed per day. For analyses on the role of drinking habits, a distinction was made between regular and binge drinking. Regular drinking was defined as drinking alcohol more often than once a week and binge drinking as drinking more than 1 L of beer, 0.4 L of wine or 0.08 L of spirits at one session. Additional analyses were carried out using a more stringent definition of binge drinking, i.e. drinking more than 2 L of beer, 0.7 L of wine or 0.2 L of spirits at one session. We then carried out a detailed analysis of the relationship between alcohol consumption and seroprevalence of H. pylori infection. This analysis included stratification of the participants by type of consumed alcoholic beverages, by the amount and frequency of alcohol consumed and by drinking pattern. To derive a smoothed dose response curve for the relationship between total alcohol consumption and H. pylori infection, we compared the seroprevalence of infection among persons within moving windows of alcohol consumption with the seroprevalence among nondrinkers. 14 We chose windows to include 30% of alcohol drinkers, each with an overlap of two-thirds between neighbouring windows (<30th, 10 40th, 20 50th,, th percentile). We quantified the relation between levels of alcohol consumption, frequency of alcohol consumption or drinking patterns and H. pylori infection using odds ratios and their 95% confidence intervals (CI). In all analyses, we conducted multiple logistic regression to adjust for the following potentially confounding variables: age (in years), gender, marital status (single, married, widowed or divorced), school education ( 9, and 13 years) and smoking (current, former or never). The analyses were carried out using the Statistical Analysis System software package, version 8.2 (SAS Institute Inc, Cary, NC, USA). RESULTS After exclusion of persons without determination of H. pylori infection status (n ¼ 376, 5.3%) and with missing values in other variables considered here (n ¼ 203, 2.9%) a sample of 6545 of the 7124 (91.9%) interviewed individuals remained for analysis.

3 ALCOHOL CONSUMPTION AND H. PYLORI INFECTION 59 Table 1. Characteristics of the study population (n ¼ 6545) Characteristics n (%) Gender Male 3184 (48.7) Female 3361 (51.3) Age (years) (17.8) (22.1) (18.9) (19.5) (14.2) (7.4) Nationality German 6251 (95.5) Other 294 (4.5) School education 9 years 2808 (42.9) years 2687 (41.1) 13 years 1050 (16.0) Family status Single 1448 (22.1) Married 4331 (66.2) Widowed/divorced 766 (11.7) Smoking Current 2147 (32.8) Former 1420 (21.7) Never 2978 (45.5) H. pylori Positive 2664 (40.7) Basic characteristics of the study population are given in Table 1. About half of the participants were men. The mean age was 45.5 years and most subjects were between 25 and 64 years old. Two-thirds of the study participants were married. About half of the participants had ever smoked and about one-third were current smokers. About 85% of the study population reported some alcohol consumption (see Table 2). Among these, nearly half (44.3%) reported to drink <5 g alcohol/day on average and of the other half most persons (48.2%) consumed between 5 and 15 g/day. Wine, as the only source of alcohol, was more common (994 persons) than exclusive beer consumption (490 persons) in this population. The majority (85.1%) of participants who consumed wine only were women and the vast majority of them consumed <5 g/day on average. However, most participants who drank alcohol reported to drink different types of alcoholic beverages. The average amount of alcohol from beer (10.9 g/day) was higher than the average amount of alcohol from wine (5.6 g/day) and the total amount of alcohol (17.8 g/day) in this group of mixed drinkers was higher than in exclusive beer drinkers (14.6 g/day) and in exclusive wine drinkers (4.2 g/day). The number of consumers of spirits only was very small (n ¼ 83), and, therefore, no separate analysis was carried out for this group. Overall 2664 of 6545 study participants (40.7%) were infected with H. pylori. Seroprevalence of the infection was highest among subjects who reported drinking no alcohol (49.3%) and decreased with increasing levels of alcohol consumption. However, no further decrease in risk (and even a possible re-increase) was seen in the group of people consuming more than 50 g of alcohol on average. The inverse dose response relation between total alcohol consumption and H. pylori infection status persisted after control for potential confounding factors. Consumption of 5 g or less or between 25 and 50 g/day was associated with a 16 and 40% reduction of the odds of H. pylori infection. Sex-specific analysis revealed that the inverse dose response relationship was even stronger for women (P-value for interaction between amount of alcohol consumed and gender: ), among whom the lowest odds ratio was found in the group who reported to consume more than 50 g alcohol/day on average (odds ratio ¼ 0.25, 95% CI: ). Inverse dose response patterns were likewise seen for participants who consumed alcohol in the form of wine only and in mixed drinkers. Only in the relatively small group of exclusive beer drinkers, no clear dose response pattern emerged. A more detailed analysis of the dose response relationship between the total amount of alcohol consumed and H. pylori infection status is shown in Figure 1. This figure suggests a monotonic decrease of H. pylori infection with levels of alcohol consumption up to about 30 g/day (higher consumption levels were not covered by the moving windows approach used in this analysis, because the number of subjects consuming higher amounts of alcohol was small). Additional analyses of the association between H. pylori infection and alcohol consumption for different age strata are shown in Table 3. In all three age strata (subjects younger than 40 years of age, between 40 and 59 years of age and 60 years and older), a consistent inverse dose response relationship between amount of alcohol consumed and H. pylori infection could be observed. The relationship was most pronounced in the age group years. As Table 4 shows, the most common frequencies of alcohol consumption were one to several times a week

4 60 J. KUEPPER-NYBELEN et al. Table 2. Helicobacter pylori infection (HP+) by type of alcoholic beverages and amount of alcohol consumed Type and amount of alcohol consumption Alcohol consumption HP+ n % n % Odds ratio (95% CI) Odds ratio (95% CI)à Any alcohol None* <5 g/day ( ) 0.84 ( ) 5 <15 g/day ( ) 0.74 ( ) 15 <25 g/day ( ) 0.71 ( ) 25 <50 g/day ( ) 0.60 ( ) 50 g/day ( ) 0.66 ( ) Beer only <5 g/day ( ) 0.84 ( ) 5 <25 g/day ( ) 0.93 ( ) 25 g/day ( ) 0.93 ( ) Wine only <5 g/day ( ) 0.89 ( ) 5 <25 g/day ( ) 0.71 ( ) 25 g/day ( ) 0.31 ( ) Mixed <5 g/day ( ) 0.80 ( ) 5 <15 g/day ( ) 0.72 ( ) 15 <25 g/day ( ) 0.69 ( ) 25 <50 g/day ( ) 0.60 ( ) 50 g/day ( ) 0.60 ( ) * Reference category. Adjusted for age. à Adjusted for age, gender, marital status, school education and smoking. Adjusted * odds ratio Any alcohol (g / day) Figure 1. Smoothed dose response relation between total alcohol consumption and Helicobacter pylori infection: adjusted odds ratios (bold line) with 95% confidence bands for moving windows of alcohol consumption. (42.5%) or one to several times a month (32.0%). Most individuals (71.7%) who consumed wine only drank it one to several times a month and only about 30% drank it weekly or daily. Beer was consumed more often. Two-thirds of exclusive beer drinkers reported to drink beer weekly or daily. As to the amount of alcohol consumption, there was also an inverse dose response relationship between the frequency of alcohol consumption and H. pylori infection. Risk reduction was strongest among subjects who consumed alcohol daily (adjusted odds ratio ¼ 0.62). This pattern was seen among both mixed drinkers (odds ratio ¼ 0.61) and people who consumed wine only (odds ratio ¼ 0.46) but, again, no consistent dose response pattern was seen in the relatively small group of exclusive beer drinkers. Sex-specific analyses again revealed a particularly pronounced inverse dose response relation between frequency of alcohol consumption and H. pylori infection for women (P-value for interaction ¼ 0.03). Among women, the odds ratio for daily alcohol consumption was 0.44, with a 95% CI of

5 ALCOHOL CONSUMPTION AND H. PYLORI INFECTION 61 Table 3. Helicobacter pylori infection (HP+) by amount of alcohol consumed for different age strata Amount of alcohol consumption Alcohol consumption HP+ n % n % Odds ratio (95% CI) Odds ratio (95% CI)à years of age None* <5 g/day ( ) 0.91 ( ) 5 <15 g/day ( ) 0.83 ( ) 15 g/day ( ) 0.71 ( ) years of age None* <5 g/day ( ) 0.71 ( ) 5 <15 g/day ( ) 0.64 ( ) 15 g/day ( ) 0.57 ( ) 60 years of age None* <5 g/day ( ) 0.93 ( ) 5 <15 g/day ( ) 0.71 ( ) 15 g/day ( ) 0.64 ( ) * Reference category. Adjusted for age. à Adjusted for age, gender, marital status, school education and smoking. Table 4. Helicobacter pylori infection (HP+) by type of alcoholic beverages and frequency of alcohol consumption Type and frequency of alcohol consumption Alcohol consumption HP+ n % n % Odds ratio (95% CI) Odds ratio (95% CI)à Any alcohol Never* One to several times a month ( ) 0.83 ( ) One to several times a week ( ) 0.67 ( ) Daily ( ) 0.62 ( ) Beer only One to several times a month ( ) 0.98 ( ) One to several times a week ( ) 0.66 ( ) Daily ( ) 1.06 ( ) Wine only One to several times a month ( ) 0.86 ( ) One to several times a week ( ) 0.74 ( ) Daily ( ) 0.46 ( ) Mixed One to several times a month ( ) 0.76 ( ) One to several times a week ( ) 0.67 ( ) Daily ( ) 0.61 ( ) * Reference category. Adjusted for age. à Adjusted for age, gender, marital status, school education and smoking. Table 5 shows the results of analyses comparing H. pylori infection among regular drinkers of alcohol and binge drinkers. Average amount of alcohol consumed by regular drinkers (32.5 g/day) was nearly equal to average alcohol consumption of binge drinkers defined in the more stringent way (33.7 g/day).

6 62 J. KUEPPER-NYBELEN et al. Table 5. Helicobacter pylori infection (HP+) by drinking patterns Drinking pattern (any alcohol) n HP+ n (%) Odds ratio (95% CI) Odds ratio (95% CI) Never* (49.3) Regular drinking (38.9) 0.65 ( ) 0.69 ( ) Binge drinking (34.6) 0.76 ( ) 0.78 ( ) Binge drinkingà (35.0) 0.93 ( ) 0.91 ( ) * Reference category. Defined as drinking >1 L of beer or >0.4 L of wine or >0.08 L of spirits at one session. à Defined as drinking >2 L of beer or >0.7 L of wine or >0.2 L of spirits at one session. Adjusted for age. Adjusted for age, gender, marital status, school education and smoking. Among regular drinkers, the inverse relation between the frequency of total alcohol consumption and H. pylori (adjusted odds ratio ¼ 0.69) was stronger than among binge drinkers. In particular, the odds ratio was close to 1 for the more stringent definition of binge drinking (0.91), but the 95% CI was wide because of the relatively small number of subjects in this category. DISCUSSION To our knowledge, this study, among 6545 subjects living in Germany, is the largest among a representative population-based sample reported to date, on the relationship between alcohol consumption and infection with H. pylori. The large number of participants allowed a detailed investigation of the role of different beverages and of the amounts and habits of alcohol consumption on H. pylori infection status with careful control for potential confounders. Our analysis indicated an inverse dose response relation between the amount and frequency of alcohol consumption and infection with H. pylori at moderate levels of alcohol consumption. The inverse association with H. pylori infection was found in all age groups and it was particularly strong for women and for people with regular consumption of moderate amounts of alcohol. Our results of an inverse relation between alcohol consumption and H. pylori infection are in agreement with results of recent studies. 7 11, Within levels of alcohol consumption up to 30 g/day on average, the inverse dose response relation appears to be monotonic, which again is in agreement with the results of previous studies. However, there are also indications that risk reduction may be less pronounced at higher levels of alcohol consumption as suggested by a previous study from our group. 10 However, to assess the existence of a possible U-shaped curve between alcohol consumption and H. pylori infection, like it has been found between alcohol consumption and a variety of adverse medical outcomes, including total mortality and coronary heart disease, 18, 19 there is the need to include more heavy drinkers into the analysis. The large overall size of our study allowed us, for the first time, to assess the relationship between alcohol consumption and H. pylori infection within different age strata. The inverse relation observed in the entire study population emerged very consistently in each of the three investigated age groups, namely in the younger participants up to 40 years of age, in the subjects aged 40 to 59 years and in the subjects above 60 years of age. As a result of longer exposure at older ages, one might expect the inverse association between alcohol consumption and H. pylori infection to increase with age. The lack of such increase in our data may be the result of the fact that only current alcohol consumption was ascertained, reflecting the exposure during the last 12 months and ignoring potential changes in consumption habits over time. A potential dose response relationship with cumulative alcohol exposure should therefore be evaluated using an integrative measure on lifetime alcohol consumption in future studies. Like in previous studies, an inverse relation with H. pylori infection was seen for all alcoholic beverages suggesting that alcohol itself rather than beverage-specific substances may account for the observed association. In one study, 8 the association was slightly more pronounced for alcohol from wine than alcohol from beer, but in others consumption of beer or wine was associated with the same reduction in risk of infection. 7, 9 11 The reason for the less consistent dose response relation found for exclusive beer drinkers in this study is not clear. This result may be due to chance variation because of the

7 ALCOHOL CONSUMPTION AND H. PYLORI INFECTION 63 very low number (only 8.8%) of persons drinking beer only. In our sample, most beer drinkers drank different alcoholic beverages. They were, thus, included in the category of mixed drinkers and in that category most of the alcohol was consumed in the form of beer (10.9 g/ day) rather than wine (5.6 g/day). Therefore, the clear inverse dose response relation between alcohol consumption and H. pylori in the much larger group of mixed drinkers (n ¼ 4011) suggests that this inverse association also holds for beer drinking, despite the less clear pattern in the much smaller group of exclusive beer drinkers (n ¼ 490). Nevertheless, the apparently stronger inverse association between alcohol consumption and H. pylori infection seen among exclusive wine drinkers than among predominantly or exclusively beer-drinking subjects at equivalent amounts of alcohol (see Table 2) may suggest a higher efficacy of elimination by consuming alcohol at higher concentrations. However, other potential differences between both types of beverages or between drinkers of both types of beverages (other than those controlled for in the analysis) might also play a role. In addition to the amount of alcohol consumption, our study also considered, for the first time, the influence of drinking patterns on H. pylori infection status. It can be supposed that the frequency and regularity of alcohol consumption is associated with H. pylori infection further to the amount consumed, as it has been shown for the association between alcohol and risk of myocardial infarction, for example. 19 Our results suggest that more regular consumption of alcohol may reduce the odds of infection with H. pylori more strongly than occasional drinking of large amounts ( binge drinking ). However, there is no commonly agreed-upon definition of binge drinking in the literature, 20 and the amount of alcohol consumed in our definition of binge drinking was lower than in definitions used in other studies. 21 Despite the very large overall size of our study, the number of subjects falling into the category with the more stringent definition of binge drinking was quite limited. Hence, the role of binge drinking probably needs to be addressed in study populations, in which the pattern of occasionally drinking large amounts of alcohol is more common. Our findings of an inverse association between alcohol consumption and H. pylori seroprevalence give further support to the suggestion that moderate alcohol consumption may facilitate elimination of H. pylori. Recently, Baena et al. 22 investigated the relationship between alcohol consumption and the success of H. pylori eradication therapy. They found a dosedependent positive effect of alcohol consumption on the success of the eradication therapy. The higher the daily alcohol consumption, the better was the success of the eradication therapy. It appears plausible that the antibacterial effects of alcoholic beverages, which have clearly been demonstrated in vitro, 6 may also facilitate spontaneous elimination of the infection outside a specific eradication therapy. On the contrary, the finding that the inverse relation between alcohol consumption and H. pylori infection is only of moderate size and that a substantial proportion of alcohol drinkers do not eliminate the infection may indicate that coincidence of alcohol consumption with additional factors, such as eventual antibiotic therapy or temporal variation in gastric acidity may be needed for spontaneous elimination of the infection. In the interpretation of our results, the following limitations should be kept in mind: all analyses are based on self-reported alcohol consumption and, as in pertinent epidemiological studies, there might have been a tendency of underreporting alcohol consumption. However, in this sample, measurements of mean corpuscular volume and gamma-glutamyl-transferase from blood samples were available. The median values of these two blood parameters, which are known to be associated with alcohol consumption, showed a monotonic increase with self-reported alcohol consumption, which provides reassurance that categorization of study participants by self-reported alcohol consumption was accurately reflecting the gradient of average amount of alcohol consumed between groups. Nevertheless, only current alcohol consumption was ascertained in a quantitative manner and information on past drinking habits was not collected in detail. However, results remained essentially unchanged after exclusion of subjects who indicated that they had changed their drinking habits in additional sensitivity analyses (data not shown). The same applied for further sensitivity analyses in which subjects who had had a treatment for alcohol abuse in the past were excluded. Because of the study s cross-sectional design, a possible effect of alcohol in preventing H. pylori acquisition could not be excluded. But there is evidence from the literature that acquisition of H. pylori infection appears mainly in childhood. 4 Therefore, despite its limitations, our study supports the evidence that moderate consumption of alcoholic beverages may facilitate elimination of H. pylori

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