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Margarine Consumption, Asthma, and Allergy in Young Adults: Results of the German National Health Survey 1998
Margarine Consumption, Asthma, and Allergy in Young Adults: Results of the German National Health Survey 1998 ¨ LSCHER, PHD, GABRIELE BOLTE, PHD, GERTRUD WINKLER, PHD, BERND HO WOLFGANG THEFELD, PHD, STEPHAN K. WEILAND, MD, AND JOACHIM HEINRICH, PHD
PURPOSE: To examine whether frequent intake of margarine is associated with allergy prevalence in adults using data of a representative national health survey. METHODS: Data on 7124 subjects aged 18 to 79 years were obtained from the German National Health Survey 1998. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression, using the frequency of intake of low-fat butter, regular and low-fat margarine as explanatory variable in relation to frequent intake of regular butter as reference group. RESULTS: Frequent intake of margarine of any kind was positively associated with current asthma during the past 12 months in young adults aged 18 to 29 years (aOR, 2.33; 95% CI, 1.03–5.26). In subgroup analysis, the positive association was confined to frequent intake of low-fat margarine (4.51; 1.78–11.43) or the combination of low-fat margarine and low-fat butter (4.79; 1.84–12.44). Consumption of margarine of any kind was not related to hay fever, atopic dermatitis, and atopic sensitization to inhalant allergens. CONCLUSIONS: Frequent intake of margarine rich in n-6 PUFA is not consistently associated with allergic diseases in adults. Other constituents of low-fat margarine or certain dietary habits and lifestyle factors, characterized by use of low-fat margarine, may be related to current asthma. Ann Epidemiol 2005;15:207–213. Ó 2004 Elsevier Inc. All rights reserved. KEY WORDS:
Dietary Fats, Margarine, Asthma, Hay Fever, Atopic Dermatitis, Hypersensitivity.
INTRODUCTION To explain the increase in allergic diseases during the past decades in those countries with a Western lifestyle, several hypotheses have been proposed. One states that the increase in consumption of polyunsaturated fatty acids (PUFA) might contribute to the observed increase in allergic diseases (1, 2). Especially, a high intake of n-6 in relation to n-3 PUFA by increased consumption of, e.g., vegetable oil and margarine would enhance the production of IgE by the formation of arachidonic acid-derived eicosanoids and thus promote the development of allergic diseases (3–5). Evidence from epidemiologic studies is increasing that consumption of PUFA in the form of an increased ratio of n-6 to n-3 may in fact play a role in allergy development in children. In a cross-sectional study in children aged 3 to 5 years, a high dietary intake of n-6 PUFA, defined as use of polyunsaturated fats on bread and in cooking, was associated From the Department of Epidemiology, University of Ulm, Ulm, Germany (G.B., S.K.W.); GSF National Research Centre for Environment and Health, Institute of Epidemiology, Neuherberg, Germany (G.B., B.H., J.H.); Department 3: Life Science, University of Applied Sciences Albstadt-Sigmaringen, Sigmaringen, Germany (G.W.); and Robert Koch-Institut, Berlin, Germany (W.T). Address correspondence to: Dr. Gabriele Bolte, Department of Environmental Health, Bavarian Health and Food Safety Authority, Veterinaerstr. 2, 85764 Oberschleissheim, Germany. Tel: C49-89-31560159; Fax: C49-89-31560-458. E-mail: [email protected] Received October 6, 2003; accepted April 19, 2004. Ó 2004 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010
with an increased risk of recent asthma (6). Studies on n-3 PUFA further supported the hypothesis: Hodge et al. (7) reported a reduced asthma risk in children consuming oily fish rich in n-3 PUFA and an intervention study showed a reduction in the prevalence of wheeze in 18-month old infants supplemented with dietary n-3 PUFA (8). Data on the impact of fat consumption and allergy in adults are still rare and conflicting. No relation between the intake of n-3 PUFA and the incidence of asthma in adult women has been observed in a cohort study (9). However, the intake of n-6 PUFA has been shown to be positively related to allergic rhinoconjunctivitis in women (10). In an ecological analysis of data of the European Community Respiratory Health Survey (ECRHS) intake of monounsaturated fatty acids, but not of PUFA, was positively associated with prevalence of allergic sensitization in adults (11). Since the assessment of nutritional intake of fatty acids is difficult, several studies in children concentrated on the impact of margarine and butter as surrogate marker. The rationale behind it was that margarine may contain up to 10 to 20 times more n-6 PUFA than butter (10). Cross-sectional studies in Germany among schoolchildren demonstrated a positive association between margarine consumption and the prevalence of hay fever and atopic sensitization (12, 13). The potential adverse effect of margarine intake was also supported by a study of Dunder et al. (14) in Finland where children with an allergic disease had used less butter and consumed more margarine. 1047-2797/05/$–see front matter doi:10.1016/j.annepidem.2004.04.004
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Selected Abbreviations and Acronyms PUFA Z polyunsaturated fatty acids
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month,’’ ‘‘about once a week,’’ ‘‘several times a week,’’ ‘‘daily alternatively almost daily,’’ and ‘‘several times a day.’’ Definition of Exposure Categories
Up to now, the effect of margarine intake on allergic diseases in adults has not been studied. Thus, the aim of our study was to analyze the association of allergic diseases with intake of butter and margarine in adults using data from a representative national sample. Use of butter or margarine as bread spread is common in Germany. Therefore, we used frequency of butter and margarine intake as a surrogate marker for intake of different types of fat and different amounts of polyunsaturated fatty acids. If n-6 PUFA interfere with T-cell differentiation and IgE production, we assume that the effect would be more pronounced in younger age groups at early stages of the pathogenesis. Against the background of several studies in children we hypothesized that a potential association between frequent intake of margarine rich in n-6 PUFA and allergic diseases should be still detectable in young adults.
MATERIALS AND METHODS Study Design The German National Health Survey 1998 was a crosssectional study performed between October 1997 and March 1999. The study population comprised 7124 subjects (response rate 61%) aged 18 to 79 years (52% women) of a representative sample of the residential population with regard to age, gender, and community size (15). Data Collection In the main part of the survey, a self-administered questionnaire, interview by a physician, and medical examination were used to obtain data on disease prevalences, risk factors, health services utilization, and health-related lifestyle. For this analysis, questionnaire data were obtained from the public use file BGS98 of the Robert Koch-Institut, Berlin, Germany. Furthermore, serological test data were available identifying allergic sensitization. Food Frequency Questionnaire Frequency of intake of regular butter, low-fat butter, margarine, and low-fat margarine as spread during the past 12 months was assessed by a food frequency questionnaire comprising 29 food items. The question was, ‘‘How often do you eat the following foods or convenience products? Please consider the past 12 months.’’ The following seven answering categories were given in the questionnaire: ‘‘(almost) never,’’ ‘‘once a month or less,’’ ‘‘two to three times a
Due to the fact that many study subjects ate several types of fat as spread at the same time, the exposure categories were defined in regard to the most common patterns of frequencies of butter and margarine intake. Thereby, we defined frequent intake as intake of spread fat of the respective kind more than once a week. First, we defined four mutually exclusive main exposure categories: 1. Regular butter almost only (subjects with a frequent intake of regular butter and at the same time infrequent intake of low-fat butter and margarine of any kind, N Z 2331). According to the hypothesis of a potential detrimental effect of frequent margarine intake, this group was used as reference group in the statistical analyses. 2. Low-fat butter almost only (subjects with a frequent intake of low-fat butter and at the same time infrequent intake of margarine of any kind, N Z 628). 3. Margarine in combination with butter (subjects with a frequent intake of margarine and butter of any kind, N Z 1938). 4. Margarine almost only (subjects with a frequent intake of margarine of any kind and at the same time infrequent intake of regular and low-fat butter, N Z 1476). Second, for a more detailed analysis we further divided three of the main exposure categories into mutually exclusive subgroups according to the intake of low-fat or regular types of spread. Among those subjects who frequently ate margarine and butter (main exposure category ‘‘margarine in combination with butter’’), we differentiated between subjects who frequently ate low-fat butter and low-fat margarine (N Z 706), subjects who frequently ate regular butter and regular margarine (N Z 438), and subjects who frequently ate regular butter and low-fat margarine (N Z 186). The main exposure category ‘‘margarine almost only’’ comprised two subgroups: subjects with a frequent intake of regular margarine (N Z 602) and subjects who preferred low-fat margarine (N Z 756). The main category ‘‘low-fat butter almost only’’ was divided into the subgroups of subjects who frequently ate only low-fat butter (N Z 406) and those subjects who frequently ate low-fat butter in combination with regular butter (N Z 222). Questionnaire Data on Health Outcomes Participants were asked if they ever had one of the diseases as given in a list of 42 items (question: ‘‘Which of the following
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diseases did you ever have?’’). The answer category ‘‘asthma (bronchial asthma, lung asthma, allergic asthma)’’ was used to define prevalence of ‘‘ever asthma.’’ Prevalences of ‘‘ever hay fever’’ and ‘‘ever atopic dermatitis’’ were assessed by the categories ‘‘hay fever (allergic rhinitis), allergic conjunctivitis’’ and ‘‘neurodermatitis (itching eczema, especially on the flexural sites of the elbow and the knee, endogenous eczema, atopic eczema).’’ Current wheeze was defined as the period prevalence of wheezing during the past 12 months (question: ‘‘Did you have a whistling or grumbling sound in your chest during the past 12 months?’’). In addition to prevalence of ever asthma, two further definitions of asthma were applied. First, current asthma was defined as prevalence of ever asthma in combination with current wheeze. Second, those subjects with an asthma attack during the past 12 months or currently asthma medication were defined as having asthma (questions: ‘‘Did you have an asthma attack at any time in the past 12 months?’’, ‘‘Do you currently take any medication [e.g., inhalations, aerosols (sprays) or pills] against asthma?’’). Allergic Sensitization Allergic sensitization was assessed by measuring specific IgE to common inhalant allergens in serum, using the SX1 test (Pharmacia, Uppsala, Sweden). The allergens identified in this test are house dust mite, cat and dog epithelium, cladosporium herbarum, pollen of timothy grass, rye, birch, and mugwort. It is assumed that these allergens cover 90% of all relevant inhalation allergens in central Europe. The classification of the final test results as positive or negative was based on the recommendations of the test manufacturer. Statistical Analysis Those subjects with missing data for all four types of spread or exceptional infrequent intake (intake of all kinds of fat as spread never or up to once a week at the most) were excluded from further analyses to avoid bias introduced by certain dietary needs due to, e.g., chronic diseases (N Z 751 out of 7124). Thus, 6373 out of 7124 study subjects remained for analysis. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) for the association of health outcomes with the type of fat consumed were calculated by logistic regressions using the Statistical Analysis Systems software package version 8.2 (SAS Institute Inc., Cary, NC, USA). We stratified the analyses by age, using the age groups 18 to 29 years, 30 to 39 years, and 40 to 79 years. Odds ratios were adjusted for gender, body mass index, region (East or West Germany), and socioeconomic status as defined by education. In addition, change-in-estimate was tested by additionally adjusting for smoking status and for obesity (body
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mass index > 30 kg/m2) instead of body mass index as continuous variable, respectively. Differences in proportions were assessed by c2 test of independence. RESULTS Characteristics of the study subjects are given in Table 1. The body mass index was slightly lower in the youngest age group (mean SD 24.0 4.0 kg/m2) compared with the whole study population (mean SD 26.7 4.6 kg/m2). Prevalence of obesity defined as body mass index > 30 kg/m2 was low in that age group (8.0%) compared with study subjects aged 30 to 39 years (13.7%) and 40 to 79 years (27.3%). Women reported more frequently than men to ever having had hay fever (16.6% vs. 14.3%, p Z 0.014) and atopic dermatitis (6.3% vs. 5.2%, p Z 0.064). Men were more often sensitized to common inhalant allergens compared with women (34.4% vs. 25.5%, p ! 0.001). There was no gender difference in the prevalence of asthma. In the age group 18 to 29 years, the proportion of women affected by asthma tended to be higher, but these differences were not statistically significant (current asthma: 5.0% vs. 3.6%, p Z 0.251). We analyzed the data according to the most frequent patterns of spread consumption (Table 2). The largest group
TABLE 1. Characteristics of the study subjects (N Z 6373) Characteristics Gender: Female Male Age: 18–29 years 30–39 years 40–79 years Region: West Germany East Germany Educational degree: !10 years 10 years >10 years Current smoker Obesity (BMI > 30 kg/m2) Frequent spread intake (> once a week) during the past 12 months Regular margarine Low-fat margarine Regular butter Low-fat butter Prevalences of health outcomes Asthma ever Current asthma Asthma attack in past 12 months or currently asthma medication Hay fever ever Atopic dermatitis ever Sensitisation to inhalant allergens (SX1)
n/N
%
3307/6373 3066/6373 1084/6373 1392/6373 3897/6373 4063/6373 2310/6373 2704/6246 2162/6246 1380/6246 2107/6367 1334/6336
51.9 48.1 17.0 21.8 61.2 63.8 36.2 43.3 34.6 22.1 33.1 21.1
1607/6314 2226/6334 3559/6361 1892/6333
25.5 35.1 56.0 29.9
406/6214 212/6321 275/6277
6.5 3.4 4.4
956/6167 359/6207 1791/6017
15.5 5.8 29.8
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TABLE 2. Proportion of study subjects with frequent intake (Oonce a week) of butter and margarine as spread during the past 12 months (N Z 6373) All Main categories
Subgroups
n
Women %
n
%
Men n
18–29 years %
Regular butter almost only Total 2331 36.6 1173 35.5 1158 37.8 Low-fat butter almost only Total 628 9.9 343 10.4 285 9.3 Low-fat butter only 406 6.4 220 6.7 186 6.1 Low-fat and regular butter 222 3.5 123 3.7 99 3.2 Margarine in combination Total 1938 30.4 1051 31.8 887 28.9 with butter Low-fat margarine and low-fat butter 706 11.1 420 12.7 286 9.3 Regular margarine and regular butter 438 6.9 221 6.7 217 7.1 Low-fat margarine and regular butter 186 2.9 99 3.0 87 2.8 Margarine almost only Total 1476 23.2 740 22.4 736 24.0 Regular margarine only 602 9.5 273 8.3 329 10.7 Low-fat margarine only 756 11.9 404 12.2 352 11.5
comprised those study subjects who ate regular butter more than once a week and the other types of spread once a week or less (36.6%). This group was defined as reference group for the multivariate analyses. Frequent margarine intake was reported by the study subjects in combination with frequent butter intake (30.4%) or with infrequent butter intake (23.2%). We subdivided these groups further to differentiate between regular and low-fat margarine intake. Subjects eating frequently low-fat butter (9.9%) were analyzed as a separate group. First, we analyzed the association between frequent intake of margarine as the main category and allergic
30–39 years
40–79 years
n
%
n
%
n
%
423 124 86 38 297
39.0 11.4 7.9 3.5 27.4
521 138 97 41 382
37.4 9.9 7.0 3.0 27.4
1387 366 223 143 1259
35.6 9.4 5.7 3.7 32.3
84 96 20 240 118 102
7.8 8.9 1.9 22.1 10.9 9.4
143 104 28 351 167 163
10.3 7.5 2.0 25.2 12.0 11.7
479 238 138 885 317 491
12.3 6.1 3.5 22.7 8.1 12.6
diseases. In young adults, frequent intake of margarine almost only was associated with current asthma (aOR 2.33; 95% CI, 1.03–5.26), but not with prevalence of ever asthma and asthma defined as asthma attack during past 12 months or currently asthma medication (Table 3). Gender-stratified analysis showed that the association with current asthma was confined to women (women: aOR 3.06; 95% CI, 1.11– 8.47; men: 1.36; 0.32–5.88). Additional adjustment for current smoking had no effect (aOR 2.28; 95% CI, 1.01– 5.15). Restricting the analyses to those subjects who were sensitized did not change the effect estimates substantially (data not shown). There was no association between
TABLE 3. Association between margarine consumption and asthma, hay fever, atopic dermatitis, and sensitization in the age group 18–29 years (N Z 1084)
Asthma ever n/N aOR (95% CI) Current asthma n/N aOR (95% CI) Asthma attack or medication n/N aOR (95% CI) Hay fever ever n/N aOR (95% CI) Atopic dermatitis ever n/N aOR (95% CI) Sensitization n/N aOR (95% CI)
Regular butter almost only (N Z 423)
Low-fat butter almost only (N Z 124)
Margarine in combination with butter (N Z 297)
Margarine almost only (N Z 240)
32/412 1.00
8/122 0.88 (0.37–2.08)
24/287 1.17 (0.67–2.07)
19/231 1.13 (0.61–2.08)
12/419 1.00
4/124 1.11 (0.30–4.07)
16/294 2.15 (0.99–4.71)
14/236 2.33 (1.03–5.26)
15/420 1.00
3/123 0.46 (0.10–2.07)
15/293 1.51 (0.72–3.16)
13/236 1.45 (0.66–3.19)
90/400 1.00
20/122 0.72 (0.41–1.26)
54/284 0.85 (0.57–1.25)
57/227 1.15 (0.77–1.71)
39/409 1.00
12/119 1.07 (0.53–2.15)
20/290 0.71 (0.40–1.26)
25/228 1.17 (0.68–2.01)
182/390 1.00
44/117 0.71 (0.46–1.10)
109/276 0.76 (0.55–1.05)
94/225 0.83 (0.59–1.17)
aOR: Adjusted odds ratios were calculated by multiple logistic regression with frequent intake of regular butter as reference group. Odds ratios were adjusted for region, socioeconomic status, body mass index, and gender.
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frequent intake of margarine and hay fever, atopic dermatitis, and allergic sensitization. Second, we further analyzed subgroups of exposure categories to assess the potential effect of different types of margarine in young adults (Table 4). The numbers of subjects in the subgroups low-fat margarine and regular butter (N Z 20) and low-fat butter and regular butter (N Z 38) as given in Table 2 were too low in the youngest age group to allow for multivariate analyses. Those subjects consuming predominantly low-fat margarine had elevated odds ratio for all asthma outcome variables, reaching statistical significance in case of current asthma (aOR, 4.51; 95% CI 1.78–11.43). Frequent intake of low-fat margarine and low-fat butter was also associated with current asthma (aOR, 4.79; 95% CI, 1.84–12.44). Again, additional adjusting for current smoking did not alter the effect estimates. Furthermore, adjusting for obesity as dichotomous variable instead of BMI did not change the effect estimates (data not shown). The association between asthma and frequent intake of low-fat margarine in young adults was mainly due to women, because 68 women and only 34 men preferred that type of spread fat. Women of the age group 18 to 29 years who preferred low-fat products (margarine and/or butter) lived more often in East Germany compared with women consuming other types of spread (50.6% vs. 25.8%, p ! 0.001), had more often completed 10 years of schooling, but not more (54.2% vs. 41.4%, p Z 0.020) and had a slightly
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higher body mass index (mean SD, 24.1 4.5 kg/m2 vs. 23.1 4.0 kg/m2). In contrast to the results for low-fat margarine, there was no association between frequent intake of regular margarine and asthma in young adults (Table 4). Moreover, there was no relationship between the type of fat consumed and hay fever, atopic dermatitis and allergic sensitization. In the age groups 30 to 39 years and 40 to 79 years, neither frequent intake of low-fat margarine alone nor regular margarine was associated with health outcomes (data not shown). DISCUSSION Our results based on data of a representative population sample in Germany showed that young adults eating frequently low-fat margarine alone or in combination with low-fat butter had increased odds for asthma, but not for hay fever, atopic dermatitis and allergic sensitization. The strengths of our study lie in the representativeness of the study population and in the large sample size. Since we had to rely on self-reported data on allergic diseases, we applied several definitions for current asthma as has been done in the international studies of children (ISAAC) and adults (ECRHS) (16, 17). Moreover, we analyzed data on allergic sensitization as an objective marker. Several limitations of the study have to be taken into account. First, we focused on margarine and butter as food items with distinctively different composition of fatty acids
TABLE 4. Association between consumption of different types of margarine and asthma, hay fever, atopic dermatitis, and sensitisation in the age group 18–29 years (N Z 1084)
Asthma ever n/N aOR (95% CI) Current asthma n/N aOR (95% CI) Asthma attack or medication n/N aOR (95% CI) Hay fever ever n/N aOR (95% CI) Atopic dermatitis ever n/N aOR (95% CI) Sensitization n/N aOR (95% CI)
Regular butter almost only (N Z 423)
Low-fat butter only (N Z 86)
Regular margarine and regular butter (N Z 96)
Regular margarine only (N Z 118)
Low-fat margarine and low-fat butter (N Z 84)
Low-fat margarine only (N Z 102)
32/412 1.00
6/84 1.17 (0.46–2.94)
10/95 1.32 (0.60–2.89)
4/112 0.49 (0.17–1.43)
10/82 1.98 (0.91–4.28)
13/100 1.94 (0.94–4.01)
12/419 1.00
3/86 1.74 (0.47–6.44)
5/95 1.58 (0.49–5.04)
3/116 1.01 (0.28–3.69)
8/83 4.79 (1.84–12.44)
10/101 4.51 (1.78–11.43)
15/420 1.00
2/85 0.74 (0.16–3.33)
6/95 1.93 (0.72–5.14)
3/115 0.77 (0.22–2.74)
5/83 1.85 (0.64–5.32)
9/101 2.42 (0.97–6.05)
90/400 1.00
16/85 0.95 (0.52–1.75)
13/93 0.55 (0.28–1.06)
22/111 0.86 (0.50–1.48)
17/79 1.07 (0.59–1.96)
30/97 1.56 (0.93–2.63)
39/409 1.00
10/83 1.30 (0.61–2.79)
4/94 0.42 (0.14–1.20)
15/115 1.46 (0.77–2.79)
5/82 0.61 (0.23–1.63)
9/95 1.00 (0.46–2.18)
182/390 1.00
34/80 0.94 (0.57–1.56)
35/91 0.67 (0.42–1.09)
47/109 0.84 (0.54–1.30)
36/82 1.01 (0.61–1.64)
41/97 0.92 (0.57–1.47)
aOR: Adjusted odds ratios were calculated by multiple logistic regression with frequent intake of regular butter as reference group. Odds ratios were adjusted for region, socioeconomic status, body mass index, and gender.
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as has been done in previous studies in children (12–14). However, fat used as spread on bread is only a surrogate marker for intake of different types of fat. We were not able to estimate total polyunsaturated fatty acid intake from various food sources, because the food frequency questionnaire that was applied was not designed to accurately measure the total intake of polyunsaturated fatty acids or other nutrients. Second, due to the design of the food frequency questionnaire, we were not able to adequately control for consumption of antioxidants such as vitamin C which have been proposed to play a role in the etiology of asthma (18). Third, the cross-sectional design did not enable us to analyze the temporal sequence. Therefore, we concentrated on two internationally applied definitions of asthma which take symptoms and medication during the past 12 months into account. In addition, our result that the association between low-fat margarine intake and asthma was confined to young adults may argue against reverse causation. We did not have any information about the dietary habits of the study subjects during childhood. Eating behavior of young adults, however, might quite closely reflect the food usage patterns of childhood and adolescence. Overweight may act as a confounder of this association because subjects experiencing overweight might prefer lowfat products and an increased body mass index has been shown to be related to asthma in young adults (19), in women (20) and in girls (21). Therefore we included body mass index and obesity, respectively, as a potential confounder in our multivariate analyses. Our rationale for analyzing the data stratified by age was that a frequent dietary intake of margarine would have a greater influence in younger age groups at early stages of the pathogenesis if one assumes that ingredients of margarine influence allergy development by interfering with IgE production and T-helper cell differentiation (4). Though we observed an association between frequent intake of low-fat margarine and current asthma, in our opinion these results do not support the hypothesis of a biological mechanism linking dietary intake of margarine rich in n-6 PUFA with allergic diseases. Referring to total fat content, in terms of total fat content, low-fat margarines are especially rich in n-6 PUFA compared with regular margarines. In Germany, low-fat margarines have a content of approximately 31% linoleic acid compared with 22% in regular margarines (22). But referring to 100 g edible portion, low-fat margarines have a lower content of n-6 PUFA compared with regular margarine (12% linoleic acid vs. 17.6%). If one assumes the same amount of daily margarine consumption, those subjects preferring low-fat margarine would consume less n-6 PUFA than those eating regular margarine, but would have elevated odds for asthma.
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Moreover, we did not observe any associations between margarine intake and hay fever and allergic sensitization which have been demonstrated in other studies in children (12–14). In addition to n-6 PUFA, monounsaturated fatty acids (MUFA) may play a role in allergy development. Intake of MUFA was associated with allergic sensitization in adults in an ecological study of ECRHS data (11). In contrast, an ecological analysis of ISAAC data did not show any association of total MUFA intake with wheeze, allergic rhinoconjunctivitis, and atopic eczema in children (23). Comparable to n-6 PUFA, regular margarine has a higher content of oleic acid than butter in Germany (26.8 g/100 g edible portion vs. 18.5 g/100 g), but low-fat margarine has a lower content (12.7 g/100 g) (21). Neither intake of regular margarine nor low-fat margarine was associated with sensitization in our study. Besides n-6 PUFA and MUFA, another component of margarines which differs between regular and low-fat margarine may be related to allergic diseases. Trans fatty acids may interfere with the metabolism of essential polyunsaturated fatty acids by impairing the activity of delta 6 desaturase, thus decreasing the biosynthesis of arachidonic acid and prostaglandins from linoleic acid (24, 25). Thus, it may be speculated that trans fatty acids in margarines could at least partly counteract the proposed detrimental effect of n-6 PUFA. Elaidic acid, the isomer predominating in partially hydrogenated vegetable oils, has been shown to inhibit delta 6 desaturase in vitro more efficiently than trans-vaccenic acid, which is the main isomer in ruminant fat (26, 27). In Germany, the trans fatty acid content in fat-reduced margarines (1.3% of all identified fatty acid methyl esters) was lower than in vegetable margarines (1.6%) and sunflower margarines (4.1%) (28). However, results of an ecological analysis of European ISAAC data do not support this speculation by demonstrating a positive association between intake of trans fatty acids in hydrogenated plant fat and symptom prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema in children (29). In conclusion, we found an association between current asthma and consumption of low-fat margarine, but not of regular margarine. It is unlikely that this relationship is causal due to the modulation of the synthesis of IgE and inflammatory mediators by n-6 PUFA, because low-fat margarines have a lower n-6 PUFA content than regular margarines and because no association was observed for other outcomes such as hay fever and sensitization. Besides the possibility that the observed association is a finding by chance only, other constituents of low-fat margarine or certain dietary habits and lifestyle factors, characterized by use of low-fat margarine, may be related to asthma, especially in young women.
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We thank the Robert Koch-Institut, Berlin, Germany, especially, Dr. Heribert Stolzenberg, for making the data of the German National Health Survey 1998 available.
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PURPOSE: To examine whether frequent intake of margarine is associated with allergy prevalence in adults using data of a representative national health survey. METHODS: Data on 7124 subjects aged 18 to 79 years were obtained from the German National Health Survey 1998. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression, using the frequency of intake of low-fat butter, regular and low-fat margarine as explanatory variable in relation to frequent intake of regular butter as reference group. RESULTS: Frequent intake of margarine of any kind was positively associated with current asthma during the past 12 months in young adults aged 18 to 29 years (aOR, 2.33; 95% CI, 1.03–5.26). In subgroup analysis, the positive association was confined to frequent intake of low-fat margarine (4.51; 1.78–11.43) or the combination of low-fat margarine and low-fat butter (4.79; 1.84–12.44). Consumption of margarine of any kind was not related to hay fever, atopic dermatitis, and atopic sensitization to inhalant allergens. CONCLUSIONS: Frequent intake of margarine rich in n-6 PUFA is not consistently associated with allergic diseases in adults. Other constituents of low-fat margarine or certain dietary habits and lifestyle factors, characterized by use of low-fat margarine, may be related to current asthma. Ann Epidemiol 2005;15:207–213. Ó 2004 Elsevier Inc. All rights reserved. KEY WORDS:
Dietary Fats, Margarine, Asthma, Hay Fever, Atopic Dermatitis, Hypersensitivity.
INTRODUCTION To explain the increase in allergic diseases during the past decades in those countries with a Western lifestyle, several hypotheses have been proposed. One states that the increase in consumption of polyunsaturated fatty acids (PUFA) might contribute to the observed increase in allergic diseases (1, 2). Especially, a high intake of n-6 in relation to n-3 PUFA by increased consumption of, e.g., vegetable oil and margarine would enhance the production of IgE by the formation of arachidonic acid-derived eicosanoids and thus promote the development of allergic diseases (3–5). Evidence from epidemiologic studies is increasing that consumption of PUFA in the form of an increased ratio of n-6 to n-3 may in fact play a role in allergy development in children. In a cross-sectional study in children aged 3 to 5 years, a high dietary intake of n-6 PUFA, defined as use of polyunsaturated fats on bread and in cooking, was associated From the Department of Epidemiology, University of Ulm, Ulm, Germany (G.B., S.K.W.); GSF National Research Centre for Environment and Health, Institute of Epidemiology, Neuherberg, Germany (G.B., B.H., J.H.); Department 3: Life Science, University of Applied Sciences Albstadt-Sigmaringen, Sigmaringen, Germany (G.W.); and Robert Koch-Institut, Berlin, Germany (W.T). Address correspondence to: Dr. Gabriele Bolte, Department of Environmental Health, Bavarian Health and Food Safety Authority, Veterinaerstr. 2, 85764 Oberschleissheim, Germany. Tel: C49-89-31560159; Fax: C49-89-31560-458. E-mail: [email protected] Received October 6, 2003; accepted April 19, 2004. Ó 2004 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010
with an increased risk of recent asthma (6). Studies on n-3 PUFA further supported the hypothesis: Hodge et al. (7) reported a reduced asthma risk in children consuming oily fish rich in n-3 PUFA and an intervention study showed a reduction in the prevalence of wheeze in 18-month old infants supplemented with dietary n-3 PUFA (8). Data on the impact of fat consumption and allergy in adults are still rare and conflicting. No relation between the intake of n-3 PUFA and the incidence of asthma in adult women has been observed in a cohort study (9). However, the intake of n-6 PUFA has been shown to be positively related to allergic rhinoconjunctivitis in women (10). In an ecological analysis of data of the European Community Respiratory Health Survey (ECRHS) intake of monounsaturated fatty acids, but not of PUFA, was positively associated with prevalence of allergic sensitization in adults (11). Since the assessment of nutritional intake of fatty acids is difficult, several studies in children concentrated on the impact of margarine and butter as surrogate marker. The rationale behind it was that margarine may contain up to 10 to 20 times more n-6 PUFA than butter (10). Cross-sectional studies in Germany among schoolchildren demonstrated a positive association between margarine consumption and the prevalence of hay fever and atopic sensitization (12, 13). The potential adverse effect of margarine intake was also supported by a study of Dunder et al. (14) in Finland where children with an allergic disease had used less butter and consumed more margarine. 1047-2797/05/$–see front matter doi:10.1016/j.annepidem.2004.04.004
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Selected Abbreviations and Acronyms PUFA Z polyunsaturated fatty acids
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month,’’ ‘‘about once a week,’’ ‘‘several times a week,’’ ‘‘daily alternatively almost daily,’’ and ‘‘several times a day.’’ Definition of Exposure Categories
Up to now, the effect of margarine intake on allergic diseases in adults has not been studied. Thus, the aim of our study was to analyze the association of allergic diseases with intake of butter and margarine in adults using data from a representative national sample. Use of butter or margarine as bread spread is common in Germany. Therefore, we used frequency of butter and margarine intake as a surrogate marker for intake of different types of fat and different amounts of polyunsaturated fatty acids. If n-6 PUFA interfere with T-cell differentiation and IgE production, we assume that the effect would be more pronounced in younger age groups at early stages of the pathogenesis. Against the background of several studies in children we hypothesized that a potential association between frequent intake of margarine rich in n-6 PUFA and allergic diseases should be still detectable in young adults.
MATERIALS AND METHODS Study Design The German National Health Survey 1998 was a crosssectional study performed between October 1997 and March 1999. The study population comprised 7124 subjects (response rate 61%) aged 18 to 79 years (52% women) of a representative sample of the residential population with regard to age, gender, and community size (15). Data Collection In the main part of the survey, a self-administered questionnaire, interview by a physician, and medical examination were used to obtain data on disease prevalences, risk factors, health services utilization, and health-related lifestyle. For this analysis, questionnaire data were obtained from the public use file BGS98 of the Robert Koch-Institut, Berlin, Germany. Furthermore, serological test data were available identifying allergic sensitization. Food Frequency Questionnaire Frequency of intake of regular butter, low-fat butter, margarine, and low-fat margarine as spread during the past 12 months was assessed by a food frequency questionnaire comprising 29 food items. The question was, ‘‘How often do you eat the following foods or convenience products? Please consider the past 12 months.’’ The following seven answering categories were given in the questionnaire: ‘‘(almost) never,’’ ‘‘once a month or less,’’ ‘‘two to three times a
Due to the fact that many study subjects ate several types of fat as spread at the same time, the exposure categories were defined in regard to the most common patterns of frequencies of butter and margarine intake. Thereby, we defined frequent intake as intake of spread fat of the respective kind more than once a week. First, we defined four mutually exclusive main exposure categories: 1. Regular butter almost only (subjects with a frequent intake of regular butter and at the same time infrequent intake of low-fat butter and margarine of any kind, N Z 2331). According to the hypothesis of a potential detrimental effect of frequent margarine intake, this group was used as reference group in the statistical analyses. 2. Low-fat butter almost only (subjects with a frequent intake of low-fat butter and at the same time infrequent intake of margarine of any kind, N Z 628). 3. Margarine in combination with butter (subjects with a frequent intake of margarine and butter of any kind, N Z 1938). 4. Margarine almost only (subjects with a frequent intake of margarine of any kind and at the same time infrequent intake of regular and low-fat butter, N Z 1476). Second, for a more detailed analysis we further divided three of the main exposure categories into mutually exclusive subgroups according to the intake of low-fat or regular types of spread. Among those subjects who frequently ate margarine and butter (main exposure category ‘‘margarine in combination with butter’’), we differentiated between subjects who frequently ate low-fat butter and low-fat margarine (N Z 706), subjects who frequently ate regular butter and regular margarine (N Z 438), and subjects who frequently ate regular butter and low-fat margarine (N Z 186). The main exposure category ‘‘margarine almost only’’ comprised two subgroups: subjects with a frequent intake of regular margarine (N Z 602) and subjects who preferred low-fat margarine (N Z 756). The main category ‘‘low-fat butter almost only’’ was divided into the subgroups of subjects who frequently ate only low-fat butter (N Z 406) and those subjects who frequently ate low-fat butter in combination with regular butter (N Z 222). Questionnaire Data on Health Outcomes Participants were asked if they ever had one of the diseases as given in a list of 42 items (question: ‘‘Which of the following
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diseases did you ever have?’’). The answer category ‘‘asthma (bronchial asthma, lung asthma, allergic asthma)’’ was used to define prevalence of ‘‘ever asthma.’’ Prevalences of ‘‘ever hay fever’’ and ‘‘ever atopic dermatitis’’ were assessed by the categories ‘‘hay fever (allergic rhinitis), allergic conjunctivitis’’ and ‘‘neurodermatitis (itching eczema, especially on the flexural sites of the elbow and the knee, endogenous eczema, atopic eczema).’’ Current wheeze was defined as the period prevalence of wheezing during the past 12 months (question: ‘‘Did you have a whistling or grumbling sound in your chest during the past 12 months?’’). In addition to prevalence of ever asthma, two further definitions of asthma were applied. First, current asthma was defined as prevalence of ever asthma in combination with current wheeze. Second, those subjects with an asthma attack during the past 12 months or currently asthma medication were defined as having asthma (questions: ‘‘Did you have an asthma attack at any time in the past 12 months?’’, ‘‘Do you currently take any medication [e.g., inhalations, aerosols (sprays) or pills] against asthma?’’). Allergic Sensitization Allergic sensitization was assessed by measuring specific IgE to common inhalant allergens in serum, using the SX1 test (Pharmacia, Uppsala, Sweden). The allergens identified in this test are house dust mite, cat and dog epithelium, cladosporium herbarum, pollen of timothy grass, rye, birch, and mugwort. It is assumed that these allergens cover 90% of all relevant inhalation allergens in central Europe. The classification of the final test results as positive or negative was based on the recommendations of the test manufacturer. Statistical Analysis Those subjects with missing data for all four types of spread or exceptional infrequent intake (intake of all kinds of fat as spread never or up to once a week at the most) were excluded from further analyses to avoid bias introduced by certain dietary needs due to, e.g., chronic diseases (N Z 751 out of 7124). Thus, 6373 out of 7124 study subjects remained for analysis. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) for the association of health outcomes with the type of fat consumed were calculated by logistic regressions using the Statistical Analysis Systems software package version 8.2 (SAS Institute Inc., Cary, NC, USA). We stratified the analyses by age, using the age groups 18 to 29 years, 30 to 39 years, and 40 to 79 years. Odds ratios were adjusted for gender, body mass index, region (East or West Germany), and socioeconomic status as defined by education. In addition, change-in-estimate was tested by additionally adjusting for smoking status and for obesity (body
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mass index > 30 kg/m2) instead of body mass index as continuous variable, respectively. Differences in proportions were assessed by c2 test of independence. RESULTS Characteristics of the study subjects are given in Table 1. The body mass index was slightly lower in the youngest age group (mean SD 24.0 4.0 kg/m2) compared with the whole study population (mean SD 26.7 4.6 kg/m2). Prevalence of obesity defined as body mass index > 30 kg/m2 was low in that age group (8.0%) compared with study subjects aged 30 to 39 years (13.7%) and 40 to 79 years (27.3%). Women reported more frequently than men to ever having had hay fever (16.6% vs. 14.3%, p Z 0.014) and atopic dermatitis (6.3% vs. 5.2%, p Z 0.064). Men were more often sensitized to common inhalant allergens compared with women (34.4% vs. 25.5%, p ! 0.001). There was no gender difference in the prevalence of asthma. In the age group 18 to 29 years, the proportion of women affected by asthma tended to be higher, but these differences were not statistically significant (current asthma: 5.0% vs. 3.6%, p Z 0.251). We analyzed the data according to the most frequent patterns of spread consumption (Table 2). The largest group
TABLE 1. Characteristics of the study subjects (N Z 6373) Characteristics Gender: Female Male Age: 18–29 years 30–39 years 40–79 years Region: West Germany East Germany Educational degree: !10 years 10 years >10 years Current smoker Obesity (BMI > 30 kg/m2) Frequent spread intake (> once a week) during the past 12 months Regular margarine Low-fat margarine Regular butter Low-fat butter Prevalences of health outcomes Asthma ever Current asthma Asthma attack in past 12 months or currently asthma medication Hay fever ever Atopic dermatitis ever Sensitisation to inhalant allergens (SX1)
n/N
%
3307/6373 3066/6373 1084/6373 1392/6373 3897/6373 4063/6373 2310/6373 2704/6246 2162/6246 1380/6246 2107/6367 1334/6336
51.9 48.1 17.0 21.8 61.2 63.8 36.2 43.3 34.6 22.1 33.1 21.1
1607/6314 2226/6334 3559/6361 1892/6333
25.5 35.1 56.0 29.9
406/6214 212/6321 275/6277
6.5 3.4 4.4
956/6167 359/6207 1791/6017
15.5 5.8 29.8
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TABLE 2. Proportion of study subjects with frequent intake (Oonce a week) of butter and margarine as spread during the past 12 months (N Z 6373) All Main categories
Subgroups
n
Women %
n
%
Men n
18–29 years %
Regular butter almost only Total 2331 36.6 1173 35.5 1158 37.8 Low-fat butter almost only Total 628 9.9 343 10.4 285 9.3 Low-fat butter only 406 6.4 220 6.7 186 6.1 Low-fat and regular butter 222 3.5 123 3.7 99 3.2 Margarine in combination Total 1938 30.4 1051 31.8 887 28.9 with butter Low-fat margarine and low-fat butter 706 11.1 420 12.7 286 9.3 Regular margarine and regular butter 438 6.9 221 6.7 217 7.1 Low-fat margarine and regular butter 186 2.9 99 3.0 87 2.8 Margarine almost only Total 1476 23.2 740 22.4 736 24.0 Regular margarine only 602 9.5 273 8.3 329 10.7 Low-fat margarine only 756 11.9 404 12.2 352 11.5
comprised those study subjects who ate regular butter more than once a week and the other types of spread once a week or less (36.6%). This group was defined as reference group for the multivariate analyses. Frequent margarine intake was reported by the study subjects in combination with frequent butter intake (30.4%) or with infrequent butter intake (23.2%). We subdivided these groups further to differentiate between regular and low-fat margarine intake. Subjects eating frequently low-fat butter (9.9%) were analyzed as a separate group. First, we analyzed the association between frequent intake of margarine as the main category and allergic
30–39 years
40–79 years
n
%
n
%
n
%
423 124 86 38 297
39.0 11.4 7.9 3.5 27.4
521 138 97 41 382
37.4 9.9 7.0 3.0 27.4
1387 366 223 143 1259
35.6 9.4 5.7 3.7 32.3
84 96 20 240 118 102
7.8 8.9 1.9 22.1 10.9 9.4
143 104 28 351 167 163
10.3 7.5 2.0 25.2 12.0 11.7
479 238 138 885 317 491
12.3 6.1 3.5 22.7 8.1 12.6
diseases. In young adults, frequent intake of margarine almost only was associated with current asthma (aOR 2.33; 95% CI, 1.03–5.26), but not with prevalence of ever asthma and asthma defined as asthma attack during past 12 months or currently asthma medication (Table 3). Gender-stratified analysis showed that the association with current asthma was confined to women (women: aOR 3.06; 95% CI, 1.11– 8.47; men: 1.36; 0.32–5.88). Additional adjustment for current smoking had no effect (aOR 2.28; 95% CI, 1.01– 5.15). Restricting the analyses to those subjects who were sensitized did not change the effect estimates substantially (data not shown). There was no association between
TABLE 3. Association between margarine consumption and asthma, hay fever, atopic dermatitis, and sensitization in the age group 18–29 years (N Z 1084)
Asthma ever n/N aOR (95% CI) Current asthma n/N aOR (95% CI) Asthma attack or medication n/N aOR (95% CI) Hay fever ever n/N aOR (95% CI) Atopic dermatitis ever n/N aOR (95% CI) Sensitization n/N aOR (95% CI)
Regular butter almost only (N Z 423)
Low-fat butter almost only (N Z 124)
Margarine in combination with butter (N Z 297)
Margarine almost only (N Z 240)
32/412 1.00
8/122 0.88 (0.37–2.08)
24/287 1.17 (0.67–2.07)
19/231 1.13 (0.61–2.08)
12/419 1.00
4/124 1.11 (0.30–4.07)
16/294 2.15 (0.99–4.71)
14/236 2.33 (1.03–5.26)
15/420 1.00
3/123 0.46 (0.10–2.07)
15/293 1.51 (0.72–3.16)
13/236 1.45 (0.66–3.19)
90/400 1.00
20/122 0.72 (0.41–1.26)
54/284 0.85 (0.57–1.25)
57/227 1.15 (0.77–1.71)
39/409 1.00
12/119 1.07 (0.53–2.15)
20/290 0.71 (0.40–1.26)
25/228 1.17 (0.68–2.01)
182/390 1.00
44/117 0.71 (0.46–1.10)
109/276 0.76 (0.55–1.05)
94/225 0.83 (0.59–1.17)
aOR: Adjusted odds ratios were calculated by multiple logistic regression with frequent intake of regular butter as reference group. Odds ratios were adjusted for region, socioeconomic status, body mass index, and gender.
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frequent intake of margarine and hay fever, atopic dermatitis, and allergic sensitization. Second, we further analyzed subgroups of exposure categories to assess the potential effect of different types of margarine in young adults (Table 4). The numbers of subjects in the subgroups low-fat margarine and regular butter (N Z 20) and low-fat butter and regular butter (N Z 38) as given in Table 2 were too low in the youngest age group to allow for multivariate analyses. Those subjects consuming predominantly low-fat margarine had elevated odds ratio for all asthma outcome variables, reaching statistical significance in case of current asthma (aOR, 4.51; 95% CI 1.78–11.43). Frequent intake of low-fat margarine and low-fat butter was also associated with current asthma (aOR, 4.79; 95% CI, 1.84–12.44). Again, additional adjusting for current smoking did not alter the effect estimates. Furthermore, adjusting for obesity as dichotomous variable instead of BMI did not change the effect estimates (data not shown). The association between asthma and frequent intake of low-fat margarine in young adults was mainly due to women, because 68 women and only 34 men preferred that type of spread fat. Women of the age group 18 to 29 years who preferred low-fat products (margarine and/or butter) lived more often in East Germany compared with women consuming other types of spread (50.6% vs. 25.8%, p ! 0.001), had more often completed 10 years of schooling, but not more (54.2% vs. 41.4%, p Z 0.020) and had a slightly
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higher body mass index (mean SD, 24.1 4.5 kg/m2 vs. 23.1 4.0 kg/m2). In contrast to the results for low-fat margarine, there was no association between frequent intake of regular margarine and asthma in young adults (Table 4). Moreover, there was no relationship between the type of fat consumed and hay fever, atopic dermatitis and allergic sensitization. In the age groups 30 to 39 years and 40 to 79 years, neither frequent intake of low-fat margarine alone nor regular margarine was associated with health outcomes (data not shown). DISCUSSION Our results based on data of a representative population sample in Germany showed that young adults eating frequently low-fat margarine alone or in combination with low-fat butter had increased odds for asthma, but not for hay fever, atopic dermatitis and allergic sensitization. The strengths of our study lie in the representativeness of the study population and in the large sample size. Since we had to rely on self-reported data on allergic diseases, we applied several definitions for current asthma as has been done in the international studies of children (ISAAC) and adults (ECRHS) (16, 17). Moreover, we analyzed data on allergic sensitization as an objective marker. Several limitations of the study have to be taken into account. First, we focused on margarine and butter as food items with distinctively different composition of fatty acids
TABLE 4. Association between consumption of different types of margarine and asthma, hay fever, atopic dermatitis, and sensitisation in the age group 18–29 years (N Z 1084)
Asthma ever n/N aOR (95% CI) Current asthma n/N aOR (95% CI) Asthma attack or medication n/N aOR (95% CI) Hay fever ever n/N aOR (95% CI) Atopic dermatitis ever n/N aOR (95% CI) Sensitization n/N aOR (95% CI)
Regular butter almost only (N Z 423)
Low-fat butter only (N Z 86)
Regular margarine and regular butter (N Z 96)
Regular margarine only (N Z 118)
Low-fat margarine and low-fat butter (N Z 84)
Low-fat margarine only (N Z 102)
32/412 1.00
6/84 1.17 (0.46–2.94)
10/95 1.32 (0.60–2.89)
4/112 0.49 (0.17–1.43)
10/82 1.98 (0.91–4.28)
13/100 1.94 (0.94–4.01)
12/419 1.00
3/86 1.74 (0.47–6.44)
5/95 1.58 (0.49–5.04)
3/116 1.01 (0.28–3.69)
8/83 4.79 (1.84–12.44)
10/101 4.51 (1.78–11.43)
15/420 1.00
2/85 0.74 (0.16–3.33)
6/95 1.93 (0.72–5.14)
3/115 0.77 (0.22–2.74)
5/83 1.85 (0.64–5.32)
9/101 2.42 (0.97–6.05)
90/400 1.00
16/85 0.95 (0.52–1.75)
13/93 0.55 (0.28–1.06)
22/111 0.86 (0.50–1.48)
17/79 1.07 (0.59–1.96)
30/97 1.56 (0.93–2.63)
39/409 1.00
10/83 1.30 (0.61–2.79)
4/94 0.42 (0.14–1.20)
15/115 1.46 (0.77–2.79)
5/82 0.61 (0.23–1.63)
9/95 1.00 (0.46–2.18)
182/390 1.00
34/80 0.94 (0.57–1.56)
35/91 0.67 (0.42–1.09)
47/109 0.84 (0.54–1.30)
36/82 1.01 (0.61–1.64)
41/97 0.92 (0.57–1.47)
aOR: Adjusted odds ratios were calculated by multiple logistic regression with frequent intake of regular butter as reference group. Odds ratios were adjusted for region, socioeconomic status, body mass index, and gender.
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as has been done in previous studies in children (12–14). However, fat used as spread on bread is only a surrogate marker for intake of different types of fat. We were not able to estimate total polyunsaturated fatty acid intake from various food sources, because the food frequency questionnaire that was applied was not designed to accurately measure the total intake of polyunsaturated fatty acids or other nutrients. Second, due to the design of the food frequency questionnaire, we were not able to adequately control for consumption of antioxidants such as vitamin C which have been proposed to play a role in the etiology of asthma (18). Third, the cross-sectional design did not enable us to analyze the temporal sequence. Therefore, we concentrated on two internationally applied definitions of asthma which take symptoms and medication during the past 12 months into account. In addition, our result that the association between low-fat margarine intake and asthma was confined to young adults may argue against reverse causation. We did not have any information about the dietary habits of the study subjects during childhood. Eating behavior of young adults, however, might quite closely reflect the food usage patterns of childhood and adolescence. Overweight may act as a confounder of this association because subjects experiencing overweight might prefer lowfat products and an increased body mass index has been shown to be related to asthma in young adults (19), in women (20) and in girls (21). Therefore we included body mass index and obesity, respectively, as a potential confounder in our multivariate analyses. Our rationale for analyzing the data stratified by age was that a frequent dietary intake of margarine would have a greater influence in younger age groups at early stages of the pathogenesis if one assumes that ingredients of margarine influence allergy development by interfering with IgE production and T-helper cell differentiation (4). Though we observed an association between frequent intake of low-fat margarine and current asthma, in our opinion these results do not support the hypothesis of a biological mechanism linking dietary intake of margarine rich in n-6 PUFA with allergic diseases. Referring to total fat content, in terms of total fat content, low-fat margarines are especially rich in n-6 PUFA compared with regular margarines. In Germany, low-fat margarines have a content of approximately 31% linoleic acid compared with 22% in regular margarines (22). But referring to 100 g edible portion, low-fat margarines have a lower content of n-6 PUFA compared with regular margarine (12% linoleic acid vs. 17.6%). If one assumes the same amount of daily margarine consumption, those subjects preferring low-fat margarine would consume less n-6 PUFA than those eating regular margarine, but would have elevated odds for asthma.
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Moreover, we did not observe any associations between margarine intake and hay fever and allergic sensitization which have been demonstrated in other studies in children (12–14). In addition to n-6 PUFA, monounsaturated fatty acids (MUFA) may play a role in allergy development. Intake of MUFA was associated with allergic sensitization in adults in an ecological study of ECRHS data (11). In contrast, an ecological analysis of ISAAC data did not show any association of total MUFA intake with wheeze, allergic rhinoconjunctivitis, and atopic eczema in children (23). Comparable to n-6 PUFA, regular margarine has a higher content of oleic acid than butter in Germany (26.8 g/100 g edible portion vs. 18.5 g/100 g), but low-fat margarine has a lower content (12.7 g/100 g) (21). Neither intake of regular margarine nor low-fat margarine was associated with sensitization in our study. Besides n-6 PUFA and MUFA, another component of margarines which differs between regular and low-fat margarine may be related to allergic diseases. Trans fatty acids may interfere with the metabolism of essential polyunsaturated fatty acids by impairing the activity of delta 6 desaturase, thus decreasing the biosynthesis of arachidonic acid and prostaglandins from linoleic acid (24, 25). Thus, it may be speculated that trans fatty acids in margarines could at least partly counteract the proposed detrimental effect of n-6 PUFA. Elaidic acid, the isomer predominating in partially hydrogenated vegetable oils, has been shown to inhibit delta 6 desaturase in vitro more efficiently than trans-vaccenic acid, which is the main isomer in ruminant fat (26, 27). In Germany, the trans fatty acid content in fat-reduced margarines (1.3% of all identified fatty acid methyl esters) was lower than in vegetable margarines (1.6%) and sunflower margarines (4.1%) (28). However, results of an ecological analysis of European ISAAC data do not support this speculation by demonstrating a positive association between intake of trans fatty acids in hydrogenated plant fat and symptom prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema in children (29). In conclusion, we found an association between current asthma and consumption of low-fat margarine, but not of regular margarine. It is unlikely that this relationship is causal due to the modulation of the synthesis of IgE and inflammatory mediators by n-6 PUFA, because low-fat margarines have a lower n-6 PUFA content than regular margarines and because no association was observed for other outcomes such as hay fever and sensitization. Besides the possibility that the observed association is a finding by chance only, other constituents of low-fat margarine or certain dietary habits and lifestyle factors, characterized by use of low-fat margarine, may be related to asthma, especially in young women.
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We thank the Robert Koch-Institut, Berlin, Germany, especially, Dr. Heribert Stolzenberg, for making the data of the German National Health Survey 1998 available.
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