The current cross-sectional study of pregnant Japanese women revealed that higher meat intake was independently associated with a higher prevalence of rhinoconjunctivitis. There were no significant associations between intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, or cholesterol or the ratio of n-3 to n-6 polyunsaturated fatty acid intake and the prevalence of rhinoconjunctivitis.
Our results are not consistent with the hypothesis that decreased intake of n-3 polyunsaturated fatty acids and increased intake of n-6 polyunsaturated fatty acids might have contributed to the recent increase in the prevalence of allergic disorders [4
], a hypothesis that is supported by several other studies. In two cross-sectional studies of German children, a significant positive association was observed between margarine intake and allergic rhinitis [5
]. A significant inverse association between fish intake and allergic rhinitis was shown in two cohort studies of children in Norway [9
] and Sweden [10
]. A recent prebirth cohort study in Finland found that higher maternal α-linolenic acid intake during pregnancy was significantly related to a reduced risk of allergic rhinitis in children by 5 years of age, while a significant positive association was found between the ratio of n-6 to n-3 polyunsaturated fatty acid intake during pregnancy and childhood allergic rhinitis [12
]. On the other hand, there was no relationship between fish intake and allergic rhinitis in a cross-sectional study of Italian children [8
]. In a Finnish study, the differences in consumption of margarine and fish were not significant between children with allergic rhinitis and those without [7
]. With regard to studies in adults, a cross-sectional study of German adults showed significant positive associations between margarine intake and the ratio of n-6 to n-3 polyunsaturated fatty acid intake and hay fever in men, but not in women [14
]. In a case-control study of German adults, higher eicosapentaenoic acid intake was significantly associated with a reduced risk of hay fever [13
]. In young adult Japanese women, a significant inverse relationship was observed between intake of marine origin n-3 polyunsaturated fatty acids [16
] or seafood [17
] and allergic rhinitis. A significant inverse relationship between α-linolenic acid intake and the prevalence of allergic rhinitis was found in German adults [15
]. The discrepancies among studies may be explained, at least in part, by differences in the study populations and designs, dietary assessment methods, definitions of allergic rhinitis, and confounders.
Japanese people eat considerably more fish than do people in Western countries. The mean values for daily intake of eicosapentaenoic and docosahexaenoic acids in this population were 0.17 g and 0.29 g, respectively. In many parts of Europe, the daily combined intake of eicosapentaenoic acid and docosahexaenoic acid by adults is < 100 mg [24
]. A beneficial association between n-3 polyunsaturated fatty acid intake and rhinoconjunctivitis might be detected among populations whose fish intake is low. Alternatively, unknown active agents in fish might have interfered with the beneficial effect of marine-origin n-3 polyunsaturated fatty acids in rhinoconjunctivitis. For example, methylmercury and dioxins are accumulated in fish and shellfish through the marine food web. A significant correlation between fish consumption and hair mercury levels was found, and hair mercury levels were much higher in Japanese women residing in Canada than in Canadian women [25
To our knowledge, this study is the first to show a significant positive association between meat intake and the prevalence of rhinoconjunctivitis. The current findings regarding meat intake are in partial agreement with those of a previously cited Japanese study of female university students that showed a significant positive relationship between meat intake and the prevalence of wheeze, but not between meat intake and pollen allergy [17
]. The present findings are also partially consistent with those of a prebirth cohort study in Japan that reported that higher maternal meat intake during pregnancy was significantly associated with an increased risk of suspected atopic eczema, which was based on a physician's diagnosis of atopic eczema or possible atopic eczema, in infants aged 3-4 months [26
], although such intake was not related to the risk of wheeze or eczema based on the ISAAC criteria in the children aged 16-24 months [27
]. In reports using baseline data from the prebirth cohort study in Japan, there were no associations between meat intake and the prevalence of asthma, atopic eczema, or allergic rhinitis in pregnant women [16
]. Several studies showed no relationships between meat intake and wheeze and/or asthma in children [30
] and adults [37
]. Furthermore, a significant inverse association was found between red meat intake and doctor-diagnosed asthma in a cross-sectional study of young Australian adults [38
]. These observations are at variance with the current results. The positive association between meat intake and rhinoconjunctivitis in this study is not ascribed to saturated fatty acid intake because saturated fatty acid intake was not related to rhinoconjunctivitis. The other constituents in meat may affect the development of rhinoconjunctivitis. Cooking meat at high temperatures results in the formation of carcinogenic compounds, such as heterocyclic amines and polycyclic aromatic hydrocarbons [39
]. Also, meat intake results in exposures to N
-nitroso compounds, which can form endogenously [40
] and exogenously in nitrite-preserved meats [41
]. Our results regarding meat intake might be ascribed to these possible carcinogens; however, there is no epidemiological evidence for relationships between these carcinogens and allergic disorders. Alternatively, meat intake might be a marker of a dietary pattern that is related to rhinoconjunctivitis. Or, some unknown non-dietary factors related to meat intake may have confounded the observed association. Higher meat intake is likely to be linked to a westernized lifestyle which may be related to rhinoconjunctivitis among Japanese.
This study has methodological advantages. Study subjects were homogeneous in that they were all pregnant. We took into consideration extensive information on potential confounders. Adjustment was not made for external factors such as aeroallergens and air pollution, however. The definition of rhinoconjunctivitis was based on the questions of the ISAAC, although validation tests of these questions have not been performed for young Japanese adults.
There are methodological limitations, however. Our DHQ could only approximate consumption. The validity of our DHQ seems reasonable, as described above, although the correlation coefficient for polyunsaturated fatty acids was 0.37 [19
]. The possibility of exposure misclassification would bias the estimates of the associations toward the null. Our DHQ was designed to assess dietary intake for one month prior to completing the questionnaire. Information on dietary supplements that included eicosapentaenoic acid and docosahexaenoic acid was not available; however, it might not be necessary to take such supplements into consideration among our study subjects because pregnant Japanese women are generally not advised to take such supplements. Only a small number of our participants used vitamin C (4.6%), multivitamin (5.5%), and calcium (5.6%) supplements at least once a week, although 26.2% used vitamin B complex at least once a week. Substantial changes in diet in the previous month were experienced by 502 pregnant women because of nausea gravidarum (473 women), maternal and fetal health (27 women), and other reasons (2 women). The results of a sensitivity analysis excluding these 502 women were similar to those in the overall analysis: the adjusted OR for rhinoconjunctivitis in the highest quartile of meat intake was 1.47 (95% CI: 1.01-2.15, P
for trend = 0.04).
The participation rate could not be calculated because the exact number of eligible pregnant women who were provided with a set of leaflets explaining the KOMCHS, an application form, and a self-addressed and stamped return envelope by the 423 collaborating obstetric hospitals was not available. We were not able to analyze the differences between participants and non-participants, because information on personal characteristics such as age, socioeconomic status, and history of allergic disorders was not available for non-participants. It is likely, however, that our subjects were not a representative sample of Japanese women in the general population. In fact, educational levels in the present study population were higher than in the general population. According to the 2000 population census of Japan, the proportions of women aged 30 to 34 years in Fukuoka Prefecture with < 13, 13-14, ≥ 15, and an unknown number of years of education were 52.0%, 31.5%, 11.8%, and 4.8%, respectively [42
]. The corresponding figures for the current study were 24.5%, 33.1%, 42.4%, and 0.0%, respectively. The present population might therefore have had greater awareness of health topics than did the general population.
The cross-sectional nature of the study did not permit the assessment of causality because of the uncertain temporality of the association. Therefore, the findings from the present cross-sectional study do not necessarily indicate a causal relationship between meat intake and rhinoconjunctivitis.
The interface between allergy/immunology and pregnancy should be discussed, as it may have an influence on the association of interest. It has been suggested that pregnancy involves a shift to the Th2 side of the immune response [43
] although Chaouat et al. have pointed out the importance of the role of natural killer cells and IL-12, IL-15, and IL-18 tripods in successful or failed pregnancies in humans beyond the Th1/Th2 paradigm [44
]. The hormonal changes in pregnancy are often invoked to explain the apparent association between rhinitis symptoms and pregnancy. However, rhinitis ascribed solely to pregnancy may not be a distinct entity because most pregnant women do not have significant nasal symptoms [43