The current results show that higher consumption levels of PUFAs, n-3 PUFAs, α-linolenic acid, n-6 PUFAs, and linoleic acid are independently associated with an increased prevalence of eczema whereas intake of arachidonic acid is independently inversely related to the prevalence of eczema. Consumption of eicosapentaenoic and docosahexaenoic acid and the ratio of n-3 to n-6 PUFA intake were not associated with eczema. Only arachidonic acid intake was statistically significantly related to the prevalence of rhinoconjunctivitis, showing a clear inverse linear trend. Our results are at variance with those of an Australian study that reported no associations between n-3 and n-6 PUFA intake and childhood eczema . Partial agreement was noted with the results of studies that showed a positive association between margarine intake and eczema and no relationship between fish intake and allergic rhinitis [14–16], but our results are at variance with reports of a significant inverse relationship between fish intake and eczema and allergic rhinitis [11–13] and with reports of a significant positive association between margarine intake and allergic rhinitis [17, 18]. Previously, using data from the RYUCHS, we reported that higher intake levels of PUFAs, n-3 PUFAs, n-6 PUFAs, and linoleic acid were significantly related to an increased prevalence of wheeze , though we found no associations between intakes of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid, or the ratio of n-3 to n-6 PUFA intake, and wheeze . Exposure-response relationships were not found between the intake of any type of PUFA and the prevalence of asthma . Those findings are in partial agreement with the current results. With regard to arachidonic acid, our results are in partial agreement with those from the KOALA Birth Cohort Study, which showed that the risk of eczema in the first 12 months of life significantly decreased with increasing levels of arachidonic acid in plasma phospholipids in pregnancy, although there was no relationship between the arachidonic acid levels and eczema later in life . The current results are inconsistent with those of a cross-sectional study showing a positive association between concentrations of arachidonic acid in serum phospholipids and hay fever in German adults . The direction of the relationship between arachidonic acid and allergic disorders might change according to the timing of the exposure: an inverse relationship may exist starting in utero and continuing through childhood, whereas a positive relationship may exist in adulthood.
Linoleic acid can be converted to arachidonic acid, which is usually the major substrate for eicosanoid synthesis . Eicosanoids, which consist of prostaglandins, thromboxanes, leukotrienes, and other oxidized derivatives, are generated from arachidonic acid by cyclooxygenase and lipoxygenase enzymes . Some eicosanoids are implicated in clinical manifestations of allergic disorders, although individual prostaglandins might augment or inhibit inflammation related to allergic reactions, depending upon their specific action [30, 31]. One current paradigm is that prostaglandin D2, prostaglandin F2α, and thromboxane A2 increase allergic inflammation whereas prostaglandin E2 and prostaglandin I2 inhibit allergen-induced inflammatory responses . Given the positive relationships between linoleic acid intake and the production of prostaglandin D2, prostaglandin F2α, and thromboxane A2, the current results showing an association of linoleic acid intake with an increased prevalence of eczema might be considered reasonable, although no relationship between linoleic acid intake and rhinoconjunctivitis was shown. On the other hand, higher arachidonic acid intake may have led to increased production of prostaglandin E2 and prostaglandin I2, with a consequent decrease in eczema and rhinoconjunctivitis in the subjects studied.
Long chain n-3 PUFAs inhibit arachidonic acid incorporation into cell membranes and inhibit arachidonic acid metabolism to eicosanoids . Given that higher α-linolenic acid intake especially inhibits the production of prostaglandin E2 and prostaglandin I2, the present results concerning α-linolenic acid intake and eczema also might be reasonable although a null relationship between such intake and rhinoconjunctivitis was found.
In Japan, fish intake is high. The mean values for daily intake of eicosapentaenoic and docosahexaenoic acids in this population were 0.11 g and 0.27 g, respectively. In many parts of Europe, the daily intake of eicosapentaenoic acid + docosahexaenoic acid by adults is < 100 mg . In a nested case-control study of Australian children that showed a significant positive association between the ratio of n-6 to n-3 PUFAs in the diet and the risk of asthma , the mean value of daily n-3 PUFA intake and the ratio of n-3 to n-6 PUFA intake among 169 controls were 1.05 g and 0.065, respectively; these values were much lower than the corresponding figures in this study (2.03 g and 0.199, respectively). Therefore, protective associations of n-3 PUFA intake and the ratio of n-3 to n-6 PUFA intake with eczema and rhinoconjunctivitis might be detected when consumption of n-3 PUFAs is very low. Alternatively, unrecognized active agents in fish might have counteracted the benefit of marine-origin n-3 PUFAs in eczema and rhinoconjunctivitis. For example, methylmercury and dioxins are accumulated in fish and shellfish through the marine food web. One study has found a significant correlation between fish consumption and hair mercury levels, reporting that hair mercury levels were much higher in Japanese women residing in Canada than in Canadian women .
Eggs, meat, fish, milk, and sweets are major sources of arachidonic acid intake among Japanese people . Meat, milk, and sweets are also major sources of trans fatty acid intake among Japanese people . Arachidonic acid intake may be to some extent correlated with trans fatty acid intake. In this study, data on trans fatty acid intake were not available because the Standard Tables of Food Composition in Japan do not include information on trans fatty acids. In the KOALA Birth Cohort Study, higher concentrations of trans fatty acids from a rumenic source in human breast milk were associated with a lower risk of eczema at 2 years of age . In contrast, an ecological study using data from the International Study of Asthma and Allergies in Childhood showed positive relationships between trans fatty acid intake and the prevalences of asthma, eczema, and rhinoconjunctivitis .
The current study had methodological advantages. Study subjects were homogeneous in terms of age and geographical background. That the study included a large number of both subjects and confounders was likely to minimize problems due to small sample size, inadequate data on potential confounders, and reduced statistical power. However, residual confounding could not be ruled out. In particular, no adjustment was made for data on allergen exposure and the home environment. The core questions used to assess the outcomes under study had been validated by the International Study of Asthma and Allergies in Childhood phase-I study, but validation tests of the questions had not been performed in this population. Moreover, no attempt was made to ascertain outcome status through reviews of medical records.
Other weaknesses include the fact that dietary data were obtained through a self-administered dietary assessment questionnaire (i.e., BDHQ). Because actual dietary habits were not observed, the results should be interpreted with caution, although the validity of the BDHQ appears reasonable, as described above. The estimates of consumption of specific types of PUFAs derived from the BDHQ might not reflect long-term intake by subjects. Nevertheless, subjects with eczema or rhinoconjunctivitis were likely to be unaware of the possible ill effects of PUFA intake. The consequence would have been underestimation in our results. Information on dietary supplements was not available in the present study; their use, however, is uncommon in Japan . The BDHQ was answered by parents in the case of elementary schoolchildren and by students and/or parents in the case of junior high school students. Dietary data on children and adolescents is, in the main, prone to reporting error . We cannot predict whether possible selective misreporting of dietary intake would systematically deflate or inflate the estimates of these dietary variables. In any case, random misclassification in our study was likely, and it probably weakened the evidence for any true relationships. Information on self-reported body weight and height was not validated, and thus body mass index might have been biased.
Only 61.2% of the eligible subjects were included in the current analysis, suggesting that selection bias might have been inevitable. In fact, as mentioned above, there was a significant difference between the excluded participants and study subjects with regard to several factors.
Okinawa has unique characteristics regarding its geographical location, as it is located at the southern extremity of Japan, is close to Taiwan, and is the only prefecture in Japan situated in a subtropical climate zone. Moreover, Okinawa is less developed than the mainland because it only reverted to Japanese administration in 1972. The distribution of a variety of environmental factors including diet and socioeconomic status as well as allergy in Okinawa is likely to differ from that in the mainland of Japan. For example, according to the criteria of the International Study of Asthma and Allergies in Childhood, the prevalences of eczema and rhinoconjunctivitis in the previous 12 months were 14.5% and 23.9%, respectively, among Japanese adolescents in Suita City, an urban area in the mainland . Because Japanese cedar pollinosis is a major public health problem in the mainland of Japan, this finding with regard to rhinoconjunctivitis is not unexpected. Because Okinawa has comparatively few Japanese cedars, however, people in Okinawa are not as likely to experience rhinoconjunctivitis. We should, therefore, be cautious in generalizing the present results to Japanese children in the mainland. Another limitation is that we could not take clustering of conditions within families into consideration, as no information was available on familial relationships among the subjects. This lack of data might influence relationships of interest.