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3 Department of Epidemiology and Preventive Medicine and 4 Department of Prevention for Lifestyle-Related Diseases, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan and 5 Sakihai Institute, Gifu 500-8842, Japan
* To whom correspondence should be addressed. E-mail: chisato{at}gifu-u.ac.jp.
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ABSTRACT |
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 TOP ABSTRACT IntroductionSubjects and MethodsResultsDiscussionLITERATURE CITED |
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Introduction |
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TOPABSTRACTIntroductionSubjects and MethodsResultsDiscussionLITERATURE CITED |
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50,000 Chinese Singaporeans, Butler et al. (9) observed no significant association between risk of asthma and dietary patterns characterized by consumption of vegetables, fruits, and soy food items. Allergic rhinitis is a common clinical condition in many parts of the world (10,11). In Japan, pollinosis induced by a cedar pollen antigen is the most common seasonal allergic rhinitis. A recent review reported that the prevalence of pollinosis was 24.5% in the general population in urban areas and had increased >2.6-fold during the past 20 y (12). It is worthwhile to study the effects of soy isoflavone intake on the risk of this condition. The existence of allergic rhinitis, including pollinosis, might affect one's diet, including soy intake; therefore, the association between diet and cedar pollinosis should be explored in prospective studies. This study examined the association between soy isoflavone intake and the development of cedar pollinosis in a cohort of Japanese men and women (Takayama Study) (13).
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Subjects and Methods |
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TOPABSTRACTIntroductionSubjects and MethodsResultsDiscussionLITERATURE CITED |
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35 y completed a baseline self-administered questionnaire that included questions on demographic characteristics, smoking and drinking habits, diet, exercise, and medical and reproductive histories, yielding a participation rate of 85.3%. Diet was assessed with a validated 169-item semiquantitative FFQ. The questionnaire asked participants how often on average they consumed each of the food items listed and what was the usual serving size of each item during the year prior to the study. We included 9 food items for soy products (miso soup, tofu, deep-fried tofu, fried bean curd, dried bean curd, fermented soy beans, houba-miso, soymilk, and boiled soy beans). These 9 items and some other dishes including soy products as ingredients were accounted for to obtain the estimates for total amount (g) of soy products and isoflavone intake. Isoflavone intake (mg/d) from soy products was estimated using isoflavone concentration in these soy foods (14). The foods and nutrients were estimated from the frequency of ingestion and portion size using the Japanese Standard Tables of Food Composition, 4th and 5th editions (15). Detailed information about the questionnaire, including its validity and reproducibility, has been described elsewhere (16,17). For example, the Spearman correlation coefficients between the questionnaire and 12 daily diet records kept over a 1-y period for intake of soy products and soy isoflavones were 0.75 and 0.75 in men (P < 0.001), respectively. The corresponding values for women were 0.68 and 0.62 (P < 0.01).
In July 2002, we conducted a follow-up survey seeking information about experiences with cedar pollinosis. The questionnaire was developed with reference to that reported by Endo et al. (18). We sought information about 4 signs of cedar pollinosis: sneezing, nasal emission, nasal obstruction, and itchy eyes. Cedar pollinosis was considered to occur when at least 3 of the 4 signs were present and at least one of them occurred only during spring. We checked the validity of this questionnaire prior to its administration based on diagnosis made by an otolaryngologist using nasal examination, nasal provocation test, intracutaneous test, and pollen-specific IgE positivity as the gold standard. The sensitivity and specificity were 0.80 and 0.65, respectively. The participants were asked to record their age when each symptom had first occurred. For identified cases of cedar pollinosis, an individual's age at the onset was determined to be the time when the earliest symptom was observed. The details of the questionnaire and its validity check have been described elsewhere (19).
The study subjects for the follow-up survey were restricted to those who were <70 y of age at the baseline (n = 26,546). Among them, between September 1992 and March 2000, all those who died (n = 1120) or moved to another city (n = 1058) in this cohort were certified by the use of the residential registry. For the remainder of the follow-up until July 2002, we could not obtain residential registry data regarding death and relocation; however, using the obituaries issued by the city, we identified an additional 404 deaths. Of the 23,964 persons to whom we sent the questionnaire after excluding these individuals known to be dead or having moved to another city, 1460 had moved (inside or outside of the city), 18 had died (according to family members), and 51 were physically unable to complete the questionnaire. Of the remaining 22,437 persons, 14,975 (66.7%) responded to the questionnaire. Informed consent was as obtained from each subject. This study was approved by the ethical board of the Gifu University Graduate School of Medicine.
For the present analysis, subjects who reported having allergic diseases or using allergy medications at the baseline (522 men and 1029 women) were excluded. Those who reported having cancer (62 men and 212 women) were also excluded, because their diet, including soy intake, might be affected by the disease. Furthermore, those known to have had pollinosis before the baseline (441 men and 671 women) according to their response to the follow-up survey were excluded. In addition, 809 (315 men and 494 women) were excluded because of incomplete responses to the questions concerning cedar pollinosis. Hence, the analytic population consisted of 11,229 subjects (5334 men and 5895 women).
The association of soy isoflavone intake at the baseline with the risk of cedar pollinosis was examined using a Cox proportional hazard model. The specified endpoint of this study was the onset of cedar pollinosis. For each subject, person-years of follow-up were calculated from the study entry (September, 1992) to the date of onset of cedar pollinosis or the end of the study (July, 2002), whichever came first. Intakes of soy products and soy isoflavones were adjusted for total energy after log-transformation by using the residual method proposed by Willett (20). Energy-adjusted soy product and soy isoflavone intake was categorized by quartile based on the distribution among the study population at baseline. The hazard ratios (HR)6 and their 95% CI of cedar pollinosis for each category of soy intake were computed compared with the lowest intake category. Analyses were performed separately in men and women and adjusted for the following covariates: age, marital status, smoking status, years of education, and occupational history of farming. The chi-square test or linear regression analysis was used to evaluate the association between soy isoflavone intake and potential confounders.
As early symptoms related to cedar pollinosis would result in a change in dietary habits, including soy intake, we repeated the analysis described above after excluding cases of cedar pollinosis occurring during the first 3 y of the follow-up. All the statistical analyses were performed using SAS programs.
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Results |
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TOPABSTRACTIntroductionSubjects and MethodsResultsDiscussionLITERATURE CITED |
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Discussion |
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TOPABSTRACTIntroductionSubjects and MethodsResultsDiscussionLITERATURE CITED |
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So far, biological data have not provided strong evidence supporting an increased or decreased risk of cedar pollinosis by consumption of soy isoflavone. The T-helper cell (Th)2 response is predominant in cedar pollinosis, as it is in other types of allergic rhinitis. Cytokines derived by Th2 cells, such as interleukin (IL)-4 and IL-5, are likely to play an important role in the pathogenesis of cedar pollinosis (21). The results of laboratory as well as animal studies concerning the effects of genistein on IL-4 and IL-5 have been inconsistent, with the production of IL-4 or IL-5 suppressed by genistein in some studies (22–24) but enhanced in other studies (25–27). To our knowledge, there has been no human study examining the relationship between soy isoflavone intake and IL-4 or IL-5 level. Ryan-Borchers et al. (28), who measured other immunological markers, found that isoflavone intervention in postmenopausal women resulted in increased B cell populations but no change in interferon 
and T cell populations. The increased B cells may indicate that cytokines such as IL-4 and IL-5 stimulated the proliferation of B cells and, thereby, the production of IgE by B cells (29), but this interpretation is speculative. The inflammatory process is also intrinsic to allergic diseases, including cedar pollinosis, beyond the Th1/Th2 mechanism (29). Some human studies have assessed the relationship between soy intake and inflammatory markers, but again, the results have been inconclusive. Ryan-Borchers et al. (27) reported that isoflavone intervention did not alter plasma concentrations of IL-2, tumor necrosis factor (TNF)
, and C-reactive protein (CRP). A diet high in soy isoflavone increased serum IL-6 but not TNF and CRP in middle-aged men and women (30). Soymilk consumption decreased TNF but did not affect IL-6 in postmenopausal women (31). A soy protein diet did not affect CRP and IL-6 in moderately hypercholesterolemic adults (32). In studies among postmenopausal women (33,34), neither soy isoflavone nor soy protein affected CRP. In another study, soy nut consumption decreased CRP and IL-18 in postmenopausal women with metabolic syndrome (35).
Our results are not consistent with the results of the previous epidemiological study showing an inverse association between soy isoflavone intake and risk of allergic rhinitis, including cedar pollinosis (8). This discrepancy may be explained by differences in the study populations, design, and diseases of interest. In the previous study, the study population was exclusively pregnant women and a broader category of allergic rhinitis covering seasonal and perennial allergic rhinitis was included (8).
If the cross-sectional nature of the previous study had lead to an inverse association between soy isoflavone intake and risk of allergic rhinitis, even in this study, we should be cautious of inferring causal relationship between soy isoflavone intake and cedar pollinosis. Because the information of soy isoflavone intake was obtained at the baseline but the identification of cases was based on the follow-up questionnaire, misclassification of disease status due to recall might have occurred at baseline. However, a more serious limitation is that individuals with preclinical signs related to cedar pollinosis may have tried to avoid soy foods. Soybean has long been known as a possible cause of food allergy. Similarly, those who had past experiences of allergy and were potentially at an elevated risk of other allergic diseases, such as cedar pollinosis, may have avoided soy foods. To minimize such effects, we excluded those who had a history of allergy and repeated the analysis excluding early-onset cases during the follow-up. However, even the inclusion of those with previous allergic histories did not affect the results, nor did the analysis excluding early-onset cases. In addition, we observed that soy isoflavone intake was associated with increased risk of asthma in this population (data not shown). Although we still cannot deny the possibility that subjects who had avoided soy foods were more likely to be affected by cedar pollinosis as well as asthma, the discrepancy in results between asthma and cedar pollinosis in relation to soy isoflavone intake suggests that such a possibility is not very great. Nonetheless, because allergic experiences often extend back to childhood, a prospective study including a younger population is desirable. To our knowledge, there have been no reports demonstrating any cross-reactivity between cedar pollen and soy products.
The limitation of the diagnosis of the cedar pollinosis based on self-reporting of the symptoms should also be concerned. Cedar pollinosis is a highly prevalent seasonal disorder that is often undiagnosed by physicians. Therefore, to identify cases, we used a questionnaire asking about various symptoms related to this disease rather than asking whether the subjects had been diagnosed by physicians. There has been no other validated questionnaire to identify cedar pollinosis cases. The specificity of the questionnaire was not high in the present study. Although such a misclassification would not be dependent on soy intake, it would bias the study toward the null.
Diet was assessed at only 1 time point. It is possible that change in diet over time may have affected the outcome variable. For example, some persons may have increased soy intake, expecting benefits of soy on general health after the baseline. If soy isoflavone intake is truly associated with the risk of cedar pollinosis, they would be at either increased or decreased risk, but our study will be biased toward the null. Our questionnaire was designed to measure an individual's relative intakes of foods and nutrients rather than absolute values. Although we presented the median values of soy isoflavone intake, the absolute value may have been overestimated by our questionnaire. The FFQ, like all methods of dietary assessment, is subject to measurement error, which might have attenuated associations. The combination of low specificity and low correlation between questionnaire and diet records means that the data should only be taken as suggestive.
The response rate was not very high in this study. In addition, we could not obtain the pollen allergy status for subjects who had died or moved during the follow-up period. It is possible that subjects with high or low intakes of soy isoflavones were more likely to have participated in the present study when they had symptoms of cedar pollinosis. These possibilities could have affected the results.
In conclusion, we found no evidence of a significant association between soy isoflavone intake and risk of cedar pollinosis. Further studies on not only cedar pollinosis but also other types of allergic rhinitis in relation to soy isoflavone intake are warranted, given the limited data currently available.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Author disclosures: C. Nagata, K. Nakamura, K. Fujii, T. Kawachi, N. Takatsuka, S. Oba, and H. Shimizu, no conflicts of interest.
6 Abbreviations used: CRP, C-reactive protein; HR, hazard ratio; IL, interleukin; Th, T-helper cell; TNF, tumor necrosis factor.
Manuscript received 25 March 2008. Initial review completed 14 April 2008. Revision accepted 1 May 2008.
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LITERATURE CITED |
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1. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr. 1997;17:353–81.[Medline]
2. Cassidy A, Albertazzi P, Nielsen IL, Hall W, Williamson G, Tetens I, Atkins S, Cross H, Manios Y, et al. Critical review of health effects of soybean phyto-oestrogens in post-menopausal women. Proc Nutr Soc. 2006;65:76–92.[Medline]
3. Zhang R, Li Y, Wang W. Enhancement of immune function in mice fed high doses of soy daidzein. Nutr Cancer. 1997;29:24–8.[Medline]
4. Guo TL, White KL Jr, Brown RD, Declos KB, Newbold RR, Weis C, Germolec DR, McCay JA. Genistein modulates splenic natural killer cell activity, antibody-forming cell response, and phenotypic marker expression in F0 and F1 generation of Sprague-Dawley rats. Toxicol Appl Pharmacol. 2002;181:219–27.[Medline]
5. Yellayi S, Zakroczymski MA, Selvraj V, Valli VE, Ghanta V, Helferich WG, Cooke PS. The phytoestrogen genistein suppresses cell-mediated immunity in mice. J Endocrinol. 2003;176:267–74.[Abstract]
6. Curran EM, Judy BM, Newton LG, Lubahn DB, Rottinghaus GE, Macdonald RS, Franklin C, Estes DM. Dietary soy phytoestrogens and alpha signalling modurate interferon gamma production in response to bacterial infection. Clin Exp Immunol. 2004;135:219–25.[Medline]
7. Woods RK, Walters EH, Raven JM, Wolfe R, Ireland PD, Thien FC, Abramson MJ. Food and nutrient intakes and asthma risk in young adults. Am J Clin Nutr. 2003;78:414–21.
8. Miyake Y, Sasaki S, Ohya Y, Miyamoto S, Matsunaga I, Yoshida T, Hirota Y, Oda H. Soy, isoflavones, and prevalence of allergic rhinitis in Japanese women: the Osaka Maternal and Child Health Study. J Allergy Clin Immunol. 2005;115:1176–83.[Medline]
9. Butler L, Koh W-P, Lee H-P, Tseng M, Yu MC, London SJ. Prospective study of dietary patterns and persistent cough with phlegm among Chinese Singaporeans. Am J Respir Crit Care Med. 2006;173:264–70.
10. Holgate ST, Broide D. New targets for allergic rhinitis: a disease of civilization. Nat Rev Drug Discov. 2003;2:902–14.[Medline]
11. Latvala J, Von Hetzen L, Lindholm H, Haahtela T. Trends in prevalence of asthma and allergy in Finnish young men: nationwide study 1966–2003. BMJ. 2005;330:1186–7.
12. Kaneko Y, Motohashi Y, Nakamura H, Endo T, Eboshida A. Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis. Int Arch Allergy Immunol. 2005;136:365–71.[Medline]
13. Shimizu H. The basic report on Takayama Study. Gifu (Japan): Department of Public Health, Gifu University School of Medicine; 1996.
14. Wakai K, Egami I, Kato K, Kawamura T, Tamakoshi A, Lin Y, Nakayama T, Wada M, Ohno Y. Dietary intake and sources of isoflavones among Japanese. Nutr Cancer. 1999;33:139–45.[Medline]
15. The Science and Technology Agency of Japan. Standard tables of food composition in Japan. 4th and 5th rev eds. Tokyo: Kagawa Nutrition University Press; 2001.
16. Shimizu H, Ohwaki A, Kurisu Y, Takatsuka N, Ido M, Kawakami N, Nagata C, Inaba S. Validity and reproducibility of a quantitative food frequency questionnaire for a cohort study in Japan. Jpn J Clin Oncol. 1999;29:38–44.
17. Nagata C, Takatsuka N, Kawakami N, Shimizu H. Soy product intake and hot flashes in Japanese women: results from a community-based prospective study. Am J Epidemiol. 2001;153:790–3.
18. Endo T. Project report of the cedar pollinosis study for Science and Technology Agency; 2000. p. 20–47.
19. Nagata C, Nakamura K, Fujii K, Kawach T, Takatsuka N, Shino O, Shimizu H. Smoking and risk of cedar pollinosis in Japanese men and women. Int Arch Allergy Immunol. In press 2008.
20. Willett W. Implication of total energy intake for epidemiological analyses. In: Willett W, editor. Nutritional epidemiology. Oxford: Oxford University Press; 1990. p. 245–71.
21. Kimura H, Shibata Y, Minakami H, Hashizume S, Oba H, Sakaguchi M, Otsuki K, Kozawa K, Kato M. Release of IL-4 and IL-5 from human peripheral blood mononuclear cells co-cultured with Japanese cedar pollen antigen in vitro. Cell Biol Int. 2001;25:841–4.[Medline]
22. Minoguchi K, Yamashita N, Oda N, Takeno M, Kaneoka H, Sakane T. Protein tyrosine phosphorylation: a possible common signalling pathway in human Th1 and Th2 cell clones. Int Arch Allergy Immunol. 1999;118:30–6.[Medline]
23. Min B, Oh SR, Lee HK, Takatsu K, Chang IM, Min KR, Kim Y. Sophoricoside analogs as the IL-5 inhibitors from Sophora japonica. Planta Med. 1999;65:408–12.[Medline]
24. Kogiso M, Sakai T, Mitsuya K, Komatsu T, Yamamoto S. Genistein suppresses antigen-specific immune responses through competition with 17 β-estradiol for estrogen receptors in ovalbumin-immunized BALB/c mice. Nutrition. 2006;22:802–9.[Medline]
25. Guo TL, Auttachoat W, Chi RP. Genistein enhancement of respiratory allergen trimellitic anhydride-induced IgE production by adult B6C3F1 mice following in utero and postnatal exposure. Toxicol Sci. 2005;87:399–408.
26. Sakai T, Kogiso M, Mitsuya K, Komatsu T, Yamamoto S. Genistein suppresses development of spontaneous atopic-like dermatitis in NC/Nga mice. J Nutr Sci Vitaminol (Tokyo). 2006;52:293–6.[Medline]
27. Park J, Chung SW, Kim SH, Kim ST. Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites. Toxicol Appl Pharmacol. 2006;212:188–99.[Medline]
28. Ryan-Borchers TA, Park JS, Chew BP, McGuire MK, Fournier LR, Beerman KA. Soy isoflavones modulate immune function in healthy postmenopausal women. Am J Clin Nutr. 2006;83:1118–25.
29. Kidd P. Th1/Th2 balance: the hypothesis, its limitation, and implications for health and disease. Altern Med Rev. 2003;8:223–46.[Medline]
30. Jenkins DJA, Kendall CWC, Connelly PW, Jackson C-JC, Parker T, Faulkner D, Vidgen E. Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism. 2002;51:919–24.[Medline]
31. Huang Y, Cao S, Nagamani M, Anderson KE, Grady JJ, Lu L-JW. Decreased circulating levels of tumor necrosis factor- in postmenopausal women during consumption of soy-containing isoflavones. J Clin Endocrinol Metab. 2005;90:3956–62.
32. Hilpert KF, Kris-Etherton PM, West SG. Lipid response to a low-fat diet with or without soy is modified by C-reactive protein status in moderately hypercholesterolemic adults. J Nutr. 2005;135:1075–9.
33. Hall W, Vafeiadou K, Hallund J, Bügel S, Koebnick C, Reimann M, Ferrari M, Branca F, Talbot D, et al. Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interaction with genotype and equol production. Am J Clin Nutr. 2005;82:1260–8.
34. Hanson LN, Engelman HM, Alkel DL, Schalinske KL, Kohut ML, Reddy MB. Effects of soy isoflavones and phytate on homocystein, C-reactive protein, and iron status in postmenopausal women. Am J Clin Nutr. 2006;84:774–80.
35. Azadbakht L, Kimigar M, Mehrabi Y, Esmaillzadeh A, Hu FB, Willett WC. Soy consumption, markers of inflammation, and endothelial function. A cross-over study in postmenopausal women with the metabolic syndrome. Diabetes Care. 2007;30:967–73.
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