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Keywords:

  • antioxidants;
  • diet;
  • EPIC;
  • fatty acids;
  • hay fever

Abstract

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

Background:  The objective of the investigation was to explore in a prospective study the associations between dietary intake of fatty acids, antioxidants and hay fever manifestation in adulthood.

Methods:  Three hundred and thirty-four hay fever cases with adult onset of clinical symptoms from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort were identified during follow-up and matched with 1336 controls. Dietary intake data were obtained by means of validated food frequency questionnaires. The influence of dietary fatty acid and vitamin intake on hay fever risk was estimated by means of unconditional logistic regression.

Results:  High intake of oleic acid was positively associated with hay fever [odds ratio (OR): 2.86, 95% confidence intervals (95% CI): 1.22–6.70], whereas high intake of eicosapentaenoic acid was inversely related to hay fever (OR: 0.45, 95% CI: 0.22–0.93). Furthermore, high β-carotene intake increased the risk of hay fever (OR: 1.69, 95% CI: 1.09–2.63) while increasing intake of vitamin E was a protective factor (OR: 0.38, 95% CI: 0.17–0.85). In grouped analyses, the effects of β-carotene and vitamin E were mainly observed among women and ex-/current-smokers; in these subgroups, linoleic acid increased the risk of hay fever.

Conclusions:  In conclusion, the present results provide further evidence that dietary factors might affect the risk of clinical manifestation of hay fever. However, the effects in smokers and women may suggest different biological mechanisms for the investigated nutrients, which need further research.

Hay fever or seasonal allergic rhinitis is characterized by a prolonged immunoglobulin E (IgE) mediated inflammation after allergen exposure (1). It affects, with regional differences, 9.5–40.9% of the European population (2, 3). Genetic and environmental factors including air pollution, housing conditions and other lifestyle factors have been linked to its etiology. Findings have increasingly been interpreted in the conceptual framework of the ‘hygiene hypothesis’ which explains the increasing occurrence of atopic diseases by a shift to T-helper cell 2 (Th2) triggered immune responses because of decreased childhood contacts to infectious agents, important stimulants for the Th1 reaction (4).

Recent research is led by the observation that a substantial contribution to increasing allergic sensitization might additionally arise from dietary factors, crucial components of the typical western lifestyle pattern (5). Special attention was assigned to dietary fat intake, after a study among children in former Eastern Germany linked elevated margarine consumption positively and butter consumption inversely with hay fever (6). A role of dietary fat intake in the etiology of atopic diseases would fit into the above cited hypothesis, since fat intake and specifically the composition of the ingested dietary fatty acids are known to modulate immune reactions (7). As potential mechanisms their influence on membrane composition, their impact on the production of immune mediators such as prostaglandins and leukotrienes (LTs), and their differential effects on the regulation of Th1 and Th2 cytokines are discussed (8).

Particularly, differences in the consumption of n-3 and n-6 fatty acids have been related to the prevalence of allergic diseases (9, 10). In a typical western diet the proportion of n-6 polyunsaturated fatty acids (PUFA) is much higher than that of n-3 PUFA (11). The main dietary sources for eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6) as members of the n-3 PUFA family, are fish and other marine food, which are scarce in most western diets (12). Important sources for the main n-6 PUFAs, linoleic acid (C18:2) and arachidonic acid (AA) (C20:4), are vegetable and animal fat, respectively. By the competitive metabolism of EPA and AA via the cyclooxygenase and lipooxygenase pathways, specifically the ratio of n-6 and n-3 PUFAs may influence the production of immune mediators such as prostaglandins, LTs, thromboxanes, and epoxy-compounds. The metabolism of the n-6 PUFAs and AA leads to the formation of prostaglandin E2 (PGE2), which is an important immune regulator known to suppress Th1 activation and enhance Th2 activation thereby accelerating the formation of IgE in B cells (13).

Under unbalanced (patho-)physiological conditions such as deficiency of antioxidants or chronic inflammation the enzymatic metabolism of PUFAs leads to an increased internal exposure to free radicals. Additionally, autoxidation of the double bonds may substantially contribute to an enhanced radical load. Recent work indicates that this ‘oxidative stress’ might regulate Th1 and Th2 cytokines differentially in favor of a Th2 response (14). It can be hypothesized that, dietary antioxidants such as β-carotene, vitamins C and E, might contribute to the pathogenesis of allergies by their anti-oxidative properties thus decreasing the risk of hay fever. An inverse association between IgE plasma levels and a high intake of vitamin E is described (15, 16). Taken together there is evidence that dietary factors may influence the inflammatory response following allergen-specific challenge and thus have impact on the clinical onset of allergic disease.

Therefore, the present evaluation aims to examine prospectively within European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg the potential effect of dietary fatty acids and antioxidants on the risk of hay fever among adults.

Data collection

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

The EPIC is a prospective multicentre study that has been implemented to further the understanding of the association between diet and chronic diseases with emphasis on cancer (17). In Heidelberg from June 1994 until October 1998 about 25 500 subjects aged 35–65 years in women and 40–65 years in men were recruited (18, 19). The baseline assessment of the cohort comprised a dietary measurement by means of a self-administered food frequency questionnaire (FFQ) (20, 21), a computerized lifestyle interview and standardized anthropometric measurements (22). The response rate of the first follow-up, which took place between 1998 and 2000, was 93.5% .

During the median follow-up time of 2.1 years, 334 hay fever cases with first manifestation of clinical symptoms were identified through comparison of baseline and follow-up data. Cases were based on the participants’ responses on the lifestyle follow-up questionnaire asking specifically for a diagnosis confirmed by a physician. Of 344 persons 189 (54.9%) noted the year of hay fever diagnosis, which was in median 1.3 years after baseline assessment. Furthermore, of 143 cases information on the specific allergens was available. Most often pollens (45.8%) and house dust mites (23.6%) were mentioned. The control group comprised of 1336 randomly selected cohort members without self-reported prevalent hay fever or other atopic diseases, that were matched (4 : 1) to the cases by sex and age group (5 years).

Variable definition

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

The information on the consumption of fatty acids, antioxidants, and nutrients are based on the self-administered FFQ. The nutrient intake was calculated on the base of the national food tables BLS, Version II.3 (23). Based on the distributions among the controls, the quartiles for the dietary intake of food groups, fatty acids and antioxidants were calculated.

Education was categorized as low (no more then 9 years of schooling without a specific vocational training), middle (high school degree (10 years) and/or vocational or technical training) and high (13 years of high school and/or a university degree). Sports activity was classified as ‘yes’ when any sports activity was mentioned. Participants were re-categorized as nonsmokers when less than 3 months of regular smoking was reported, as ex-smokers when smoking was quitted for at least 1 year before the baseline interview, and as smokers when present smoking was reported or when smoking was quitted <1 year before the baseline interview. Body mass index (BMI) was calculated as weight in kg/height in m2.

Statistical methods

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

A case–control evaluation frequency matched for sex and age was conducted. Mean, standard deviation, minimum, and maximum as well as quartiles were calculated using the SAS procedure univariate.

The quartile cut points were based on consumption levels among controls corresponding to the values of the 25, 50, and 75 percentiles. The associations between dietary intake and the risk of hay fever were assessed fitting unconditional logistic regression models. Analyses grouped by sex and smoking habits were performed.

For each dietary variable the relationship between hay fever was explored separately by logistic regression without involvement of other nutrient variables. A multivariate basic model to evaluate the influence of fatty acids and antioxidants simultaneously on the risk of hay fever was fitted. In further models the ratios of fatty acids were included separately replacing the corresponding dietary fatty acids. In additional models EPA and DHA as n-3 PUFAs and vitamins were replaced by their main dietary sources, i.e. fish as well as fruits, fruit juice and vegetables, respectively. Odds ratios (OR) and the corresponding 95% confidence intervals (95% CI) were calculated using the PROC LOGISTIC procedure of the statistical software package SAS release 8.2 (SAS Institute, Cary, NC). Tests for trend with two-sided P-values were calculated by using the median values for each category as continuous exposure score.

Results

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

Table 1 shows the basic characteristics of cases and controls. Between the groups no differences regarding BMI and median follow-up time existed. Significant differences can be seen for smoking habits (P = 0.001) and educational level (P = 0.042). No group differences were found for sports activities (P = 0.692).

Table 1.  Sample characteristics hay fever cases and matched controls
VariableCases n = 334Controls n = 1336P-value*
n%n%
  1. * Chi2-test, † Wilcoxon test, ‡ First follow up.

  2. BMI, body mass index.

Age (matching variable)
 <50 years17351.869251.8 
 50–59 years12136.248436.2 
  ≥60 years  4012.016012.0 
Sex (matching variable)
 Male11434.145634.1 
 Female22065.988065.9 
Educational level
 High (university)  23  6.9  92  6.90.042
 Medium (professional training)17652.780059.9 
 Low (no professional training)13540.444433.2 
Sports acitivity
 Yes19056.977658.10.692
 No14443.156041.9 
Smoking status
 Never13339.855441.50.001
 Ex13038.939129.3 
 Current  7121.339129.3 
 Median25–75 percentileMedian25–75 percentileP-value†
Follow-up time (years after recruitment)‡  2.11.7–2.7    2.01.7–2.60.102
BMI (kg/m2)25.3523.0–28.0  25.222.8–28.10.725

Table 2 shows the relationship between the intake of fatty acids and antioxidants and the risk of hay fever in the adjusted model. An increasing intake of C18:1 (oleic acid) was positively associated with hay fever (P-value for trend 0.040). For the highest consumption group (4. quartile) the risk of hay fever was almost threefold (OR: 2.86, 95% CI: 1.22–6.70) compared with the lowest consumption group (1. quartile). With increasing intake of C20:5 (EPA) the risk of hay fever symptoms decreased. For the group with the highest intake (4. quartile) the relationship was significant (OR: 0.45, 95% CI: 0.22–0.93). For individuals with low intake (2. quartile) of C18:2 (linoleic acid) the risk of hay fever was higher than in the reference category (OR: 1.61; 95% CI: 1.01–2.58), an effect which did not extend to the upper quartiles. For the intake of other fatty acids no significant effects on hay fever risk were found. Surprisingly, an increasing ratio of n-6 to n-3 PUFA tended to decrease hay fever risk (P = 0.031 for trend), an effect which remained after adjustment.

Table 2.  Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for the association between the dietary intake of fatty acids and vitamins and the clinical manifestation of hay fever in adults
Nutrient1. Quartile (lowest)2. Quartile3. Quartile4. Quartile (highest)P for trend
  1. * Cut-points of the quartiles.

  2. †  Micronutrient variables were examined simultaneously in the model, multivariate adjusted for adjustment variables.

  3. ‡  Replaced the fatty acids C18:2, and C20:4, C18:3 C20:5, and C22:6, respectively in the basis model, multivariate adjusted.

  4. The model included as adjustment variables: age (<50, 50–59 and ≥60 years), total energy intake (kcal/d, continuous), body mass index (continuous), smoking status (never, ex, current), sex, educational level (high, middle, low), sports activity (yes, no).

  5. SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids.

SFA (no. of cases)8176 84 93  
SFA* (g/d)<22.722.7–28.7 28.7–37.5 >37.5  
SFA† (OR/95% CI)11.200.71–2.021.410.68–2.931.270.50–3.210.996
MUFA        
 C16:1 (no. of cases)8776 80 90  
 C16:1* (g/d)<1.21.2–1.5 1.5–2.0 >2.0  
 C16:1† (OR/95% CI)10.670.39–1.170.550.25–1.200.530.20–1.430.160
 C18:1 (no. of cases)8076 78 100  
 C18:1* (g/d)<16.816.3–20.8 20.8–26.6 >26.6  
 C18:1† (OR /95%CI)11.220.73–2.041.480.74–2.952.861.22–6.700.040
n-6 PUFA        
 C18:2 (no. of cases)7688 87 83  
 C18:2* (g/d)<7.27.2–9.4 9.4–12.4 >12.4  
 C18:2† (OR/95%CI)11.611.01–2.581.700.92–3.161.600.72 –3.540.333
 C20:4 (no. of cases)8586 83 80  
 C20:4* (mg/d)<100100–140.7 140.7–202.5 >202.5  
 C20:4† (OR/95%CI)11.010.68–1.500.880.54–1.440.670.36–1.270.040
n-3 PUFA        
 C18:3 (no. of cases)8273 87 92  
 C18:3* (g/d)<0.90.9–1.2 1.2–1.5 >1.5  
 C18:3† (OR/95%CI)10.830.51–1.340.990.54–1.841.050.50–2.230.526
 C20:5 (no. of cases)8776 85 86  
 C20:5 (mg/d)<30.230.2–55.1 55.1–95.9 >95.9  
 C20:5†(OR/95% CI)10.710.46–1.100.660.38–1.150.450.22–0.930.071
 C22:6 (no. of cases)7784 82 91  
 C22:6* (mg/d)<83.483.4–113.6 113.6–194.5 >194.5  
 C22:6† (OR/95% CI)11.470.89–2.421.720.84–3.522.340.91– 5.980.006
Vitamins        
 Retinol (no. of cases)7993 85 77  
 Retinol* (μg/d)<417.8417.8–596.4 596.4–873.5 >873.5  
 Retinol† (OR/95% CI)11.190.81–1.751.030.67–1.590.870.53–1.410.370
  β -Carotene (no. of cases)8359 84 108  
  β -Carotene* (mg/d)<1.71.7–2.2 2.2–2.9 >2.9  
  β -Carotene† (OR/95% CI)10.770.51–1.151.180.78–1.771.691.09–2.630.116
 Vit. C (no. of cases)8384 86 81  
 Vit. C* (g/d)<70.970.9–94.7 94.7–125.5 >125.5  
 Vit. C† (OR/95% CI)10.990.67–1.451.000.67–1.510.890.56–1.420.132
 Vit. E (no. of cases)8582 80 87  
 Vit. E* (g/d)<8.38.3–10.3 10.3–13.1 >13.1  
 Vit. E† (OR/95%CI)10.710.44–1.140.460.25–0.860.380.17–0.850.067
 Vit. D (no. of cases)8175 83 95  
 Vit. D* (μg/d)<1.71.7–2.5 2.5–3.6 >3.6  
 Vit. D† (OR/95% CI)10.900.57–1.441.070.57–2.031.410.62–3.200.113
n-6/n-3 ratio (no. of cases)9792 80 65  
 n-6/n-3 ratio*<5.85.8–6.9 6.9–8.1 >8.1  
 n-6/n-3 ratio†‡ (OR/95% CI)10.990.70–1.390.870.60–1.260.700.45–1.100.031

Furthermore, an increasing consumption of β-carotene was positively associated with hay fever (P-value for trend 0.116). For the highest intake group the association with hay fever reached statistical significance (OR: 1.69; 95% CI: 1.09–2.63). For increasing intake of vitamin E a trend towards a decreased risk was observed (P-value for trend 0.067). For individuals with high intake of vitamin E (3. and 4. quartile) the inverse effects were significant (OR: 0.46, 0.38, respectively). For the replacement of micronutrients by the corresponding food groups (fish or fruit, fruit juice and vegetable, butter and margarine, respectively) no association with hay fever risk was observed (data not shown).

Subsequently, the data was analyzed by sex (Table 3) and smoking status (Table 4). Among men no significant associations were seen, whereas among women the intake of C18:2 was associated with a higher risk of hay fever with OR of 1.82 and 2.09 in the second and third quartile. Moreover, an increasing intake of β-carotene (4. quartile) was positively associated with hay fever risk (P-value for trend 0.134). In the group of nonsmokers an increase in risk for high C18:1 intake (OR: 4.82; 95% CI: 1.05–22.19) and an inverse effect for higher C20:5 was observed (OR: 0.31; 95% CI: 0.10–0.99). Among ex- and current smokers significant effects on hay fever risk were seen for high intake of β-carotene (positive association, P-value for trend 0.060) and vitamin E (inverse association, P-value for trend 0.133). In this subgroup, linoleic acid intake in the third quartile was significantly associated with hay fever risk.

Table 3.  Odds Ratios (OR) and corresponding 95% confidence intervals (95% CI) for the association between the consumption of selected fatty acids and vitamins and the clinical manifestation of hay fever by gender
Nutrient1. Quartile (lowest)2. Quartile3. Quartile4. Quartile (highest)P for trend
OR95% CIOR95% CIOR95% CI
  1. * Micronutrients were examined simultaneously in the model, multivariate adjusted for adjustment variables.

  2. The model included as adjustment variables: age (<50, 50–59 and ≥60 years), total energy intake (kcal/d, continuous), body mass index (continuous), smoking status (never, ex, current), sex, educational level (high, middle, low), sports activity (yes, no), C16:1, C18:3, C20:4, vitamins C, A, D.

Male (n = 570)
 C18:1*11.370.42–4.531.070.22–5.133.530.56–22.190.129
 C18:2*11.080.40–2.880.950.26–3.491.020.22–4.820.876
 C20:5*10.640.26–1.580.500.18–1.420.380.11–1.310.127
  β -Carotene*10.480.37–1.511.640.80–3.351.250.57–2.740.556
 Vit. E*10.920.35–2.420.590.17–2.030.470.11–2.080.045
Female (n = 1100)
 C18:1*11.250.70–2.231.700.76–3.782.630.96–7.250.008
 C18:2*11.821.05–3.182.091.01–4.331.530.57–4.090.616
 C20:5*10.730.44–1.200.720.36–1.450.400.15–1.070.044
  β -Carotene*10.760.45–1.271.020.60–1.721.961.12–3.430.134
 Vit. E*10.660.38–1.160.400.19–0.840.380.14–1.020.110
Table 4.  Odds Ratios (OR) and corresponding 95% confidence intervals (95% CI) for the association between the consumption of selected fatty acids and vitamins and the clinical manifestation of hay fever by smoking status
Nutrient1. Quartile (lowest)2. Quartile3. Quartile4. Quartile (highest)P for trend
  1. * Micronutrients were examined simultaneously the model, multivariate adjusted for adjustment variables.

  2. The models included as adjustment variables: age (<50, 50–59 and ≥60 years), total energy intake (kcal/d, continuous), body mass index (continuous), smoking status (never, ex, current), educational level (high, middle, low), sports activity (yes, no), C16:1, C18:3, C20:4, vitamins C, A, D, and sex in the model grouped by smoking habits.

Non-smokers (n = 687)
 C18:1*11.330.57–3.132.900.88–9.514.821.05–22.190.014
 C18:2*11.280.58–2.811.000.35–2.831.070.29–3.940.913
 C20:5*10.610.31–1.220.670.27–1.640.310.10–0.990.092
  β -Carotene*10.580.30–1.110.930.49–1.771.150.57–2.350.486
 Vit. E*11.610.73–3.550.730.26–2.050.930.25–3.520.638
Ex or current smokers (n = 983)
 C18:1*11.200.61–2.361.030.41–2.572.450.82–7.300.131
 C18:2*11.810.98–3.322.251.02–4.971.730.61–4.890.465
 C20:5*10.730.41–1.300.640.30–1.350.550.21–1.470.133
  β -Carotene*10.870.51–1.501.330.77–2.322.211.22–4.000.060
 Vit. E*10.470.25–0.880.380.17–0.850.260.09–0.740.133

Discussion

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

We used the frame of the prospective EPIC cohort to investigate the relationship between dietary intake of fatty acids and vitamins and occurrence at a relatively older age of a first diagnosis of hay fever, i.e. clinical manifestation of hay fever. The time lag between the assessment of dietary habits and the hay fever diagnosis was in median 2.1 years. We found associations between the intake of several fatty acids (C18:1, C18:2, C20:5) and vitamins (vitamin E, β-carotene) with the risk of hay fever. However, the association between linoleic acid (C18:2), β-carotene and vitamin E and hay fever was related to smoking habits and gender, whereas others (C18:1, C20:5) were found independently. As these nutrients act biologically differently, the consistency and mechanistic plausibility of these findings has to be examined carefully.

Monounsaturated fatty acids

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

The present study found an increasing intake of the MUFA oleic acid (C18:1) significantly associated with an increasing hay fever risk. This observation is consistent with the results of Heinrich et al. who reported that dietary intake of energy adjusted MUFA was positively related to the prevalence of atopy (3). Among the main dietary sources of cis-C18:1 in the typical German diet are meat, meat products, butter, milk, milk products and cheese. As the intake of trans-C18:1 is provided by ruminant fat and margarine, it may be therefore speculated that a higher intake of C18:1 may correlate with an increasing intake of trans-C18:1. There is evidence that the configuration (cis-, trans-) of monounsaturated fatty acids influences immune modulation. Weiland et al. found that the intake of trans-fatty acids is associated with allergic disease (24). It was suggested that trans-fatty acids may promote an increase in IgE, mediated by the modulation of the desaturation and chain elongation of n-6 and n-3 fatty acids and thereby influences the prostaglandin and LT synthesis (25).

Polyunsaturated fatty acids

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

We found indications for an inverse association between dietary intake of the n-3 PUFA EPA (C20:5) and the incidence of allergic rhinitis with a significantly decreased OR in the highest intake quartile. No association was observed for α-linolenic acid (C18:3) and DHA (C22:6) or the overall intake of n-3 PUFA.

Among the n-6 PUFA, some indication for a relationship of the intake of linoleic acid (C18:2) could be observed. However, this finding was only statistically significant in specific intake quartiles (2. quartile for the whole study population and second and third quartile for ex or current smokers) and is not supported by the trend test.

The results found in smokers, particularly in smoking women, would fit with the oxidative stress hypothesis of allergic respiratory diseases as discussed in Bowler and Crapo (26). In a situation with a high radical load the double bonds of the main dietary PUFA are autoxidized, but may be prevented by vitamin E. In women, there is some evidence that a high linoleic acid intake may increase lipid peroxidation products (in certain conditions) which may be mediated by redox cycling of hydroxyestradiol compounds (27).

The literature provides a report from Japan describing a positive association between allergic rhino conjunctivitis and the intake of n-6 PUFA. However, that study could not find any significant association with the intake of SFA, MUFA, and n-3 PUFA (10). We could not corroborate previous links between butter vs margarine consumption and the prevalence of hay fever and asthma among children which were suggested to explain higher rates in West compared with East Germany (6, 9, 28, 29).

The n-6 and n-3 PUFA are both substrates of cyclooxygenase and lipoxygenase enzymes, leading, however, to molecules with different effects on inflammatory processes. Prostaglandin E2, a n-6 derived product, is known to shift the Th1/Th2 balance in the Th2 direction, which favors Th2 determined diseases such as allergies (7). In contrast, an increasing availability of the EPA as a n-3 PUFA inhibits the conversion of AA to PGE2 and LT B4 and can be expected to be negatively associated with allergic rhinitis (30).

The described biological mechanism suggests that the risk of hay fever increases with an increasing ratio of n-6 vs n-3 intake. Unexpectedly, in our study this relationship tended to decrease. This result might be caused by counterbalancing effects of the fatty acids within the n-3 and n-6 PUFA families.

Vitamin E

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

Our study indicates a decreasing risk of hay fever with increasing vitamin E intake. Although the trend is not statistically significant a decreased risk is statistically confirmed in the two upper quartiles of vitamin intake.

Two other studies addressed vitamin E intake in relation to atopic diseases. Consistent with our result is the finding of Fogerty et al. (15) who reported an inverse relationship between vitamin E intake and risk of atopy. Though addressing asthma, a study by Troisi shall be mentioned who investigated the impact of diet on adult-onset of asthma and observed compared to the lowest quintile, a risk reduction for the highest quintile of vitamin E intake derived from diet but not from supplements (31).

Vitamin E is an oxidant scavenger crucial for the protection of cell membranes from damage by reactive oxygen species and is found in high concentrations in the membranes of immune cells (32). Vitamin E is an important factor for normal immune function and its supplementation in the elderly was shown to significantly enhance cell-mediated immunity (33). The anti-oxidant properties of vitamin E as well as its negative effect on the production of PGE2 may be contributing factors to the inverse association of increasing vitamin E intake and hay fever seen in this study.

β-Carotene

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

For β-carotene, we observed a strongly increasing risk with increasing level of vitamin intake. This relationship is largely because of a particular strong association among smokers, while the tendency is much weaker among nonsmokers.

Though addressing a quite different issue, it appears worth taking into consideration that a risk increasing effect of high intake of β-carotene, particularly in smokers, has also been found in vitamin intervention trials for lung cancer (34, 35). Oxidants in cigarette smoke appear to induce β-carotene autoxidation, that promotes carcinogenesis and – as suggested in this study – probably also processes linked to allergic rhinitis. Another possible mechanism for the risk-increasing effect among smokers may be related to a β-carotene induced production of the cytochrom P450 carcinogen-bioactivating enzymes in the lung (36). Their activation of tobacco-smoke compounds to reactive metabolites may also increase oxidative stress and thereby impact on allergy pathogenesis. It may be that β-carotene impacts in a similar fashion also on other enzyme activities and proteins involved in the etiology of hay fever, for example the secretion of cytokines. In an intervention study with prolonged tomato juice consumption increasing concentrations of plasma β-carotene and ascorbic acid were associated with an elevated secretion of interleukin (IL)-4 whereas the IL-2 production was reduced (37). Interleukin-4 promotes the Th2 clonal expansion and limits the proliferation of Th1 cells (38). This Th1/Th2 imbalance towards Th2 function may underlie the association between high β-carotene intake and hay fever. This is also supported by recent in vitro data by Stephensen et al. who reported a strong enhancement of Th2 development in mice treated with vitamin A (39).

Sociodemographic factors

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

The analysis by gender revealed stronger effects of β-carotene and vitamin E intake on hay fever risk in women than in men. Bolte et al. observed in a gender stratified analysis among children, that the association between margarine consumption was associated with allergic sensation only among boys (29). Clinical and experimental evidence support the hypothesis of gender differences in immune reactions (40, 41). Gender emerges as an important factor in immunmodulation via sex hormones and glucocorticoids (42).

In the present study hay fever was associated with educational level and smoking habits. Among people with hay fever less current smokers but more ex-smokers were observed. Some persons may have changed their smoking habits because they felt smoking was exacerbating their symptoms in an early stage. This observation is consistent with observations of Annesi-Maesano et al. (43) who reported an association between seasonal allergic rhinitis and ex-smoking.

Individuals with hay fever tended to have a lower level of education than the controls. However, when compared with the whole cohort, the distribution is not statistically significant (6.4% in the low 57.7% in the middle and 35.9% high educational level). The prevalence of hay fever has often been linked to higher social classes (44).

Limitations of the study

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

The present evaluation deals with self-reported cases of physician diagnosed hay fever, a fact which may limit the impact of the results. On one hand, the self-diagnosis might lead to over-reporting. On the other hand, hay fever is a seasonal heterogeneous disorder with a high prevalence that is often undiagnosed (45). The EPIC tried to limit over-reporting by asking not for a self-diagnosis, but exclusively for hay fever which was diagnosed by a physician. Furthermore, in an investigation of self-reported prevalent cases at baseline of the same cohort a good agreement between reported hay fever and plasma IgE values was found (46).

Questionnaire data on dietary habits may also be biased. However, for the EPIC cohorts in Germany the FFQ data for food groups and selected nutrients were validated by comparison with the results of twelve 24-h diet recalls (19). No evaluation of single fatty acids was performed; however, the results for total fat, SFA, MUFA, and PUFA were in an acceptable range with adjusted correlation coefficients of 0.62, 0.75, 0.51, and 0.43 (19). For dietary fatty acid intake results as assessed by means of 24-h diet recalls a good agreement with the plasma phospholipid fatty acid composition was found at the group level, which refers also to the n-6/n-3 ratio (47). Vitamins were not included in the above mentioned FFQ validation study.

Conclusion

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

In conclusion, the present results provide further evidence that dietary factors might affect the risk and onset of clinical symptoms of hay fever. The dietary intake of oleic acid (C18:1), linoleic acid (C18:2) and EPA (C20:5), β-carotene and vitamin E influences the hay fever risk in adults. For linoleic acid (C18:2), β-carotene and vitamin E the effects occurred particularly among ex or current smokers with high oxidative load which is in accordance with the oxidative stress hypothesis. Among women higher dietary intake of linoleic acid (C18:2) may increase lipid peroxidation via the estrogen metabolism. High intake of EPA (C20:5) decreases the risk of hay fever in both genders and indicating a common underlying mechanism such as the immune modulation. It is possible that the association of oleic acid (C18:1) intake with the clinical manifestation of hay fever in both genders is explained by a concomitantly increased intake of trans-C18:1. Typical western diets may increase oxidative stress and therefore contribute to the increasing prevalence of atopic diseases. Dietary intervention studies might provide a well-suited framework to examine whether a change in usual dietary habits towards a pattern with less fat (reactive metabolites) and more fruits and vegetables (antioxidants) leads to a decline in the onset of clinical symptoms of allergies in adults.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References

The authors give thanks to the volunteers who participated in EPIC. Furthermore, we thank the EPIC team for documentation and D. Zoller for the calculation of the food and nutrient data. Supported by grants from the European Community (SI2.326938) and Deutsche Krebshilfe e.V.(70-2488).

References

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Data collection
  5. Variable definition
  6. Statistical methods
  7. Results
  8. Discussion
  9. Monounsaturated fatty acids
  10. Polyunsaturated fatty acids
  11. Vitamin E
  12. β-Carotene
  13. Sociodemographic factors
  14. Limitations of the study
  15. Conclusion
  16. Acknowledgments
  17. References
  • 1
    Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108: S147S334.
  • 2
    European Community Respiratory Health Survey (ECRHS). Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma mediators in the European Community Respiratory Health Survey (ECRHS). Eur Res J 1996;9: 687695.
  • 3
    Heinrich J, Richter K, Frye C, Meyer I, Wolke G, Wjst M et al. European Community respiratory Health Survey in Adults (ECRHS). Pneumologie 2002;56: 297303.
  • 4
    von Mutius E. Infection: friend or foe in the development of atopy and asthma? The Epidemiological evidence. Eur Respir J 2001;18: 872881.
  • 5
    Filipiak B, Heinrich J, Nowak D, Wichman HE. The distribution in specific IgE and the prevalence of allergic symptoms in the 25–64 years old inhabitants of an eastern and a western German city – results from Augsburg and Erfurt. Eur J Epidemiol 2001;17: 7784.
  • 6
    von Mutius E, Weiland SK, Fritzsch C, Duhme H, Keil U. Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet 1998;351: 862866.
  • 7
    Kankaanpää P, Sutas Y, Salminen S, Liechtenstein A, Isolauri E. Dietary fatty acids and allergy. Ann Med 1999;31: 282287.
  • 8
    Connor WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr 2000;71(Suppl.):171S175S.
  • 9
    Hirsch T, Kempe G. Consumption of Omega-3 and Omega-6 fatty acids in former East and West Germany and changes in East Germany after the reunification. Respir Med 1999;93: 213216.
  • 10
    Wakai K, Okamoto K, Tamakoshi A, Lin Y, Nakayama T, Ohno Y. Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross-sectional study in Japan. Ann Epidemiol 2001;11: 5964.
  • 11
    Simopoulos AP. Omega n-3-fatty acids in health and disease and in growth and development. Am J Clin Nutr 1991;54: 438463.
  • 12
    Sanders TA. Polysaturated fatty acids in the food chain in Europe. Am J Clin Nutr 2000;71(1 suppl.):176S178S.
  • 13
    Calder PC. Polysaturated fatty acids, inflammation and immunity. Lipids 2001;36: 10071024.
  • 14
    Malmberg KJ, Arulampalam V, Ichihara F, Petersson M, Seki K, Andersson T et al. Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated with block of NF-kappaB activation. J Immunol 2001;167: 25952601.
  • 15
    Fogarty A, Lewis S, Weiss S, Britton J. Dietary vitamin E, IgE concentrations, and atopy. The Lancet 2000;356: 15731574.
  • 16
    Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels. Int J Dermatology 2002;41: 146150.
  • 17
    Riboli E, Kaaks R. The EPIC project: rationale and study design. European Prospective Investigation into cancer and Nutrition. Int J Epidemiol 1997;26(Suppl. 1):S6S14.
  • 18
    Boeing H, Korfmann A, Bergmann MM. Recruitment Procedures of EPIC-Germany. European Prospective Investigation into cancer and Nutrition. Ann Nutr Metab 1999;43: 205215.
  • 19
    Boeing H, Wahrendorf J, Becker N. EPIC-Germany-A source for studies into diet and risk of chronic diseases. European Investigation into Cancer and Nutrition. Ann Nutr Metab 1999;43: 195204.
  • 20
    Bohscheid-Thomas S, Hoting I, Boeing H, Wahrendorf J. Reproducibility and relative validity of energy and macronutrient intake of a food frequency questionnaire developed for the German part of the EPIC project. Int J Epidemiol 1997;26(Suppl. 1):S71S81.
  • 21
    Boeing H, Bohlscheid-Thomas S, Voss S, Schneeweiss S, Wahrendorf J. The relative validity of vitamin intakes derived from a Food frequency questionnaire compared to 24h-hour recalls and biological measurements: results from the EPIC pilot study in Germany. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 1997;26(Suppl. 1):S82S90.
  • 22
    Klipstein-Grobusch K, Georg T, Boeing H. Interviewer variability in anthropometric measurements and estimates of body composition. Int J Epidemiol 1997;26: 174180.
  • 23
    Bundeslebensmittelschlüssel (German Food Composition Table) II.3, BGVV, Berlin, Germany, 1989.
  • 24
    Weiland SK, von Mutius E, Hüsing A, Asher MI. Intake of trans fatty acids and prevalence of childhood asthma and allergies in Europe. Lancet 1999;353: 20402041.
  • 25
    Precht D, Molkentin J. Trans fatty acids may impair biosynthesis of long-chain polysaturates and growth in men. Die Nahrung 1995;39: 343374.
  • 26
    Bowler RP, Capro JD. Oxidative stress in allergic respiratory diseases. J Allergy Clin Immunol 2002;110: 349355.
  • 27
    Hagenlocher T, Nair J, Becker N, Korfmann A, Bartsch H. Influence of dietary fatty acid, vegetable, and vitamin intake on etheno-DNA adducts in white blood cells of healthy female volunteers: a pilot study. Cancer Epidemiol Biomarkers Prev 2001;10: 11871191.
  • 28
    von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Roell G, Thielmann HH. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med 1994;149: 358364.
  • 29
    Bolte G, Frye C, Hoelscher B, Meyer I, Wjst I, Heinrich J. Margarine consumption and allergy in children. Am J Respir Crit Care Med 2001;163: 277279.
  • 30
    James MJ, Gibson RA, Cleland LG. Dietary polysaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 2000;71(Suppl.):343S348S.
  • 31
    Troisi RJ, Willett WC, Weiss ST, Trichopoulos D, Rosner B, Speizer FE. A prospective study of diet and adult-onset asthma. Am J Respir Crit Care Med 1995;151: 14011408.
  • 32
    Ricciarelli R, Zingg J-M, Azzi A. Vitamin E: protectile role of a Janus molecule. FASEB J 2001;15: 23142325.
  • 33
    Serafini M. Dietary vitamin E and T cell-mediated function in the elderly: effectiveness and mechanism of action. Int J Devl Neuroscience 2000;18: 401410.
  • 34
    Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996;88: 15601570.
  • 35
    Omenn GS, Goodman GE, Thornquist M, Balmes J, Cullen MR, Glass A et al. Effects of a combination of β-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334: 11501155.
  • 36
    Paolini M, Cantelli-Forti G, Perocco P, Pedulli GF, Abdel-Rahman SZ, Legator MS. Co-carcinogenic effect of beta-carotene. Nature 1999;398: 760761.
  • 37
    Watzl B, Bub A, Blockhaus M, Herbert BM, Lührmann PM, Neuhäuser-Berthold et al. Prolonged tomato Juice consumption has no effect on cell-mediated immunity of well-nourished elderly men and women. Nutr 2000;130: 17191723.
  • 38
    Fernandez-Botran R, Sanders VM, Mosmann TR, Vitetta ES. Lymphokine mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med 1988;168: 543558.
  • 39
    Stephensen CB, Rasooly R, Jiang X, Ceddia MA, Weaver CT, Chandraratna RA et al. Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway. J Immunol 2002;168: 44954503.
  • 40
    Whitaker CC, Reingold SC, O'Looney PA. A gender gap in autoimmunity. Science 1999;283: 12771278.
  • 41
    Arythrea BH. Hypophesael–Pituitary–Adrenal axis in autoimmune and rheumatic disease. Immunol Res 1998;18: 93102.
  • 42
    Da Silva JAP. Sex hormones and glucocorticoids: interactions with the immune system. Ann N Y Acad Sci 1999;876: 102117.
  • 43
    Annesi-Maesano I, Oryszczyn MP, Neukirch F, Kauffmann F. Relationship of upper airway disease to tobacco smoking and allergic markers: a cohort study followed up for 5 years. Int Arch Allergy Immunol 1997;114: 193201.
  • 44
    Chen JT, Krieger N, Van Den Eeden SK, Quesenberry CP. Different slopes for different folks: sociodemographic and racial/ethnic disparities in asthma and hay fever among 173,859 U.S. men and women. Envir Health Perspect 2002;110(Suppl. 2):211216.
  • 45
    Sibbald B, Rink E. Epidemiology of seasonal and perennial rhinitis: clinical presentation and medical history. Thorax 1991;46: 895901.
  • 46
    Nieters A, Linseisen J, Becker N. The Association of Polymorphisms in Th1, Th2 Cytokines with Hay Fever and Serum IgE Levels in EPIC Heidelberg. 2002: submitted.
  • 47
    Linseisen J, Schulze MB, Saadation-Elahi M, Kroke A, Miller AB, Boeing H. Quantity and quality of dietary fat, carbohydrate and fibre intake in the EPIC-Germany cohorts. Ann Nutr Metab 2003;47: 3746.