Abstract
Background: PUFAs may influence the risk of asthma; however, long-term prospective studies including objective biomarkers of PUFA intake are lacking. Objectives: The objective was to investigate the role of dietary intake and plasma concentrations of n-3 and n-6 (ω-3 and ω-6) PUFAs in childhood and adolescence for the development of asthma and lung function up to young adulthood. Methods: The study included participants from the Swedish prospective birth cohort BAMSE. Dietary intake of PUFAs was calculated from FFQs (n = 1992) and plasma proportions of PUFAs were measured in phospholipids (n = 831). We analyzed the n-3 PUFA α-linolenic acid (ALA; 18:3n-3); the sum of very-long-chain (VLC) n-3 PUFAs: EPA (20:5n-3), DHA (22:6n-3), and docosapentaenoic acid (22:5n-3); and the n-6 PUFAs linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6). Asthma was assessed by questionnaires at 8, 16, and 24 y and lung function was measured by spirometry at 24 y. Results: A high (≥median) self-reported dietary intake of LA at 8 y and AA at 16 y was associated with increased risk of prevalent asthma at 24 y (OR: 1.41; 95% CI: 1.10, 1.82 and OR: 1.32; 95% CI: 1.02, 1.70, respectively). In contrast, plasma proportions of ALA, ∑VLC n-3 PUFAs, and AA at 8 y, as well as LA at 16 y, were inversely associated with prevalent asthma at 24 y (e.g., OR: 0.55; 95% CI: 0.38, 0.81 for ∑VLC n-3 PUFAs). No consistent associations were observed with lung function. Conclusions: High dietary intake of certain n-6 PUFAs in childhood or adolescence may be associated with increased risk of asthma up to young adulthood, whereas dietary biomarkers of certain n-3 and n-6 PUFAs in plasma may be associated with decreased risk. Thus, the role of diet compared with altered metabolism of PUFAs needs further investigation to improve dietary preventive strategies for asthma.
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Key Points
This study showed that higher intake of the VLC n–3 PUFAs EPA (20:5n–3) and DHA (22:6n–3) from fish in childhood was inversely associated with incident asthma up to adolescence only among participants with a common genetic variant (minor G allele), which has previously been associated with lower plasma concentrations of VLC n–3 PUFAs. Findings from the BAMSE birth cohort and other previous studies have indicated that long-chain PUFAs may influence subsequent development of asthma in childhood, suggesting a possible favorable role of VLC n–3 PUFAs. However, it remains unknown if this influence persists into adulthood, and the role of the major n–6 PUFAs in plasma, LA and arachidonic acid (AA; 20:4n–6), respectively, is yet unclear. In addition, it is still unclear if long-chain PUFAs found in fish and vegetable oils are associated with lung function or other objective markers of disease severity. Therefore, the aim of the present study was to investigate the role of dietary intake and plasma concentrations of long-chain n–3 PUFAs and the 2 major n–6 PUFAs (LA and AA) in childhood and adolescence for the development of asthma and lung function up to young adulthood.
In the present longitudinal cohort study, it was observed that high self-reported dietary intakes of the n–6 fatty acids LA at 8 y and AA at 16 y were associated with increased risk of asthma at 24 y. In contrast, high plasma concentrations of these fatty acids (AA at 8 y and LA at 16 y) were associated with decreased risk. There was no association between self-reported dietary intake of n–3 PUFAs and asthma, whereas plasma concentrations of ALA and VLC n–3 PUFAs at 8 y were associated with decreased risk of asthma at 24 y. Overall, no consistent associations were observed between PUFAs and lung function.
n–3 PUFAs may protect against asthma and other allergic diseases through their anti-inflammatory properties. n–3 PUFAs can lower inflammation through several different pathways including inhibition of eicosanoids (e.g., prostaglandins and leukotrienes) and through production of inflammation-resolving resolvins. It has also been suggested that allergic individuals may have an altered fatty acid metabolism, with lower blood concentrations of VLC PUFAs, despite similar intake (47, 48). However, in the BAMSE study, we have previously compared the correlation between dietary intake and plasma concentrations of PUFAs between allergic and nonallergic individuals and found no differences (11). In addition, the longitudinal analyses of incident asthma further indicate that PUFA concentrations influence the risk of asthma and not the opposite.
In contrast to n–3 PUFAs, n–6 PUFAs were previously often described as proinflammatory, although little evidence exists to support such effects in humans, because several randomized feeding studies have shown that even overfeeding with dietary LA or intake at high doses does not cause any increase in inflammatory markers, despite a several-fold increase in the dietary n–6:n–3 ratio. The role of n–6 PUFAs in inflammation has been shown to be complex, with both proinflammatory and anti-inflammatory properties, and dependent on the type of n–6 fatty acid.
In conclusion, this longitudinal study of a population-based cohort shows that, in childhood and adolescence, higher plasma proportions of the n–3 PUFA ALA and VLC n–3 PUFAs, as well as the 2 n–6 PUFAs LA and AA, were associated with reduced risk of asthma up to young adulthood. Because these PUFAs measured in plasma overall are established biomarkers of dietary intake, our results may suggest that higher intakes of these PUFAs are associated with lowered asthma risk. In contrast, higher self-reported dietary intakes of n–6 PUFAs were associated with increased risk of asthma at 24 y. No consistent associations were observed with lung function. Future studies should focus on increasing the understanding regarding potential mechanisms behind these associations, which may contribute to strengthening dietary guidelines and to interventions to prevent asthma in the general population.