|SCHUSTER, GERTRUD - University Of California|
|BRATT, JENNIFER - University Of California|
|KENYON, NICHOLAS - University Of California|
Submitted to: American Journal of Respiratory Cell and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/17/2013
Publication Date: 3/1/2014
Citation: Schuster, G.U., Bratt, J., Jiang, X., Pedersen, T.L., Grapov, D., Adkins, Y.C., Kelley, D.S., Newman, J.W., Kenyon, N.J., Stephensen, C.B. 2014. Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice. American Journal of Respiratory Cell and Molecular Biology. doi: 10.1165/rcmb.2013-0136OC.
Interpretive Summary: Fish oil supplements are effective in decreasing risk of some chronic inflammatory diseases, including arthritis and heart disease. Studies in humans have also shown a benefit in exercise-induced asthma but not in allergic asthma. Fish oil is a mixture of fatty acids with potentially different activities. Two of the most abundant are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To determine if these fatty acids may have greater benefit alone rather than as a mixture we tested each, plus a mixture of the two, versus a control diet with no EPA or DHA in a mouse model of allergic asthma. Unexpectedly the DHA group produced more severe disease, which suggests that very high intake of DHA alone from supplements could have unexpected risks in asthma patients.
Technical Abstract: The effects of fish oil supplements on diminishing airway inflammation in asthma have been studied in mouse models and human intervention trials with varying results. However, the independent effects of the main omega-3 PUFAs found in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered alone have not been studied. Here we investigated the effects of consuming highly purified EPA (1.5% w/w of diet), DHA (1.5% w/w), an equal mixture of the two (0.75% EPA and 0.75% DHA), and a control diet without added long-chain omega-3 PUFAs on airway inflammation and hyper responsiveness using an OVA exposure model of asthma. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (mol %) of 9.0 ± 0.6, 3.2 ± 0.2, 6.8 ± 0.5, and 0.01 ± 0.0 %, respectively. DHA contents were 6.8 ± 0.1, 15.6 ± 0.5, 12.3 ± 0.3 and 3.8 ± 0.2%, respectively. Mice fed DHA only had the highest levels of eosinophils and IL-6 in bronchoalveolar lavage among the four groups (p < 0.05); similar trends were seen for macrophages, IL-4 and IL-13 but not TNF'' Mice fed DHA only also had the highest airway resistance though the difference was significant only when compared to the EPA/DHA group (p < 0.05), which had the lowest. Although both EPA and DHA can have distinct effects on anti-inflammatory pathways, these results indicate that providing DHA alone may promote inflammation, providing further reason to examine the immune-modulating effects of these fatty acids independently.