Abstract
BACKGROUND: Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and derivatives, play a key role in the resolution of inflammation. Higher intake has been linked to decreased morbidity in several diseases, though effects on respiratory diseases like COPD are understudied. METHODS: The National Health and Nutrition Examination Survey (NHANES), with a focus on dietary assessment, provides a unique opportunity to explore relationships between omega-3 intake and morbidity in respiratory diseases marked by inflammation in the United States (US) population. We investigated relationships between ALA or EPA + DHA intake and respiratory symptoms among US adults with COPD, as well as variation in relationships based on personal characteristics or exposures. RESULTS: Of 878 participants, mean age was 60.6 years, 48% were current smokers, and 68% completed high school. Omega-3 intake was, 1.71 ± 0.89 g (ALA), and 0.11 ± 0.21 g (EPA + DHA). Logistic regression models, adjusting for age, gender, race, body mass index, FEV1, education, smoking status, pack-years, total caloric intake, and omega-6 (linoleic acid, LA) intake demonstrated no primary associations between omega-3 intake and respiratory symptoms. Interaction terms were used to determine potential modification of relationships by personal characteristics (race, gender, education) or exposures (LA intake, smoking status), demonstrating that at lower levels of LA intake, increasing ALA intake was associated with reduced odds of chronic cough (pint = 0.015) and wheeze (pint = 0.037). EPA + DHA, but not ALA, was associated with reduced symptoms only among current smokers who did not complete high school. CONCLUSIONS: Individual factors should be taken into consideration when studying the association of fatty acid intake on respiratory diseases, as differential responses may reveal susceptible subgroups.
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Key Points
Chronic obstructive pulmonary disease (COPD) development and morbidity is driven by a combination of host factors and exposures, which increase inflammation in the lung. Few studies have addressed the effects of omega-3 intake on COPD disease morbidity, and fewer account for intake of omega-6. Using a nationally-representative sample from the US population (the National Health and Nutrition Examination Survey, NHANES), the relationship between omega-3 fatty acid intake and respiratory symptoms among individuals with COPD, accounting for omega-6 fatty acid intake was assessed. The study included an assessment as to whether race, gender, and socioeconomic status, and additionally smoking status modified the relationship between fatty acid intake and respiratory outcomes.
Analyses presented within a national cohort of adults with COPD demonstrated unique associations between omega-3 intake and respiratory symptoms within susceptible subgroups. Specifically, increased intake of omega-3 (ALA or EPA + DHA) were associated with reduced respiratory symptom prevalence among individuals with lower omega-6 (LA) intake and current smokers with lower education/socioeconomic status.
There is strong rationale for a protective effect of omega-3 fatty acids in the lungs, critical in inflammatory lung diseases such as COPD and supporting plausibility of results. Downstream products of EPA and DHA include specialized pro-resolving mediators, found within the lung and circulation [6] which have the ability to promote resolution of inflammation. These include resolvins, protectins, and maresins, which work by regulating neutrophil infiltration, cytokine production, and macrophage clearance of apoptosed inflammatory leukocytes, culminating in dampening and resolution of inflammatory response. Less is known about the mechanisms by which ALA reduces inflammation. While a variable and limited quantity of ALA is metabolized to EPA and DHA (< 10% each), preliminary work has demonstrated ALA’s ability to inhibit nitric oxide production and TNF-alpha gene expression stimulated by lipopolysaccharide in murine macrophages distinct from the mechanisms of EPA and DHA.
It was noted that beneficial associations between ALA and respiratory symptoms were only present among those with low omega-6 (LA) intake. This is a reasonable contingency, given: (1) conversion of ALA to EPA + DHA may be inhibited by increased concentrations of LA and (2) LA and its metabolite arachidonic acid are known substrates for production of pro-inflammatory eicosanoids which may counteract the anti-inflammatory properties of ALA.
NHANES is a nationally representative dataset, and our findings can therefore be extrapolated to the U.S. adult population with COPD. The extensive characterization of the cohort permitted examination of multiple subgroups and identification of characteristics associated with receptivity to beneficial effects of omega-3 intake: low omega-6 intake, and low socioeconomic status and current smokers. The study demonstrated a lack of primary associations between ALA or EPA + DHA in the absence of accounting for omega-6 intake, and did not observe effect modification by race or gender. EPA + DHA intake levels were low compared to ADA recommendations, which may have influenced the ability to detect associations. However, the lack of associations in these subgroups in a nationally-representative cohort are an important aspect of our findings, as they may help to focus future investigations. While the causal impact of a diet high in omega-3 cannot be established from the present observational study, this work reinforces the need for additional investigations, including more objective measurements such as biomarkers, and adds to the evidence base supporting clinical trials of dietary change in inflammatory lung diseases including COPD.
Within a U.S. population with COPD, this research demonstrated associations between ALA intake and lower odds of respiratory symptoms among individuals with average or lower than average intake of pro-inflammatory omega-6. Further, EPA + DHA intake demonstrated a protective effect on respiratory symptoms in subgroups exposed to a myriad of non-dietary inflammatory hazards, specifically, current smokers from low socioeconomic status. A clear understanding of the dietary effects of omega-3 on respiratory outcomes in COPD is yet to emerge; however, the context in which these effects are studied will be an important consideration. Personal characteristics and environmental exposures may be critical to identifying individuals and subpopulations with the greatest opportunity for benefit.