DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

Abstract

Evidence has accumulated over the last twenty years that smokers who frequently ingest fish are at lower risk for both chronic obstructive pulmonary disease (COPD) and lung cancer. Plasma phospholipid levels of DHA, but not EPA, have been reported to correlate inversely with risk for COPD in smokers, suggesting that DHA may be primarily responsible for the apparent protection afforded to lungs of smokers by fish consumption. Meanwhile, evidence is emerging that certain metabolites of DHA - including 4 - hydroxy hexenal (4-HHE), 17 - oxo - DHA, and resolvin D1 - can activate Nrf2 - mediated transcription of heme oxygenase - 1 and other antioxidant / cytoprotective enzymes. Since the oxidant stress imposed by cigarette smoke exposure could be expected to promote peroxidation of membrane DHA and hence boost production of 4 - HHE, DHA in lung membranes may in effect up-regulate the protective feedback mechanism whereby oxidative stress provokes Nrf2 - mediated induction of cytoprotective enzymes. DHA can also give rise to the autacoid resolvin D1, which, via activation of a receptor, suppresses NF - kappaB activation and the consequent production of pro-inflammatory cytokines. Resolvin D1 can also inhibit macrophage NADPH oxidase and promote an anti-inflammatory M2 phenotype in lung macrophages. Not surprisingly, inhalation of resolvin D1 has a marked anti-inflammatory impact on the lungs of mice exposed to tobacco smoke. These considerations help to rationalize the epidemiology linking fish consumption to lung health, and suggest that smokers who can’t or won’t quit their habit would be well advised to consume fish or DHA supplements regularly. Higher intakes of fruits and vegetables - likely in part because many of these contain Nrf2 - activating phytochemicals - likewise are associated with lower risk for COPD, and can be recommended for smokers.