Randomization to Omega-3 Fatty Acid Supplementation and Endothelial Function in COPD: The COD-Fish Randomized Controlled Trial
John S. Kim, Michael A. Thomashow, Natalie Yip, Kristin M. Burkart, Christian M. Lo Cascio, Daichi Shimbo, R. Graham Barr
Abstract
RATIONALE: Studies suggest a pathogenic role of endothelial dysfunction in chronic obstructive lung disease (COPD). Omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation improves endothelial function in other diseases but has not been examined in COPD. OBJECTIVE: We hypothesized that n-3 PUFA supplementation would improve systemic endothelial function in COPD. We performed a pilot randomized, placebo-controlled, double-blind, phase 2 superiority trial (NCT00835289). METHODS: Adults with moderate and severe stable COPD (79% with emphysema on computed tomography [CT]) were randomized to high-dose fish oil capsules or placebo daily for 6 months. The primary endpoint was percentage change in brachial artery flow-mediated dilation (FMD) from baseline to 6 months. Secondary endpoints included peripheral arterial tonometry, endothelial microparticles (EMPs), 6-minute walk distance, respiratory symptoms, and pulmonary function. RESULTS: =0.01). There were no significant changes in other secondary endpoints. There were 4 serious adverse events determined to be unrelated to the study (3 in the fish oil arm and 1 in the placebo arm). CONCLUSION: Randomization to n-3 PUFAs for 6 months did not change systemic endothelial function in COPD. Changes in EMPs and SGRQ suggest n-3 PUFAs might have biologic and clinical effects that warrant further investigation.