Inflammatory markers after supplementation with marine n-3 or plant n-6 PUFAs: a randomized double-blind crossover study.

Abstract

n-3 (e.g., EPA/DHA) and n-6 (e.g., LA) fatty acids are suggested to have opposite effects on inflammation, but results are inconsistent and direct comparisons of n-3 and n-6 are lacking. In a double-blind, randomized crossover study, females (n=16) and males (n=23) aged 30-70 years with abdominal obesity were supplemented with 3-4g/d EPA/DHA (fish oil) or 15-20g/d LA (safflower oil) for 7 weeks, with a 9-week washout phase. Cytokines and chemokines (multiplex assay), acute-phase proteins (MALDI-TOF mass spectrometry), endothelial function (vascular reaction index (VRI)), blood pressure, fatty acid composition (RBCMs/serum/adipose tissue, GC-MS/MS) and adipose gene expression (microarrays, qPCR) were measured. While significant differences between treatments in relative change scores were found for systolic blood pressure (n-3 vs. n-6: -1.81% vs. 2.61%, p=0.003), no difference between n-3 and n-6 were found for any circulatory inflammatory markers. However, compared to baseline, n-3 was followed by reductions in circulating TNF (-24.9%, p<0.001), RANTES (-12.1%, p<0.001), and MIP-1β (-12.5%, p=0.014), and n-6 by lowered TNF (-18.8%, p<0.001), RANTES (-7.37%, p=0.027), MCP-1 (-7.81%, p=0.020), and MIP-1β (-14.2%, p=0.010). Adipose tissue showed significant treatment differences in weight percent of EPA (n-3 vs. n-6: 50.2%* vs. -1.38%, p<0.001, *: significant within-treatment change score), DHA (16.0%* vs. -3.67%, p<0.001), and LA (-0.033 vs. 4.91%*, p<0.001). Adipose transcriptomics revealed overall down-regulation of genes related to inflammatory processes after n-3 and up-regulation after n-6, partly correlating with changes in circulatory markers. These data point to tissue-specific pro-inflammatory effects of high n-6 intake, but a net systemic anti-inflammatory effect as for n-3.