Relationship between Polyunsaturated Fatty Acids and Inflammation: evidence from cohort and Mendelian randomization analyses

Abstract

Dietary polyunsaturated fatty acids (PUFAs) are thought to influence the risk of various chronic diseases by modulating systemic inflammation. Omega-3 and omega-6 FAs are thought to have anti- and pro-inflammatory roles, respectively, but it is unclear whether these associations are causal. We tested associations of PUFAs with three blood-based biomarkers of systemic inflammation, namely C-reactive protein (CRP), glycoprotein acetyls (GlycA) and interleukin 6 (IL-6), in a population cohort (n=2748) and using Mendelian randomization analysis (a genetic causal inference method). We provide consistent evidence that omega-6 PUFAs increase GlycA levels, but omega-3 FAs do not lower levels of inflammatory markers. Additionally, we found that a higher omega-6:omega-3 ratio increases levels of all three inflammatory markers; CRP (mean difference=0.17; 95% CI=0.13, 0.20), GlycA (mean difference=0.16; 95% CI=0.13, 0.20) and IL-6 (mean differene=0.19; 95% CI=0.15, 0.22) in the cohort analysis. Our findings suggest that future public health messaging should encourage reducing the consumption of omega 6 FAs and maintaining a healthy balance between omega 3 and omega 6 FAs, rather than focusing on omega-3 FA supplementation. This is because dietary omega-3 supplementation alone is unlikely to help reduce systemic inflammation or inflammation-related disease.