The Effect of n-3 LCPUFA on Immune Function and Cardiovascular Risk Factors

• Fatty acid composition of PMBC - before and after 2 mo of interventions and after 2 mo of follow-up
  
• Ex vivo cytokine production (e.g. IL-6, TNF-α, IL-10, and interferon-γ) in whole blood and PBMC cultures after 24 h of stimulation - before and after interventions and after follow up
  
• Plasma CRP, IL-6 & fibrinogen - before, after and follow-up
  
• Plasma lipid profile: TAG, cholesterol, LDL & HDL - before, after and follow-up
  
• Blood pressure - before, after and follow-up
  

• Anthropometric measures - before, after & follow-up
  
• Ex vivo cytokine production in isolated monocytes - after intervention only
  
• Endothelial function (PWV and/or arterial compliance) - before & after
  
• Superoxide production in full blood samples - before & after
  
• Plasma insulin/glucose - before, after and follow-up
  
• Plasma markers of endothelial function (e.g. VCAM-1, ICAM-1, Matrix metallo proteinases, E- & P-selectin, nitrite and endothelin-1) - before and after
  
• Plasma CD40L - before, after and follow-up
  
• RBC fatty acid composition - before, after and follow-up
  
• Coagulation factors (e.g. PAI, tPA, factor VII) - before, after and follow-up
  
• Folate/homocysteine - before. after and follow-up
  
• Lipoprotein(a) - before, after and follow-up
  

In a controlled, double-blinded human intervention study the effects of fish oil versus control (olive oil) and of a high versus low consumption of n-6 polyunsaturated fatty acids are investigated. Sixty-seventy healthy men will be randomized to oil capsules and to substitute their dietary fats with one of two types of oil and butter-product that we provide. Outcome variables are ex vivo cytokine production in full blood and isolated immune cells after 24 h of stimulation with bacteria or bacterial components, blood pressure and arterial function, plasma concentrations of cholesterol, triacylglycerol, C-reactive protein and a number of other markers of endothelial function and cardiovascular risk.

The hypotheses are that both increased intake of n-3 polyunsaturated fatty acids (from fish oil) and a low consumption of n-6 polyunsaturated fatty acids increase incorporation of docosahexanoic acid in immune cell membranes and that this decreases the inflammatory response and potential and improve overall cardiovascular disease risk.

The mechanistic aspects of this will be further explored by in vitro studies with monocytes cultured in the presence of varying amounts of polyunsaturated fatty acids.