Habitual Dietary Intake of n-3 and n-6 Fatty Acids in Relation to Inflammatory Markers Among US Men and Women

  • Pischon T
  • Hankinson S
  • Hotamisligil G
 et al. 
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Abstract

Background—Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardio-vascular disease; however, high intake of n-6 fatty acids may attenuate the known beneficial effects of n-3 fatty acids. Methods and Results—We investigated habitual dietary n-3 fatty acid intake and its interaction with n-6 fatty acids in relation to the plasma inflammatory markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and R2) among 405 healthy men and 454 healthy women. After adjustment for other predictors of inflammation, intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was inversely associated with plasma levels of sTNF-R1 and sTNF-R2 (Pϭ0.03 and PϽ0.001, respectively) and somewhat less so for C-reactive protein (Pϭ0.08). n-3 ␣-linolenic acid and n-6 cis-linoleic acid were not significantly related to the inflammatory markers. We found little if any association between n-3 fatty acid (EPAϩDHA) intake and tumor necrosis factor receptors among participants with low intake of n-6 but a strong inverse association among those with high n-6 intake (Pϭ0.04 and 0.002 for interaction of n-3 with n-6 on sTNF-R1 and sTNF-R2, respectively). Conclusions—These results suggest that n-6 fatty acids do not inhibit the antiinflammatory effects of n-3 fatty acids and that the combination of both types of fatty acids is associated with the lowest levels of inflammation. The inhibition of inflammatory cytokines may be one possible mechanism for the observed beneficial effects of these fatty acids on chronic inflammatory-related diseases. (Circulation. 2003;108:155-160.) D ietary intake of polyunsaturated fatty acids (PUFAs) favorably affects cardiovascular disease (CVD). 1 The improvement in blood lipid levels by dietary PUFAs only partially explains these beneficial effects. Inflammation may be essential in the origin of atherosclerosis, and inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-␣ are independent risk factors for CVD. 2,3 n-3 fatty acids have antiinflammatory properties and are frequently used clinically to treat symp-toms of inflammatory diseases, such as rheumatoid arthritis or Crohn's disease. 4 Only a few studies have investigated the effects of n-3 fatty acid intake on plasma IL-6 and TNF-␣ levels in humans in vivo, but these have been small and inconsistent. 5–7 Competition with n-6 fatty acids may be the reason for the observed discrepancies of the effects of n-3 fatty acids on cytokines. 8 Both n-3 and n-6 fatty acids are substrates for human eicosanoid production, and they share the same enzymes for the synthesis of prostaglandins and leukotrienes (Figure 1). Eicosanoids derived from n-3 fatty acids have fewer inflammatory properties than those derived from n-6 fatty acids. Thus, the ratio of n-3 to n-6 fatty acid intake may be crucial to inflammatory processes. The aim of the present study was to investigate the habitual dietary n-3 and n-6 fatty acid intake in relation to the inflammatory markers CRP, IL-6, and soluble TNF receptors 1 and 2 (sTNF-R1 and sTNF-R2), markers of TNF-␣ activity.

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Authors

  • Tobias Pischon

  • Susan E Hankinson

  • Gökhan S Hotamisligil

  • Nader Rifai

  • Walter C Willett

  • Eric B Rimm

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