Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women

Circulation. 2003 Jul 15;108(2):155-60. doi: 10.1161/01.CIR.0000079224.46084.C2. Epub 2003 Jun 23.


Background: Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardiovascular 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 (P=0.03 and P<0.001, respectively) and somewhat less so for C-reactive protein (P=0.08). n-3 alpha-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 (EPA+DHA) 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 (P=0.04 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / blood
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cohort Studies
  • Cross-Sectional Studies
  • Eicosanoids / biosynthesis
  • Energy Intake
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated / metabolism*
  • Feeding Behavior*
  • Female
  • Follow-Up Studies
  • Health Personnel / statistics & numerical data
  • Humans
  • Inflammation / blood*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Reference Values
  • Sex Factors
  • Surveys and Questionnaires
  • United States


  • Antigens, CD
  • Biomarkers
  • Eicosanoids
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • C-Reactive Protein