Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects

Am J Clin Nutr. 2007 Feb;85(2):385-91. doi: 10.1093/ajcn/85.2.385.


Background: Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in alpha-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects.

Objective: The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMCs) from subjects fed the experimental diets.

Design: A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (n = 23) were assigned to 3 experimental diets: a diet high in ALA (ALA diet; 6.5% of energy), a diet high in linoleic acid (LA diet; 12.6% of energy), and an average American diet (AAD) for 6 wk. Serum interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations and the production of IL-6, IL-1beta, and TNF-alpha by PBMCs were measured.

Results: IL-6, IL-1beta, and TNF-alpha production by PBMCs and serum TNF-alpha concentrations were lower (P < 0.05 and P < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-alpha was inversely correlated with ALA (r = -0.402, P = 0.07) and with eicosapentaenoic acid (r = -0.476, P = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by PBMCs (r = -0.423, P < 0.05).

Conclusions: Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1beta, and TNF-alpha production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-alpha release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cytokines / biosynthesis*
  • Cytokines / drug effects*
  • Dietary Fats / metabolism
  • Dietary Fats / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypercholesterolemia / metabolism*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Overweight
  • Postmenopause
  • alpha-Linolenic Acid / metabolism
  • alpha-Linolenic Acid / pharmacology*


  • Cytokines
  • Dietary Fats
  • alpha-Linolenic Acid