Am J Clin Nutr, 2007, Volume 85; Pages 385-391.

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

Zhao, G. Etherton, TD. Martin, KR. Gillies, PJ. West, SG. Kris-Etherton, PM.

Key Findings:

This ground-breaking study was one of the first to show on the basis of a randomized clinical study that ALA reduces a number of markers of inflammation including interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) in cultured peripheral blood mononuclear cells. The ant-inflammatory actions of ALA may be an underlying mechanism whereby ALA helps to reduce the risk of CVD. The results are even more significant in that they were occurred as part of a high in omega 6 fatty acids. The authors strongly recommend the inclusion of ALA in the diet, such as flaxseed and flaxseed oil, and consider this an important component of heart healthy lifestyles.

ABSTRACT

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. (Authors Abstract)

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