Journal Name:
Am. J. Clin. Nutr.
Article Title:
Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects
Date Written:
2007
Volume:
85
Number:
0
Page:
385
Author(s):
Zhao, G.; Etherton, T.D.; Martin, K.R.; Gillies, P.J.; West, S.G.; Kris-Etherton, P.M.
Article:
ALA has been shown to markedly reduce the recurrence rate after a first myocardial infarction. Epidemiologic studies have also shown that a higher intake of ALA protects against fatal ischemic heart disease in women and is associated with a reduced prevalence of coronary artery disease in both men and women. ALA can decrease the risk of cardiovascular disease (CVD) through various biological mechanisms, including reductions in lipids, in lipoproteins, and in the inflammatory markers C-reactive protein (CRP) and cell adhesion molecules.
The role of ALA in reducing inflammation is important because inflammatory events are central in the pathogenesis of atherosclerosis. Activated macrophages and lymphocytes secrete proinflammatory cytokines, including interleukin (IL)-6, IL-1, and tumor necrosis factor-alpha (TNF-alpha). These cytokines then activate the endothelial expression of cell adhesion molecules and mediate a series of inflammatory responses such as the up-regulation of acute phase protein expression.
Flaxseed oil consumption inhibits IL-1 and TNF-alpha synthesis and may reduce cytokine production by peripheral mononuclear cells (PBMC). The present controlled clinical study evaluated whether 2 diets high in ALA (3.6% and 6.5% of energy) within the context of diets also high in LA (12.6% and 10.5% of energy) would elicit an antiinflammatory effect as measured by decreases in both serum cytokine concentrations and in the production of proinflammatory cytokines by cultured PBMCs obtained from subjects fed the experimental diets.
The results indicated that changes in serum ALA were inversely correlated with changes in PBMC TNF-alpha concentrations, and PBMC ALA and EPA concentrations also were inversely correlated with the production of TNF-alpha. These data suggest that the increased incorporation of ALA and EPA into PBMC lipids may, in part, account for the observed differences in proinflammatory cytokine release in response to a diet high in ALA.
The finding that PBMC TNF-alpha concentrations decreased with the ALA diet may be important in the prevention or treatment of heart disease. The lack of a significant decrease in serum IL-6 and IL-1 in subjects consuming the LA and ALA diets could be explained, in part, by the marked variability in these endpoints. Importantly, there was a trend for serum TNF-alpha to decrease with the ALA diet. Collectively, the data from the present study and the results from two previous studies by this group showed that ALA beneficially affects multiple CVD risk factors. Given that inflammation is an important component of all steps in the progression of atherosclerosis, it appears that ALA exerts its cardioprotective effect in a manner that involves many components of the inflammatory response. Importantly, the responses we observed occurred in a high n-6 fatty acid environment. Thus, strategies to increase ALA in the diet are important from the perspective of vascular inflammation to reduce CVD risk. Incorporating food sources of ALA in the diet, such as canola oil, is important for the next generation of dietary strategies to reduce CVD risk.
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