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

Alpha-linolenic acid (ALA) has been shown to reduce the risk of cardiovascular disease (CVD) via decreases in serum lipid profiles (lipids, lipoproteins), as well as inflammatory markers such as C-reactive protein (CRP) and cell adhesion molecules.  These authors previously reported that a diet high in ALA decreases lipid and inflammatory CVD risk factors in hypercholesterolemic subjects.  Using a similar study protocol, the objective of the present study was to investigate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMC’s) in moderately hypercholesterolemic men and women. 

Twenty men aged 36-69 yrs and 3 postmenopausal women aged 55-65 yrs participated in this randomized, controlled, 3-diet, 3-period, crossover study.  All participants had moderate hypercholesterolemia (serum total cholesterol 4.81-7.11 mmol/L) and were overweight or obese (BMI 25-35).  The postmenopausal women had not received hormone replacement therapy in the previous 6-months to the study.  Participants were assigned to a sequence of 3 experimental diets, each for a 6-week period separated by a 3-week break between diet periods.  Experimental diets have been described previously.  Briefly:  1) Average American Diet (ADD; control):  provided 35.9% total energy from fat, 13% energy from saturated fat (SFA), 13% from monounsaturated fat (MUFA), and 9.0% energy from polyunsaturated fat (7.7% LA; 0.8% ALA); 2) ALA Diet: provided 37.0% total energy from fat, 8.0 energy from SFA, 12.0% from MUFA, 17% energy from PUFA (10.5% LA; 6.5% ALA); 3) LA Diet: provided 37.0% total energy from fat, 8.0% energy from SFA, 12.0% from MUFA, 16.0% energy from PUFA (12.6% LA; 3.6% ALA).  Walnuts and walnut oil were the primary source PUFA in the diets, and also helped contribute to the ALA levels in the test diets.  In addition, flaxseed oil, which is particularly high in ALA, was used to increase the ALA content in the high ALA diet.  Fasting blood samples were collected at the end of each dietary period for subsequent analysis of endpoint assays.  Endpoint assays included PBMC production, and serum levels of IL-6, IL-1b, and TNF-a following the three dietary periods.  

No change in serum concentrations of IL-6 and IL-1b was observed after consumption of any of the experimental diets.  However, decreased levels of serum TNF-a were observed following the ALA diet when compared to the LA diet and AAD.  Production of IL-6, IL-1b, and TNF-a by PBMC was also lower following the ALA diet when compared to the LA diet and AAD.  TNF-a produced by PBMC’s was inversely associated with ALA and EPA concentrations in PBMC lipids following the ALA diet.  Changes in serum ALA were inversely correlated with changes in TNF-a production by PBMC’s. 

An increased intake of dietary ALA exerts anti-inflammatory effects as seen via the inhibition of IL-6, IL-1b, and TNF-a production in PBMC culture. ALA in the form of walnuts, walnut oil, and flaxseed oil should be incorporated into the diet as part of an evolving dietary strategy to reduce the risk of CVD.