Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women.

A growing body of evidence suggests that certain markers of inflammation are predictive of cardiovascular disease (CVD).  Inflammatory markers include C-reactive protein (CRP), increased expression of interleukin (IL)-6, and tumor necrosis factor alpha (TNF-a).  Both clinical and epidemiological evidence suggests that ALA is associated with a reduced risk of CVD.  However, the exact mechanism by which ALA exerts its cardioprotective effect remains unclear.  The objective of the present study was to investigate the effect of ALA on a number of CVD risk factors including CRP, markers of endothelial activation, and lipids and lipoproteins in moderately hypercholesterolemic men and women. 

Twenty men (36-60 yrs) and three women (55-65 yrs) who were moderately hypercholesterolemic (serum total cholesterol 5.17-6.21 mmol/L) participated in this randomized, controlled, 3-diet, 3-period, crossover study.  All subjects were non-smokers, had no documented atherosclerotic disease, inflammatory disease, diabetes mellitus, uncontrolled hypertension, or any other systemic diseases.   Subjects were assigned to consume a sequence of test diets that consisted of the following:  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.  Each diet period was consumed for a 6-week period, separated by an ~ 3 week washout period.  Blood samples were obtained at the end of each dietary period for subsequent analysis of serum CRP and cell adhesion molecules, lipid and lipoprotein profiles, and serum fatty acid profiles. 

Changes in serum fatty acid profiles reflected the fatty acid composition of the test diets.  When compared to the AAD, serum total omega 6 fatty acids were higher following consumption of the LA diet.  Serum total omega 3 PUFA (ALA, EPA, DPA, but not DHA) were higher after consumption of both the LA and ALA diets, when compared to the AAD.  Participants consuming the ALA diet resulted in lower serum total omega 6 PUFA (LA and arachidonic acid (AA)) and higher serum total omega 3 PUFA (ALA, EPA, and DPA) when compared to those consuming the LA diet.   A decrease in CRP was observed following the ALA diet, whereas a tendency to decrease CRP was observed following the LA diet.  Both high PUFA diets resulted in a similar reduction in intercellular cell adhesion molecule-1 when compared to ADD (-19.1% for ALA, -11.0% for LA).  However, a greater decrease in VCAM-1 (-15.6% vs. –3.1%) and E-selectin (-14.6% vs. 8.1%) was observed for the ALA diet compared to the LA diet, respectively.  Changes in CRP and VCAM-1 were inversely associated with changes in serum EPA, or EPA + DPA following consumption of the ALA diet.  Both the LA and ALA diets resulted in a decrease in serum total and LDL cholesterol, and triglyceride values. 

A low LA:ALA diet decreased lipid and lipoprotein levels and elicited vascular anti-inflammatory effects.  These findings provide additional support for the importance of ensuring adequate ALA intake as a strategy to markedly lower CVD risk.