Elsevier

Atherosclerosis

Volume 167, Issue 2, April 2003, Pages 237-242
Atherosclerosis

Dietary α-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients

https://doi.org/10.1016/S0021-9150(02)00427-6Get rights and content

Abstract

Background: Inflammation plays an important role in the pathogenesis of coronary artery disease. We examined whether dietary supplementation with α-linolenic acid (ALA, 18:3n-3) affects the levels of inflammatory markers in dyslipidaemic patients. Methods: We recruited 76 male dyslipidaemic patients (mean age=51±8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=50) or to 15 ml of safflower oil (rich in linoleic acid (LA, 18:2n-6)) per day (n=26). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 3 months. Blood lipids and C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) levels were determined prior and after intervention. CRP and SAA were measured by nephelometry and IL-6 by immunoassay. Results: Dietary supplementation with ALA decreased significantly CRP, SAA and IL-6 levels. The median decrease of CRP was 38% (1.24 vs. 0.93 mg/l, P=0.0008), of SAA 23.1% (3.24 vs. 2.39 mg/l, P=0.0001) and of IL-6 10.5% (2.18 vs. 1.7 pg/ml, P=0.01). The decrease of inflammatory markers was independent of lipid changes. Dietary supplementation with LA did not affect significantly CRP, SAA and IL-6 concentrations but decreased cholesterol levels. Conclusions: Dietary supplementation with ALA for 3 months decreases significantly CRP, SAA and IL-6 levels in dyslipidaemic patients. This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease.

Introduction

There is substantial evidence that inflammation plays a central role in all phases of the atherosclerotic process [1]. Our understanding of atherosclerosis has evolved beyond the view that it is a bland lipid storage disease. Clinical studies show correlation of circulating acute phase reactants or cytokines with increased risk for future vascular events and raise the possibility of active contribution to their pathogenesis [2], [3].

Dietary fats rich in α-linolenic acid (ALA, 18:3n-3) have been reported to modulate some of the inflammatory responses in experimental animal models [4] and clinical trials [5]. ALA is an essential fatty acid present in vegetable oils. It is the precursor for the formation of the marine long chain n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) (20:5n-3) and docosahexaenoic acid (DHA) (22:6n-3) which can displace arachidonic acid (20:4n-6) and reduce the production of proinflammatory eicosanoids prostaglandin E2 and leukotriene B4. Arachidonic acid is derived by desaturation and elongation of linoleic acid (LA) (18:2n-6).

Epidemiological studies indicate that there is an inverse association between dietary ALA and risk of myocardial infarction [6], [7], [8]. In the Lyon Diet Heart Study a Mediterranean diet rich in ALA was beneficial in secondary prevention of myocardial infarction [9]. A number of studies have also investigated the effect of ALA on blood lipid levels and indicated that its possible antiatherogenic properties are not due to the improvement in blood lipid profile [10], [11], [12], [13], [14].

As there is no study to correlate dietary ALA with inflammatory markers we investigated whether dietary supplementation with ALA affects the levels of acute phase reactants C-reactive protein (CRP) and serum amyloid A (SAA) and the cytokine interleukin-6 (IL-6) in dyslipidaemic patients.

Section snippets

Subjects

Subjects were recruited from the Department of Cardiology of ‘Laiko’ Hospital and were then screened regarding their health status, medication usage, diet and exercise pattern. Subjects with presence of infection, endocrine, liver or vascular disease, blood pressure >145/95 mmHg, on medication known to affect lipoprotein metabolism, habitual consumption of >30 units alcohol per week, smoking habits (⩾10 cigarettes per day) or habitual undertaking of >6 h of vigorous exercise per week were

Baseline characteristics

A total number of 76 subjects completed the study. ALA and LA group were matched for age (50.4±7.3 vs. 52±7.7, P=0.33) and body mass index (28.42±3.44 vs. 28±3.19, P=0.63). The percentage of light smokers (<10 cigarettes per day) was similar in the two groups (24 vs. 23%, P=0.85). None of the participating subjects changed his smoking habits during the intervention period. The n-6:n-3 ratios were comparable in the background diets of the two groups (7.5:1 and 7:1) while after the

Discussion

Our study indicates that dyslipidaemic patients demonstrate a significant reduction in inflammatory indices when supplied with ALA but not with LA diet for 3 months.

We did not use exactly the same amounts of ALA and LA supplements in the ALA and LA groups, respectively. This occurred because we were aiming to lower the n-6:n-3 ratio at physiologically realistic levels. Our target was to decrease the n-6:n-3 ratio in the ALA group and to increase the n-6:n-3 ratio in the LA group. Therefore,

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