Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man

doi:10.1016/j.atherosclerosis.2007.04.047

Atherosclerosis

Volume 197, Issue 1, March 2008, Pages 290-296

https://doi.org/10.1016/j.atherosclerosis.2007.04.047 Get rights and content

Abstract

Background

Dietary intake of fish rich in omega-3 fatty acids is associated with a reduction in cardiovascular events. The mechanisms for this are uncertain and previous studies investigating effects on platelet function have produced inconsistent results. Platelet-monocyte aggregation is a sensitive marker of platelet activation and may contribute to the initiation and progression of atherothrombosis. This study assessed the effect of dietary intervention with oily fish on platelet-monocyte aggregation in healthy subjects.

Methods

Fourteen subjects had their diet supplemented with 500 g of oil-rich fish per week for 4 weeks. A control group of 14 subjects received no dietary intervention over a 4-week period. Platelet-monocyte aggregates were assessed with flow cytometry.

Results

Dietary intervention with fish led to an increase in omega-3 fatty acids in plasma phospholipids (14.2 ± 3.4% versus 5.8 ± 1.3%, P < 0.001). In contrast to the control group, platelet-monocyte aggregates were reduced by 35% following dietary intervention with oily fish (16.0 ± 9.0% versus 24.8 ± 10.9%, P < 0.01), and returned to basal levels 4 weeks after discontinuation of supplementation. There was an inverse correlation between platelet-monocyte aggregation and plasma omega-3 fatty acid concentrations (r = −0.421, P = 0.006). There were no changes in the plasma markers of platelet activation, soluble P-selectin or soluble CD40 ligand.

Conclusions

We have demonstrated, for the first time, that dietary intervention with oil-rich fish reduces platelet-monocyte aggregation in man. Our results suggest that reduced platelet activation provides a potential mechanism through which fish oils confer their cardiovascular preventative benefits.

Introduction

Consumption of fish oil may protect against cardiovascular disease [1]. Data from observational studies suggest that fish intake is inversely associated with fatal coronary heart disease [2], and randomized controlled trials of dietary fish or fish oil supplementation after myocardial infarction demonstrate a reduction in mortality [3], [4]. These effects are believed to be due to the high amounts of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present in fish oil. EPA and DHA must be obtained from dietary sources and recent guidelines from the American Heart Association recommend the consumption of oily fish at least twice weekly for individuals with and without coronary heart disease [5]. However, not all randomised controlled trials have shown a benefit [6], and the underlying mechanisms through which cardiac protection might be conferred remain uncertain.

The effects of fish oil on platelet function and thrombosis are controversial. Although fish oils were originally thought to act by reducing platelet aggregation through effects on eicosanoid metabolism [7], subsequent studies have produced contradictory results [8]. Alternative mechanisms of action have been proposed including effects on arrhythmias, inflammation, endothelial function and atherosclerotic plaque stability [9], [10], [11], [12]. Indeed, it has been suggested that there is little evidence for a major antithrombotic effect of fish oils at the moderate doses shown to reduce mortality in the secondary prevention trials [13].

Most previous studies investigating the effects of fish oils on platelet function have relied on in vitro platelet aggregometry and plasma assays of soluble markers of platelet activation [8]. These techniques are poorly suited to the detection of potentially subtle effects induced by dietary changes. Reproducibility is unsatisfactory and the tests are difficult to standardize [14]. Platelet aggregometry can only measure ex vivo changes in platelet reactivity to a single external stimulus, and sample manipulation required for both methods leaves them particularly vulnerable to artefactual in vitro activation.

Modern flow cytometric techniques allow platelets to be analyzed directly in their physiological environment of whole blood with minimal sample manipulation. Circulating platelet-monocyte aggregates, formed by the binding of activated platelets to leukocytes via a P-selectin dependent mechanism [15], can be readily measured in this way and have emerged as a highly sensitive marker of platelet activation [16]. The adhesion of activated platelets to monocytes also has important functional consequences, and can induce the expression of cytokines, chemokines, adhesion molecules and tissue factor [17]. Consistent with these biological effects, circulating platelet-monocyte aggregates appear to promote atherosclerotic lesion formation and are increased in stable coronary heart disease and acute coronary syndromes [18], [19].

We therefore investigated whether supplementing the diet of healthy individuals with a moderate intake of oil-rich fish would reduce platelet activation and platelet-monocyte aggregation.

Section snippets

Study participants and design

Twenty-eight healthy male volunteers aged between 21 and 28 years were enrolled into the study. Exclusion criteria included those taking regular medication, those with clinical evidence of atherosclerotic vascular disease, hypertension, diabetes mellitus, hypercholesterolemia, an intercurrent illness likely to be associated with an acute phase inflammatory response, and renal or hepatic insufficiency. Ethical approval was obtained from the Lothian Research Ethics Committee and all subjects

Baseline characteristics

Baseline characteristics were similar between the fish supplementation and control groups (Table 1). Study participants were young and there were no differences in body mass index, smoking status, or lipid profile.

Effect of fish intervention on plasma phospholipid fatty acid composition

The plasma phospholipid fractions of omega-3 and omega-6 fatty acids did not differ between groups at baseline. Dietary intervention with fish led to an increase in the percentage of total omega-3 fatty acids (14.2 ± 3.4% versus 5.8 ± 1.3%, P < 0.001), EPA (5.2 ± 2.1% versus 1.0 ± 0.3%, P <

Discussion

We have demonstrated, for the first time, that dietary intervention with oil-rich fish is associated with a reversible reduction in platelet-monocyte aggregation in man. There was an inverse correlation between platelet-monocyte aggregation and the plasma levels of EPA and DHA, consistent with the effects being related to the omega-3 content of oily fish. Our results suggest that reduced platelet activation could represent an important mechanism through which dietary fish confer their putative

Conclusion

We have demonstrated that dietary intervention with moderate amounts of oil-rich fish can reduce platelet-monocyte aggregation in man. Platelet-monocyte aggregates are sensitive markers of platelet activation and contribute to the initiation and progression of atherosclerosis. This could represent a previously unreported mechanism through which fish oils might confer their potential cardiovascular benefits. Most previous studies assessing the effects of fish oils on platelet function have used

Acknowledgements

We would like to thank Shona Johnstone for technical assistance with flow cytometry, and Lianne Milligan for performing analysis of the weighed food records. JD was supported by a British Heart Foundation Project Grant (PG/2003/009).

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Fish consumption is associated with a reduced risk of cardiovascular diseases (CVDs) partly ascribed to the high content of long-chain (LC) n–3 PUFAs; however, not all fish types are equally rich in these components. To date, it is not clear whether the beneficial effects of fish consumption are shared by fatty and lean fish. Therefore, the aim of this meta-analysis was to synthesize knowledge regarding the relation between the intake of fatty fish or lean fish and the risk of cardiovascular events and all-cause mortality. We conducted a systematic search in PubMed, Web of Science, and Embase until May 2021 for full text with a prospective design involving humans providing data for the highest compared with the lowest fish consumption categories. Summary risk ratios (RRs) and 95% CIs were estimated using a random-effects model. Out of 1902 articles retrieved from the literature search, 19 reports met the criteria for inclusion in the meta-analysis. Altogether, studies on fatty fish comprised 1,320,596 person-years of follow-up, 20,531 incident coronary heart disease (CHD) cases, 9256 incident CVD cases, and 104,763 total deaths. Studies on lean fish comprised 937,362 person-years of follow-up, 21,636 incident CHD cases, 7315 incident CVD cases, and 16,831 total deaths. An inverse association was present for fatty fish with CHD incidence (RR: 0.92; 95% CI: 0.86, 0.97), CHD mortality (RR: 0.83; 95% CI: 0.70, 0.98), and total mortality (RR: 0.97; 95% CI: 0.94, 0.99). This was not the case for lean fish. The summary estimates for CVD incidence and mortality did not show significant association with both fatty fish and lean fish consumption. The study findings are innovative in highlighting that the health benefits so far linked to fish consumption are, in fact, driven by fatty fish.
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Citation Excerpt :
Other studies had not found an influence of lipid emulsions containing n-3 fatty acid on platelet function25,26 or after a diet with high linoleic acid versus high oleic acid.27 Furthermore, previous studies showed that dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man.28 Overall, TG may accelerate platelet aggregability but some kinds of fatty acids such as n-3 fatty acid inhibit it.
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Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study participants and design

Baseline characteristics

Effect of fish intervention on plasma phospholipid fatty acid composition

Discussion

Conclusion

Acknowledgements

Lancet

Lancet

Am J Clin Nutr

Am J Clin Nutr

Lancet

Methods

Blood

J Diabetes Complications

Nutr Metab Cardiovasc Dis

Atherosclerosis

Omega 3 fatty acids and cardiovascular disease-fishing for a natural treatment

BMJ

Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies

Circulation

Fish consumption, fish oil, omega 3 fatty acids, and cardiovascular disease

Circulation