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Cardiac physiology and clinical efficacy of dietary fish oil clarified through cellular mechanisms of omega-3 polyunsaturated fatty acids

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Abstract

Reduced cardiac mortality and morbidity have long been observed in association with omega-3 long chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish consumption, without clear physiological explanation. This review seeks to identify mechanisms of action based on evidence: of physiological effects, active components and effective intakes. Fish oil pleiotropic effects reveal actions that are either intrinsic: effects on cardiac function dependent upon membrane incorporation; or extrinsic: indirect cardiac effects through vascular disease. Extrinsic actions require EPA + DHA doses >3 g/day. Intrinsic effects derive from usual dietary intakes, <1 g/day and include improved myocardial oxygen efficiency, heart rate, nutritional preconditioning against ischaemic injury, arrhythmias and heart failure. Myocardial Na+ and K+ currents are non-selectively modulated by omega-3 and omega-6 PUFA to stabilise cells in vitro, but not by fish oil-induced membrane change. In contrast, cellular Ca2+ overload involved in ischaemic injury, arrhythmia and spontaneous pacemaker activity are modulated by both dietary fish oil and in vitro omega-3 LC-PUFA. A potential linking role of bioactive epoxy and hydroxy PUFA derivatives requires investigation. Omega-3 DHA predominates over EPA in population intake, is preferentially incorporated into myocardium and is selectively active in heart rate and arrhythmia modulation, but EPA predominates in clinical trials. Myocardial selectivity for DHA and independent intrinsic and extrinsic physiological mechanisms underpinning diverse clinical endpoints can explain some contradictory outcomes of clinical trials. Intrinsic modulation of intracellular Ca2+ handling provides a unifying physiologically plausible basis for intrinsic fish oil actions and insight to nutritional optimisation of cardiac function.

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Abbreviations

[Ca2+] i :

Intracellular Ca2+ concentration

AA:

Arachidonic acid

ALA:

Alpha-linolenic acid

DHA:

Docosahexaenoic acid

DPA:

Docosapentaenoic acid

EET:

Epoxyeicosatrienoic acids

EPA:

Eicosapentaenoic acid

ETYA:

Eicosatetraynoic acid

GISSI:

Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico

HDoHE:

Hydroxydocosahexaenoic acids

HETE:

Hydroxyeicosatetraenoic acids

HRV:

Heart rate variability

I f :

Funny current

IP3 :

Inositol trisphosphate

I TO :

Transient outward current

LA:

Linoleic acid

LC:

Long chain

PUFA:

Polyunsaturated fatty acids

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  1. Graduate School of Medicine and Centre for Human Applied Physiology, University of Wollongong, Wollongong, NSW, 2522, Australia

    Peter L. McLennan

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Communicated by Nigel A. S. Taylor.

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McLennan, P.L. Cardiac physiology and clinical efficacy of dietary fish oil clarified through cellular mechanisms of omega-3 polyunsaturated fatty acids. Eur J Appl Physiol 114, 1333–1356 (2014). https://doi.org/10.1007/s00421-014-2876-z

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