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Pharmacokinetics and Safety Profile of Omega-3 Polyunsaturated Fatty Acids

  • Juan Tamargo
  • María Tamargo
Chapter

Abstract

Omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) play an important role in the regulation of cellular membrane structure and function. They are essential for mammalian cells as they are not able to synthesize their precursor α-linolenic acid (18:3n-3), which can then be converted to more biologically active n-3 PUFA, EPA, and DHA, by a series of desaturation and elongation reactions. In recent years, it has been found that increased intake of n-3 PUFA is associated with a reduced risk of cardiovascular morbidity and mortality. Fish is the main dietary source of n-3 PUFA, although the concentration of n-3 PUFA is below the large amounts required to achieve the therapeutic benefits derived from EPA and DHA. This led to the development of formulations of n-3 PUFA containing high concentrations of purified EPA and DHA in a fixed, predefined ratio, with higher but different oral bioavailability and reasonable patient compliance to be used for dietary supplementation. This article reviews the pharmacokinetic profile of n-3 PUFA, including the digestion and bioavailability, tissular distribution (incorporation in plasma lipids, blood cells, and cell membranes), metabolism (β-oxidation, enzymatic biotransformation, synthesis of eicosanoids and other lipid mediators such as resolvins and protectins), and excretion. Factors that modulate oral bioavailability of n-3 PUFA (chemical and galenic formulations, food intake) are also analyzed. Additionally, the safety profile of n-3 PUFA, with particular attention to an increased bleeding risk, drug interactions, and contraindications, is reviewed.

Keywords

Absorption Adverse effects Bioavailability DHA Distribution Drug interactions EPA Excretion Galenic formulations Metabolism n-3 PUFA Pharmacokinetics 

Notes

Acknowledgment

We thank P Vaquero for her invaluable technical assistance. This work was supported by grants from the Ministerio de Ciencia e Innovación (SAF2011-30088, SAF2011-30112), Instituto de Salud Carlos III (PI11/01030, Red Española de Investigación Cardiovascular RD12/0042/0011), and Comunidad Autónoma de Madrid (S2012/BMD-2374).

Disclosure

The authors state no conflict of interest and have received no payment in preparation of this manuscript.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Pharmacology, School of MedicineUniversidad ComplutenseMadridSpain
  2. 2.Department of CardiologyHospital Gregorio MarañónMadridSpain

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