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Early modifications of fatty acid composition in plasma phospholipids, platelets and mononucleates of healthy volunteers after low doses of n-3 polyunsaturated fatty acids

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objectives

Although previous data suggested that only doses of 4 g/day or higher of n-3 polyunsaturated fatty acids (PUFA) have had a beneficial effect in the prevention of atherosclerosis and cardiovascular diseases, the GISSI-Prevenzione Study in a 3-year trial showed that 1 g/day reduced total and cardiovascular mortality in over 11,000 post-infarction patients. The aim of this study was to investigate the time course and the extent of incorporation of n-3 fatty acids in plasma and blood cells after 1 g/day of n-3 PUFA, the dose effective in the GISSI-Prevenzione in comparison with higher doses.

Methods

Thirty-six healthy volunteers were given 1, 2 and 4 g/day of n-3 PUFA ethyl esters for 12 weeks, followed by a 4-week washout. Blood was collected at weeks 0, 1, 2, 4, 8, 12 and 16 and used for lipid profile analysis and measurement of fatty acid composition in plasma phospholipids, platelets and mononucleates.

Results

Total n-3 PUFA increased by 2.0-, 2.2- and 2.9-fold versus baseline after 12-week treatment with 1, 2 and 4 g respectively. A statistically significant raise of total n-3 PUFA was seen in platelets and mononucleates. Among individual n-3 PUFA, 22:5 n-3 was enriched early and dose dependently in plasma phospholipids, platelets and mononucleates; the raise of 22:6 n-3 was less marked especially in platelets and mononucleates.

Conclusions

One gram per day of n-3 PUFA induces fast (within 1 week) and striking changes in blood composition of PUFA that may well explain their beneficial effects against cardiovascular diseases.

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Acknowledgements

Work partially supported by Pronova, Lysaker, Norway. The experiments were conducted according to the 1996 revision of the Declaration of Helsinki and with the Italian current laws.

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Authors and Affiliations

  1. Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 , Milano, Italy

    Delia Di Stasi, Roberto Bernasconi & Maria Teresa Tacconi

  2. Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy

    Roberto Marchioli, Rosa Maria Marfisi & Gianni Tognoni

  3. Fleming Research, Milano, Italy

    Giovanna Rossi

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  1. Delia Di Stasi
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  2. Roberto Bernasconi
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  3. Roberto Marchioli
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  7. Maria Teresa Tacconi
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Correspondence to Maria Teresa Tacconi.

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Delia Di Stasi and Roberto Bernasconi contributed equally to this work.

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Di Stasi, D., Bernasconi, R., Marchioli, R. et al. Early modifications of fatty acid composition in plasma phospholipids, platelets and mononucleates of healthy volunteers after low doses of n-3 polyunsaturated fatty acids. Eur J Clin Pharmacol 60, 183–190 (2004). https://doi.org/10.1007/s00228-004-0758-8

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  • DOI: https://doi.org/10.1007/s00228-004-0758-8

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