Early modifications of fatty acid composition in plasma phospholipids, platelets and mononucleates of healthy volunteers after low doses of n-3 polyunsaturated fatty acids.
OBJECTIVE
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.
Di Stasi
Delia
D
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy.
Bernasconi
Roberto
R
Marchioli
Roberto
R
Marfisi
Rosa Maria
RM
Rossi
Giovanna
G
Tognoni
Gianni
G
Tacconi
Maria Teresa
MT
D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000737:chemistry* / Q000187:drug effects; D002214:Capsules; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000517:prevention & control / Q000628:therapy; D002986:Clinical Trials as Topic; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D009000:Monocytes / Q000737:chemistry* / Q000187:drug effects; D010743:Phospholipids / Q000097:blood / Q000737:chemistry*; D013997:Time Factors; D024505:Tocopherols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014280:Triglycerides / Q000097:blood / Q000737:chemistry
D002214:Capsules; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D010743:Phospholipids; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D024505:Tocopherols