title: The time course of erythrocyte membrane fatty acid concentrations during and after treatment of non-human primates with increasing doses of an omega-3 rich phospholipid preparation derived from krill-oil.
abstract: BACKGROUND
  A commonly used measure to reflect the intake of the long-chain omega-3 fatty acids EPA and DHA is the omega-3 index, defined as the sum of EPA + DHA as % of total fatty acids in erythrocyte membrane. When the omega-3 index changes it follows that the relative fractions of other fatty acids in the membrane are also changed. In the present study, increasing doses of a preparation of omega-3 rich phospholipids extracted from krill oil were administered orally to non-human primates for 12 weeks and the time course of EPA, DHA and 22 other fatty acids in erythrocytes was determined bi-weekly during treatment and for 8 weeks after cessation of treatment. Plasma concentrations of six endocannabinoid-type mediators being downstream metabolites of some fatty acids analyzed in erythrocytes were also determined.
  
  
  METHODS
  Six diabetic, dyslipidemic non-human primates were included, three in a vehicle control group and three being treated with the omega-3 rich phospholipid preparation. The vehicle control and test items were given daily by gavage and the test item doses were 50, 150 and 450 mg phospholipids/kg/day. Each dose level was given for four weeks. Blood was sampled at baseline and thereafter bi-weekly. Fatty acids were determined in erythrocytes by methylation followed by gas-chromatography. Endocannabinoids and endocannabinoid-like mediators were analyzed in plasma by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.
  
  
  RESULTS
  The treatment resulted in a dose-related increase in the fraction of EPA and DHA in erythrocyte membranes and a dose-related decrease of other poly-unsaturated fatty acids, in particular omega-6 polyunsaturated fatty acids. Erythrocyte concentrations of saturated fatty acids remained unchanged throughout the experiment. Plasma concentrations of endocannabinoids and endocannabinoid-like mediators changed accordingly as those being downstream arachidonic acid decreased, downstream of the saturated palmitic and oleic acids remained unchanged while a downstream EPA metabolite increased.
  
  
  CONCLUSIONS
  Increasing the omega-3 index by administering an omega-3 rich phospholipid extracted from krill oil did not alter the ratio of unsaturated vs. saturated fatty acids in the erythrocyte membranes but only the relative concentrations of unsaturated fatty acids, in particular unsaturated omega-6 fatty acids. Concentrations of saturated fatty acids remained unchanged.
authors.affiliation: Aker Biomarine Antarctic AS, Oksenoyveien 10, N-1366, Lysaker, Norway. petter-arnt.hals@akerbiomarine.com.
authors.forename: Petter-Arnt
authors.identifier: http://orcid.org/0000-0003-4542-1290
authors.initials: PA
authors.lastname: Hals
authors.affiliation: Crown Bioscience (Taicang) Inc., Science and Technology Park, 6 Beijing West Road, Taicang, Jiangsu Province, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, NA, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, NA, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Crown Bioscience (Taicang) Inc., Science and Technology Park, 6 Beijing West Road, Taicang, Jiangsu Province, People's Republic of China.
authors.forename: Yong-Fu
authors.initials: YF
authors.lastname: Xiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D033201:Euphausiacea / Q000737:chemistry*; D005227:Fatty Acids / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D063388:Endocannabinoids; D005227:Fatty Acids; D043371:Fatty Acids, Omega-6; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides
keywords: DHA; EPA; Endocannabinoids; Long-chain omega-3 fatty acids; Omega-3 index; Phospholipids