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Title:   Author  item
                                            KEENAN, ALISON - University Of Californiaitem
                                            Pedersen, Theresaitem
                                            FILLAUS, KRISTI - University Of South Dakotaitem
                                            LARSON, MARK - University Of South Dakotaitem
                                            SHEARER, GREGORY - University Of South Dakotaitem
                                            Newman, John
  Submitted to: Journal of Lipid Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 5/24/2012
                                    Publication  Date: 5/24/2012
                                    Citation: Keenan, A.H., Pedersen, T.L., Fillaus, K., Larson, M.K., Shearer, G.C., Newman, J.W. 2012. Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers. Journal of Lipid Research. doi: 10.1194.Interpretive Summary: Baseline concentrations of highly unsaturated omega-3 fatty acid (n3-HUFA) may influence the ability of dietary n3-HUFA to affect changes in concentrations of esterified fatty acids and their metabolites.  This study evaluates the influence of basal n3-HUFA and n3-HUFA metabolite status on the efficacy of n3-HUFA consumption.  Blood was collected from fasting subjects (n=30) before and after treatment (4 wk; 11 ± 2 mg/kg/d n3-HUFA ethyl esters). Esterified fatty acids (n=24) were quantified in erythrocytes, platelets, and plasma by gas chromatography with mass spectrometry.   Esterified oxygenated lipid metabolites with important biological properties (n=61) were quantified in plasma by liquid chromatography with tandem mass spectrometry.  Treatment with n3 HUFAs increased n3 HUFAs and decreased n6 HUFAs in all reservoirs and increased plasma n3-oxylipins without changing average plasma n6-oxylipin concentrations.  As subject basal n3-HUFAs increased, treatment-associated changes decreased, and this behavior was reflected in the percent of 20:5n3 + 22:6n3 in red blood cell membrane fatty acids, i.e. the omega-3 index.   To maintain an omega-3 index of 8%, and putatively reduce cardiovascular disease risk, our analyses suggest a maintenance dose of 7 mg/kg/d n3-HUFA ethyl esters for a 70 kg individual.  Thus, the basal omega-3 index may have clinical utility to establish efficacious therapeutic experimental feeding regimens, and to evaluate the USDA Dietary Guideline recommendations for n3 HUFA consumption.
                                Technical Abstract: Objective:  Baseline concentrations of highly unsaturated omega-3 fatty acid (n3-HUFA) may influence the ability of dietary n3-HUFA to affect changes in concentrations of esterified fatty acids and their metabolites.  This study evaluates the influence of basal n3-HUFA and n3-HUFA metabolite status on the efficacy of n3-HUFA consumption. 

Methods and Results:  Blood was collected from fasting subjects (n=30) before and after treatment (4 wk; 11 ± 2 mg/kg/d n3-HUFA ethyl esters). Esterified fatty acids (n=24) were quantified in erythrocytes, platelets, and plasma by GC-MS.   Esterified oxylipins (n=61) were quantified in plasma by LC-MS/MS.  Treatment with n3 HUFAs increased n3 HUFAs and decreased n6 HUFAs in all reservoirs and increased plasma n3-oxylipins without changing plasma n6-oxylipin concentrations.  As subject basal n3-HUFAs increased, treatment-associated changes decreased, and this behavior was reflected in the percent of 20:5n3 + 22:6n3 in red blood cell membrane fatty acids, i.e. the omega-3 index.   To maintain an omega-3 index of 8%, and thus reduce cardiovascular disease risk, our analyses suggest a maintenance dose of 7 mg/kg/d n3-HUFA ethyl esters for a 70 kg individual.  

Conclusion: The basal omega-3 index may have clinical utility to establish efficacious therapeutic experimental feeding regimens, and to evaluate the USDA Dietary Guidelines recommendations for n3 HUFA consumption.


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