ARS | Publication request: Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 24, 2012
Publication Date: May 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.