Quantitation of Human Whole‐Body Synthesis‐Secretion Rates of Docosahexaenoic Acid and Eicosapentaenoate Acid from Circulating Unesterified α‐Linolenic Acid at Steady State |
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| Authors: | Yu‐Hong Lin Joseph R. Hibbeln Anthony F. Domenichiello Christopher E. Ramsden Nicholas M. Salem Chuck T. Chen Haksong Jin Amber B. Courville Sharon F. Majchrzak‐Hong Stanley I. Rapoport Richard P. Bazinet Bernard V. Miller III |
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| Affiliation: | 1. Section of Nutritional Neuroscience, LMBB, DICBR, NIAAA, NIH, 5625 Fishers Lane Rm 3N07, Bethesda, MD, USA;2. Lipid Mediators of Inflammation and Pain Unit, Laboratory of Clinical Investigation, NIA, NIH, Baltimore, MD, USA;3. DICBR, NIAAA, NIH, Bethesda, MD, USA;4. School of Agriculture, Food and Wine, University of Adelaide, Adelaide, SA, Australia;5. Pharmacy Department, NIH Clinical Center, NIH, Bethesda, MD, USA;6. Nutrition Department, NIH Clinical Center, NIH, Bethesda, MD, USA;7. Department of Nutritional Science, University of Toronto, Toronto, ON, M5S 3E2, Canada;8. NIDDK, NIH, Bethesda, MD, USA |
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| Abstract: | The rate at which dietary α‐linolenic acid (ALA) is desaturated and elongated to its longer‐chain n‐3 polyunsaturated fatty acid (PUFA) in humans is not agreed upon. In this study, we applied a methodology developed using rodents to investigate the whole‐body, presumably hepatic, synthesis‐secretion rates of esterified n‐3 PUFA from circulating unesterified ALA in 2 healthy overweight women after 10 weeks of low‐linoleate diet exposure. During continuous iv infusion of d5‐ALA, 17 arterial blood samples were collected from each subject at ?10, 0, 10, 20, 40, 60, 80, 100, 120, 150, 180, and 210 min, and at 4, 5, 6, 7, and 8 h after beginning infusion. Plasma esterified d5‐n‐3 PUFA concentrations were plotted against the infusion time and fit to a sigmoidal curve using nonlinear regression. These curves were used to estimate kinetic parameters using a kinetic analysis developed using rodents. Calculated synthesis‐secretion rates of esterified eicosapentaenoate, n‐3 docosapentaenoate, docosahexaenoic acid, tetracosapentaenate, and tetracosahexaenoate from circulating unesterified ALA were 2.1 and 2.7; 1.7 and 5.3; 0.47 and 0.27; 0.30 and 0.30; and 0.32 and 0.27 mg/day for subjects S01 and S02, respectively. This study provides new estimates of whole‐body synthesis‐secretion rates of esterified longer‐chain n‐3 PUFA from circulating unesterified ALA in human subjects. This method now can be extended to study factors that regulate human whole‐body PUFA synthesis‐secretion in health and disease. |
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| Keywords: | Hepatic synthesis‐secretion Kinetics Low‐linoleate diet Mass spectrometry Tetracosahexaenoic acid |
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