Analysis of omega-3 and omega-6 polyunsaturated fatty acid metabolism by compound-specific isotope analysis in humans

Abstract

Natural variations in the ¹³C:¹²C ratio (carbon-13 isotopic abundance [δ¹³C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ¹³C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m²) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ¹³C were determined. The H6 intervention exhibited increases in plasma LNA δ¹³C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ¹³C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ¹³C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ¹³C.

Keywords: EPA; arachidonic acid; fatty acid metabolism; human plasma; isotope ratio MS; linoleic acid; lipids; nutrition; omega-3 fatty acids; omega-6 fatty acids.