Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Sep;64(9):100424.
doi: 10.1016/j.jlr.2023.100424. Epub 2023 Aug 10.

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

Daniel K Chen  1 , Adam H Metherel  1 , Kimia Rezaei  1 , Camilla Parzanini  1 , Chuck T Chen  1 , Christopher E Ramsden  2 , Mark Horowitz  2 , Keturah R Faurot  3 , Beth MacIntosh  4 , Daisy Zamora  5 , Richard P Bazinet  6
Affiliations
Randomized Controlled Trial

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

Daniel K Chen et al. J Lipid Res. 2023 Sep.

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest R. P. B. has received industrial grants, including those matched by the Canadian government, and/or travel support related to work on brain fatty acid uptake from Arctic Nutrition, Bunge Ltd, DSM, Fonterra, Mead Johnson, and Nestle, Inc. Moreover, R. P. B. is on the executive of the International Society for the Study of Fatty Acids and Lipids and held a meeting on behalf of Fatty Acids and Cell Signaling, both of which rely on corporate sponsorship. R. P. B. has given expert testimony in relation to supplements and the brain and holds the Canada Research Chair in Brain Lipid Metabolism. None of the other authors report a conflict of interest related to research presented in this article.

Figures

Fig. 1
Fig. 1
Changes in plasma LNA (A) concentration of total lipids, (B) total lipid δ13C content, (C) concentration of PLs, (D) concentration of CEs, (E) concentration of TGs, and (F) concentration of FFAs from baseline (week 0) to 4, 10, and 16 weeks for low n-3, high n-6 (H6; blue), high n-3, high n-6 (H3H6; red), and high n-3, low n-6 (H3; green) dietary groups. ∗ represents a significant effect of diet at the respective time point compared with baseline, as determined by one-way repeated-measures ANOVA with Fisher’s least significant difference post hoc test, P < 0.05, n = 10, means ± SEM.
Fig. 2
Fig. 2
Changes in plasma ARA (A) concentration of total lipids, (B) total lipid δ13C content, (C) concentration of PLs, (D) concentration of CEs, (E) concentration of TGs, and (F) concentration of FFAs from baseline (week 0) to 4, 10, and 16 weeks for low n-3, high n-6 (H6; blue), high n-3, high n-6 (H3H6; red), and high n-3, low n-6 (H3; green) dietary groups. Statistically significant effects were determined by one-way repeated-measures ANOVA, P > 0.05, n = 10, means ± SEM.
Fig. 3
Fig. 3
Changes in plasma EPA (A) concentration of total lipids, (B) total lipid δ13C content, (C) concentration of PLs, (D) concentration of CEs, (E) concentration of TGs, and (F) concentration of FFAs from baseline (week 0) to 4, 10, and 16 weeks for low n-3, high n-6 (H6; blue), high n-3, high n-6 (H3H6; red), and high n-3, low n-6 (H3; green) dietary groups. ∗ represents a significant effect of diet at the respective time point compared with baseline, as determined by one-way repeated-measures ANOVA with Fisher’s least significant difference post hoc test, P < 0.05, n = 10, means ± SEM.
Fig. 4
Fig. 4
Changes in plasma DHA (A) concentration of total lipids, (B) total lipid δ13C content, (C) concentration of PLs, (D) concentration of CEs, (E) concentration of TGs, and (F) concentration of FFAs from baseline (week 0) to 4, 10, and 16 weeks for low n-3, high n-6 (H6; blue), high n-3, high n-6 (H3H6; red), and high n-3, low n-6 (H3; green) dietary groups. ∗ represents a significant effect of diet at the respective time point compared with baseline, as determined by one-way repeated-measures ANOVA with Fisher’s least significant difference post hoc test, P < 0.05, n = 10, means ± SEM.
Fig. 5
Fig. 5
Changes in plasma ALA (A) concentration of total lipids, (B) total lipid δ13C content, (C) concentration of PLs, (D) concentration of CEs, (E) concentration of TGs, and (F) concentration of FFAs from baseline (week 0) to 4, 10, and 16 weeks for low n-3, high n-6 (H6; blue), high n-3, high n-6 (H3H6; red), and high n-3, low n-6 (H3; green) dietary groups. Statistically significant effects were determined by one-way repeated-measures ANOVA, P > 0.05, n = 10, means ± SEM.
Fig. 6
Fig. 6
Comparison of the δ13C of (A) LNA, (B) ARA, (C) EPA, (D) DHA, (E) ALA between total lipids (TLs; black), PLs (orange), CEs (red), TGs (purple), and FFAs (blue) at weeks 0, 4, 10, and 16 for the combination of all dietary interventions. Superscripts represent a significant correlation between the respective lipid fraction and total lipids at the indicated time point as determined by Pearson correlation, aP < 0.05, bP < 0.01, cP < 0.001, n = 5–30, means ± SEM.
See this image and copyright information in PMC

References

    1. Lacombe R.J.S., Giuliano V., Colombo S.M., Arts M.T., Bazinet R.P. Compound specific isotope analysis resolves the dietary origin of docosahexaenoic acid (DHA) in the mouse brain. J. Lipid Res. 2017;58:2071–2081. - PMC - PubMed
    1. Brand W.A., Coplen T.B. Stable isotope deltas: tiny, yet robust signatures in nature. Isotopes Environ. Health Stud. 2012;48:393–409. - PubMed
    1. Brand W.A., Coplen T.B., Vogl J., Rosner M., Prohaska T. Assessment of international reference materials for isotope-ratio analysis (IUPAC Technical Report) Pure Appl. Chem. 2014;86:425–467.
    1. Smith B.N., Epstein S. Two categories of c/c ratios for higher plants. Plant Physiol. 1971;47:380–384. - PMC - PubMed
    1. Nakamura K., Schoeller D.A., Winkler F.J., Schmidt H.L. Geographical variations in the carbon isotope composition of the diet and hair in contemporary man. Biomed. Mass Spectrom. 1982;9:390–394. - PubMed

Publication types