One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL)
Olga V. Demler,
Yanyan Liu,
Heike Luttmann-Gibson,
Jeramie D. Watrous,
Kim A. Lagerborg,
Hesam Dashti,
Franco Giulianini,
Mallory Heath,
Carlos A. Camargo,
William S. Harris,
Jay G. Wohlgemuth,
Allen M. Andres,
Saumya Tivari,
Tao Long,
Mahan Najhawan,
Khoi Dao,
James G. Prentice,
Julia A. Larsen,
Olivia I. Okereke,
Karen H. Costenbader,
Julie E. Buring,
JoAnn E. Manson,
Susan Cheng,
Mohit Jain,
Samia Mora
Affiliations
Olga V. Demler
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Yanyan Liu
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Heike Luttmann-Gibson
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Jeramie D. Watrous
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Kim A. Lagerborg
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Hesam Dashti
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Franco Giulianini
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Mallory Heath
Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Carlos A. Camargo
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
William S. Harris
OmegaQuant Analytics, Sioux Falls, SD 57106, USA
Jay G. Wohlgemuth
Quest Diagnostics, San Juan Capistrano, CA 92673, USA
Allen M. Andres
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Saumya Tivari
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Tao Long
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Mahan Najhawan
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Khoi Dao
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
James G. Prentice
Quest Diagnostics, San Juan Capistrano, CA 92673, USA
Julia A. Larsen
Quest Diagnostics, San Juan Capistrano, CA 92673, USA
Olivia I. Okereke
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Karen H. Costenbader
Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Julie E. Buring
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
JoAnn E. Manson
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Susan Cheng
Smidt Heart Institute, Cedars-Sinai Medical Ctr, Los Angeles, CA 90048, USA
Mohit Jain
Department of Pharmacology, University of California San Diego, La Jolla, CA 92037, USA
Samia Mora
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) p-values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.
