title: Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial.
abstract: Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P<0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P<0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P<0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.
authors.affiliation: Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, University of North Carolina-Chapel Hill, NC, USA Department of Biostatistics, School of Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA Nutrition Research and Metabolism Core, North Carolina Translational Clinical Sciences Institute, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA Department of Pediatric Gastroenterology, Hepatology and Nutrition, University of California, San Diego, San Diego, CA, USA School of Medicine and Pharmacology, Royal Perth Hospital, The University of Western Australia, Perth, Australia Division of Gastroenterology and Hepatology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Ramsden
authors.forename: Keturah R
authors.initials: KR
authors.lastname: Faurot
authors.forename: Daisy
authors.initials: D
authors.lastname: Zamora
authors.forename: Chirayath M
authors.initials: CM
authors.lastname: Suchindran
authors.forename: Beth A
authors.initials: BA
authors.lastname: MacIntosh
authors.forename: Susan
authors.initials: S
authors.lastname: Gaylord
authors.forename: Amit
authors.initials: A
authors.lastname: Ringel
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hibbeln
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.forename: Anne
authors.initials: A
authors.lastname: Barden
authors.forename: Chanee
authors.initials: C
authors.lastname: Lynch
authors.forename: Rebecca
authors.initials: R
authors.lastname: Coble
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.forename: Olafur
authors.initials: O
authors.lastname: Palsson
authors.forename: David A
authors.initials: DA
authors.lastname: Barrow
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Mann
mesh_terms: D000328:Adult; D004032:Diet; D004435:Eating; D004912:Erythrocytes / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000627:therapeutic use*; D005260:Female; D020773:Headache Disorders / Q000178:diet therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D011788:Quality of Life; D012959:Socioeconomic Factors; D016896:Treatment Outcome
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6
keywords: Clinical trial; Headache; Migraine; Omega-3; Omega-6