{"doi":"10.17615/hr60-3968","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.","journal":null,"year":2020,"id":138654,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":420405,"name":"Christopher E. Ramsden","orcid":"0000-0002-4058-7630","position":1,"is_corresponding":false},{"id":600712,"name":"Anne Barden","orcid":"0000-0001-7631-0767","position":2,"is_corresponding":false},{"id":425639,"name":"Olafur S. Palsson","orcid":"0000-0002-4480-3708","position":3,"is_corresponding":false},{"id":368065,"name":"Chirayath Suchindran","orcid":null,"position":4,"is_corresponding":false},{"id":302637,"name":"Ariel E. Feldstein","orcid":"0000-0001-7202-3840","position":5,"is_corresponding":false},{"id":460020,"name":"Amit Ringel","orcid":null,"position":6,"is_corresponding":false},{"id":233817,"name":"Joseph R. Hibbeln","orcid":"0000-0002-4141-5611","position":7,"is_corresponding":false},{"id":3992,"name":"Trevor A. Mori","orcid":"0000-0002-5264-9229","position":8,"is_corresponding":false},{"id":601103,"name":"David A. Barrow","orcid":"0000-0003-2096-7262","position":9,"is_corresponding":false},{"id":420404,"name":"Keturah R. Faurot","orcid":"0000-0001-6122-7821","position":10,"is_corresponding":false},{"id":421360,"name":"J. Douglas Mann","orcid":null,"position":11,"is_corresponding":false},{"id":601241,"name":"Chanee Lynch","orcid":null,"position":12,"is_corresponding":false},{"id":489182,"name":"Susan Gaylord","orcid":"0000-0002-5119-9633","position":13,"is_corresponding":false},{"id":600713,"name":"Emilie Mas","orcid":"0000-0003-2848-9613","position":14,"is_corresponding":false},{"id":592854,"name":"Rebecca Coble","orcid":null,"position":15,"is_corresponding":false},{"id":420401,"name":"Daisy Zamora","orcid":"0000-0003-2114-5156","position":16,"is_corresponding":false},{"id":540996,"name":"Beth MacIntosh","orcid":"0000-0002-4532-1532","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:06.651725Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}