title: Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for chronic daily headache: protocol for a randomized clinical trial.
abstract: BACKGROUND
  Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity.
  
  
  METHODS
  Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks.
  
  
  RESULTS
  Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence.
  
  
  BACKGROUND
  ClinicalTrials.gov (NCT01157208).
authors.affiliation: Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, NIH, Bethesda, MD, USA. chris.ramsden@nih.gov
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Ramsden
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Mann
authors.forename: Keturah R
authors.initials: KR
authors.lastname: Faurot
authors.forename: Chanee
authors.initials: C
authors.lastname: Lynch
authors.forename: Syed Taha
authors.initials: ST
authors.lastname: Imam
authors.forename: Beth A
authors.initials: BA
authors.lastname: MacIntosh
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hibbeln
authors.forename: James
authors.initials: J
authors.lastname: Loewke
authors.forename: Sunyata
authors.initials: S
authors.lastname: Smith
authors.forename: Rebecca
authors.initials: R
authors.lastname: Coble
authors.forename: Chirayath
authors.initials: C
authors.lastname: Suchindran
authors.forename: Susan A
authors.initials: SA
authors.lastname: Gaylord
mesh_terms: D002908:Chronic Disease; D002985:Clinical Protocols; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D005260:Female; D006261:Headache / Q000178:diet therapy*; D006801:Humans; D008297:Male; D010349:Patient Compliance
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6