title: Flaxseed modulates inflammatory and oxidative stress biomarkers in cystic fibrosis: a pilot study.
abstract: BACKGROUND
  Cystic fibrosis (CF) leads to advanced lung disease despite aggressive care. Persistent inflammation and oxidative stress contribute to exacerbations and disease progression. Flaxseed (FS), a dietary botanical supplement with high fiber, lignan phenolics, and omega-3 fatty acids has anti-inflammatory and antioxidant properties in murine models of acute and chronic lung injury. This pilot study was designed to determine whether CF patients could tolerate FS, evaluate circulating FS metabolites, and study biomarkers of lung damage, as a prelude to studying clinical outcomes.
  
  
  METHODS
  10 CF patients and 5 healthy volunteers consumed 40 g of FS daily for 4 weeks with safety and tolerability being assessed. Urine was evaluated for systemic oxidative stress and plasma for FS metabolites (enterolignans) and cytokine levels. Buccal swabs were analyzed for gene expression of Nrf2-regulated antioxidant enzymes including Heme Oxygenase-1 (HO-1) and NAD(P)H Quinone Oxidoreductase 1 (NQO1).
  
  
  RESULTS
  All subjects completed the study without serious adverse events. Plasma levels of enterolignans were detectable in both healthy controls and CF volunteers. CF patients were stratified based on plasma enterolignan levels after 2 weeks of FS administration into high- (174 to 535 nM ED and 232 to 1841 nM EL) and low- (0 to 32 nM ED and 0 to 40 nM EL) plasma lignan cohorts. The low enterolignan level cohort experienced a statistically significant drop in urinary inflammatory IsoP and plasma TNFα levels, while demonstrating higher average NQO1 mRNA levels in buccal epithelium compared to high-lignan patients.
  
  
  CONCLUSIONS
  This pilot study demonstrated that FS is tolerated by CF patients. FS metabolites could be detected in the plasma. Future studies will assess appropriate dosing and target populations for FS, while exploring clinical outcomes.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT02014181 .
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, 835W Gates Building, 3600, Spruce Street, Philadelphia, PA, 19104, USA. turowsj@ccf.org.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Turowski
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, 835W Gates Building, 3600, Spruce Street, Philadelphia, PA, 19104, USA. rpietrofesa@hotmail.com.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Pietrofesa
authors.affiliation: Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. jalawson@mail.med.upenn.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.affiliation: Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. melpo@mail.med.upenn.edu.
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, 835W Gates Building, 3600, Spruce Street, Philadelphia, PA, 19104, USA. Denis.Hadjiliadis@uphs.upenn.edu.
authors.forename: Denis
authors.initials: D
authors.lastname: Hadjiliadis
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005260:Female; D019597:Flax / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology; D008517:Phytotherapy; D010865:Pilot Projects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012639:Seeds / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D017705:Lignans; D010636:Phenols; D010936:Plant Extracts; D051547:Heme Oxygenase-1