BMC Complement Altern Med. 2015 May 13;15:148. doi: 10.1186/s12906-015-0651-2.

Flaxseed modulates inflammatory and oxidative stress biomarkers in cystic fibrosis: a pilot study.

Turowski JB1, Pietrofesa RA2, Lawson JA3, Christofidou-Solomidou M4, Hadjiliadis D5.

• 1Division 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.
• 2Division 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.
• 3Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. jalawson@mail.med.upenn.edu.
• 4Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. melpo@mail.med.upenn.edu.
• 5Division 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.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT02014181 .

PMID:

25963404