Randomized controlled trial2016Open access

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial

Wise RA, Holbrook JT, Criner G, Sethi S, Rayapudi S, Sudini KR, Sugar EA, Burke A, Thimmulappa R, Singh A, Talalay P, Fahey JW, Berenson CS, Jacobs MR, Biswal S, Broccoli Sprout Extract Trial Research Group

PloS one · 101 citations

How it was studied

Design
Randomized controlled trial (indexed by PubMed)
Studied in
People
Main outcome
Health markers and function
Intake measured by
Not stated

Who paid for it

Funding
Independent funding
Government
National Heart, Lung, and Blood Institute
Government
NHLBI NIH HHS
Grants
National Heart, Lung, and Blood Institute (U01 HL105569); National Heart, Lung, and Blood Institute (5U01HL105569)

Based on 2 listed funder(s) and full-text disclosure statement.

Publication

Published
2016-11-10 · PLoS One · vol. 11 · issue 11 · p. e0163716
Publisher
Public Library of Science
Cited
121 citations · more than 96% of similar papers · 5.1× the field average
Impact
Top 10% most cited in its field
References
33 works
Access
Open access (journal) · CC-BY
Research areas
Genomics, phytochemicals, and oxidative stress · Curcumin's Biomedical Applications · Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Keywords
Sulforaphane, COPD, Placebo, Medicine, Oxidative stress, Inflammation, Internal medicine, Randomized controlled trial, Pulmonary function testing, Immunology, Gastroenterology, Pathology, Cancer research
MeSH
humans, pulmonary disease, chronic obstructive, isothiocyanates, sulfoxides, administration, oral, double-blind method, gene expression regulation, oxidative stress, aged, middle aged, female, male, nf-e2-related factor 2

15 authors

From US

  • Robert A. Wise · correspondingJohns Hopkins University; Johns Hopkins Medicine
  • Janet T. HolbrookJohns Hopkins University
  • Gerard J. CrinerTemple University
  • Sanjay SethiVA Western New York Healthcare System
  • Sobharani RayapudiJohns Hopkins University
  • Kuladeep R. SudiniJohns Hopkins University

Abstract

Background

COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).

Methods

This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.

Results

Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels.

Conclusion

Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.

Trial registration

Clinicaltrials.gov: NCT01335971.

Abstract via Europe PMC. Copyright remains with the authors or publisher (CC0).

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