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PLoS One. 2016 Nov 10;11(11):e0163716. doi: 10.1371/journal.pone.0163716. eCollection 2016.

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

Author information

1
Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
2
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
3
Temple University, Philadelphia, Pennsylvania, United States of America.
4
University at Buffalo, SUNY and VA WNY Healthcare system, Buffalo, New York, United States of America.

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.

PMID:
27832073
PMCID:
PMC5104323
DOI:
10.1371/journal.pone.0163716
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Dr. Wise reports grants and personal fees from Boehringer Ingelhelm, Sunovion, and AstraZeneca/Medimmune, and personal fees from Bristol-Myers-Squibb, GlaxoSmithKline, Mylan, Novartis, Pfizer, Pulmonx, Spiration, Roche/Genentech, Janssen, Merck, Teva, Forest Labs, and Sanofi/Mannkind, outside of submitted work. Drs. Fahey and Talalay report multiple US and foreign issued patents related to broccoli sprouts and sulforaphane. Dr. Biswal reports a pending patent on methods for targeting Nrf2 pathway for oxidative stress related disease. The relevant patents held by Drs. Fahey, Talalay and Biswal are listed below. Drs. Fahey and Talalay have relinquished all ownership and any fiduciary or management involvement in Brassica Protection Products (BPP). They are no longer either Board Members or equity holders. In addition, they have instructed JHU NOT to collect the ‘inventor’s share’ of any royalties that may accrue to JHU from the patents originating with their work on broccoli sprouts, licensed to BPP or anyone else. This does not alter our adherence to PLOS ONE policies on sharing data and materials. 1998 Fahey JW, P Talalay."Method of Preparing a Food Product from Cruciferous Seeds". U.S. Patent 5,725,895. 1999 Fahey JW, P Talalay. “Cancer Chemoprotective Food Products.” U.S. Patent 5,968,505. 1999 Fahey JW, P Talalay. “Method of Preparing a Food Product From Cruciferous Sprouts.” U.S. Patent 5,968,567. 2001 Fahey JW, P Talalay. “Method of Preparing a Food Product From Cruciferous Sprouts.” U.S. Patent 6,177,122. 2001 Fahey JW, P Talalay. “Cancer Chemoprotective Food Products.” U.S. Patent 6,242,018. 2001 Fahey JW, P Talalay, J Troyer. Airlift Bioreactor for Harvesting Sprouts. U.S. Patent Application 09/450,753 and PCT WO 01/39591 A2. 2003 Fahey JW. Development of Novel, Highly Chemoprotectant Crucifer Germplasm. U.S. Patent 6,521,818. 2004 Fahey JW. Treatment of Helicobacter with Isothiocyanates. U.S. Patent 6,737,441. 2004 Fahey JW. Method for the direct extraction of isothiocyanates into the seed oil from glucosinolate-containing plant seeds. U.S. Provisional Patent Application # 60/635,998 and U.S. Patent Application (2005). 2007 Fahey JW and P Talalay. “Cancer Chemoprotective Food Products.” U.S. Patent 7,303,770 B2. 2008 Fahey JW. Treatment of Helicobacter with Isothiocyanates. U.S. Patent 7,402,569. 2010 Talalay P, JW Fahey, A Talalay. Formulations for Treatment with Glucosinolates. U.S. Provisional Patent Application #61/383,853.

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