Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.
Level 2 - randomized trial
Phase 2 randomized, double-blind, placebo-controlled trial
PubMed 27832073 · doi:10.1371/journal.pone.0163716
What was done
A phase 2, parallel, double-blind, randomized, placebo-controlled trial evaluated oral sulforaphane in 89 patients meeting GOLD criteria for COPD across three US academic medical centers. Participants able to tolerate bronchoscopies were assigned (1:1:1) to placebo, 25 μmoles, or 150 μmoles of sulforaphane daily for four weeks. The primary outcome was change in Nrf2 target gene expression (NQO1, HO1, AKR1C1, AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included markers of oxidative stress, airway inflammation, and pulmonary function tests.
What was found
Sulforaphane was absorbed as confirmed by plasma metabolite levels and was well tolerated. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 across groups, with no consistent pattern and no statistically significant difference from baseline. Changes in airway inflammation measures and pulmonary function tests also showed no significant differences between the sulforaphane and placebo groups.
Why it matters
Despite strong preclinical evidence that sulforaphane stimulates antioxidant defenses via Nrf2, oral administration in COPD patients failed to alter target gene expression or clinical markers over four weeks.
Limits
The sample size was modest (89 participants across three arms) and the treatment duration was short (four weeks). The cohort was restricted to individuals able to undergo bronchoscopy, which may exclude more severe COPD phenotypes, and specific quantitative data and confidence intervals for secondary endpoints were omitted from the abstract.
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