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

Randomized, double-blind, placebo-controlled trial in adults with COPD who were able to undergo bronchoscopy. Participants were active or former smokers aged 40 years or older with physician-diagnosed COPD and at least a 10 pack-year smoking history, recruited from three U.S. academic medical centers.

Oral sulforaphane extracted from broccoli sprouts was given once daily for 4 weeks at two dose levels: 25 μmoles/day (4.4 mg/day) or 150 μmoles/day (26.6 mg/day). The active regimen was compared with placebo in a randomized, double-blind trial.

Oral sulforaphane did not produce a meaningful biological or clinical benefit in COPD. It did not increase Nrf2 target gene expression in alveolar macrophages or bronchial epithelial cells, and the authors reported no effect on oxidative stress markers, inflammation, lung function, or patient-reported outcomes versus placebo. Key alveolar macrophage fold-changes at 4 weeks remained close to 1 for NQO1, HO1, AKR1C1, AKR1C3, Nrf2, and Keap1, with no significant dose effects; in bronchial epithelial cells, most markers were also unchanged. Sulforaphane was absorbed and generally well tolerated, although bad taste was reported in 24% and 31% of the active-dose groups versus 7% with placebo, and two unrelated serious adverse events occurred in the low-dose group.

The study was short duration (4 weeks) and relatively small, limiting power to detect modest effects. It enrolled a bronchoscopy-eligible COPD subgroup from academic centers, which may limit generalizability. Several analyzable sample sizes were smaller than the randomized numbers for biomarker outcomes, and one isolated gene signal did not change the overall negative interpretation.