Effect of Broccoli Sprouts on Nasal Response to Live Attenuated Influenza Virus in Smokers: A Randomized, Double-Blind Study

Abstract

BackgroundSmokers have increased susceptibility and altered innate host defense responses to influenza virus infection. Broccoli sprouts are a source of the Nrf2 activating agentsulforaphane, and short term ingestion of broccoli sprout homogenates (BSH) has been shown to reduce nasal inflammatory responses to oxidant pollutants.ObjectivesAssess the effects of BSH on nasal cytokines, virus replication, and Nrf2-dependent enzyme expression in smokers and nonsmokers.MethodsWe conducted a randomized, double-blind, placebo-controlled trial comparing the effects of BSH on serially sampled nasal lavage fluid (NLF) cytokines, viral sequence quantity, and Nrf2-dependent enzyme expression in NLF cells and biopsied epithelium. Healthy young adult smokers and nonsmokers ingested BSH or placebo (alfalfa sprout homogenate) for 4 days, designated Days -1, 0, 1, 2. On Day 0 they received standard vaccine dose of live attenuated influenza virus (LAIV) intranasally. Nasal lavage fluids and nasal biopsies were collected serially to assess response to LAIV.ResultsIn area under curve analyses, post-LAIV IL-6 responses (P = 0.03) and influenza sequences (P = 0.01) were significantly reduced in NLF from BSH-treated smokers, whileNAD(P)H: quinoneoxidoreductasein NLF cells was significantly increased. In nonsmokers, a similar trend for reduction in virus quantity with BSH did not reach statistical significance.ConclusionsIn smokers, short term ingestion of broccoli sprout homogenates appears to significantly reduce some virus-induced markers of inflammation, as well as reducing virus quantity. Nutritional antioxidant interventions have promise as a safe, low-cost strategy for reducing influenza risk among smokers and other at risk populations.Trial RegistrationClinicalTrials.gov NCT01269723

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

“…The doses of sulforaphane used in our study were comparable to or exceeded doses shown to stimulate anti-inflammatory pathways in other in vivo studies [21, 30, 31], however, the length of exposure in our study was longer than in those studies. Since we did not measure outcomes at earlier time points, we could have missed transient effects on the Nrf2 pathway.…”

“…However, in alveolar macrophages from COPD patients, sulforaphane did increase Nrf2 target gene expression and enhanced bacterial phagocytosis in vitro [13], which indicates a capacity for stimulation. Daily doses of sulforaphane for three or four days also were associated with enhanced phase 2 antioxidant enzyme expression in nasal cells from normal human volunteers [21], and altered responses to live-attenuated influenza vaccine (LAIV) [30] and diesel exhaust particles in nasal lavage cells [31], which indicates that oral doses can influence respiratory tract cells in vivo . However, similar to our study, Noah et al did not see effects on cytokine production or Nrf2 target gene expression in nasal epithelial cells after dosing subjects with sulforaphane [30].…”

“…Daily doses of sulforaphane for three or four days also were associated with enhanced phase 2 antioxidant enzyme expression in nasal cells from normal human volunteers [21], and altered responses to live-attenuated influenza vaccine (LAIV) [30] and diesel exhaust particles in nasal lavage cells [31], which indicates that oral doses can influence respiratory tract cells in vivo . However, similar to our study, Noah et al did not see effects on cytokine production or Nrf2 target gene expression in nasal epithelial cells after dosing subjects with sulforaphane [30]. It is unlikely that COPD patients suffer an irreversible loss of Nrf2 pathways that makes them resistant to Nrf2 stimulation since alveolar macrophages from COPD patients respond to sulforaphane in vitro [13].…”

A Randomized Controlled Trial of the Effect of Broccoli Sprouts on Antioxidant Gene Expression and Airway Inflammation in Asthmatics

“…Similarly, another trial reported protective effects of BS homogenate against inflammation induced by live attenuated influenza virus. BS ingestion was associated with reduced viral titres and inflammation in smokers without any significant or sustained activation of Phase-II antioxidant genes 12 .…”

“…The active intervention consisted of consumption of 100 grams of BS daily and the placebo consisted of 100g of AS daily for three days. AS have low SFN precursor content and a similar texture and appearance to BS and have been used successfully in other BS trials 10, 12 . BS or AS were added to sandwiches prepared by the Johns Hopkins ICTR Nutrition Core on the day of the study visit.…”