TY - JOUR
T1 - Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers
AU - Bauman, Julie E.
AU - Hsu, Chiu Hsieh
AU - Centuori, Sara
AU - Guillen-Rodriguez, Jose
AU - Garland, Linda L.
AU - Ho, Emily
AU - Padi, Megha
AU - Bageerathan, Vignesh
AU - Bengtson, Lisa
AU - Wojtowicz, Malgorzata
AU - Szabo, Eva
AU - Sherry Chow, H. H.
N1 - Funding Information:
This single-center study was conducted at the University of Arizona Cancer Prevention Clinic (Tucson, AZ, USA) and sponsored by the U.S. National Cancer Institute (NCI) Division of Cancer Prevention through the Cancer Prevention Agent Development Program: Early Phase Clinical Research (HHSN2612012000311). The protocol was approved by the NCI Central Institutional Review Board and carried out in accordance with the Declaration of Helsinki and Good Clinical Practice. All participants provided written informed consent. The study was registered with clinicaltrials.gov (NCT03402230). Key inclusion criteria included: male or female aged ≥18 years; current tobacco smoker with ≥20 pack years of self-reported smoking exposure and a current average use of ≥10 cigarettes/day; Karnofsky performance status ≥70%; adequate organ and marrow function. Key exclusion criteria included: history of invasive cancer within the past 2 years; regular use of supraphysiologic steroid doses; uncontrolled intercurrent illness.
Funding Information:
Funding: This trial was funded by the U.S. National Cancer Institute (NCI) Division of Cancer Prevention through the Cancer Prevention Agent Development Program: Early Phase Clinical Research (HHSN2612012000311). Tobacco carcinogen and buccal gene expression assays, and biostatistical and bioinformatics analyses, were supported by the Shared Resources of the University of Arizona Cancer Center (P30CA023074). Avmacol® was provided by Nutramax, Inc.
Funding Information:
This trial was funded by the U.S. National Cancer Institute (NCI) Division of Cancer Prevention through the Cancer Prevention Agent Development Program: Early Phase Clinical Research (HHSN2612012000311). Tobacco carcinogen and buccal gene expression assays, and biostatistical and bioinformatics analyses, were supported by the Shared Resources of the University of Arizona Cancer Center (P30CA023074). Avmacol? was provided by Nutramax, Inc.
Publisher Copyright:
© 2022, MDPI. All rights reserved.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Consumption of cruciferous vegetables, rich in the isothiocyanate glucoraphanin, is associated with reduced risk of tobacco-related cancers. Sulforaphane, released by hydrolysis of glucoraphanin, potently induces cytoprotective phase II enzymes. Sulforaphane decreased the incidence of oral cancer in the 4NQO carcinogenesis model. In residents of Qidong, China, broccoli seed and sprout extracts (BSSE) increased detoxification of air pollutants benzene and acrolein, also found in tobacco smoke. This randomized, crossover trial evaluated detoxification of tobacco carcinogens by the BSSE Avmacol® in otherwise healthy smokers. Participants were treated for 2 weeks with both low and higher-dose BSSE (148 µmol vs. 296 µmol of glucoraphanin daily), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxification of benzene, measured by urinary excretion of its mercapturic acid, SPMA. Secondary endpoints included bioavailability, detoxification of acrolein and crotonaldehyde, modulation by GST genotype, and toxicity. Forty-nine participants enrolled, including 26 (53%) females with median use of 20 cigarettes/day. Low and higher-dose BSSE showed a mean bioavailability of 11% and 10%, respectively. Higher-dose BSSE significantly upregulated urinary excretion of the mercapturic acids of benzene (p = 0.04), acrolein (p < 0.01), and crotonaldehyde (p = 0.02), independent of GST genotype. Retention and compliance were high resulting in early study completion. In conclusion, BSSE significantly upregulated detoxification of the tobacco carcinogens benzene, acrolein, and crotonaldehyde in current tobacco smokers.
AB - Consumption of cruciferous vegetables, rich in the isothiocyanate glucoraphanin, is associated with reduced risk of tobacco-related cancers. Sulforaphane, released by hydrolysis of glucoraphanin, potently induces cytoprotective phase II enzymes. Sulforaphane decreased the incidence of oral cancer in the 4NQO carcinogenesis model. In residents of Qidong, China, broccoli seed and sprout extracts (BSSE) increased detoxification of air pollutants benzene and acrolein, also found in tobacco smoke. This randomized, crossover trial evaluated detoxification of tobacco carcinogens by the BSSE Avmacol® in otherwise healthy smokers. Participants were treated for 2 weeks with both low and higher-dose BSSE (148 µmol vs. 296 µmol of glucoraphanin daily), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxification of benzene, measured by urinary excretion of its mercapturic acid, SPMA. Secondary endpoints included bioavailability, detoxification of acrolein and crotonaldehyde, modulation by GST genotype, and toxicity. Forty-nine participants enrolled, including 26 (53%) females with median use of 20 cigarettes/day. Low and higher-dose BSSE showed a mean bioavailability of 11% and 10%, respectively. Higher-dose BSSE significantly upregulated urinary excretion of the mercapturic acids of benzene (p = 0.04), acrolein (p < 0.01), and crotonaldehyde (p = 0.02), independent of GST genotype. Retention and compliance were high resulting in early study completion. In conclusion, BSSE significantly upregulated detoxification of the tobacco carcinogens benzene, acrolein, and crotonaldehyde in current tobacco smokers.
KW - broccoli seed and sprout extract
KW - clinical trial
KW - detoxification
KW - glucoraphanin
KW - smokers
KW - sulforaphane
KW - tobacco carcinogens
UR - http://www.scopus.com/inward/record.url?scp=85128786168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85128786168&partnerID=8YFLogxK
U2 - 10.3390/cancers14092129
DO - 10.3390/cancers14092129
M3 - Article
AN - SCOPUS:85128786168
VL - 14
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 9
M1 - 2129
ER -