Abstract LB221: Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokers

Abstract

Abstract Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokersJulie E. Bauman, Chiu-Hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry ChowIntroduction: Diets high in cruciferous vegetables are associated with reduced risk of tobacco-related cancers. Crucifers are rich in the phytochemical glucoraphanin (GR), which is hydrolyzed by myrosinase to its bioactive form, sulforaphane (SF). SF upregulates the NRF2 transcription factor and downstream target genes in the antioxidant response element. As GR is concentrated in broccoli seeds relative to mature plants, broccoli seed preparations (BSP) are under development as chemopreventive agents. BSP increased detoxication of air pollutants including benzene in Qidong, China. Methods: We conducted a randomized crossover trial evaluating the detoxication of benzene and other tobacco carcinogens by the BSP Avmacol, tablets comprised of broccoli seed powder and broccoli sprout extract, in otherwise healthy smokers (≥ 20 pack-years). Each subject was treated with low and high dose BSP (70 vs. 140 GR equivalents daily for 2 weeks), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxication of benzene, measured by change in urinary excretion of its mercapturic acid metabolite (S-phenyl mercapturic acid, SPMA). Secondary endpoints included detoxication of the carcinogens acrolein and crotonaldehyde, and SF bioavailability assessed by urinary SF metabolites.Results: 49 subjects were randomized from Feb 2018-Nov 2019: 26 female, mean age 56.3. Treatment-related adverse events (AE) were gastrointestinal; most common were grade 1-2 bloating/cramping/abdominal pain (11; 22%), grade 1 diarrhea (11; 22%), grade 1 flatulence (10; 20%). No grade ≥ 3 AE were observed. One subject withdrew after unrelated AE. Compliance with BSP and biomarker measurements was 98%. Primary and secondary endpoints are presented in the Table. Conclusion: The BSP Avmacol was bioavailable as SF metabolites and significantly increased the acute detoxication products of benzene and acrolein in heavy smokers. Dose LevelChange in Metabolite (IQR)a; N=48P-ValueΔ SF MetabolitesbLow Dose19.93 (6.50, 49.00) nmol/mg Cr<0.0001High Dose40.75 (13.61, 91.89) nmol/mg Cr<0.0001Δ Benzene (SPMA)bLow Dose0.59 (-0.79, 4.65) pmol/mg Cr0.03High Dose0.84 (-1.30, 3.39) pmol/mg Cr0.06Δ Acrolein (3-hydroxypropyl mercapturic acid, 3-HPMA)bLow Dose418.05 (-1943.97, 2268.00) pmol/mg Cr0.47High Dose2250.31 (-1675.74, 7723.57) pmol/mg Cr0.01Δ Crotonaldehyde (3-hydroxy-1-methylpropyl mercapturic acid, 3-HMPMA)bLow Dose-837.57 (-3716.93, 4903.17) pmol/mg Cr0.83High Dose981.94 (-1710.04, 4621.08) pmol/mg Cr0.08aChange: End of Treatment – Baseline; IQR: Interquartile RangebSF metabolites, SPMA, 3-HPMA, and 3-HMPMA were normalized to urine creatinine Citation Format: Julie E. Bauman, Chiu-Hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry Chow. Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB221.