Dose-dependent detoxication of the airborne pollutant benzene in a randomized trial of broccoli sprout beverage in Qidong, China

Abstract

Background: Airborne pollutants have collectively been classified as a known human carcinogen and, more broadly, affect the health of hundreds of millions of people worldwide. Benzene is a frequent component of air pollution, and strategies to protect individuals against unavoidable exposure to this and other airborne carcinogens could improve the public's health. Earlier clinical trials in Qidong, China, demonstrated efficacy in enhancing the detoxication of benzene using a broccoli sprout beverage.

Objectives: A randomized, placebo-controlled, multidose trial of a broccoli sprout beverage was designed to determine the lowest effective concentration that enhances benzene detoxication adjudged by enhanced excretion of the urinary biomarker, S-phenylmercapturic acid (SPMA).

Methods: Following informed consent, 170 subjects were randomly assigned in 5 blocks of 34 each to drink either a placebo beverage (n = 55) or 1 of 3 graded concentrations of a broccoli sprout beverage [full (n = 25), one-half (n = 35), and one-fifth (n = 55)] for 10 consecutive days. Concentrations of SPMA arising through induced benzene conjugation with glutathione were quantified by MS in sequential 12-h overnight urine collections during the intervention.

Results: MS was also used to quantify urinary sulforaphane metabolites in each dosing regimen that resulted in a median 24-h urinary output of 24.6, 10.3, and 4.3 µmol, respectively, confirming a dose-dependent de-escalation of the inducing principle within the beverage. A statistically significant increase in benzene mercapturic acids in urine was found for the high-dose group (+63.2%) during the 10-d period. The one-half dose (+11.3%) and one-fifth dose groups (-6.4%) were not significantly different from placebo controls.

Conclusions: An intervention with a broccoli sprout beverage enhanced the detoxication of benzene, an important airborne pollutant, when dosed at a concentration evoking a urinary elimination of ∼25 µmol sulforaphane metabolites per day, and it portends a practical and frugal population-based strategy to attenuate associated long-term health risks of air pollution. This trial was registered at clinicaltrials.gov as NCT02656420.

Keywords: air pollution; broccoli; glucoraphanin; mercapturic acids; randomized clinical trial; sulforaphane.

Copyright © American Society for Nutrition 2019.

Figures

FIGURE 1

CONSORT plot of the intervention trial. Of the 170 participants, 169 completed the entire trial. SF metabolites were analyzed in all samples from the 3 broccoli sprout beverage dose groups but not those from participants receiving placebo beverages. The smaller number of SPMA analyses reflects the catastrophic failure of the MS near the completion of the fourth out of 5 randomization blocks. CONSORT, Consolidated Standards of Reporting Trials; SF, sulforaphane; SPMA, S-phenylmercapturic acid.

FIGURE 2

Urinary excretion of sulforaphane and its metabolites (SF-cysteine and SF-mercapturic acid) in micromoles per 24-h collections from participants randomly assigned to receive full, one-half, or one-fifth doses of the broccoli sprout beverage. Individual data points are represented by lines, with median concentrations by day represented by squares. The solid horizontal lines depict the estimated geometric mean from an intercept-only linear mixed model with random intercepts and corresponding 95% CIs displayed as dashed horizontal lines. SF, sulforaphane.

FIGURE 3

AQI in Qidong during the study period of January 2016. The solid line is the 1-h value, and bars are 24-h values. Values are means of measures at 2 monitors near the study site. Colors are those used to define China AQI categories: “good” (green), “moderate” (yellow), “lightly polluted” (orange), “medially polluted” (red), “heavily polluted” (purple). AQI, air quality index; q.d., daily.

FIGURE 4

Individual subject average urinary excretion of SPMA per overnight 12 h (nanomoles per 12 h) in each dose group. Dashes depict geometric means within each dose group, with corresponding 95% CIs displayed as vertical bounds. P values are based on a linear regression model with placebo as the reference. SPMA, S-phenylmercapturic acid.

FIGURE 5

Relation between urinary excretion of SF and its metabolites and urinary SPMA. Percentage difference compared with placebo (one-fifth dose: red; one-half dose: blue; full dose: green) for the excretion of SPMA in overnight urine compared with the average SF concentrations in micromoles in the same 12-h overnight urine. The numbers of samples analyzed for SF metabolites/12 h were 55, 35, and 24 for one-fifth, one-half, and full doses, respectively, and 44, 26, and 20 samples were analyzed for determination of percentage differences in urinary SPMA excretion from placebo. The data point on the right (black) represents the findings from the prior study (full dose) for comparison (6). In that study, 137 participants received the full dose. SF, sulforaphane; SPMA, S-phenylmercapturic acid.

FIGURE 6

Relation between urinary excretion of SF and its metabolites and urinary SPMA. Individual subjects’ average SPMA compared with their average SF metabolites during 24 h with a Lowess regression. The numbers of samples analyzed for SF metabolites/12 h were 55, 35, and 24 for one-fifth, one-half, and full doses, respectively, and 44, 26, and 20 samples were analyzed for determination of percentage differences in urinary SPMA excretion from placebo. SF, sulforaphane; SPMA, S-phenylmercapturic acid.