Clinical Trial of Two Study Drinks in Detoxification of Environmental Toxicants and Carcinogens

Overview

The goal of this research is to determine if consuming one of two study drinks will help enhance the detoxification of multiple environmental toxicants and cancer causing agents, particularly in subjects who are null for glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), or both. If our research supports this idea, this drink could be an inexpensive dietary component, which could promote good health.

Volatile organic carcinogens and toxicants are ubiquitous environmental and endogenous compounds to which virtually all humans are exposed. All of these compounds are detoxified by metabolic processes that ultimately result in conjugation with glutathione and excretion of mercapturic acids in urine. Glutathione conjugation can be upregulated by isothiocyanates through the Nrf2 pathway and related routes of metabolism. This study will examine if watercress consumption, resulting in exposure to milligram amounts of 2-phenethyl isothiocyanate (PEITC) per day, will enhance the detoxification of benzene, acrolein and other related volatile toxicants and carcinogens. One of the two drinks contains PEITC released from freeze dried watercress while the other drink contains maltodextrin. Benzene causes acute myeloid leukemia/acute non-lymphocytic leukemia in humans, and a positive association has been observed between benzene exposure and acute lymphocytic leukemia, chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin lymphoma. Acrolein is highly toxic and causes nasal tumors in rats. Benzene is classified as "carcinogenic to humans" by the International Agency for Research on Cancer, and acrolein as "probably carcinogenic to humans." Mercapturic acids of the volatile toxicants and carcinogens propylene oxide, crotonaldehyde, methyl vinyl ketone, methacrolein, and acrylonitrile will also be quantified. The study will be a randomized, placebo-controlled, single-blind, phase II clinical trial with a crossover study design. Participants will be assigned to active (freeze dried watercress) or placebo (maltodextrin) study product for 14 days, then undergo a 4-week wash-out period, and will then be crossed over to the other product for another 14 days. During the treatment phase, subjects will consume the watercress beverage or placebo, three times per day. The target dose will be 40 mg/day of PEITC. Subjects may be titrated down if they report being unable to tolerate the full dose. Urine, oral swabs, and saliva will be collected.

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Outcomes