Healthy
Conditions
Brief summary
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.
Detailed description
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.
Interventions
Freeze dried watercress containing gluconasturtiin, which when added to provided water with flavor powder, will result in a total target dose of up to 40 mg/day of 2-phenethyl isothiocyanate (PEITC). Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks.
Maltodextrin added to provided water with flavor powder. Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks.
Sponsors
Study design
Eligibility
Inclusion criteria
* Adult Male or female. Participants can be smokers or non-smokers * In good physical health * In stable and good mental health * Not using any medications that may affect the Nrf2 pathway * Women who are not pregnant or nursing or planning to become pregnant * Participants have provided written informed consent to participate in the study
Exclusion criteria
* Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data as determined by the licensed medical professional * Vital signs outside of the allotted range * Not willing to abstain from eating cruciferous vegetables during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Carcinogen Detoxification of Metabolites in Urine. | 2 Months | Carcinogen detoxification metabolites in urine. Biomarkers to be analyzed: 2-cyanoethyl mercapturic acid (CEMA), 3-hydroxypropyl mercapturic acid (HPMA1), 2-hydroxypropyl mercapturic acid (HPMA2), phenyl mercapturic acid (SPMA), 3-hydroxy-1-methylpropyl mercapturic acid (HMPMA1), 3-hydroxy-2-methylpropyl mercapturic acid (HMPMA2), and 3-hydroxy-3-methylpropyl mercapturic acid (HMPMA3), |
Countries
United States
Participant flow
Recruitment details
300 participants randomized to treatment arms. 188 analyzed for study objectives.
Participants by arm
| Arm | Count |
|---|---|
| Freeze Dried Watercress Preparation Then Placebo Participants were randomly assigned to the watercress then placebo arm. During the treatment phase, participants consumed the watercress beverage 3 times per day (around the time of breakfast, lunch and dinner) for 14 days. Participants had a 4-week washout period before switching to the placebo beverage for 14 days. The placebo was consumed in the same pattern 3 times per day around meals as the watercress beverage. | 108 |
| Placebo Then Freeze Dried Watercress Preparation Participants were randomly assigned to the placebo then watercress arm. During the treatment phase, participants consumed the placebo beverage, 3 times per day (around the time of breakfast, lunch and dinner) for 14 days. Participants had a 4-week washout period before switching to the watercress beverage for 14 days. The watercress beverage was consumed in the same pattern 3 times per day around meals as the placebo beverage. | 80 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | self- withdrawal or PI withdrawal | 26 | 26 |
Baseline characteristics
| Characteristic | Freeze Dried Watercress Preparation Then Placebo | Placebo Then Freeze Dried Watercress Preparation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 108 Participants | 80 Participants | 188 Participants |
| Race/Ethnicity, Customized Non-White | 25 participants | 14 participants | 39 participants |
| Race/Ethnicity, Customized White | 83 participants | 66 participants | 149 participants |
| Region of Enrollment United States | 108 participants | 80 participants | 188 participants |
| Sex: Female, Male Female | 69 Participants | 57 Participants | 126 Participants |
| Sex: Female, Male Male | 39 Participants | 23 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 300 | 0 / 300 |
| other Total, other adverse events | 188 / 300 | 50 / 300 |
| serious Total, serious adverse events | 0 / 300 | 0 / 300 |
Outcome results
Carcinogen Detoxification of Metabolites in Urine.
Carcinogen detoxification metabolites in urine. Biomarkers to be analyzed: 2-cyanoethyl mercapturic acid (CEMA), 3-hydroxypropyl mercapturic acid (HPMA1), 2-hydroxypropyl mercapturic acid (HPMA2), phenyl mercapturic acid (SPMA), 3-hydroxy-1-methylpropyl mercapturic acid (HMPMA1), 3-hydroxy-2-methylpropyl mercapturic acid (HMPMA2), and 3-hydroxy-3-methylpropyl mercapturic acid (HMPMA3),
Time frame: 2 Months
Population: Number analyzed differs due to incomplete markers in analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | SPMA | 0.60 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | HMPMA1 | 381.91 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | HMPMA2 | 218.68 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | CEMA | 7.26 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | HMPMA3 | 518.58 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | HPMA2 | 329.25 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | HMPMA | 1189.24 ng/mL |
| Freeze Dried Watercress Preparation | Carcinogen Detoxification of Metabolites in Urine. | HPMA1 | 3052.39 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | HMPMA | 891.42 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | HPMA2 | 316.70 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | SPMA | 0.44 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | CEMA | 6.11 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | HMPMA1 | 307.68 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | HMPMA2 | 180.82 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | HMPMA3 | 388.80 ng/mL |
| Placebo | Carcinogen Detoxification of Metabolites in Urine. | HPMA1 | 1843.29 ng/mL |