A randomized crossover trial found that a concentrated watercress beverage significantly increased urinary byproducts associated with processing six environmental toxicants, including a 65.6% increase for an acrolein metabolite and 37.3% for a benzene metabolite.
By yourNEWS Media Newsroom.
A concentrated watercress beverage increased urinary markers showing the processing and excretion of several common environmental toxicants in a randomized clinical trial, with researchers reporting particularly large changes in metabolites associated with acrolein and benzene.
The peer-reviewed study, conducted by researchers at the University of Minnesota and published in Carcinogenesis, tested whether watercress could enhance a major pathway the human body uses to process and remove potentially harmful chemicals.
Among 188 participants who met the study’s compliance criteria, urinary mercapturic acids associated with six of the seven chemicals researchers monitored increased significantly during the watercress intervention compared with the placebo period. The largest changes were a 65.6% increase in 3-hydroxypropyl mercapturic acid, a metabolite associated with acrolein, and a 37.3% increase in S-phenyl mercapturic acid, which is associated with benzene. Both results had P values below 0.001.
The other significant increases involved metabolites of acrylonitrile, crotonaldehyde, methacrolein and methyl vinyl ketone. The metabolite associated with propylene oxide increased by 4%, but that change was not statistically significant in the full compliant study population.
The findings measure chemical metabolism and urinary excretion rather than disease outcomes. The trial did not determine whether drinking watercress prevents cancer, reduces long-term disease risk or protects people from the health consequences of a specific pollution exposure.
Researchers nevertheless described the results as evidence that watercress can affect a biological pathway involved in processing environmental toxicants and carcinogens.
The study enrolled 240 adults at two Minnesota sites — the University of Minnesota Twin Cities campus in the Minneapolis-St. Paul area and The Hormel Institute in Austin, Minnesota. Of the participants included in the compliant analysis, 125 were women and 152 were nonsmokers.
Investigators used a randomized, single-blind crossover design. Rather than comparing one permanent watercress group against a separate permanent control group, participants received both interventions at different times.
For two weeks, participants consumed a beverage containing freeze-dried watercress three times each day. During another two-week period, they received a matched maltodextrin placebo beverage three times daily. The treatment periods were separated by a four-week washout intended to minimize carryover from the first intervention into the second. Participants were randomly assigned to the order in which they received the two products.
That crossover structure allowed researchers to compare participants largely against themselves. Stable differences such as genetics are therefore less likely to explain differences between the treatment periods, although a crossover trial cannot eliminate every potential change in diet, behavior or environmental exposure occurring over time.
The watercress preparation delivered approximately 40 milligrams per day of 2-phenethyl isothiocyanate, commonly abbreviated PEITC.
Watercress is an unusually rich dietary source of PEITC. The compound is produced from a precursor in the plant called gluconasturtiin when watercress is chewed, chopped or otherwise physically disrupted. Previous research has examined PEITC and other isothiocyanates for their effects on enzymes involved in metabolizing carcinogens and other foreign chemicals.
Investigators measured compounds called mercapturic acids in participants’ urine.
Mercapturic acids are formed after reactive chemicals or their metabolites are conjugated through pathways involving glutathione. Measuring them in urine provides researchers with a way to estimate the amount of certain chemicals that has undergone that metabolic process and been prepared for excretion.
The trial therefore did not simply measure whether participants had been exposed to acrolein or benzene. It measured specific urinary products resulting from the body’s processing of those compounds.
The strongest response involved acrolein.
Median urinary 3-HPMA, the mercapturic acid associated with acrolein, increased from 1,843 picomoles per milligram of creatinine during the placebo period to 3,052 during watercress consumption — a 65.6% increase.
Acrolein can be generated by combustion and high-temperature heating processes. Human exposure can occur through tobacco smoke, vehicle exhaust, wildfire smoke and other combustion sources. The researchers specifically noted the relevance of their findings to atmospheric pyrolysis products generated during wildfires.
Benzene produced the second-largest increase highlighted by the study.
Median levels of S-phenyl mercapturic acid rose from 0.44 to 0.60 picomoles per milligram of creatinine during the watercress period, representing a 37.3% increase.
Benzene is encountered in sources including tobacco smoke, gasoline and combustion emissions and is classified as carcinogenic to humans. The researchers described acrolein as probably carcinogenic to humans and benzene as an established human carcinogen.
Mercapturic acid associated with methyl vinyl ketone increased 32.1%, while the marker for methacrolein rose 31.4%.
The crotonaldehyde marker increased 24.1%, and the acrylonitrile-associated marker increased 18.8%.
All six changes were statistically significant in the compliant population, with P values of 0.002 or lower.
The results were particularly consistent among nonsmokers, who accounted for 152 of the 188 compliant participants. All seven measured biomarkers increased significantly in that subgroup, with changes ranging from 12.4% for the propylene oxide-related metabolite to 70.7% for the acrolein-related marker.
Only 36 participants in the compliant population smoked cigarettes. Among those participants, significant increases were observed in metabolites associated with acrolein, benzene, crotonaldehyde and methyl vinyl ketone.
The acrolein-associated marker increased 38.9% among smokers, while the benzene marker rose 29.6%.
Researchers assessed adherence partly by measuring PEITC-NAC, a urinary metabolite produced following PEITC exposure.
Participants who consumed less than one-quarter of their assigned watercress beverages generally showed smaller increases in the toxicant biomarkers than participants meeting the study’s compliance standard, offering additional evidence that the intervention itself contributed to the observed differences.
The research builds on previous human studies examining PEITC directly.
The University of Minnesota investigators had previously administered about 40 milligrams per day of PEITC and observed increased urinary excretion of metabolites associated with benzene, acrolein and crotonaldehyde. That earlier work helped determine the PEITC dose selected for the watercress trial.
Other studies have established that isothiocyanates from cruciferous vegetables are absorbed and subsequently detectable through their metabolites in blood and urine. Laboratory and animal research extending back decades has also examined isothiocyanates as possible chemopreventive compounds because of their effects on carcinogen metabolism.
In animal experiments, various isothiocyanates have inhibited tumor development under some experimental conditions, including cancers of the lung, esophagus, liver, intestine and other organs. Those findings helped prompt research into whether similar biological mechanisms could have relevance in humans.
Such laboratory findings should not be interpreted as evidence that consuming watercress has been proven to prevent human cancer.
The current trial measured metabolic biomarkers over two-week treatment periods. It was not designed to follow participants long enough to determine whether they later developed cancer or other diseases at different rates.
Researchers said PEITC was likely an important contributor to the observed effect because it is the major isothiocyanate derived from watercress and has previously demonstrated effects on carcinogen metabolism.
The mechanism involves the glutathione S-transferase system, part of the body’s broader chemical-defense machinery. Glutathione can bind to reactive compounds, after which they undergo additional metabolic steps and may ultimately be excreted as mercapturic acids in urine.
Isothiocyanates have been studied for their ability to affect enzymes involved in both activation and detoxification of carcinogens. Experimental research has found that some compounds in the class can alter Phase I and Phase II metabolism, increasing excretion of certain carcinogens while reducing their interaction with DNA under particular conditions.
Researchers did not, however, find a significant correlation between the amount of PEITC-NAC excreted by individual participants and the magnitude of change in each toxicant biomarker. The study therefore supports PEITC as a likely mechanism but does not establish that PEITC alone accounts for every observed effect.
The trial also has practical limitations.
The beverage used a relatively high concentration of freeze-dried watercress specifically to provide approximately 40 milligrams of PEITC per day. Researchers acknowledged that the drink had an unpleasant taste and said the concentration used in the experiment may be impractical for routine consumption.
They recommended additional studies using smaller amounts of freeze-dried watercress and trials involving watercress in its normal food form, in which PEITC is produced during chewing.
That limitation is important when translating the findings into dietary advice.
A secondary health report discussing the research recommended eating raw organic watercress in salads several times a week, adding it to smoothies and pairing it with other cruciferous vegetables such as broccoli sprouts and arugula. It also suggested emphasizing such foods around periods of pollution exposure, including smoky days and long commutes.
Those suggestions go beyond what the clinical trial directly tested.
The researchers studied a standardized, freeze-dried watercress beverage delivering roughly 40 milligrams of PEITC daily. The trial did not determine how much ordinary fresh watercress would be needed to reproduce the same biomarker changes, whether occasional servings produce comparable effects or whether increasing watercress intake during a particular pollution event reduces subsequent health risks.
The investigators themselves specifically called for research using watercress in its natural form.
The study also did not establish that increased urinary mercapturic acids mean that all toxicant exposure has been neutralized.
The biomarkers demonstrate increased processing through the glutathione-related pathway and increased urinary excretion of the measured metabolites. People can still experience biological effects from a chemical before it is metabolized and eliminated, and exposure levels can vary substantially depending on smoking, occupation, air pollution and other circumstances.
Researchers described the findings as particularly relevant to widespread low-level exposure that people cannot completely avoid, including combustion products generated by wildfires.
The study’s significance, they said, lies in demonstrating in a controlled human experiment that a food-derived intervention can measurably alter the way the body processes multiple environmental chemicals.
The trial was registered as NCT03978117. The peer-reviewed paper appeared in volume 47 of Carcinogenesis and was authored by Stephen S. Hecht and colleagues at the University of Minnesota’s Masonic Cancer Center.
Researchers concluded that the freeze-dried watercress beverage significantly increased urinary mercapturic acids for six of the seven environmental toxicants and carcinogens they monitored, with increases ranging from 18.8% to 65.6% among compliant participants.
Further research will be needed to determine whether those short-term changes translate into measurable reductions in disease risk and whether ordinary servings of fresh watercress can produce comparable effects.
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