New Evidence for the Protective Effects of Fruits and Veggies

07/12/07 The age-old refrain, "Eat your vegetables!" gets scientific support as researchers present the latest findings on cancer prevention at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention, being held December 5 - 8 in Philadelphia, Pennsylvania.

Today, researchers present new data that demonstrate how diets full of raw vegetables -- particularly broccoli sprouts -- and black raspberries could prevent or slow the growth of some common forms of cancer.

Black raspberries may protect against esophageal cancer by reducing oxidative stress in patients with Barrett's esophagus (BE), a pre-cancerous condition that usually arises due to gastroesophageal reflux disease, report researchers at The Ohio State University.

According to the researchers, BE patients have a 30- to 40-fold increased risk of developing esophageal adenocarcinoma (EAC), the fastest growing cancer in terms of incidence in the United States. EAC is a deadly cancer with a 15 percent five-year survival rate; an estimated 14,000 people will die from esophageal cancer in the U.S. in 2007. Moreover, a number of treatment options are available to BE patients for symptom relief, researchers say, but none has proven curative or eliminated the risk of cancer progression.

"In addition to gastroesophageal reflux disease, increasing body mass index or body fatness is strongly associated with EAC development; whereas, plant-based diets and particularly increased fruit consumption has been associated with decreased risk for EAC," said Laura A. Kresty, Ph.D., assistant professor of at Ohio State University.

According to Kresty, research using animal models of BE showed that black raspberries inhibited chemically induced oral, esophageal and colon cancers. The studies showed that berries reduced measures of oxidative stress (the destruction done to cells by oxygen ions or small reactive molecules containing oxygen), decreased DNA damage, inhibited cellular proliferation rates, and reduced the number of pre-cancerous cells in the esophagus and colon.

"We can give black raspberries before we have any initiated cells, or we can administer after we already know we have initiated cells," Kresty said. "What's promising about the berries is that they work in both cases, and in multiple models. There aren't nearly as many agents that work in the latter scenario."

In this study, BE patients ate 32 or 45 grams (female and male, respectively) of freeze-dried black raspberries daily for 26 weeks. After 26 weeks, patients experienced a statistically significantly decline in the mean urinary levels of 8-Isoprostane, an indicator of global oxidative stress and DNA damage -- both processes linked to the development of BE and EAC. According to Kresty, 58 percent of patients experienced marked individual level declines of 8-Isoprostane. Among 37 percent of BE patients, the black raspberry regimen also resulted in the increased expression of tissue levels of GSTpi. GSTpi is an enzyme that detoxifies carcinogens and reactive oxidants and is typically reduced in Barrett's epithelium compared to normal esophageal epithelium.

"Black raspberries have a good profile in terms of tolerability -- many of the potential toxic side effects associated with a new drug are less of an issue because we are simply administering a food in a non-traditional manner," Kresty said. "Patients seem amenable to such an approach, they understand it and enjoy being able take positive action for potential health gains."

Your mom was right when she told you to eat your broccoli, or at least your broccoli sprouts. Researchers have found that this rich source of isothiocyanates (ITCs) -- a well-known class of cancer prevention agents -- could play a direct role in preventing bladder cancer.

"The bladder is like a storage bag, and cancers in the bladder occur almost entirely along the inner surface, the epithelium, that faces the urine, presumably because this tissue is assaulted all the time by noxious materials in the urine," said senior author Yuesheng Zhang, M.D., Ph.D, professor of oncology at Roswell Park Cancer Institute. "The ITCs in broccoli sprout extracts after oral ingestion are selectively delivered to the bladder epithelium through urine excretion."

Using a rat model of bladder cancer, Zhang and his colleagues found that freeze-dried aqueous extract of broccoli sprouts significantly, and dose-dependently, inhibited bladder cancer development. The incidence, multiplicity, size and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no observable changes in the bladder. This protective effect of the extracts was associated with a significant increase in the bladder of several enzymes that are known to protect against oxidants and carcinogens, Zhang says.

In the body, ITCs are metabolized to dithiocarbamates (DTCs). The researchers measured the levels of ITCs and DTCs in the blood, tissue and urine of the rats fed with the extracts. More than 70 percent of the ITCs present in the extracts were excreted into the urine as ITC equivalents (ITCs + DTCs) in 12 hours after a single oral dose, indicating high bioavailability and rapid urinary excretion.

What is more striking, Zhang says, is that the concentrations of ITC equivalents in the urine of extracts-treated rats were two to three orders of magnitude higher than those in plasma, indicating that the bladder epithelium is most exposed to orally dosed ITCs. Indeed, tissue levels of ITC equivalents in the bladder were significantly higher than in the liver, demonstrating that the ITCs in the extracts are efficiently and selectively delivered to the bladder epithelium through urinary excretion, Zhang concludes.

While researchers have long known that cruciferous vegetables are chock full of isothiocyanates (ITCs), which are a well-known class of cancer prevention agents especially promising in bladder cancer chemoprevention, they didn't know how much one needed to eat to reap the protective benefits.

Researchers from Roswell Park Cancer Institute report that three or more servings a month of raw cruciferous vegetables like broccoli, cabbage and cauliflower, may reduce bladder cancer risk by approximately 40 percent, overall.

The Roswell Park team surveyed the dietary habits of 275 individuals with incident, primary bladder cancer and 825 individuals without cancer. The researchers surveyed patients about their pre-diagnostic intake of raw and cooked cruciferous vegetables, their smoking habits and other cancer risk factors. They observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable consumption. When compared to smokers who ate less than three servings of raw vegetables, non-smokers who ate at least three servings a month were almost 73 percent less likely to develop bladder cancer, the researchers say.

A key factor in the research was that it's a survey of raw cruciferous vegetables. Previous research had surveyed intake of any cruciferous vegetables -- cooked or not -- and results proved inconsistent. Cooking significantly reduces the availability of ITCs for absorption into the body, according to researchers.

"Cooking can reduce 60 to 90 percent of ITCs," says Li Tang, M.D., Ph.D. of Roswell Park Cancer Institute and lead researcher on this study. "Heating destroys the enzyme that converts the precursor glucosinolates into ITCs, and also destroys ITCs already formed, which is why you need to eat raw cruciferous vegetables to receive the food's maximum benefit."