September 20,
1997
People who eat lots of produce -- especially vegetables -- lower their risk of developing many common cancers, such as malignancies of the breast, lung, stomach, and prostate. Based on this common observation, the National Cancer Institute and numerous other public and private health organizations now advocate that people eat at least five servings of fruits and vegetables daily.
We the people haven’t been too receptive to that message, however. According to new survey data compiled by the U.S. Department of Agriculture, 60 percent of the population fails to meet its recommended intake of vegetables -- three to five servings per day (based on an individual’s size and calorie intake) -- and 75 percent of us don’t eat the recommended 2 to 4 servings of fruits daily. Indeed, 48 percent of us fail to down even one serving of fruit daily, an amount equal to one medium apple or 3/4 cup of fruit juice.
Moreover, even among those fulfilling the quantitative recommendations for these food groups, what’s selected seldom comes from those foods that studies have suggested are especially protective. For instance, dark green vegetables are among those that have been associated most strongly with cancer protection. Yet a typical U.S. resident eats no more than one serving a week of such vegetables through age 30 and then 1.2 servings per week after that.
Broccoli appears especially beneficial -- owing to its relatively high concentrations of sulforaphane, a compound that turns on detoxifying enzymes in the body (SN: 3/21/92, p. 183). Indeed, over the past few years researchers at the Johns Hopkins Medical Institutions in Baltimore have demonstrated that in animals exposed to chemical carcinogens, diets rich in sulforaphane dramatically cut cancer development.
Ironically, broccoli remains one of the least popular vegetables. No doubt contributing to its lackluster appeal is the fact that perhaps one-quarter of the population contains "supertaster" genes that allow the tongue to detect some bitterness in this and other beneficial brassica vegetables (The Bitter Truth).
But a new report out of Hopkins’ Brassica Chemoprevention Laboratory, this week, points out there are other options available today for enriching the diet with sulforaphane -- and more choices coming down the pike.
In the Sept. 16 Proceedings of the National Academy of Sciences (PNAS), Paul Talalay and his team at Hopkins report finding that newly sprouted seeds of broccoli and related members of the mustard (Brassica) family contain a chemical -- glucoraphanin -- that is converted into sulforaphane when the plant’s cell walls are broken, as during chewing. What happens is that a normally sequestered enzyme, known as myrosinase (pronounced my-ros-i-nace), gets released and triggers the glucoraphanin's transformation into sulforaphane.
Knowing this, Talalay says, "I cannot eat any of these [brassicas] now without chewing and waiting for the bite that occurs -- a sudden sharp taste." The same reaction causes the delayed kick to a peppery radish as it’s eaten. Owing to this myrosinase reaction, Talalay says, brassica sprouts "are much more interesting than alfalfa sprouts, which I think taste like straw." And the good news for people who don’t like or can’t tolerate broccoli, he says, is that broccoli sprouts don’t taste like broccoli.
In their new study, Talalay, Jed W. Fahey and Yuesheng Zhang grew different brassicas from seeds to determine when the sulforaphane precursor developed. And they found it present in the seed in startling concentrations. As the seed sprouted, it didn’t make any more, but it also didn’t lose any. So 3-day-old seedlings still represented a particularly enriched source of the glucoraphanin.
While young broccoli sprouts exhibited high concentrations of the sulforaphane precursor, so did those of related plants -- including arugula, bok choy, Brussels sprouts, cabbage, cauliflower, Chinese cabbage, collards, water cress, daikon, kale, kohlrabi, mustard, and conventional turnips. Sprouted seeds of each of these plants contain 10 to 100 times as much of the cancer-inhibiting compound as do mature, field grown plants.
Among these, broccoli and cauliflower cultivars invariably proved the top performers. To measure a cultivar’s potential anticancer activity, they extracted materials from its sprouts and ran them through an assay that measured their ability to activate certain detoxifying enzymes known as phase-2 enzymes.
They quantified the effect of these compounds in terms of their ability to increase the activity in a test tube of a common phase-2 enzyme (quinone reductase). One unit of activity corresponded to a doubling in this enzyme’s activity. Seed dealers offer some 80 different cultivated varieties of broccoli alone, and Talalay’s team found that there was wide variability in what a given cultivar could deliver. In their new study, each gram of 3-day-old broccoli sprouts exhibited 92,500 to 769,000 units of activity. Cauliflower sprouts ranged from 50,000 to 560,000 units per gram.
Unfortunately, he notes, vegetable sellers don’t identify their broccoli by cultivar, nor will a consumer be able to tell one from another -- or their likely glucoraphinin richness -- by eye.
Mature broccoli not only contains glucoraphinin but also a host of related compounds not seen in the sprouts. Mostly indole glucosinolates, these additional chemicals have evolved to detoxify foreign compounds in our diet, usually through the activation of both phase-2 enzymes and a class of enzyme systems called phase-1.
The phase-1 systems tend to take a fairly nonreactive compound, such as the polycyclic aromatic hydrocarbons formed during combustion, and subtly alter them to make them slightly more water soluble. It’s a step that makes it easier for the body to excrete them.
Agents that activate phase-1 enzymes, however, "occasionally react with negatively charged bases in our DNA, causing damage and setting in motion mutations and carcinogenesis," Talalay says. "So while most chemicals that enter the body are in themselves innocuous, some can be converted by phase-1 enzymes into highly reactive carcinogens."
Phase-2 enzymes can trigger antioxidant reactions and other chemical changes that can often defuse toxic transformations initially wrought by the phase-1 enzymes. This has led some cancer biologists to speculate that whether a potential carcinogen damages DNA will depend on the balance between active phase-1 and phase-2 enzymes, Talalay explains. It’s also led his lab to seek out dietary constituents -- like sulforaphane and its precursor -- that selectively activate phase-2 enzymes only. And that’s another advantage the sprouts have over the mature plant, he says: They trigger the preferential phase-2 enzyme activity almost exclusively.
"I see his point" -- why focusing on phase-2 enzyme inducers appears so rational, says cancer researcher John M. Pezzuto of the University of Illinois at Chicago. "On the other hand, I don’t see that anyone is saying that normal, mature broccoli is dangerous." Indeed, he says, "I personally find it difficult to believe that the phase-1 enzyme inducers in our diet are hazardous." However, he says that until there is a better understanding of the overall balance of these enzymes and their effect on human health, "perhaps it is prudent to stick with [advocating a boosting of intake] of just these phase-2 enzyme inducers."
Marion Nestle is less convinced. Head of nutrition and food studies at New York (City) University, she jokes that "no rational person can understand this arcane world of phase-1 and phase-2 enzymes" -- at least how they play out in terms of effects in the body. In a commentary slated for publication in an upcoming issue of the PNAS, she cites work by Bruce Ames indicating that even phase-2 enzyme systems can sometimes transform a chemical from nontoxic to toxic.
Though she acknowledges that, in general, phase-2 enzymes are less likely than phase-1 enzymes to do this, she says that it’s still too early to understand what the significance of modifying dietary sulforaphane intake will be. Then again, she adds, it’s hard to imagine anyone overdosing on sprouts. "So if you want to eat broccoli sprouts, go ahead," she says.
If you want to eat them, you first must find them. While some shops do market sprouts of cabbage, radish, and mustard, Talalay notes that broccoli sprouts are rare.
Though he expects that to change soon, based on his lab’s new data, he is concerned that growers will rush to promote any sprout without concern for whether it actually contains large amounts of glucoraphinin. Conditions under which a broccoli is sprouted and grown can affect its phase-2-enzyme activity, at least as much as cultivar type, he says.
So how can a consumer know if the local grocer is a purveyor of the enriched ones? He hopes to take some of the guesswork out of the selection process by establishing a Brassica Foundation, with an independent nonprofit testing laboratory, to certify the purity of sprouts, their sulforaphane potential, and the production methods used to grow them. Sprout marketers who won its certification would then be able to label their product -- much as appliance manufacturers today advertise the safety validation of their designs and products through an Underwriters Laboratory approval seal on their labeling.
Growers will have to pay for the testing and certification of their products and operations. Any profits from the enterprise -- which Talalay hopes will get underway early next year -- will be pumped back into research on the dietary chemoprevention of cancer.
Isolating the active ingredients in healthy foods also opens the prospect of one day adding it to foods or encapsulating it as a vitaminlike dietary supplement. Indeed, Pezzuto and his colleagues have already created one synthetic analog of sulforaphane that may be used in this way. Ironically, what prompted its development was cost.
Explains Pezzuto, he was hoping to follow up on Talalay’s earlier studies. But when he shopped around for a commercial source of sulforaphane, the price estimates he got back were astronomical: $60,000 for the quantities needed for his planned research. So his lab’s medicinal chemists studied the compound’s structure and designed what they hoped would prove a functionally equivalent compound.
Not only does it work, they reported in Cancer Research earlier this year, but "we can produce the amount we needed for just a few hundred dollars," Pezzuto told Science News Online.
The new substance, which they call sulforamate, appears to have about the same potency as the original broccoli-derived compound in activating phase-2 enzymes. Like the natural compound, sulforamate also proved a potent inhibitor of precancerous changes -- at least in mouse mammary glands exposed to chemical carcinogens while growing in the laboratory.
However, "in certain ways, the synthetic looks superior [to the original]," Pezzuto says. For instance, his test-tube studies suggest that sulforaphane can prove toxic to cells if administered in concentrations 42 times higher than those needed to inhibit cancer development. The analog, by contrast, appears to remain nontoxic at concentrations more than three times that high. "On the basis of these results, the sulforaphane analog can be regarded as a readily available promising new cancer chemopreventive agent," he and his colleagues say.
Perhaps, but Nestle would still prefer people to eat the whole vegetable, not just some pharmacologically active extract or analog. Remember, she says, in addition to the active agent, the whole food also contains fiber, other antioxidants, and a host of vitamins and minerals.
Indeed, diets rich in a range of fruits and vegetables may well deliver therapeutic doses of these pharmacologic ingredients, because as Pezzuto is finding, brassicas aren't the only foods rich in constituents that turn on phase-2 enzymes. In an article soon to be published in the Journal of Agricultural and Food Chemistry, Pezzuto and his coworkers report finding an extract of tomatillos -- the "husk tomatoes" used in making salsa verde and many other southwestern dishes -- that can do the trick. The agents responsible belong to a family of chemicals known as withanolides.
In test-tube studies, two of these compounds proved roughly equivalent to sulforaphane. A third (known as withaphysacarpin) "would be judged superior," the scientists report. Moreover, like sulforaphane the tomatilla agents seem heat-stable. Pezzuto says, "We were able to do things like boil the [tomatilla] extract and put it in salsa and still see the [phase-2] enzyme activity."
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Each dish contains the same amount of anticancer compound. |
Related Reading
Cleveland, L.E., et al. 1997. Pyramid servings data: Results from USDA’s 1994 Continuing Survey of Food Intakes by Individuals. A report by USDA’s Food Surveys Research Group (March), available at http://www.barc.usda.gov/bhnrc/foodsurvey/home.htm
Fackelmann, K. 1997. The bitter truth: Do some people inherit a distaste for broccoli? Science News 152(July 12):24.
Fahey, J.W., Y. Zhang, and P. Talalay. 1997. Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proceedings of the National Academy of Sciences 94(Sept. 16):10367.
Gerhäuser, C., . . . and J.M. Pezzuto. 1997. Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes. Cancer Research 57(Jan. 15):272.
Kennelly, E.J., . . . J.M. Pezzuto, and A.D. Kinghorn. 1997. Induction of quinone reductase by withanolides isolated from Physalis philadelphica (tomatillos). Journal of Agricultural and Food Chemistry (in press).
Raloff, J. 1997. Anticancer agent sprouts up unexpectedly. Science News 152(Sept. 20):183.
______. 1997. Resolve to eat healthier. Science News Online (Jan. 4).
______. 1996. Veggies -- defense against breast cancer. Science News Online (July 20).
______. 1994. Broccoli inhibits cancer -- mostly. Science News 146(Dec. 24 & 31):442.
______. 1990. Another reason to eat your broccoli raw. Science News 137(June 9):367.
______. 1989. To stymie cancer, eat broccoli raw. Science News 136(Nov. 25):351.
Stroh, M. 1992. Inside Broccoli: A weapon against cancer. Science News 141(March 21):183.
Yuesheng, Z. P. Talalay, et al. 1992. A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proceedings of the National Academy of Sciences 89:2399.
Yuesheng, Z. ... P. Talalay. 1995. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proceedings of the National Academy of Sciences 91:3147.
Sources
Linda E. Cleveland
Food Surveys Research Group
Beltsville Human Nutrition Research Center
Agricultural Research Service
US Department of Agriculture
4700 River Road., Unit 83
Riverdale, MD 20737
Marion Nestle
Department of Nutrition and Food Studies
New York University
35 W. 4th Street, 10th Floor
New York, NY 10012-1172
John M. Pezzuto
Department of Medicinal Chemistry and Pharmacognosy
College of Pharmacy
University of Illinois at Chicago
833 S. Wood Street
Chicago, IL 60612
Paul Talalay
Department of Pharmacology and Molecular Sciences
Johns Hopkins School of Medicine
725 North Wolfe Street
Wood Basic Science
Room 406
Baltimore, MD 21205
This week's Food for Thought is prepared by Janet Raloff, senior editor of Science News.
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