We’ve all seen the T.V. Mom, apron cinched around her waist, holding a bowl of steaming greens and admonishing you to “Eat your vegetables— they’re good for you.”
Turns out Mom knows her science. Some foods, like vegetables, are good for you; others are not. According to David Williams, more than one-third of cancers are directly related to what we eat. That’s as strong as the connection between cancer and tobacco.
Williams is a biochemist with Oregon’s Agricultural Experiment Station and professor of environmental and molecular toxicology at Oregon State University. He’s also a principal investigator at the Linus Pauling Institute, an OSU-based research institute devoted to finding out all the ways in which food promotes health and prevents disease.
The institute recommends eating at least five servings of fruits and vegetables daily (sorry, potatoes don’t count), eating fish rich in omega-3 fatty acids and avoiding sugar, hydrogenated fats and refined grains.
Williams and his colleagues George Bailey and Rod Dashwood are associated with the institute’s Cancer Chemoprotection Program. The program’s mission is to identify the active agents, called phytochemicals (phyto means “plant”) inside these cancer-fighting plants and develop them into forms, such as dietary supplements, that people can use to help prevent cancer.
In 2000, there were about 1.25 million cancer diagnoses in the United States. “Cancer represents a health-care cost of billions of dollars, and the cost in human suffering is immeasurable,” says Williams. “If dietary chemoprevention can reduce the incidence of cancer by even a few percentage points it will enormously reduce this financial and human toll.”
Williams, Bailey and Dashwood are looking at phytochemicals in three common plants: broccoli, spinach and tea. Their work is part of a $6.5 million, five-year research project funded by the National Cancer Institute.
Williams is studying how a substance derived from broccoli and Brussels sprouts is transmitted from a mother to her unborn offspring, lending them protection against lymphomas and perhaps lung cancer. Dashwood, a professor of environmental and molecular toxicology, is looking at how green tea prevents colon cancer caused (at least partly) by carcinogens in charred meat. And Bailey, an OSU distinguished professor in the same department, recently completed a study of the cancer-preventing capabilities of a form of chlorophyll.
Chlorophyll is, of course, the green stuff that enables a plant to make its food from sunlight, and it’s abundant in spinach. Bailey found the derivative chlorophyllin to be very effective in lowering the risk factor for liver cancer caused by aflatoxin, a toxin that develops in moldy grain and peanuts. Bailey conducted the study in the Qidong province of China, where poor techniques for storing corn and a chronically high rate of hepatitis B combine to cause fatal liver cancer in about 10 percent of the people.
It’s well known that certain fruits and vegetables are blessed with cancer-fighting agents. Alliums (onions and garlic), crucifers (broccoli, cabbage and Brussels sprouts) and green leafy vegetables protect against a host of cancers, including those of the of the esophagus, colon, lung, prostate, breast, liver and skin. Cancer-fighting agents are also packed in citrus fruits, berries, grapes, vegetable oils, nuts and tea.
In fact, a lucrative industry has grown up around extracts of fruits and vegetables, leading to a blizzard of “nutraceuticals”—over-the-counter supplements touting all kinds of health-giving benefits. Even ketchup bottles announce that the lycopene in tomatoes is a cancer-preventing agent—and so, the label implies, you should eat as much ketchup as possible.
All hype aside, there’s no doubt that you should eat your spinach. But why? What are these powerful substances, and how do they work in the body?
“Three different types of cancer chemoprotective compounds have been identified,” says Williams. “The first type inhibits the formation of a cancer-causing agent; the second blocks the development of the cancer; and the third suppresses the cancer once it starts.” And some phytochemicals protect against cancer in more than one way.
A cancer consists of cells that are growing abnormally. The reason is that the DNA in them, which contains the body’s genetic information, has been damaged by a carcinogen, a cancer-causing agent, and can no longer regulate the cells’ normal growth.
When you take a bite of preserved meat—say, Polish sausage—the nitrite used to preserve the meat combines with digestive agents in your saliva to form a carcinogen called a nitrosamine. Vitamin C, an inhibiting agent slows the formation of these nitrosamines. Some studies (but not all) imply a cancer-protective role for vitamin C.
A blocking agent blocks the development of a substance that could damage DNA and cause cancer from becoming an effective carcinogen. Some blocking agents, such as vitamins C and E, are antioxidants.They tie up free radicals, which are formed in the body during normal metabolism and also when it is exposed to cigarette smoke or other pollutants. A free radical is a molecule with an unpaired electron and it’s very reactive. The unpaired electron wants to find a partner, so it extracts electrons from “nucleophiles” in proteins and DNA. This causes a reaction called oxidation. If the cells’ antioxidant defenses are exhausted, oxidation eventually breaks down the cell and the tissue. Vitamin E and other blocking agents intercept these free radicals and keep them from attacking protein and DNA in cells.
Suppressing agents, including some substances found in green tea, slow the growth of precancerous and cancerous cells. Dashwood is interested in the interaction between phytochemicals in tea and mutagens in cooked meat.
In the 1970s scientists discovered that cooking meat at high temperatures creates mutagens, substances that can change a person’s DNA to allow the growth of cancer cells. Uncooked meat, Dashwood explains, has amino acids—organic (carbon-containing) molecules that serve as the building blocks of proteins. Cooking the meat induces a chemical change, fusing amino acids together and producing mutagens called heterocyclic amines.
The most abundant of these heterocyclic amines is PhIP, one that Dashwood has been testing for the past several years. “If we feed animals PhIP and they also drink tea, can we prevent cancer? The answer is yes, and at concentrations similar to those consumed by people.”
Dashwood is working with mice known to be susceptible to pre-cancerous polyp formation in the gastrointestinal tract. He found that mice that drank tea, which contains powerful antioxidants, developed significantly fewer polyps.
The most effective tea in this experiment, Dashwood found, was white tea—the leaves of the Camellia sinensis plant before they’re processed. Next most effective was green tea, which is lightly processed.
Now Dashwood wants to know if white tea offers the same protection in humans. In his human study, volunteers will ingest a tiny amount of PhIP, the equivalent of what you’d get in one hamburger, once a month for six months. They’ll drink water after the first dose and white tea after the second and take caffeine after the third. In the fourth month they will take an extract of one of the antioxidant compounds found in tea.
Dashwood will test their urine and blood for a week after each dose. He wants to see how fast the PhIP will be metabolized and excreted. His hypothesis is that the tea will act as a blocking agent, ridding the body of PhIP the fastest.
In the fifth month, the volunteers will take chlorophyllin. The following month they’ll take chlorophyll—the green substance in plant leaves from which chlorophyllin is derived. “We want to test both forms, and this will tie our study in with the work of Dr. Bailey,” says Dashwood.
For several years Bailey has studied how chlorophyllin combats aflatoxin in rainbow trout. He and his OSU team found that chlorophyllin binds itself to the aflatoxin in the same way a smear of peanut butter sticks to a piece of bread—creating an open-faced “sandwich” that stabilizes the aflatoxin, enabling the trout to excrete it without digesting or absorbing it. Dashwood and Bailey want to know, among other things, whether chlorophyllin will work in the same way against PhIP.
For his part, Williams is working on the potential of phytochemicals to protect the most vulnerable of living things, the developing fetus. The U.S. Environmental Protection Agency lists more than 70,000 synthetic chemicals to which we’re exposed. Some of these chemicals, including polychlorinated biphenyls (PCBs) and dioxin, are present in the fat tissue of pregnant women and the milk of nursing mothers, and thus are potentially harmful to fetuses and infants.
“We’ve long recognized how important prenatal nutrition is in promoting healthy babies,” he says. “Might we be able to protect fetuses and infants against cancer by supplementing the mothers’ diets with phytochemicals?”
In one of his studies, Williams exposed pregnant mice to a cancer-causing substance called DBP, which comes from the burning of organic material. Common sources are auto and diesel exhaust, tobacco smoke and charcoal-broiled meat. The offspring of DBP-exposed mother mice have high rates of lymphoma beginning at about two or three months of age.“Lymphomas are one of the most common cancers in children,” Williams says, “and prenatal exposure to chemical carcinogens may be a factor.”
One group of mice was also fed various levels of indole-3-carbinol, a phytochemical found abundantly in cruciferous vegetables such as broccoli and Brussels sprouts (“all the things I don’t like to eat,” Williams says with a smile). Williams found that of the mice born to mothers who’d received the DBP but no phytochemical, more than half were dead after 40 weeks. In contrast, of the mice born to mothers that got both the DBP and the phytochemical, about one quarter of them died from lymphoma after 40 weeks. The indole-3-carbinol cut the death rate in half.
To examine indole-3-carbinol’s action more closely, Rosita Proteau, a collaborator with Williams from OSU’s College of Pharmacy, is using a device in which semipermeable membranes mimic the action of the human gut. This technique, used by drug companies to predict absorption of new drugs, enables researchers to measure rates of absorption of different phytochemicals and their components. It’s the same model that helped Bailey and his colleagues figure out the “sandwich” action of chlorophyllin and aflatoxin.
The membrane model will help determine which of the components of the indole-3-carbinol is actually doing the job. “Indole-3-carbinol is unstable in acid, including the acid in the gut,” says Williams, “so it breaks down into different components that are absorbed at different rates.” The membrane model will help him examine the absorption rate of each component and determine which of them is actually doing the job.
This is important because indole-3-carbinol may be a double-edged sword. Taken by healthy people, it might block cancer from developing. However, some animal studies show that when it’s taken long-term after exposure to a carcinogen it seems to make the tumors grow faster. It’s important to separate the components to understand which ones inhibit cancer and which ones promote it.
Because human biochemistry is complicated, the scientists are careful not to imply that phytochemicals are a magic bullet. “The active components are not the same as the whole food,” says Williams. “Whole foods contain many other components that work together and generally promote health.”
Take tea, for example. “Brewed tea as a beverage has nine major chemicals, and the antioxidant EGCG is one of them,” Dashwood explains. “If you take these nine chemicals and make a mix of them, an ‘artificial tea’ so to speak, it will appear chemically similar to real tea, but it will have only half the efficacy of real tea. In other words, the chemicals of interest to many scientists are the major constituents, but they don’t always tell the whole story. There are other trace compounds in tea that appear to synergize with the major ones to create the maximum protective effect.”
Nevertheless, says Williams, it’s part of the scientists’ job to look for ways to use phytochemicals to promote human health. “It’s easy to tell somebody to eat five servings a day of fruits and vegetables,” he says. “But there are places in the world where people can’t afford that, and there are people in this country with greater nutritional needs, such as the poor, the elderly, and pregnant women. Supplements may be a reasonable alternative for them.”
As for the rest of us, we’d do well to listen to Mom, and follow Popeye’s advice: Strong to the finish, ’cause we eat our spinach.
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