The message from the most thorough examinations to date of the benefits of diets high in fruits and vegetables is that higher consumption of fruits and vegetables decreases the risk of heart disease, but the benefit to cancer risk is less clear.
"But that's not to say there's absolutely no benefit for fruits and vegetables," said Walter Willett, M.D., Dr.P.H., who studies diet and cancer at the Harvard School of Public Health in Boston. He cited recent studies that have found an association between lycopene from tomatoes and reduced prostate cancer risk. "So if you get down to much more detail, there may be some things going on. But if you just stand back and look broadly at [eating five servings of fruits and vegetables each day], it's probably not going to have much benefit."
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Another report, published in January in the Journal of the American Medical Association, examined the risk of breast cancer among 285,526 women in the European Prospective Investigation into Cancer and Nutrition. After a median follow-up of 5.4 years, the authors found no associations between fruit and vegetable intake and risk of breast cancer. Analysis of produce subgroups, such as citrus fruits or green leafy vegetables, also yielded no significant results. The authors, from a variety of European institutions, allow that the relatively short follow-up period leaves the door open for future findings of benefits.
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Early Enthusiasm
In contrast to these recent results, early enthusiasm for fruits and vegetables' propensity to reduce cancer risk ran high. In 1989, the National Research Council's report Diet and Health called for consumers to double daily servings of fruits and vegetables from 2.5 to 5. After reviewing available research, the committee wrote that "green and yellow vegetables and citrus fruits tend to protect against cancer of the lung, stomach, and colon, but the actual mechanisms for this effect have not been documented." In 1991, the National Cancer Institute translated the NRC's recommendations into the National 5 A Day for Better Health program, which enlisted fruit and vegetable producers to push the public health message. NCI spent $40 million on the program during its first 5 years.
The program received a boost in 1996 when the World Cancer Research Fund examined 4,500 published reports and concluded that if everyone ate "at least five servings a day, cancer rates could be reduced by more than 20%." The fund will update its word on diet and cancer next year when it completes a review of some 10,000 published reports.
An internal NCI evaluation completed in 2000 also concluded that fruits and vegetables reduce the risk of cancer. The agency went even further to state that "although evidence also has emerged for a role of vegetables and fruit in reducing the risk of cardiovascular disease, obesity, and diabetes, the most impressive body of evidence exists for protection against cancer."
Despite the new evidence, the program recently upped its recommendation to 9 servings of fruits and vegetables a day for men and 7 for women. Lorelei DiSogra, Ed.D., director of the program at NCI, said that agency staff continually review new evidence as it appears.
Methodology Differences
How to explain the discrepancies between the old studies and the new? Most commentators point to differences in methodology. Whereas the new studies follow volunteers' eating habits over several years, nearly all of the evidence marshaled in favor of 5 A Day relies on weaker retrospective casecontrol studies. Critiques of retrospective studies usually point to the potential for recall bias, in which people with cancer report their diet differently than people without cancer. Another well-studied phenomenon also could be in play, one in which research volunteers tend to skew their answers to reflect what they perceive the "right" answer to be.
But Willett, for one, said that another type of bias is a bigger concernselection bias. He calls it a "built-in problem" with casecontrol studies. Whereas nearly all patients with cancerthe "cases"agree to participate in diet research, finding matched "controls" in the community becomes more difficult. "In the early 1970s, 90% of people you approached in Boston would participate," said Willett. "But now that's fallen to 50% or 60%." Those who do agree to participate tend to be "highly motivated and health conscious." The result: controls who eat a lot of fruits and vegetables and cases who eat an average amount. "It means that even if there is no association, it looks like the cases eat fewer fruits and vegetables than controls," said Willett.
However, Arthur Schatzkin, Ph.D., from the NCI's Nutritional Epidemiology Branch, counters Willett's argument by saying that, in fact, the prospective studies also have flaws. In an editorial in the same issue of JNCI as Willett's study (see Vol. 96, No. 21, p. 1564), Schatzkin points out that small errors in the dozen or so variables analyzed in prospective studies might reinforce each other and mask real benefits. He argues that the food questionnaires used in the large studies should be taken with a few more grains of salt. "Researchers should really look hard at their [questionnaires] and elevate the level of uncertainty assigned to null results," he said. He also suggests exploration of biomarker tests or other "real-time" measurements, such as Internet-based daily diaries, that could help validate food questionnaires.
Although their interpretation of diet and cancer studies differs, both Willett and Schatzkin agree on the bottom line: Studying diet and cancer is complicated. They both point out that all the large studies to date focus on the diets of adults. But what if diet during childhood and adolescence plays a large role in carcinogenesis?
"Causation of cancer is a lifetime process," said Willett. "And it needs to be studied that way." Sensing this trend, Willett's Harvard team began looking a few years ago at diet data from high school and early adult life. In three different datasets, researchers have identified trends that show that vitamin E and vegetable intake may be associated with a decreased risk of breast cancer in later life. "That needs more confirmation, but if it holds up it could be very important," said Willett. "[Early diet] is an area that published studies just haven't addressed."
In contrast to the fruit and vegetable conundrum, epidemiologists are also looking at associations between fat intake and specific micronutrients and various cancers. Folic acid deficiency is widely recognized as a risk factor for several cancers, and vitamin D deficiency is a hot new area. Phytoestrogens from vegetables and isoflavones from soy are being seriously pursued as possible risk reducers.
As for the message of the 5 A Day program, a researcher close to the program who asked not to be identified said, "We've seen [contradictory research] headed our way for quite some time." And in direct contrast to NCI's 2000 evaluation, the program is beginning to emphasize heart disease rather than cancer as the main target of fruit and vegetable consumption.
But despite the waning scientific support for produce as a cancer risk reducer, few have anything negative to say about fruits and vegetables. Willett, one of the 5 A Day program's loudest skeptics, said that the program "has almost certainly done some good." Then he added this caveat: "In the long run, if we want to reduce cancer [risk] we're going to have to look at other things and not put too much hope in fruits and vegetables."
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