5 A Day for Better Health Program Evaluation Report: Evidence

The recommendation to consume at least 5 servings of vegetables and fruit per day is supported by a diverse and convincing body of evidence. The most fundamental case can be made on the basis of well-established principles of nutritional adequacy. Vegetables and fruit are important sources of several essential nutrients, including vitamin C, folate and other B vitamins, pro-vitamin A and other carotenoids, potassium, calcium, and iron. Vegetables and fruit also provide dietary fiber.

The recommendation to consume vegetables and fruit for protection from chronic diseases draws primarily upon epidemiologic evidence linking higher consumption of vegetables and fruit to lower rates of cancer, cardiovascular diseases, and other chronic diseases. A large majority of relevant expert reviews have concluded that higher consumption of vegetables and fruit will reduce chronic disease risks, and no reviews have found evidence of adverse effects.^1-5 Highlights of the evidence follow.

Cancer

The largest body of evidence relating vegetable and fruit consumption to health has examined effects on cancer risk. The most extensive review to date has been published by an international interdisciplinary panel convened by the World Cancer Research Fund (WCRF). This review concluded that, "Overall, when cancers of all anatomical sites are taken together, 78 percent have shown a significant decrease in risk for higher intake of at least one vegetable and/or fruit category examined."³ The review identified 217 observational epidemiologic studies (196 case-control studies and 21 prospective cohort studies) that evaluated at least one association of fruit or vegetable intake with incidence of any type of cancer. For a variety of variables describing vegetable consumption, 69 to 80 percent of studies found an inverse association with cancer risk. For fruit in general and citrus fruit in particular, 64 and 66 percent of studies, respectively, found an inverse association with cancer risk. In keeping with established criteria for the evaluation of epidemiologic research, evidence was considered conclusive (termed "convincing" in the WCRF report) if there were an adequate number (at least 20) of relevant studies, including some with prospective designs.^a The WCRF panel also required that studies be conducted in diverse populations, with control for important potential confounding factors. For example, because higher vegetable and fruit consumption is often correlated with lower fat intake and is more often observed in nonsmokers, the possible effects of fat intake and of smoking on cancer risk had to be considered in the design and analysis of studies of the effect of vegetable and fruit intakes on cancer risk. The overall body of evidence demonstrated conclusively that vegetables and fruit protect against cancer. The evidence was most conclusive for vegetables and fruit and cancers of the mouth and pharynx, esophagus, lung, and stomach and for vegetables alone and cancers of the colon and rectum. The association of vegetables and fruit with cancer incidence was judged to be strong, particularly for vegetables, with about a halving of risk overall found to be associated with consuming at least 5 servings of vegetables and fruit per day as compared to only 1 or 2 servings.

The specific evidence of a dose-response, in which increasing intakes confer increasing protection in a graded manner, adds to the strength of the case for vegetable and fruit intakes. Such a dose-response was shown convincingly in several examples in the WCRF report.³ For example, for lung cancer, there was a halving of the relative risk as intakes increased from 150 to 400 grams (g) per day (i.e., from about 2 to about 5 servings per day, assuming 80 g per serving). Similar dose-response relations were noted for stomach cancer and both vegetables and fruit.³ Because the upper limit of the dose-response range that can be evaluated is limited by the ranges of intakes in populations studied,³ few data exist to support specific, quantitative recommendations for intakes of vegetables or fruit above 350 or 400 g per day.

The hypothesis that increasing vegetable and fruit intakes reduces cancer risk was not confirmed in one randomized trial. The U.S. Polyp Prevention Trial (PPT) tested the ability of dietary changes that included increasing vegetable and fruit intake (3.5 servings per 1,000 kcal) to prevent the recurrence of colorectal adenomas over 4 years of follow up. However, it was not designed to isolate the effect of changes in vegetable and fruit intake from the other changes targeted (e.g., increased whole grain intake and lower fat intake).⁶ In any case, the trial found that there was no difference in the recurrence of adenomas between the intervention and control groups. Thus, in the particular cancer-risk situation tested in the PPT, neither the increase in vegetable and fruit intake (about 2 servings per day), nor any of the other dietary changes, had a protective effect. This finding does not, however, rule out protection by vegetables and fruit against other types of cancers or in populations with different colon cancer risk profiles. It also is not clear whether a longer observation period or dietary changes earlier in life might yield significant risk reduction.

The lack of human experimental data leaves open the question of whether vegetables and fruit might only be a marker for some other aspect of dietary or lifestyle behavior with which they are closely correlated. However, the consistency of the association of vegetable and fruit intakes with cancer risk in populations with diverse lifestyles supports the conclusion that vegetables and fruit per se are responsible for the effect.

An important conclusion of the WCRF review was that the evidence supported a broad recommendation for increasing vegetable and fruit consumption for reducing cancer risk, rather than recommendations for specific types of vegetables and fruit. The numerous imperfections in the evidence base were acknowledged, including the wide variability in inclusion criteria, grouping, or specificity when defining and measuring vegetable and fruit intakes, as well as the possibility of overreporting or overestimating absolute intake levels. One reason that the recommendation for vegetable and fruit consumption remains broad is that the specific protective constituents in vegetables and fruit, alone or in combination, have not been identified with certainty. Relevant substances in vegetables and fruit include phytochemicals such as dithiolthiones, flavonoids, glucosinolates, and allium compounds, as well as carotenoids, other antioxidants, vitamins, folate, and minerals such as selenium and calcium. A large number of plausible mechanisms can explain how these various nutrients or bioactive constituents in vegetables and fruit can prevent or arrest carcinogenesis, and some are supported by animal and in vitro experiments.

Testing hypotheses experimentally requires large-scale, long-term studies as well as a best guess about which set of bioactive constituents to feed and at what level. The dose of vegetables and fruit associated with a particular effect can be reasonably estimated, but the specificity required to translate this information into a dose of any particular constituent does not exist in the present set of studies. Because of these uncertainties, the null findings of the chemoprevention trials of beta carotene do not detract substantially from the conclusion that vegetables and fruit reduce cancer risk. These findings, however, raise the question of whether any single constituent of vegetables and fruit or single pathway will be found responsible for protection from cancer. Multiple agents acting on multiple pathways, in parallel or interactively, are probably responsible. If so, the results of the chemoprevention trials argue in favor of recommending vegetables and fruit as foods, rather than attempting to achieve the effect with vitamin or mineral supplements.³

Other Health Benefits

Epidemiologic studies also have demonstrated or suggested associations of vegetables and fruit or their constituents with reduction in risk of cardiovascular disease (CVD, i.e., heart disease, stroke, hypertension, atherosclerosis), cataracts, chronic obstructive pulmonary disease (COPD), and other conditions.⁷ For example, Klerk et al. estimated that vegetable and fruit consumption was associated with a 20 to 40 percent reduction in the occurrence of coronary heart disease (CHD) based on a review of 12 epidemiologic studies conducted after 1994.⁸ Ness and Powles⁹ also found a reduced risk of CHD based on their review of 39 studies. The inverse association of vegetables and fruit or, from the Nurses' Health Study, vegetables alone, with stroke may be even larger than that for CHD.¹⁰ The evidence supporting a role for constituents of vegetables andfruit in protection against the development of cataracts and COPD has increased in recent years, and vegetables and fruit also may confer protection from conditions such as diabetes mellitus and diverticulosis because of their high content of dietary fiber.⁷

Using the criteria for inferring causality employed in the WCRF review,³ the literature on the association between vegetables and fruit and these other health outcomes must be considered less comprehensive and less convincing than that for cancer. However, this additional literature is important in several respects. It extends the rationale for increasing vegetable and fruit consumption to include protection from CVD, which is the major cause of premature death in most populations.¹¹ In addition, because CVD is more common than cancer and because intermediate variables that can serve as surrogate CVD endpoints have been characterized, clinical trials can be conducted to directly ascertain whether increasing vegetable and fruit intakes will reduce CVD risks. One such trial, the Dietary Approaches to Stop Hypertension (DASH) trial, demonstrated large reductions in blood pressure in association with either of two diets that were high in vegetables and fruit.¹² The broader evidence also confirms that health effects, when observed across a variety of outcomes, are consistently in a protective direction. This evidence eliminates any concern that recommending increased consumption to prevent cancer would elevate the risks of some other condition.

Safety Considerations

The WCRF review noted that "there is the theoretical possibility that consumption of vegetables and fruits might increase health risk because of the presence of certain microconstituents or contaminants," including goitrogens, nitrates, both naturally occurring and from fertilizer residues, pesticide residues, and contamination with aflatoxin.³ They concluded that "there is no evidence at present that any vegetables and fruit, properly stored and cleaned, have any significant adverse health effects."³

Sensory and Consumer Issues

Marketing studies on the determinants of food consumption invariably show that consumer choices are determined largely by taste.¹³ Dietary intake, as measured by reported frequencies of food consumption, also is closely associated with food likes and dislikes.¹⁴ Many bioactive phyto-nutrients in vegetables and fruit are bitter, sour, spicy, pungent, and/or astringent, and therefore elicit various degrees of aversiveness among consumers.^15-19 By contrast, high-fat and high-sugar foods usually have desirable sensory characteristics and meet with high consumer acceptance.²⁰ This is because responses to tastants and trigeminal irritants (such as the capsaicin in hot peppers or the piperin in black pepper) are innate, and they dictate that consumers reject bitter-tasting stimuli and trigeminal irritants because they may signal potentially harmful chemicals, such as poisonous plant alkaloids. Olfactory preferences, on the other hand, are learned, with exposure driving preference. Furthermore, some genetic taste markers, such as sensitivity to the bitter taste of phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP),²¹ have been linked to an increased avoidance of bitter foods and beverages (including some vegetables and fruit) in the diet.^22,23 Those individuals sensitive to PTC and PROP—so-called tasters or super-tasters—may therefore be at increased risk. The dilemma here is that the strong-tasting compounds as a group overlap extensively with the compounds that are potentially protective against cancer; therefore, removing strong-tasting compounds may reduce the protective effect.

Fortunately, food preferences are driven by both sensory and cognitive factors, and even though they begin developing early in childhood, they continue to evolve during the lifespan and can be modified. Because children's food preferences generally are guided by sensory quality rather than attitudes and beliefs about foods,²⁰ however, the palatability issues discussed above may act as an even greater barrier to the adoption of a diet high in vegetables and fruit among the young. Nonetheless, there is evidence that preferences for, and consumption of, vegetables and fruit by elementary school children can be enhanced through the use of intervention programs that emphasize cognitive factors. For example, researchers in the United Kingdom successfully used a video-based intervention program, in children's own homes and in school settings, that combined both peer modeling and rewards for eating previously refused foods, to increase (and sustain) vegetable and fruit consumption by 5-7 year-olds.^24,25

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