Eat your fruit and veggies?

ResearchBlogging.orgEat your fruits and vegetables.

Hasn’t that been a constant refrain over the years from public health authorities? Certainly, I have. The benefits of eating fruits and vegetables have been widely touted, and seemingly with good reason. A diet high in fruits and vegetables, it is said, reduces the risk of cardiovascular disease and cancer. In the case of the latter, it as claimed that potential decreases in the risks of some cancers could be as high as 50% a day. As a result, the National Cancer Institute developed the 5-A-Day program, whose goal was to increase people’s consumption of fruits and vegetables to five or more servings a day. Indeed, on the NCI website, this effort is described thusly:

In 1981, Doll and Peto concluded that about 35 percent of all cancer deaths were related to nutrition, with a plausible range of 10 to 70 percent.26 This conclusion was driven largely by data on dietary behaviors that might increase risk. Evidence for the role of plant foods in cancer risk coalesced in the late 1980s and early 1990s, based on summaries of the epidemiologic literature specific to the relationship between vegetables and fruit and cancer.

The evidence supporting the role of vegetables and fruit in cancer prevention provided a foundation for several documents that were the basis of national nutrition policy in the 1980s and 1990s. In 1982, the National Research Council (NRC) published the seminal document, Diet, Nutrition and Cancer, which summarized the research literature on the relationship between various chronic diseases and dietary patterns.36 Other Federal documents followed such as Healthy People 2000, the first Surgeon General’s Report on Nutrition, Dietary Guidelines for Americans, and the Food Guide Pyramid.

There’s no doubt that diet is critically important to health, but does it have that dramatic an effect on cancer, with a possible effect size potentially as large as 70%? Answering that question has been difficult and has been very dependent on the methodology of the studies used to address the question. Studies have been conflicting regarding the existence and magnitude of benefit of a diet rich in fruit and vegetables when it comes to preventing cancer. Enter the EPIC Study (European Prospective Investigation into Cancer and Nutrition), whose results were just published in the Journal of the National Cancer Institute (JNCI) this week and have made the news all over the world, with some news stories having titles like Fruit and vegetables have little effect on cancer risk, study finds. Is it true? Should you stop worrying about eating five portions a day of fruits and vegetables. (Given how bad I am at trying to be healthy, I never came close to that on an average day, anyway.)

Let’s looks at the study itself and its proposed answer to this question. One thing the authors note is that most prior studies concentrated on one or a few types of cancer, which can skew the results because there may be small subsets of cancers that are highly sensitive to diet while the bulk of cancer is not. Positive results lead to further studies, and these cancers for which an effect of diet was found then come to be seen as surrogates for all cancer, falsely inflating the magnitude of any effect on cancer. Surprisingly, not nearly as much research has been performed to look at the relationship between a fruit and vegetable-rich diet and overall cancer risk describing the state of the literature thusly:

The association between fruit and vegetable intake and overall cancer risk, rather than risk of specific cancers, has been less frequently studied. A total of six prospective studies that included more than 10 000 individuals have reported results on cancer incidence (5-9) or mortality (10). Of the six studies, one showed that mortality was lower in both men and women when higher amounts of green and yellow vegetables and fruits were consumed (10); three studies reported a lower incidence of cancer in women on high intake of fruits and vegetables (5,6,8); and the remaining two showed no association between cancer risk and fruit or vegetable intake. A few possible explanations for inconsistent results in the above-mentioned studies could be recall, selection bias in case- control studies, and inadequate exposure contrast and exposure misclassification in cohort studies (4).

The authors also correctly point out that most of the previous evidence linking high fruit and vegetable intake to decreased cancer risk come from retrospective case control studies rather than from prospective studies. Anyone who knows anything about epidemiology (or has just read this blog) knows that retrospective studies are inherently prone to more confounding factors that can produce false positives than prospective studies. That’s not to say prospective studies aren’t prone to such problems, only that they are less so.

Enter the EPIC study. This study encompasses over 500,000 men and women aged 25 to 70 in several European countries who were recruited between 1992 and 2000. Their dietary intake was assessed by country-specific questionnaires, and then study subject outcomes were assessed, including cancer incidence and mortality. It is the largest study of its type. In addition, it included a wide variety of subjects from various nationalities spread across Europe and consuming varied diets, making it well-suited to look at the question of what effect diet has on overall cancer risk and the risk of dying from cancer.

The results of the study were of the “good news, bad news” variety. The good news is that there was an inverse correlation between fruit and vegetable intake and cancer risk. Importantly, there was a dose-response effect, meaning that the more fruit and vegetables people ate, the lower their risk of cancer. The bad news is that the effect observed was much lower than much of hte hype. Among people who ate more than 2.5 portions a day (an additional 200 g per day) had a 3% lower risk of cancer than those who ate less than that, while those who consumed 5 portions a day had a 9% decreased risk of cancer. Eating more than 8 portions a day was associated with an 11% decreased risk of cancer. As any good epidemiological study would do, the authors corrected for lifestyle issues and other cancer risk factors, such as hormone replacement therapy, smoking, alcohol intake, physical activity, etc. By any epidemiological measure, this is a modest effect. a 3% decrease, for instance, is not very large. Even an 11% increase, while more respectable, is still not that large and requires eating a lot of fruit and vegetables, far more than most people would be able to manage.

Why are the results of this study so much more modest than previous results? As I mentioned before, most of the old studies were case control studies, in which “cases” (people with cancer) were compared to age-, sex-, and race-matched controls. Subjects were asked to recall their dietary habits, and recall bias is a very real problem in such studies. Since then, larger cohort studies, of which the EPIC study is the largest thus far, have tended to produce less dramatic results, as is expected when more rigorous studies are done to followup results from les rigorous studies. Another reason that the results of this study are less dramatic is that it looked at nearly all cancers, rather than just a few. If diet has a much more dramatic effect on a few cancers, looking at all cancer incidence will dilute out the effects, given that cancer is not just one disease but many. Indeed, EPIC results have been published for several cancers, with some cancers being affected by diet (head and neck, esophagus, and colorectal cancer, for example) and others not (breast cancer, prostate cancer, and ovarian cancer, for example). For cancers for which no correlatoin was found, the total number of cancer cases have been too small to be definitive, and there may not have been enough years of followup to rule out a protective effect that isn’t evident until later. In any case, these results are intriguing not just for their insight into how we can reduce our risk of various cancers but for limning biological differences between cancers.

So we shouldn’t bother eating our fruits and vegetables anymore, right?

Wrong. Although the effect size cancer risk reduction due to consuming lots of vegetables and fruits is modest at best, as pointed out in an accompanying editorial by Walter Willett amusingly entitled Fruits, Vegetables, and Cancer Prevention: Turmoil in the Produce Section, there is evolving evidence suggesting that high fruit and vegetable intake has a profound effect on cardiovascular health:

Even if we assume that the weak association seen in the EPIC cohort represents a true protective effect of fruits and vegetables, the question would still remain whether an effect of this magnitude should lead to clinical interventions or public health actions. Conveniently, although the evidence for benefits of fruits and vegetables against cancer was waning, data supporting benefits for cardiovascular disease were accumulating (10,11). For example, in the same population of men and women that showed no association between fruits and vegetables and total cancer, incidence of coronary heart disease or stroke was 30% lower for those consuming five or more servings per day compared with those eating less than 1.5 servings per day (12). Data from a large randomized trial showing that increasing intake of fruits and vegetables reduces blood pressure (13), a major determinant of cardiovascular disease, make the case for causality compelling, although benefits through additional pathways are also possible. Thus, recommendations and actions to increase intake of fruits and vegetables have a sound basis.

So, even though fruits and vegetables may not have much of an effect on your overall risk of cancer, they can have a significant effect on the risk of specific cancers, as well as a profound effect on cardiovascular risk. That their benefits when it comes to cancer risk reduction have arguably been oversold is unfortunate, but the heart benefits are reason enough to see what a better diet can do. Unfortunately, there’s one thing that fruit and vegetables can’t do, and that’s to taste like meat.

REFERENCES

Boffetta, P., Couto, E., Wichmann, J., Ferrari, P., Trichopoulos, D., Bueno-de-Mesquita, H., van Duijnhoven, F., Buchner, F., Key, T., Boeing, H., Nothlings, U., Linseisen, J., Gonzalez, C., Overvad, K., Nielsen, M., Tjonneland, A., Olsen, A., Clavel-Chapelon, F., Boutron-Ruault, M., Morois, S., Lagiou, P., Naska, A., Benetou, V., Kaaks, R., Rohrmann, S., Panico, S., Sieri, S., Vineis, P., Palli, D., van Gils, C., Peeters, P., Lund, E., Brustad, M., Engeset, D., Huerta, J., Rodriguez, L., Sanchez, M., Dorronsoro, M., Barricarte, A., Hallmans, G., Johansson, I., Manjer, J., Sonestedt, E., Allen, N., Bingham, S., Khaw, K., Slimani, N., Jenab, M., Mouw, T., Norat, T., Riboli, E., & Trichopoulou, A. (2010). Fruit and Vegetable Intake and Overall Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition (EPIC) JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djq072

Willett, W. (2010). Fruits, Vegetables, and Cancer Prevention: Turmoil in the Produce Section JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djq098