Eat the Celery Stalk in Your Bloody Mary

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a consultant for Cephalon, and serves on the speakers bureaus for Resmed and Respironics.

Synopsis: The more fruits and vegetables you eat, the lower your overall cancer risk.

Source: Boffetta P, et al. Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2010;102:529-537.

These investigators wanted to learn more about the relationship between fruit and vegetable intake and cancer risk. To do this, they undertook a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort for the years between 1992 and 2000. The details the EPIC study have been published1; suffice it to say that it is a rigorous, large, impressive, meticulously done cohort study evaluating the effects of diet and other lifestyle factors on a variety of health outcomes. Because of the nature of the study, the investigators have access to fairly precise information about diet and lifestyle factors. For purposes of this study, they were able to correlate fruit and vegetable intake with cancer incidence and mortality, controlling for tobacco smoking and alcohol drinking.

The initial cohort was 142,605 men and 335,873 women recruited from 23 European centers. There were significant variations among the centers in how the participants were recruited. For example, the French cohort drew from members of a health insurance plan, but participants at most of the Spanish and Italian centers included blood donors, members of several health insurance programs, employees of several enterprises, civil servants, and the general population. The cohorts of France, Norway, Utrecht, and Naples included only women. Data on diet of the participants for the preceding year were generally collected by country-specific, self-administered food-frequency questionnaires, although there was variation in how this was done. The investigators evaluated associations between cancer and intake of total fruits, total vegetables, and total fruits and vegetables combined. Of note, potatoes, other tubers, legumes, and vegetable juices were not included in the calculation. Lifestyle questionnaires collected information on education, medical history, tobacco smoking, alcohol intake, occupational and leisure time physical activities, menstrual and reproductive history, use of oral contraceptives, and hormonal therapy. Height and weight were measured at the baseline examination.

There were a variety of methods used to assess cancer incidence and mortality, but these data generally came from population-based registries, by contacting the study participants and next of kin, and by searches through health insurance records. Cancer incidence and mortality data were coded according to the ICD-10 and the second revision of the International Classification of Diseases for Oncology (ICDO-2). Nonmelanoma skin cancer was excluded from the analysis. For this study, smoking-associated cancers were considered to be cancers of the lung, kidney, upper GI tract, liver, stomach, pancreas, and bladder2; alcohol-associated cancers included cancers of the upper GI tract, breast, liver, and colorectum.3

During a follow-up period of about 9 years, 9604 men and 21,000 women were identified with cancer. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Reduced cancer risk was statistically significantly associated with increased intake of fruits and vegetables combined, and also with total vegetable intake for the entire cohort (200 g/day increased intake of fruits and vegetables combined, hazard ratio [HR] = 0.97; 100 g/day increased intake of total vegetables, HR = 0.98). The reduction in cancer risk with intake of fruits alone showed a slightly weaker inverse association (100 g/day increased intake of total fruits, HR = 0.99). Stratification by alcohol intake suggested a greater reduction (e.g., greater benefit with higher intake) in cancer risk in heavy drinkers; further, this analysis suggested that the reduction in cancer risk associated with intake for fruits and vegetables was greatest for cancers caused by smoking and alcohol. There appeared to be a "dose-response" relationship between fruit and vegetable intake and cancer risk; there was a decreased overall cancer risk for the second to the fifth quintiles of the distribution compared with the first quintile (P for trend < 0.001). Results were comparable in men and women, although the precision of the risk estimates was greater in women because of the larger number of cancers.

There were variations in fruit and vegetable intake and in cancer risk among the centers. The median intake of fruits and vegetables was 335 g/day in the entire cohort. (This is roughly 4.5 servings/day. A "portion" of fruit or vegetables is about 80 g.) The intake ranged from a low of 231 g/day in Sweden to 511 g/day in Spain. In general, intake was higher in Southern European countries than in Northern European countries. High intake of fruits and vegetables was associated with female sex, higher education, physical activity, low alcohol intake, and never-smoking status. Country-specific cancer rates in men ranged from 3.8 per 1000 person-years in the Netherlands to 10.1 per 1000 person-years in Denmark. When countries were combined according to geographic region, the decrease in overall cancer risk for a 200 g/day increase in intake of fruits and vegetables was similar in the Northern countries and in the Southern countries.

Since tobacco smoking and alcohol drinking are major causes of cancer, the investigators repeated the main analysis after stratification for these behaviors. Stratification by alcohol drinking suggested a stronger association in heavy drinkers than in moderate or non-drinkers. When cancers were stratified according to the presence of a causal association with tobacco smoking or alcohol drinking, the inverse association with higher intake of fruits and vegetables was restricted to cancers associated with smoking and drinking, and the duration of follow-up did not change the results. The authors concluded that there is a "very small inverse association between intake of total fruits and vegetables and cancer risk," and suggested that these results should be applied with caution.

Commentary

The notion that eating fruits and vegetables is good for you is sort of like Mom and apple pie. For example, the World Health Organization has recommended that people eat at least 5 portions (about 400 g) of fruits and vegetables a day to prevent cancer and other chronic diseases.4 However, conclusive evidence that high intake of fruits and vegetables reduces the risk of cancer development is scant.5,6 Most available studies have concentrated on one or a few types of cancer and/or come from case-control studies. Prospective studies have generally not supported a lower risk of cancer. Indeed, both the International Agency for Research on Cancer and the World Cancer Research Fund have downgraded the strength of the evidence for a relationship between fruit and vegetable intake and cancer risk.5,6

The putative mechanism(s) of reduced cancer risk in fruit and vegetable eaters includes antioxidant activity, modulation of detoxification enzymes, stimulation of immunologic response, modulation of hormonal level, and antiproliferative activities. It's worth pointing out, however, that specific compounds in fruits and vegetables that might be responsible for such anticarcinogenic activities of these foods may not have been identified.

The elephant in the room with regard to this topic is overall lifestyle. In the EPIC study, as in other attempts to address this issue, those who ate more fruits and vegetables had healthier lifestyles in general (lower intake of alcohol, never-smoking, and higher level of physical activity), which may have contributed to a lower cancer risk. The investigators adjusted for these known and well-established risks, but were not able to control for every facet of healthy lifestyle, and did not take into account some factors that may be associated with cancer but are not yet generally accepted to be (such as cell phone use, sleep duration, living along a polluted river, etc.).

Despite all these caveats, the current study is the strongest to date linking fruit and vegetable intake with reduced cancer risk. The strengths of the current study are the size of the population included, the detail of dietary information collected, and the rigor the investigators bring to their analyses. But the effect is very small.

So, what does this mean to our patients? Fruits and vegetables probably do have a modest effect in reducing all-cancer risk. Moreover, for those who smoke or drink alcohol, the effect of eating fruits and vegetables on cancer risk might be more important. Of course, it may be difficult to convince the person who won't quit smoking or drinking to eat more spinach.

References

1. Riboli E, et al. European Prospective Investigation into Cancer and Nutrition (EPIC): Study populations and data collection. Public Health Nutr 2002;5(6B): 1113-1124.

2. International Agency for Research on Cancer. Tobacco Smoke. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Tobacco Smoke and Involuntary Smoking. Lyon, France: IARC; 2004;83:53-1187.

3. Baan R, et al. WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of alcoholic beverages. Lancet Oncol 2007;8:292-293.

4. World Health Organization. Report of a WHO Study Group. Diet, Nutrition, and the Prevention of Chronic Diseases. Geneva, Switzerland: WHO; 1990.

5. International Agency for Research on Cancer. Fruit and Vegetables. IARC Handbooks of Cancer Prevention. Lyon, France: IARC Press; 2003:8.

6. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR; 2007.