No one can deny the importance of diet in the promotion of good health and prevention of chronic disease, including cancer. According to the American Institute for Cancer Research and the World Cancer Research Fund, 30 percent to 40 percent of all cancers could be prevented with appropriate diet, physical activity and maintaining healthy body weight.1 For years, scientists have been actively seeking specific agents in the diet-disease relationship to guide consumers toward an optimal cancer prevention diet. Increasing evidence suggests that Brassica vegetables—including broccoli, kale, collards, mustard greens, cabbage, cauliflower and many other foods in this large plant family—may be among our best allies for preventing a variety of cancers.
The diet-cancer connection
Medical advances have helped lower mortality from cancer since the early 1990s, but one in four deaths in the United States is still due to cancer.2 The best offense is most likely a good defense. But what is a good defense?
There is a general consensus that diets plays a significant role in the development of major health problems, including coronary heart disease, cancer, obesity, type 2 diabetes, hypertension, cataracts and inflammatory bowel disease.1,3,4,5,6,7,8,9,10,11 One of the common threads in the development of chronic disease is oxidative damage.5,7,10,13 Oxidative damage results from normal metabolic processes but also is influenced by lifestyle (smoking, diet, drugs) and environmental pollutants. Damage occurs when the body?s natural antioxidant defense system is unable to adequately defend against the level of free radical formation.5,10,14
Plant foods are high in antioxidants, and it is often assumed that these antioxidants protect against oxidative damage and help prevent disease. However, when isolated from foods, antioxidants, like vitamins and minerals, do not show the same protective benefits attributed to the whole foods in epidemiological dietary studies. This has been demonstrated in intervention studies with single compounds such as vitamins E and C, or beta-carotene, which failed to show protective health benefits when given alone.5,7,9
The search for one or two "magic bullet" antioxidants in the fight against disease may be futile at best. Plant foods such as grains, nuts, seeds, fruits and vegetables contain thousands of biologically active compounds—often called phytochemicals or phytonutrients—that affect health.14 Fruits and vegetables contain at least several hundred different types of antioxidants, which have both enzymatic and nonenzymatic components that prevent free radical formation, remove radicals before they cause oxidative damage, repair damage, eliminate damaged molecules and prevent mutations.7,14 The many biologically active compounds in plants have complementary and overlapping mechanisms of action that protect human health against disease development.14
The role of brassica vegetables
Increasing evidence suggests that high intake of cruciferous vegetables—the brassica vegetables—helps prevent cancer.15,16,17,18,19,20,21,22,23,24 These vegetables are all from the plant family Brassicaceae (formerly called Cruciferae) and include familiar foods such as broccoli, cauliflower, Brussels sprouts, collards, kohlrabi and kale, as well as more than 350 other plants, such as arugula, mustard, radish, daikon, watercress, horseradish and wasabi.18 Promising recent studies suggest these vegetables are uniquely effective at protecting against cancer, in part because they are a rich source of glucosinolates, compounds that seem to play an essential role in the cancer-preventive effects of these foods.18
Glucosinolates are precursors to isothiocyanates, which are essentially the active ingredients released when the plant cell walls are broken by chewing, cutting or grinding.18 Myrosinase is the plant enzyme that catalyzes the chemical reaction that releases ITC. Cooking deactivates this enzyme and thus limits the release of the active compounds; microbes present in the digestive tract also contribute to ITC release, albeit to a lesser extent.18 Different plants within the Brassica genus contain different types of glucosinolates and therefore yield very distinct ITC. For example, 35 percent to 60 percent of glucosinolates in broccoli are in the form of glucoraphanin, which is converted to sulforaphane. Glucobrassicin, another glucosinolate, is found in broccoli and brussels sprouts and is broken down into indole-3-carbinol, which is further converted to a range of other metabolites (for example, diindolylmethane) under the acidic conditions in the stomach.18 Human exposure to ITC therefore depends on types and amounts of vegetables consumed, method of preparation and how well food is chewed, as well as differences in food constituents.
Isothiocyanates, indole-3-carbinol and DIM are all critical components in the chemopreventive effects of crucifers because they affect the action of certain enzymes within the body,18,25 thus influencing the way the body deals with potential carcinogens. ITCs in cruciferous vegetables induce both Phase 1 and Phase II liver enzymes involved in metabolism and detoxification. They also directly inhibit the Phase 1 enzyme cytochrome P450 2E1, which activates carcinogens.18,26 Some of the ITCs in cruciferous vegetables are potent stimulators of Phase II enzymes25,26—detoxification enzymes that protect against the formation of cancer, mutagenesis and other types of toxicity. Sulforaphane has been shown to both induce Phase II detoxification enzymes and competitively inhibit cytochrome P450 2E1, making it especially powerful in the fight against cancer and other diseases.25,26 The biological systems involved are highly complex, but in essence, Phase II enzymes such as glutathione-S-transferases accelerate carcinogenic compounds through the process of metabolism and elimination from the body.18
Because a particular vegetable may contain a dozen different glucosinolates, eating a diet high in a variety of cruciferous veggies may be the best bet in terms of cancer prevention.13,17,18 As with most beneficial dietary components, it is likely that optimal health protection depends on a synergistic effect of nutrients, rather than one isolated ingredient. But unlike "ordinary" antioxidants such as vitamins C and E, which are used up during the process of squelching free radicals, sulforaphane, I3C, DIM and other phytonutrients stimulate the body's enzyme defense systems to detoxify potential carcinogens before they can damage cells.13
Both population and clinical studies have suggested that frequent consumption of cruciferous vegetables and the specific compounds they contain confers protection against a whole host of diseases, including coronary heart disease and stroke;3,4,10,27 cancers of the breast,15,16,17,20 colon,28,29,30 prostate,23,24 pancreas31 and kidney;32 and all-cause mortality.33
A look at the research
Breast and colon cancer are two areas in which brassica vegetables have undergone significant research. Breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer deaths among American women.3,34 Until recently, studies on vegetable consumption and protection against breast cancer have yielded disappointing results, sometimes documenting no benefit with higher vegetable intake.35,36
There are several potential explanations for this, including the possibility that looking at fruit and vegetable consumption in general may dilute the protective effects seen with specific foods. Fortunately, several population and case-control studies show that consuming broccoli and other crucifers, which provide indole-3-carbinol and sulforaphane, reduces the risk of developing breast cancer.
One of the first population-based case-control studies to show a significant inverse relationship between broccoli consumption and cancer risk was done in Sweden and reported in the Journal of the American Medical Association in 2001.15 Though this study showed no protection against breast cancer attributable to overall fruit and vegetable consumption, brassica vegetables afforded significant protection. Specifically, one to two servings a day of crucifers such as broccoli and cabbage may lower the risk of breast cancer by 20 percent to 40 percent, possibly by shifting the pathway of estrogen metabolism.15
A case-control study published in 2004 concludes breast cancer risk in premenopausal women is inversely associated with consumption of broccoli.20 The researchers propose the reduced risk could be associated with I3C, which they theorize has antiestrogenic effects.20 Other studies support the idea that broccoli and other cruciferous vegetables act on estrogens and androgens to reduce the risk of several hormone-related cancers, including breast, endometrial, cervical and prostate cancers, in both animals and humans.21,23
The degree of protection against cancer and other diseases that may be conferred by specific dietary compounds and general dietary patterns depends on a number of factors, including other lifestyle practices and genetic differences. People with a strong genetic predisposition to a particular disease may or may not benefit from consumption of brassica vegetables as much as those at lower risk. However, several studies on breast cancer suggest genetic differences do not alter the protective effect of cruciferous vegetables on breast cancer risk,15,20 and numerous other health benefits are also associated with frequent consumption of these foods.,3,4,7,10
Still, genetic differences have been shown to play a significant role in how the body responds to dietary factors. While brassica vegetables can improve detoxification and excretion of potentially harmful compounds in some individuals, not everyone responds to the same extent.35 For example, a case-control study in China found that genetic differences largely determined the degree of benefit associated with high intake of cruciferous vegetables and the ITC they contain.29 Consumption of cruciferous vegetables reduced the risk of colorectal cancer by 57 percent in individuals with both GSTM1 and T1 null genotypes, whereas there was no significant reduction in risk for those with GSTM1, T1 or P1 genotypes.29 Another case-control study supports the theory that cruciferous vegetables may not lower the risk of colon cancer for total populations, but there are subgroups for whom the vegetables may be especially important.30
A more recent study in Ireland examined the effect of supplementation with cruciferous and legume sprouts on the level of DNA damage induced by hydrogen peroxide, to further evaluate whether brassica vegetables can help reduce the risk of colon cancer.38 The researchers combined in vitro analysis with a parallel-design dietary intervention study in human subjects for 14 days. While there was no significant induction of detoxifying enzymes during the two weeks, there was significantly less DNA damage in the volunteers who consumed 113 grams of cruciferous and legume sprouts, suggesting protection against cancer and other diseases concordant with a decrease in oxidative and other damage to DNA.38
The bottom line? Though not everyone may benefit in the same way from a diet rich in cruciferous vegetables, numerous studies support the recommendation that people regularly consume ample amounts of broccoli, kale and other crucifers for protection against cancer and many other diseases. So encourage customers to "supplement" their supplements purchases with fresh veggies from the produce department.
Anne-Marie Nocton is a nutrition consultant and freelance writer based in Knoxville, Tenn.
1. Donaldson MS. Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr Journal 2004;(3)1:19.
2. Jemal A, et al. Cancer Statistics, 2005. CA Cancer J Clin 2005;55:10-30.
3. Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA 2002;288:2569-78.
4. Hung HC, et al. Fruit and vegetable intake and risk of major chronic disease. J Natl Cancer Inst 2004;96:1577-84.
5. Halvorsen BL, et al. A systematic screening of total antioxidants in dietary plants. J Nutr 2002;132:461-71.
6. Finley JW, et al. Selenium from high selenium broccoli protects rats from colon cancer. J Nutr 2000;130:2384-9.
7. Svilaas A, et al. Intakes of antioxidants in coffee, wine, and vegetables are correlated with plasma carotenoids in humans. J Nutr 2004;134:562-7.
8. Cooper DA. Carotenoids in health and disease: recent scientific evaluations, research recommendations and the consumer. J Nutr 2004;134:221s-4s.
9. Willett WC. Diet and cancer: an evolving picture. JAMA 2005;293:233-4.
10. Wu L, et al. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc Natl Acad Sci 2004; 101:7094-9.
11. Chao A, et al. Meat consumption and risk of colorectal cancer. JAMA 2005;293:172-82.
12. Norat T, et al. Meat consumption and colorectal cancer risk. Int J Cancer 2002;98:241-56.
13. Vegetable compound stops breast cancer cell growth. Nutra-ingredients-USA. www.nutraingredients-usa.com/news/ng.asp?id=54457
14. Lampe JW. Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies. Am J Clin Nutr 1999;70:475s-90s.
15. Terry P, et al. Brassica vegetables and breast cancer risk. JAMA 2001;285:2975-6.
16. Brandi G, et al. Mechanisms of action and antiproliferative properties of Brassica oleracea juice in human breast cancer cell lines. J Nutr 2005;135:1503-9.
17. Fowke J, et al. Urinary isothiocyanate levels, Brassica, and human breast cancer. Cancer Res 2003;63:3980-6.
18. Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr 2002;132:2991-4.
19. Freudenheim J, et al. Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst 1996;88:340-8.
20. Ambrosone CB, et al. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr 2004;134:1134-8.
21. Auborn KJ, et al. Indole-3-Carbinol is a negative regulator of estrogen. J Nutr 2003;133:2470s-5s.
22. Zhang S, et al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 1999;91:547-56.
23. Sarkar F, Li Y. Indole-3-Carbinol and prostate cancer. J Nutr 2004;134:3493s-8s.
24. Hsu JC, et al. Indole-3-Carbinol inhibition of androgen receptor expression and down-regulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis 2005; June 15.
25. Fahey J, et al. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci 1997;94:10367-72.
26. Jackson SJ, Singletary KW. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr 2004;134:2229-36.
27. Joshipura KJ, et al. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 1999;282:1233-9.
28. Lang NP, Thomas G. Orr Memorial Lectureship: Colon cancer from etiology to prevention. Am J Surg 1997;174:578-82.
29. Seow A, et al. Dietary isothiocyanates, glutathione-S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study. Carcinogenesis 2002;23:2055?61.
30. Slattery ML, et al. Interplay between dietary inducers of GST and the GSTM-1 genotype in colon cancer. Int J Cancer 2000;87:728-33.
31. Nishikawa A, et al. Potent chemopreventive agents against pancreatic cancer. Curr Cancer Drug Targets 2004;4:373-84.
32. Greenwald P. Clinical trials in cancer prevention: current results and perspectives for the future. J Nutr 2004;134: 3507s-12s.
33. Gago-Dominguez M, et al. Family history and risk of renal cell carcinoma. Cancer Epidemiol Biomarkers Prev 2001;10:1001-4.
34. Genkinger JM, et al. Fruit, vegetable, and antioxidant intake and all-cause, cancer, and cardiovascular disease mortality in a community-dwelling population in Washington County, Maryland. Am J Epidem 2004;160:1223-33.
35. Lampe JW, et al. Modulation of human glutathione-s-transferases by botanically defined vegetable diets. Cancer Epidemiol Biomarkers Prev 2000;9:787-93.
36. Van Gils CH, et al. Consumption of vegetables and fruits and risk of breast cancer. JAMA 2005;293:183-93.
37. Smith-Warner S, et al. Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. JAMA 2001;285:769-76.
38. Gill CI, et al. The effect of cruciferous and leguminous sprouts on genotoxicity in vitro and in vivo. Cancer Epidemiol Biomarkers Prev 2004;13:1199-205.
39. Indole-3-carbinol. Thomson Healthcare. http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/ind_0315.shtml
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