Life Extension Magazine 2004
The Coming Age of Vege-Medicine
|LE Magazine Special Edition, Winter 2004/2005|
|The Coming Age of Vege-Medicine|
The International Journal of Cancer recently put I3C (indole-3-carbinol) on the fast track when researchers at the University of Maryland discovered that the vege-compound suppresses a protein that speeds up the growth of cancer cells.1 The protein, known as MUC1, shows up in 90% of all breast, lung, pancreas, prostate, stomach, colon, and ovarian cancers.2
I3C suppressed the cancer-enhancer protein almost 80%. I3C is just one of the anti-cancer factors in broccoli and other cruciferous vegetables such as Brussels sprouts and cabbage. The MUC1 report is the latest that links cruciferous vegetables to significant health benefits. One serving of cruciferous vegetables may protect against cancer better than all the other fruits and vegetables on a person’s plate combined.3
Unfortunately, Americans eat too few cancer-fighting vegetables. The top vegetables in America are iceberg lettuce, tomatoes, and French fries.4 This is so alarming to those knowledgeable about the food-cancer connection that one study involved calling people with “motivational reminders” to eat right and not relapse into dietary purgatory.5 The government’s “Healthy People 2000” has been extended another ten years in the hopes that the message will get through in another decade. The program has presidential medals for people who choke down bona fide vegetables.6 And, that’s not all—businesses are jumping on the diet/health bandwagon too. The people who brought us “Velveeta” are hard at work on an even better way to get people to eat broccoli. It’s devising ways to sneak the vegetable into snack foods.7
And, in spite of the fact that you may be a “health nut” who eats broccoli with cauliflower chasers three times a week, you may still not be getting enough nutrition from these important vegetables. A new study shows that up to 80% of the phyto-chemicals that make broccoli healthy (glucosinolates), along with 60% of the flavonoids and other such goodies are lost from the time broccoli is picked to the time it lands on your plate.8 That’s assuming you don’t let it age in the refrigerator a week, by which time you might as well take a picture of it and eat that–at least according to this study. Take heart, however, other studies give a better prognosis and it apparently doesn’t take much broccoli to get you where you need to go.
What are those benefits, anyway, and where do you need to go? There’s no short answer to that question, but wiping out cancer cells before you, or anyone else, ever knows they exist is a good start. As you may have heard, up to 90% of all cancer is caused by environmental factors, at least two-thirds of which a person can control.9
How can cruciferous vegetables help? Broccoli and other cruciferous vegetables manufacture dozens of phyto-chemicals to protect themselves against insects, worms, the sun, grazing animals, etc. The system is elaborate. These vegetables not only manufacture phyto-chemicals that discourage creatures, they also produce factors that encourage creatures. The result is a green grab bag of vegetable-based compounds possessing very sophisticated and complex actions. Researchers are investigating the effects in human cells, with the first priority being good-cells-gone-bad—cancer.
Eat Your Broccoli
Researchers at Vanderbilt did a new-and-improved version of this type of study. Instead of looking at Americans (who might eat broccoli once a year, or once every five years), they worked with researchers in China where people eat an abundance of cruciferous vegetables all the time. When they gave the usual questionnaire to women with newly-diagnosed breast cancer, vegetables did not link up to a lower cancer risk. However, when they measured actual cruciferous vegetable metabolites in the women themselves, it emerged that the women who ate the most cruciferous vegetables halved their risk of breast cancer.13 This shows how problematic questionnaire studies can be, but more importantly, it shows a strong association between eating certain vegetables and escaping hormone-related cancer.
This sort of data is helpful, but researchers are not content with such generalities. They want to know what it is about cruciferous vegetables that prevent cancer, and how it works.
Can Vege-Compounds Kill Cancer Cells?
When they put the isothiocyanates on human breast cancer cells, the cells stopped growing and died within 48 hours. The effect was virtually identical to daunomycin at about the same amount. In a different study, the same isothiocyanates killed lung cancer cells 100% in five days.15
One of the isothiocyanates used in the chemo drug study was the cruciferous phyto-chemical, sulforaphane. Sulforaphane is undergoing tests at several universities for its ability to stop the growth of human cancers. When mice are transplanted with prostate cancer and then given sulforaphane as a supplement (or related isothiocyanate PEITC, or allyl isothiocyanate), tumors are 50-70% smaller (see figure).16-18 Cells stop growing and undergo cell death (apoptosis). The same thing happens with breast cancer.19 Human colon cancer cells also stop growing in the presence of sulforaphane,20 and bladder cancer gives up within three hours (80% of cells stop growing and fall apart (apoptosis) after treatment with sulforaphane and other isothiocyanates).21
Vege-Compounds Detoxify Cancer-Causing Chemicals
Powerful Anti-inflammatory Action That Protects Cells
The natural, organic cancer-fighters in cruciferous vegetables also discourage cancer by stopping DNA damage. In a study on human cells exposed to hydrogen peroxide and a chemical from cigarette smoke, sulforaphane and another cruciferous compound, ICZ, reduced DNA damage by more than 80%.26 Not only can these compounds protect DNA, I3C and three other vege-compounds (resveratrol, curcumin, and ellagic acid) can actually enhance the body’s DNA repair system—a discovery that surprised the researchers who were initially skeptical that plant compounds could have a significant DNA-protective effect, let alone control the system of repair.27
Because most cases of cancer can be prevented through diet and lifestyle, and because anything that kills precancerous and cancerous cells is very desirable as cancer prevention, the science of broccoli is exploding. As the poster child for cruciferous vegetables, this vegetable is getting a lot of attention, or more precisely, what is in broccoli is getting a lot of attention. From cancer researchers to snack peddlers, to oncologists looking for chemo-enhancers, everybody wants a piece of the action. And action it is! The past two years alone account for about a third of all publications on broccoli-related topics. Researchers and clinicians alike seem to realize—this is the real deal. Even as we go to press, news of another important study has arrived. Stay tuned.
Broccoli sprouts provide a more concentrated amount of beneficial phyto-nutrients than the mature plant. High-quality supplements are made from sprouts—not seeds (which may contain toxins). The amount of phyto-compounds varies widely, depending on the variety. The only way to be sure of a consistent dose of cancer-fighting vege-compounds day in, and day out, is to take a standardized supplement that provides a consistent dose.
1. Lee IJ, Han F, Baek J, et al. Inhibition of MUC1 expression of indole-3-carbinol. 2004; Int J Cancer 109:810-16.
2. Mukherjee P, Madsen CS, Ginardi AR, et al. Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer. J Immunother 2003; 26:47-62.
3. Keck AS, Finley JW. Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium. Integr Cancer Ther 2004; 3:5-12.
4. Johnston CS, Taylor CA, Hampl JS. More Americans are eating “5 a day” but intakes of dark green and cruciferous vegetables remain low. J Nutr 130:3063-67.
5. Pierce JP, Newman VA, Flatt SW, et al. Telephone counseling intervention increases intakes of micronutrient-and phytochemical-rich vegetables, fruit and fiber in breast cancer survivors. J Nutr 2004; 134:452-8.
6. Healthy People 2010. http://www.healthypeople.gov. Managed by the Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services. Accessed October 7, 2004.
7. West LG, Meyer KA, Balch BA, et al. Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kale and cabbage. J Agric Food Chem 2004; 52:916-25.
8. Vallejo F, Tomas-Barberan F, Garcia-Viguera C. Health-promoting compounds in broccoli as influenced by refrigerated transport and retail sale period. J Agric Food Chem. 2003 May 7;51(10):3029-34.
9. Cancer and the Environment: What You Need to Know: What You Can Do. Also, interview with Aaron Blair, Ph.D., Chief of Occupational Epidemiology, NCI’s Division of Cancer Epidemiology and Genetics by Nancy Nelson. June 17, 2004. Available online at http://www.cancer.gov.
10. Kolonel LN, Hankin JH, Whitemore AS, et al. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev 9:795-04.
11. Lin HJ, Probst-Hensch NM, Louie AD, et al. Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas. Cancer Epiudemiol Biomark Prev 7:647-52.
12. Michaud DS, Spiegelman D, Clinton SK, et al. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst 1999; 91:605-12.
13. Fowke JH, Chung FL, Jin F, et al. Urinary isothiocyanate levels, brassica, and human breast cancer. Cancer Res. 63:3980-6.
14 Tseng E, Scott-Ramsay EA, Morris ME. Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines. Exp Biol Med (Maywood). 2004 Sep;229(8):835-42.
15. Kuang Y-F and Chen Y-H. Induction of apoptosis in a non-small cell human lung cancer cell line by isothiocyanates is associated with p53 and p21. Food Chem Toxic 2004; 42:1711-18.
16. Singh AV, Xiao D, Lew KL, et al. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis 2004; 25:83-90.
17. Chiao JW, Wu H, Ramaswamy G, et al. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis 2004; 25:1403-8.
18. Srivastava SK, Xiao D, Lew KL, et al. Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostaet cancer xenografts in vivo. Carcinogenesis 2003; 24:1665-70.
19. Jackson SJ, Singletary KW. Sulforaphane: a natuirally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis 25:219-27.
20. Frydoonfar HR, McGrath DR, Spigelman AD. Sulforaphane inhibits growth of a colon cancer cell line. Colorectal Dis 2004; 6:28-31.
21. Tang L and Y Zhang. Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. J Nutr 2004; 134:2004-10.
22. Kim BR, Hu R, Keum YS, et al. Effets of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by sulforaphane. Cancer Res 2003; 63:7520-25.
23. Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J 2002; 364(Pt 1):301-7.
24. Jeong WS, Kim IW, Hu R, Kong AN. Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signalling pathway. Pharm Res 2004; 21:661-70.
25. Rahman KM, Li Y, Sarkar FH. Inactivation of akt and NF-kappaB play important roles during indole-3-carbinol-induced apoptosis in breast cancer cells. Nutr Cancer 2004; 48:84-94.
26. Bonnesen C, Eggleston IM, Hayes JD. Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer Res 2001; 61:6120-30.
27. Chakraborty S, Roy M, Bhattacharya RK. Prevention and repair of DNA damage by selected phytochemicals as measured by single cell gel electrophoresis. J Environ Pathol Toxicol Oncol 2004; 23:215-26.
28. Donald S, Verschoyle RD, Greaves P, et al. Dietary agent indole-3-carbinol protects remale rats against the hepatotoxicity of the antitumor drug ET-743 (trabectidin) without compromising efficacy in a rat mammary carcinoma. Int J Cancer 2004; 111:961-67.
29. Wang X, Doherty GP, Leith MK, et al. Enhanced cytotoxicity of mitomycin C in human tumour cells with inducers of DT-diaphorase. Br J Cancer 1999; 1223-30.
30. Shukla Y, Srivastava B, Arora A, Chauhan LK. Protective effects of indole-3-carbinol on cyclophosphamide-induced clastogenecity in mouse bone marrow cells. Hum Exp Toxicol 2004; 23:245-50.
31. Agrawal RC, Kumar S. Prevention of cyclophosphamide-induced micronucleus formation in mouse bone marrow by indole-3-carbinol. Food Chem Toxicol 1998;36:975-77.
32. Anderton MJ, Manson MM, Verschoyle RD, et al. Pharmacokinetics and tissue disposition of indole-3-carbinol and its acid condensation products after oral administration to mice. Clin Cancer Res 2004; 10:5233-41.
33. Fahey JW, Haristoy X, Dolan PM, et al. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci 2004; 99:7610-15.