Cancer is a general term for more than 100 distinct. TheOptionsfor CancerPrevention By Yousry Naguib, Ph.D. SCIENCE & NATURE

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1 38 Vitamin Retailer. April 2003 SCIENCE & NATURE TheOptionsfor CancerPrevention By Yousry Naguib, Ph.D. risk factors, including person's genetic make-up, immune system disorder, and exposure to radiation, sun's ultraviolet rays, tobacco, pollution, drugs such as DES (a synthetic estrogen), and a variety of chemicals such as asbestos, polycyclic, and aromatic hydrocarbons. Cancer risk could be reduced by either preventing carcinogenesis (DNA damage that leads to malignant cells), stopping carcinogenesis in its early stages or blocking the progression to invasive cancer. Dietary modification and dietary supplements show considerable promise as effective approaches for cancer prevention. In the United States, 30 to 35 percent of cancer cases are diet-related, and tobacco smoking causes another 30 to 35 percent of total cancer cases. The diet related cancers include esophagus, stomach, liver, colon, pancreas, rectum, breast, prostate, and ovary. The dietary aspects most commonly associated with these cancers are alcohol, nitrates, nitroso-amines, and fried foods. Popular diets, such as the Mediterranean and Asian diets, have been shown to provide protection against cancer due to a reduced intake of carcinogens (fewer processed foods) and an increased intake of anti-carcinogenic phyto-nutrients.l Mediterranean and Asian diets both tend to include lots of fruits and vegetables, and small amounts of protein (mostly fish) products. The Mediterranean diet also includes a relatively high intake of olive and flax oils (which supply omega-3 fatty acids), while the Asian diet includes a higher consumption of soy-based foods (which supply isoflavones). Cancer is a general term for more than 100 distinct diseases characterized by uncontrolled, abnormal growth of cells in the body. Cancer cells can spread through the bloodstream and lymphatic system to surrounding tissues (metastasis) within the body. Tumor metastasis is the most deadly characteristic of cancer. Unlike primary tumors that can be surgically removed and treated with adjuvant chemotherapy and/or radiotherapy, metastases are difficult to treat and usually prove fatal. Cancer affectsone in every three persons in developedcountries. In 1999, more than 1.2 million new cases of cancer were detected, and nearly half a million Americans died from some form of cancer. Breast cancer is the most common among women, almost 175,000 new cases each year; while for men, prostate cancer is the second most prevalent form (180,000 cases and 37,000 deaths in 1999)followinglung cancer. Cancer is the second leading cause of death in the United States (heart diseaseis first). Current estimatessay 30 percent of all Americanswill developsomekind of cancerin their lifetimes. Evidence suggests that cancer could result from a number of DIETARY SUPPLEMENTS Research studies appear to support the role of antioxidants, vitamins, minerals (selenium), and phyto-nutrients (flavonoids, carotenoids) in reducing the risk of certain cancers.2 Vitamin C, the primary water-soluble antioxidant nutrient in the diet, was found to be depleted in people afflicted with various cancers. Several studies have found a strong association between high dietary vitamin C intake (from foods) and a reduced incidence of cancers of the stomach, bladder, throat, colon and breast. Vitamin C has also been shown to regenerate vitamin E, the major fat-soluble antioxidant in our body. A case-control study in Sweden found that subjects with a high intake of vitamin C, beta-carotene, and alpha-tocophrol had a 40 to 50 percent lower risk of esophageal cancer compared to subjects with a low intake of these nutrients. 3 Vitamin D-Analysis of data from the National Health and Nutrition Examination Survey Epidemiological Study revealed that sunlight exposure and dietary vitamin D intake were associated with reduced risk of breast cancer.4 Calcium-Data from a large case-control study, involving

2 1,993 colon cancer cases and 2,410 controls, revealed that dietary calcium was inversely associated with colon cancer risk.s An ll-years followup study of 61,463 women found that those with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer risk, suggesting that high calcium intake rnight lower colorectal cancer risk.6 Selenium deficiency has been associated with an increased risk of cancers of the prostate, colon, and lung.? In one study, subjects received either 200 mcg/day of selenium or a placebo. Those receiving the selenium supplements showed significant reductions in cancer of the prostate (66 percent), colon (50 percent), and lung (40 percent) as well as an overall 50 percent reduction in cancer deaths. Selenium in dietary supplements comes from different sources, such as sodium selenite, selenomethionine, selenium-rich yeast, or high-selenium garlic. Higher doses of selenium, above 900 mcg-lmg per day, can lead to toxic effects, including gastrointestinal distress. MGN-3 (Biobran) is a patented water-soluble polysaccharide called arabinoxylan, which is composed of a heidi-cellulose extract of rice bran modified by enzymes from Shiitake mushrooms. The main chemical structure of MGN-3 compound has been identified as arabinoxylan with a xylose in its main chain and an arabinose polymer in its side chain.8a Research studies showed that MGN-3 works by stimulating the immune system, especially the natural killer (NK) cells. NK cells are the body's first line of defense against cancer and viral infection. Dr. Ghoneum at Drew University, Los Angeles, studied MGN-3 on healthy control subjects and reported more than 200 percent increase in NK activity after one to two weeks' treatment with MGN-3 at a daily dose of 30 to 45 mg per kilogram body weight.8b In a similar study involving cancer patients, the increase in NK cell activity ranged from 145 percent to 332 percent in breast cancer patients, 174 percent to 385 percent in prostate cancer patients, and 100 percent to 240 percent in leukemia patients.8c A characteristic feature unique to MGN-3 is that it does not have a cycle off, cycle on phenomenon. This is known as hyporesponsiveness of NK activity and is associated with many biological response modifiers (BRMs). Several studies showed that single administration of BRMs significantly enhanced NK cell activity. However, repeated administration of the same BRM result in depression of NK cell activity. It is interesting to note that MGN-3 treatments were followed in 32 patients for 4 years and NK activity was maintained at a high level with continuation of treatments. This places MGN-3 at an advantage over other BRMs designed to boost NK activity.8c In a most recent study Dr. Ghoneum discovered that cancer cells exposed to MGN-3 become sensitive to chemotherapy, and could be killed by a low dosage of chemo. This discovery could help cancer patients requiring higher dosage of chemo to reduce the dosage, thereby minimizing the harmful effects of high doses to healthy cells. Beta-Carotene-Although evidence from epidemiological studies indicates that mixed carotenoids from fruits and vegetables may provide protection against cancer, supplementation with beta-carotene was actually found to promote certain forms of cancer in specific populations (lung cancer in heavy smokers). Two large intervention studies known as Alpha- Tocopherol, Beta-Carotene (ATBC) study and Beta- 40 Vitamin Retailer. April 2003 Carotene and Retinol Efficacy Trial (CARET), showed a clear percent increase in lung cancer among smokers and those exposed to asbestos. The ATBC study used 20 mg doses of beta-carotene daily for 5-8 years. A related population study, the Physicians' Health Study, found no adverse effects of 25 mg/day of beta-carotene (but also no beneficial effect) but only about 10 percent of participants were smokers.9 Lycopene is another carotenoid (found in tomatoes, pink grapefruit, and watermelon) that has powerful antioxidant activity and might be effective in prevention of prostate cancer. Giovannucci (1999), at Harvard Medical School, reviewing epidemiologicalliterature, found that among 72 studies, 57 reported inverse associations between tomato intake or blood lycopene levels and cancer risk. The evidence was particularly strong for cancers of the prostate, lungs, breast and stomach.lo Grape Seed and Green Tea Extracts are both rich sources of polyphenols, which are potent antioxidants and possess antitumor properties (in animal studies). Grapes also contain resveratrol and quercetin that also have potent antioxidant properties. The inhibitory action of tea (Camellia sinensis) and tea polyphenols against cancer formation has been demonstrated in different animal studies, which showed the ability of tea polyphenols to inhibit cell proliferation and induce apoptosis.ll In one test tube study, researchers have shown that green tea and its main polyphenol compound epigallocatechin-3 gallate (EGCC) to decrease the risk of breast cancer.12 Recommended dosage of green tea supplements is in the range of mg/day, equivalent to 3-6 cups of brewed green or black tea. Isoflavones from soy or red clover possess both antioxidant and weak estrogenic activity. The anti-estrogen effect of small doses of isoflavones, such as daidzein and genistein, might be beneficial in certain forms of hormone-sensitive cancer, such as breast, uterine, and prostate. A recent study showed that individuals with the highest levels of daidzein, glycitein, and total isoflavones in their urine samples had about half the cancer risk than those with the lowest isoflavones levels. The study concluded that high intake of soy foods may reduce the risk of breast cancer. 13 In another recent study, pre-menopausal women between ages 25 and 55, free of breast cancer, were randomly assigned to receive either a dietary supplement of isoflavones (40 mg per day) or a placebo for 12 weeks. The hormone estradiol and its metabolite estrone (anticipated to be a carcinogen) decreased significantly in the isoflavone-group as compared to the placebo. The study suggested that increased isoflavone intake affects favorably estrogen metabolism, thereby demonstrating a potential to reduce the risk for breast cancer. 14 Garlic-The medicinal uses of garlic (Allium sativum) have a long history. Drawing and carvings of garlic were uncovered in Egyptian tombs, dating from 3700 Be. Its uses as a remedy for heart disease, tumors and headaches are documented in the Egyptian Codex Ebers, dating from 1550 BC. Recent studies have validated these health benefits. IS Garlic may help reduce the risk of colon cancer by as much as 30 percent-possibly via either its antioxidant properties (garlic is high in selenium) or its ability to influence certain detoxification enzyme pathways in the liver. Several population studies in China, Europe, and the u.s. have shown that people with the highest dietary consumption of garlic have a signifi-

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