Cancer

by Kim Schoenhals

There are few things more terrifying than hearing the word cancer directed toward oneself or a loved one. Many people spend their entire lives in fear of developing a malignancy, and Americans as a whole are becoming more concerned with prevention as cancer continues to be a leading cause of death.

According to the Natural Marketing Institutes (NMI) Health & Wellness Trends Databasefour years of trended data from more than 2,000 consumer respondents52.4 percent of the general population is concerned a lot and 28.3 percent is concerned a little with preventing cancer. Only 19.3 percent of the general population is not at all concerned with preventing cancer.

Image: Cancer Treaters Are More Likely To Use Supplements Than GP

Concerns aside, the Centers for Disease Control and Prevention (CDC) noted cancer is the second leading cause of death among Americans, leading to more than 553,000 deaths per year, as of 2001 estimates. Some good newsthe age-adjusted death rate decreased by 1.9 percent between 2000 and 2001, according to CDCs National Vital Statistics Report (Vol. 51, No. 5), which was released in March 2003. However, this mortality reduction has been a recent development; CDC noted 416,500 Americans died of cancer in 1980 compared to just over 553,000 in 2000.

More often, consumers are turning to complementary and alternative medicine (CAM) in the hopes of treating cancer. According to NMI, high numbers of consumers with cancer reported using vitamins (82.7 percent), minerals (61.2 percent) and herbal supplements (30.1 percent), although nearly all (96.7 percent) consumers treating cancer reported using prescription medications.

A research review out of the National Cancer Institute (NCI) indicated anywhere from 9 percent to 91 percent of cancer patients use CAM at some point after their diagnosis.1 [T]here is a paucity of data available to indicate whether these CAM practices are efficacious and safe, according to the review. Despite, or possibly because of, this controversy, there has been considerable growth of interest in CAM by the American public. This interest has also resulted in a growth of research resources. ... [NCI] is establishing programs to increase the amount and quality of CAM cancer research, support the production of high-quality CAM cancer information, and facilitate the dialogue between CAM practitioners and cancer researchers.

With countless cancer patients choosing CAM therapies, including dietary supplements, researchers are busy elucidating what role, if any, micronutrients, botanicals and other specialty ingredients have in the prevention and treatment of cancer. There is a vast amount of published research available that indicates supplement use can have positive results.

Micronutrients & Carotenoids

Of all of the natural therapies on the market, antioxidants are probably the most well-known. The word antioxidant has become a part of colloquial speech, and consumers are aware that antioxidants are necessary for preserving health and vitality. As for their role in cancer, it is believed they may help maintain a balance between the desirable and undesirable effects of reactive oxygen species, according to researchers from NCIs Division of Cancer Prevention.2 In their review, researchers stated the use of antioxidants as an adjunct therapy in cancer is a topic of heated debate. On one hand, antioxidants may reduce the toxic side effects of cancer treatment, but they may also protect cancer cells from damage. A research review published by the U.S. Preventive Services Task Force (USPSTF) in July also indicated there is insufficient evidence for recommending for or against taking vitamins in cancer prevention.3

The Food and Drug Administration (FDA) agreed that current evidence is insufficient at this point, and while it allowed a qualified antioxidant/cancer health claim in March 2003, the disclaimer language shows FDAs true feelings on the subject. While the claim reads, Consumption of antioxidant vitamins may reduce the risk of certain kinds of cancer, FDAs three recommended disclaimers all note FDA does not endorse the claim and evidence supporting the claim is limited and inconclusive.

Debates aside, a plethora of scientific investigations have focused on the use of antioxidants in cancer. Long-term use of vitamin E used by 44.2 percent of cancer patients and 38.3 percent of the general population, according to NMImay reduce bladder cancer mortality when it is used regularly for 10 years or more, according to epidemiological research conducted by the American Cancer Society (ACS).4

The different isomers of vitamin E may play a role in preventing cancer. Alpha-tocopherol was shown to have preventive effects against prostate cancer, although researchers from the National Public Health Institute in Helsinki, Finland, stated additional research would be needed to confirm this effect.5 A critical review on the potential role of alpha-tocopheryl succinate indicated the isomerboth singularly and combined with dietary micronutrientsis a useful complementary therapy for cancer because it increases tumor response and decreases the toxic effects of chemotherapy.6

Researchers at the Johns Hopkins Bloomberg School of Public Health in Baltimore saw a strong inverse association between gamma-tocopherol levels and prostate cancer risk in a case-control study of 10,456 men.7 In the same paper, researchers conducted another casecontrol study of 9,804 men and noted those who developed prostate cancer had slightly lower levels of gamma-tocopherol, even though there was not a dose-response trend in this cohort.

Like the tocopherols, the tocotrienol isomers of vitamin E may also have a preventive effect against cancer growth. Researchers from the University of Western Ontario, London, showed gamma-tocotrienol and delta-tocotrienol (derived from Tocomin palm tocotrienol complex, supplied by Carotech Inc., Edison, N.J.) significantly enhanced the inhibitory effect of tamoxifen (standard breast cancer drug) against the rate and growth of a breast cancer cell line known as MCF-7.8 Similarly, researchers at the Palm Oil Research Institute of Malaysia learned the tocotrienol-rich palm oil fraction (as Tocomin) exerted direct inhibitory effects on the growth of MCF-7 breast cancer cells, although not via an estrogen-receptor-mediated pathway.9 The same researchers conducted subsequent research and determined the tocotrienol-rich fraction of palm oil (as Tocomin) and its individual fractions (alpha, gamma and delta) inhibited the growth of another breast cancer cell line, ZR-75-1, which led to the conclusion that tocotrienols may be therapeutic when used in combination with anti-estrogen treatment.10

Another antioxidant, vitamin C, is a well-known member of the natural products industry that is used by 35.8 percent of the general population and 43.5 percent of consumers with cancer, according to NMI. One emerging role of vitamin C is its protective effect against Helicobacter pylori (H. pylori) infection, the bacteria responsible for stomach ulcers and possibly gastric cancer. Researchers at the San Francisco VA Medical Center analyzed data from 6,746 adults who enrolled in the Third National Health & Nutrition Examination Survey (NHANES III) and found higher serum levels of ascorbic acid were associated with a decreased prevalence of H. pylori, although this finding was only noted among white subjects.11

Vitamin C, while a popular supplement, is commonly consumed in food form, as numerous fruits and vegetables are high in vitamin C content. One such fruit, camu-camu (Myrciaria dubia) is an excellent source of antioxidants and may stave off free radical formation.12 A study of camu-camu conducted at State University of Maring in Brazil indicated camu-camu has one of the highest vitamin C contents of any fruit, with 2.4 g to 3 g of vitamin C per 100 g of pulp.13

Researchers at the Lineberger Comprehensive Cancer Center learned vitamin C, as well as other micronutrients found in foods such as vitamin E and beta-carotene, can reduce the risk of colon cancer by 30 percent to 70 percent.14 Like vitamins C and E, beta-carotene is an antioxidant, although rather than a vitamin classification, beta-carotene is a member of the carotenoid family. As part of the fat-soluble pigment family, beta-carotene is not alone in being studied against cancer; however, it is one of the more controversial supplements in the realm of cancer therapy.

While an animal model of lung cancer has shown beta-carotene to have a protective effect against tumor formation and metastasis,15 human trials have indicated the carotenoid may actually increase the risk of lung cancer, particularly in smokers.16

Because of beta-carotenes link to lung cancer, researchers at Dartmouth Medical School in New Hampshire evaluated the carotenoids effects on colon cancer risk.17 They learned that while beta-carotene markedly decreased cancer risk in non-smokers and non-drinkers, it doubled the risk of adenoma recurrence in subjects who smoked and consumed more than one alcoholic beverage per day. Additional research on beta-carotene in colon cancer was conducted at Catholic University in Rome, where researchers noted the carotenoid possessed growth-inhibitory and pro-apoptotic effects on tumor cells.18

In addition to beta-carotene, several carotenoids are thought to have protective effects against cancer. Researchers at the University of Hohenheim, Germany, suggested supplementation with a wide array of carotenoids might be beneficial for patients with colon cancer.19 They took biopsies from seven patients with colorectal adenomas, as well as five biopsies from healthy control subjects. Analysis indicated the colorectal cancer cases all displayed a significant reduction of carotenoid concentrations, including those of alpha-carotene, betacarotene, lutein, lycopene, zeaxanthin and beta-cryptoxanthin.

Lycopene is one of the better known carotenoids, and its role against cancer is mostly in the realms of breast and prostate cancer. Because lycopene is found in high concentrations in tomato products, many human trials have revolved around tomato consumption rather than lycopene supplements.

A research review out of Ohio State University in Columbus indicated the consumption of tomato products reduces the risk of prostate cancer.20 Researchers in Chicago randomly assigned 32 prostate cancer patients to a tomato-based diet for three weeks and noted those in the treatment group had a 17.5-percent reduction in prostate specific antigen (PSA, a marker of prostate cancer), as well as reductions of several other markers for prostate cancer.21

In vitro research out of the University of Toronto demonstrated lycopenes dose-dependent inhibitory effect against prostate cancer cells.22 A trial of 26 prostate cancer patients conducted at the Barbara Ann Karmanos Cancer Institute demonstrated supplementation with a tomato oleoresin extract (as Lyc-O-Mato, from LycoRed-Biodar, New York), which contained 30 mg of lycopene, reduced tumor size and made less involvement of surgical margins and/or extra-prostatic tissues with cancer less than in the control group.23 Similarly, researchers at Ohio State University suggested while lycopene is one of the compounds in raw and processed tomato products that may contribute to a reduced risk of prostate cancer, other carotenoids and phytochemicals in tomato products may be synergistically responsible for the health benefits.24

As for breast cancer, lycopene is an active inhibitor of the MCF-7 human breast cancer cell line, according to researchers at the Public Health College of Nanjing Medical University in China.25 A nested case-control study out of Johns Hopkins University demonstrated significantly reduced serum lycopene levels among women who developed breast cancer, and breast cancer risk was reduced by half in women in the highest fifth compared to the lowest fifth for lycopene intake.26 A similar study conducted by researchers at Ume University in Sweden showed lycopene and other plasma carotenoids may reduce the risk of developing breast cancer in postmenopausal women.27

Lycopene may also halt lung and liver cancer development. Researchers at the National Institute of Toxicology Research in Seoul, Korea, noted lycopene may be a chemopreventive agent against lung cancer in men, based on animal research.28 Lycopene supplementation also seems to reduce the risk of liver cancer, according to research presented at the American Academy of Cancer Research.29 For five years, patients at high-risk for liver cancer were given a natural tomato extract (as Lyc-O-Mato), containing 10 mg of lycopene, 10 mg of carotenoids and 50 mg of alpha-tocopherol. Study results showed liver cancer was suppressed by 50 percent in the treatment group compared to the control group.

Another carotenoid with anti-cancer potential is astaxanthin. Japanese researchers tested the anti-tumor effects of natural killer (NK) cells in mice, with and without astaxanthin supplementation.30 Astaxanthin improved the anti-tumor immune responses in rats subjected to stress. Another mouse model of cancer was investigated by researchers at the University of Minnesota, Minneapolis.31 They induced cancer in mice and found that those given astaxanthin had significantly lower tumor size and weight than control mice when supplementation was begun one and three weeks before tumor inoculation.

Just as carotenoids exhibit antioxidant properties, so can vitamin-like compounds such as coenzyme Q10 (CoQ10). Otherwise known as ubiquinone, CoQ10 has been shown in animal studies to have anti-cancer and immune-enhancing properties, according to researchers at the University of Sheffield in England.32 Researchers noted that while preliminary evidence is promising, further animal research, as well as human clinical trials, are needed to elucidate the nutrients potential role in cancer prevention.

Aside from vitamins and carotenoids, several minerals also have antioxidant properties that are believed to lend them to cancer inhibition. While zinc was actually linked to an increased risk of prostate cancer when taken in doses greater than 100 mg/d,33 additional research showed zinc to be an immune-enhancer through the promotion of T-cell responses.34 Zinc helps to regulate a wide variety of immune system activities, including white blood cells and NK cells. It is also a cofactor for the antioxidant enzyme Zn/Cu superoxide dismutase, and even moderate zinc deficiency is known to increase free radical levels and lipid peroxidation, as well as decrease endogenous antioxidant enzyme activity.35 Zinc supplementation may enhance immune activity, thereby strengthening disease resistance, according to unpublished animal research out of North Carolina State University in Raleigh that utilized a zinc-methionine complex (as OptiZinc, manufactured by Benicia, Calif.-based InterHealth Nutraceuticals Inc.).

More often than bladder or lung cancer, selenium is studied for its protective effects against prostate cancer. Animal research out of Purdue University in West Lafayette, Ind., indicated dietary selenium supplementation decreased DNA damage and increased epithelial cell apoptosis in the aging canine prostate.38 In human research, the Nutritional Prevention of Cancer Study Group at the University of Arizona, Tucson, noted supplementation with 200 mcg/d of selenium significantly reduced the overall incidence of prostate cancer, although the effect was restricted to subjects with lower baseline PSA and plasma selenium values.39

In addition to the antioxidant micronutrients, nonscavenging nutrients also have benefits against cancer. Among these, the B vitamins are thought to protect against several types of cancer. Vitamin B6 seems to inhibit colon cancer40,41 and breast cancer.42

Similarly, researchers at the Gujarat Cancer and Research Institute in India noted plasma vitamin B12 and folate levels seem to have an impact on the development of head and neck cancers.46 Researchers evaluated plasma vitamin levels from 56 controls, 156 patients with oral precancerous conditions (OPC) and 214 head and neck cancer patients. Those in the lower quartile of vitamin B12 and folate status were at a higher risk of developing OPC (and those with OPC were at an increased risk of head and neck cancer) compared to those in the higher quartiles.

Researchers at Rockefeller University, New York, reviewed chemoprevention of colon cancer and stated folic acid, as well as vitamin D and calcium can modulate and inhibit colon cancer.47 Researchers stated the micronutrients induce important molecular events and cellular actions that contribute to their tumor-modulating effects.

However, not all news regarding the two bone-building nutrients, calcium and vitamin D, is positivesome epidemiological evidence says calcium actually increases the risk of prostate cancer.48 ACS researchers conducted a prospective cohort study of 65,321 men and found total calcium intake (from diet and supplements) was associated with a modest increase in prostate cancer risk. In addition, men who had high dietary intake of calcium also were at an increased risk, although neither moderate intake levels nor dairy intake exacerbated risk.

As for vitamin D, while intake through diet and sun exposure has been shown to reduce cancer risk, the use of natural vitamin D has not been popular because of its propensity to cause hypercalcemia, according to researchers at CCS Associates in Mountain View, Calif.49 However, there are several promising synthetic analogs under development, which solve the problem of hypercalcemia and may be of therapeutic value in prostate cancer,50 breast cancer,51 and cervical and ovarian cancers.52

Botanicals

While micronutrients are essential for human health and disease prevention, several botanicals may be able to boost the bodys defenses and assist in the fight against invading pathogens and cell mutations that may lead to cancer. In the realm of botanical research, there are several big guns, with soy arguably being one of the biggest.

Image: Those Concerned With Prevention Have Highest Supplement Use

Researchers at FooYin University in Taiwan reported several soy isoflavonesgenistein, daidzein and biochanin-Ahave been linked to a reduced risk of cancer, so they conducted in vitro research to determine if the isoflavones could inhibit human hepatoma (liver cancer) cell lines.53 Their experiments indicated each of the three isoflavones inhibited growth in five lines of human hepatoma cells in a dose-dependent manner, and the three isoflavones in combination had a significant tumor-suppressive effect in a mouse study.

Genistein and soy have also been studied for their protective effects against colorectal cancer. In vitro and animal research conducted at the University of Illinois, Chicago, indicated genisteins protective effects inducing apoptosis in colon cancer cells and inhibiting colon cancer cell growth both in vitro and in vivowere enhanced when it was conjugated with the 17.1A monoclonal antibody, which is known to recognize the epithelial membrane antigen that is overexpressed in colon cancer.54

A research review of soybean, soyfood and isoflavone intake as they related to epidemiological studies of colon cancer uncovered inconsistent results, according to researchers at Kyushu University in Japan.55 Animal studies consistently showed an inhibitory effect of soyfoods and isoflavones against the formation of colonic aberrations, although they did not demonstrate an inhibitory effect against chemically induced colorectal cancer. Additionally, several case-control studies have suggested soy consumption reduces the risk of colorectal cancer, although these results are inconsistent. Researchers concluded additional epidemiological studies are needed to clarify the role soyfoods play in colorectal cancer.

While some evidence exists for soy in regard to hepatic and colorectal cancers, soy and its isoflavones have most often been studied in the realms of prostate and breast cancers. A research review of prostate cancer and soy, conducted at Nutrition Matters Inc. in Port Townsend, Wash., noted men concerned about prostate health may consider incorporating soy into their diets.56 The review uncovered in vitro research that showed genistein inhibited prostate cancer cell growth, as well as animal research that indicated isoflavone-rich soy protein and isolated isoflavones inhibited prostate tumor development. The review also mentioned a pilot intervention trial in which isoflavones appeared to benefit prostate cancer patients. More specifically, a case-control study of Chinese subjects conducted by researchers at the University of California, San Francisco, indicated soyfood and isoflavone (genistein and daidzein) consumption reduced prostate cancer risk.57

Animal research focusing on the protective effects of soy and its isoflavones has also garnered promising results. Researchers at the University of Notre Dame in Indiana studied a rat model of prostate cancer and witnessed a protective effect of soy-derived phytoestrogens.58 Researchers used Lobund- Wister (L-W) rats, which are predisposed to prostate cancer and develop the disease about 30 percent of the time. To test the protective effects of soy, researchers fed one group of L-W rats a regular diet and another group a modified starch-casein diet in which soy protein isolate and isoflavones (supplied by The Solae Co., St. Louis) replaced casein as a protein source. As expected, 30 percent of the traditionally fed rats developed prostate cancer, while only 3 percent of the soy-fed rats did. In another rat model of prostate cancer, researchers from the University of Ume in Sweden transplanted a human prostate cancer cell line (LNCaP) in mice and fed them a control diet, rye bran-based diet or a soy protein-based diet (provided by The Solae Co.).59 In the rye and soy groups, tumor cell apoptosis was increased, and only 30 percent and 50 percent of the transplanted sites developed tumors, respectively.

A human trial of genistein consumption and prostate cancer was conducted by researchers from the University of California, Davis.60 In the study, 62 men with biopsy-proven prostate cancer and elevated PSA levels were given 5 g/d of genistein concentrated polysaccharide (GCP, distributed by Maypro Industries in North America; the trademark is owned by Japan-based Amino Up Chemical) for six months. Of the 16 subjects who were on watchful waiting, GCP induced a significant drop in PSA levels among 13 of them by up to 61 percent. Researchers stated their study must be interpreted cautiously because of the small sample number, but they concluded the findings merit a larger, placebo-controlled trial in patients who are on watchful waiting. A case report of GCP in prostate cancer indicated 44 days of low-dose supplementation induced a significant drop in PSA levels with no side effects.61

As for breast cancer, in vitro research has shown genistein is functionally similar to the anti-estrogen pharmaceutical tamoxifen and induced apoptosis in a dose- and time-dependent manner in the MCF-7 human breast cancer cell line.62 Additional in vitro research with genistein indicated similar results, with the isoflavone arresting MCF-7 cell growth and decreasing proliferation.63

Animal research with genistein has also shown positive results. Researchers at the University of Illinois, Urbana-Champaign, injected mice with F3II mouse mammary adenocarcinoma cells and fed them either a diet supplemented with .6-percent soy extract (containing genistein at 750 ppm) or genistein alone.64 Mice in the soy group exhibited a 90-percent reduction in tumor weight compared to controls and a 40-percent reduction in the genistein-only group. Researchers concluded genistein, as well as other constituents in soy extract, might suppress mammary tumor growth. In human research, miso soup and isoflavone consumption is inversely associated with breast cancer occurrence, particularly in postmenopausal women.65

Issuing a word of caution, researchers at the University of Minnesota, St. Paul, noted phytoestrogens may stimulate breast cancer cell growth under certain circumstances and before recommendations regarding phytoestrogen supplementation can be made, safety with respect to breast cancer must be determined.66 NIH-funded animal research out of the University of Illinois at Urbana-Champaign indicated genistein may negate the effect of the breast cancer drug tamoxifen.67

Like soy, red clover is rich in isoflavones, which researchers in Australia studied for their effects against prostate cancer.68 Of 38 men who were diagnosed with prostate cancer and scheduled for surgery, 20 were randomly assigned to receive 160 mg/d of red clover isoflavones genistein, daidzein, formononetin and biochanin A. When biopsies from treated and non-treated men were compared, researchers learned dietary isoflavones may halt the progression of prostate cancer by inducing apoptosis in low- to moderate-grade tumors.

Researchers at Keck School of Medicine in Los Angeles conducted a population-based, case-control study and found that both soy and green tea consumption had significant, independent protective effects on breast cancer risk.69 They interviewed 501 breast cancer patients and 594 control subjects and found that green tea drinkers had a significantly reduced risk of breast cancer, as did soy consumers. However, the green tea drinkers tended not to consume soy, nor did the soy consumers tend to drink green tea.

Another big gun in cancer research, green tea was featured in a research review out of Montreal, which showed it and its catechins epigallocatechingallate (EGCG) and epigallocatechin (EGC)in addition to being antioxidants, also affect several mechanisms that play crucial roles in the development of human cancers.70 In vitro research has shown EGCG induces apoptosis and inhibits growth of a rat cancer cell line71 and a line of human cervical cancer cells,72 and EGCG and EGC decrease activity of a key molecule that is thought to increase the risk of tobacco-related cancer.73 In addition, EGCG protects normal cells against genotoxic hazard.74 Specifically, EGCG has been shown to promote keratinocyte survival and inhibit UV-induced apoptosis.75

Research into green teas protective effects against skin cancer came out of the University of Alabama at Birmingham, where researchers noted green tea is photoprotective in nature and has antioxidant and anti-inflammatory properties.76 Researchers conducted animal studies and found both topical treatment with and oral consumption of green tea polyphenols (EGC and EGCG) inhibited UV-radiation-induced skin cancer. Researchers at the University of California, Irvine, also studied green teas effects in skin cancer and noted EGCG acted as a chemopreventive agent for non-melanoma skin cancer.77 Researchers at Fudan University in Shanghai, China, conducted a population-based case-control study and found green tea protected smokers and drinkers against gastric, liver and esophageal cancers.78

In regard to prostate cancer and green tea, a human trial conducted by researchers at the Mayo Clinic and Mayo Foundation in Rochester, Minn., did not garner promising results.79 Researchers enrolled 42 patients with progressive prostate cancer who continued standard hormone therapy and were also instructed to consume 6 g/d of green tea orally in six doses, which each contained 100 calories and 46 mg of caffeine. Only one patient exhibited a decrease in PSA (defined as greater than or equal to 50 percent of baseline values), and this response was not sustained beyond two months. In addition, after one month, the median change in PSA values for the cohort was a 43-percent increase, and 69 percent of the subjects experienced green tea toxicity, including nausea, insomnia, fatigue, diarrhea, abdominal pain and confusion.

Like green tea, grapeseed extract contains antioxidant constituents that may lend it to cancer therapy and prevention. Its oligomeric proanthocyanidins (OPCs) are flavonoid-rich and may protect against cancer. Oral administration of a grapeseed proanthocyanidin extract (GSPE) was shown to significantly protect against colon cancer formation in a rat model, as noted by researchers at the University of Illinois, Urbana.80 Researchers at Creighton University School of Pharmacy & Allied Health Professionals in Omaha noted GSPE has significantly better free radical scavenging capabilities than vitamins C and E or beta-carotene, and it demonstrated significant cytotoxicity toward human breast, lung and gastric cancer cells while enhancing growth and viability of normal cells.81

An investigation into the protective nature of a novel GSPE extract showed it prevented the toxic side effects of chemotherapy by decreasing the growth inhibitory and cytotoxic effects of two chemotherapeutic agents on non-malignant human cells in vitro, and by significantly reducing the number of cells that underwent apoptosis after chemotherapy.82

Garlic, as an allium vegetable (its Latin name is Allium sativum), seems to lower the risk of prostate cancer, according to researchers at NCI.84 They conducted a population-based study of men in China and found men in the highest of three intake categories of total allium vegetables had a significantly lower risk of prostate cancer compared to those in the lowest category. Patients with diagnosed prostate cancer may also benefit from garlic supplementation, according to researchers at the Ankara University Medical Facility in Turkey.85 They recruited nine patients with prostate cancer and assigned them to consume an aqueous garlic extract daily for one month, after which time subjects exhibited significantly lowered total and free PSA levels.

Another botanical studied frequently in the realm of prostate health is saw palmetto, although it is much more often discussed in regard to benign prostatic hyperplasia than prostate cancer. While there is some concern regarding whether saw palmetto can affect serum PSA, two human clinical trials have shown it apparently has no effect on PSA levels.86,87 On a positive note for those worried about prostate cancer, researchers from Boston BioProducts Inc. in Ashland, Mass., conducted in vitro research and concluded saw palmetto may be useful in prostate cancer chemoprevention by inhibiting prostate cancer cell growth.88

An extract from French maritime pine bark may also be relevant in terms of cancer prevention. In vitro research conducted at Loma Linda University School of Medicine showed the extract (as Pycnogenol, available from Hillside, N.J.-based Natural Health Science) selectively induced death in a human mammary cancer cell line (MCF-7) but did not increase cell death in normal human mammary cells.89

Specialty Ingredients

The natural products industry has several specialty ingredients available that have been studied for their anti-cancer properties. Like the micronutrients and botanicals, natural specialty ingredients have shown anti-tumor, anti-angiogenic and anti-carcinogenic attributes.

One category popularly studied for its role in cancer is mushrooms. These medicinal fungi contain polysaccharides that are believed to have immunomodulatory properties, which may be a mechanism of action. Reishi mushroom is known to reduce tumor incidence and size, as demonstrated by animal research conducted at Hiroshima University in Japan.91 Investigation into Reishis mechanism of action has uncovered various results. Researchers at Seoul National University in Korea stated Reishi did not act through an immuneenhancing mechanism in their experiments.92 They showed Reishi had a dose- and time-dependent effect on the MCF-7 human breast cancer cell lineit inhibited cell proliferation and directly induced apoptosis in the cancer cells.

Researchers at the Methodist Research Institute investigated Reishis molecular mechanisms and noted it inhibited invasion of breast and prostate cancer cells by a common mechanism.93 Their in vitro experiments showed Reishi inhibited the expression and secretion of several factors that contribute to cancer cell motility, thereby suppressing migration of both cancer cell lines.

Like Reishi, Maitake mushroom is thought to act through various mechanisms of action, although it is more often noted to be an immuneenhancer. In vitro research conducted with human prostate cancer cells indicated Maitake beta-glucan (as Grifron-D, manufactured by Paramus, N.J.-based Maitake Products) dose-dependently caused cell death within 24 hours, according to researchers from New York Medical College in Valhalla.94

Several in vitro studies have investigated Maitakes immune-enhancing properties and its effects on cancer development. Researchers at Kobe Pharmaceutical University in Japan noted the Dfraction of Maitake activated cellular immunity and expressed antitumor effects.95 They investigated the beta-glucans anti-tumor functions in relation to its control of the balance between the T lymphocyte subsets Th-1 and Th-2, and found D-fraction decreased the activation of B cells and potentiated the activation of helper T cells, which indicated an enhancement of cellular immunity. Researchers also noted that Th-2 dominance can be due to cancer, and establishing Th-1 dominance induces cellular immunity. In subsequent animal research, the investigators learned D-fraction also affects helper cell cytokine expression; namely, D-fraction reduced the expression of the Th-2 cytokine interleukin (IL)-4 and increased expression of the Th-1 cytokine interferon (INF)-gamma.96

The same researchers conducted subsequent human research and learned Maitake D-fraction helped cancer patients maintain elevated levels of NK cells, which are directly cytotoxic to tumor cells, for one year.97 To explain this effect, researchers conducted a mouse experiment and learned the corresponding increases in tumor necrosis factor (TNF)-alpha and INF-gamma increased TNF-alpha expression in NK cells, as well as increased macrophage-derived IL-2, which activates NK cells. A subsequent human trial using Maitake MD-fraction, which contains beta-1,6 glucan with beta-1,3 branched chains, indicated oral supplementation induced cancer regression or symptom improvement.98 Specifically, cancer regression or symptom improvement was seen in 58 percent of liver cancer patients, 69 percent of breast cancer patients and 63 percent of lung cancer patients. However, less than 10 percent to 20 percent improvement was seen in leukemia, gastric cancer and brain cancer patients. Researchers also noted Maitake, when added to chemotherapy, improved immune-competent cellular activity 1.2- to 1.4-fold.

Like Maitake, the beta-glucan fractions of Agaricus blazei (A. blazei) are thought to protect against cancer development. Researchers at Tokyo University of Pharmacy and Life Science discovered A. blazeis 1,6-beta glucan showed anti-tumor activity in mice, and a high branched 1,3-beta glucan segment forms the active center of the anti-tumor activity.99 Additional animal research out of the Sumitomo Forestry Tsukuba Research Institute in Japan indicated A. blazei derivatives, when injected into tumors, induced tumor regression at doses between .1 mg and 2.5 mg; however, oral administration of A. blazei derivatives did not cause the same result.100 Researchers then treated the fraction with acid and found oral administration of the acid-treated A. blazei fraction also caused tumor regression, indicating its potential as an oral chemotherapeutic formulation. Contrarily, researchers in Brazil conducted animal research and found treatment with the aqueous extracts of A. blazei did not exert any protective effects against the development of liver cancer risk factors.101

One ingredient, AHCC (Active Hexose Correlated Compound), is a hybridization of several species of medicinal mushrooms that has immune-enhancing properties, particularly in the realm of cancer. [Editors note: Amino Up Chemical Co. in Sapporo, Japan, owns the trademark for AHCC; Purchase, N.Y.-based Maypro Industries distributes the raw material.] An in vitro study out of the Dokkyo University School of Medicine examined the effects of AHCC on apoptosis of thymocytes.103 A 4-percent concentration of AHCC in drinking water given to rats before chemically induced thymic cell apoptosis seemed to protect the thymic cells, leading researchers to conclude this may be a mechanism behind AHCCs immunomodulatory effects. AHCC may also work by increasing NK cell activity, and helping the production of IFN-gamma and IL-12, according to a study of Stage IV cancer patients.104

A human study of AHCC indicated it can improve the prognosis of postoperative cancer patients, according to researchers at the Kansai Medical University in Osaka, Japan.105 Researchers enrolled 269 patients with confirmed liver cancer, all of whom had a tumor surgically removed. Of the 269 patients, 113 received oral AHCC therapy after surgery, and researchers noted the AHCC group had a significantly longer period of no recurrence and an increased overall survival rate than the control group.

A derivative of aloe vera known as aloe-emodin is another ingredient that may have protective effects against liver cancer, according to researchers at Kaohsiung Medical University in Taiwan.106 Their in vitro study indicated aloe-emodin inhibited cell proliferation and induced apoptosis in two human liver cancer cell lines. Another constituent of aloe, a polysaccharide called aloeride, was investigated at the National Center for Natural Products Research at the University of Mississippi, where researchers determined it was a potent immunostimulant.107

Topical application of aloe vera gel may also be of use to cancer patients by alleviating some of the discomforts associated with radiation treatment, according to researchers at the University of Miami.108 Study participants began prophylactic skin care on the first day of radiation therapy, including cleansing the area with mild, unscented soap. Subjects in the treatment arm of the trial were also instructed to apply aloe vera gel liberally at various intervals throughout the day. Researchers noted those in the aloe group had a median time of five weeks before skin changes occurred, compared to three weeks among the control subjects. Also, when the cumulative dose was increased over time, adding aloe to the soap regimen seemed to have a protective effect. In contrast, researchers at the Royal Brisbane Hospital in Australia did not see this protective effect when aloe vera topical gel was used to reduce radiation-induced skin changes.109

I3C may work synergistically with the soy isoflavone genistein against breast cancer, according to research out of the North Shore-Long Island Jewish Research Institute in New York.112 Where estrogen increases the growth and survival of tumors, I3C combats the effects of estrogen, causing growth arrest and increasing apoptosis, according to the researchers. They also found that there is a synergistic effect of I3C and genistein in increasing apoptosis, meaning lower concentrations of each phytochemical can be utilized when the two are used in combination against estrogen-dependent cancer.

The same researchers conducted additional investigations with I3C and stated the dietary indole may play an important role in preventing hormone-related cancers such as those of the breast and prostate.113 They found incubating prostate cancer cells (LNCaP) with I3C for 24 hours before applying TNF-related apoptosis-inducing ligand (TRAIL) enhanced the apoptotic effects of either used separately.

In addition to I3C, the polymeric product 3,3-diindolylmethane (DIM) is also known to suppress growth of prostate cancer cells in a time- and dose-dependent manner, according to researchers at the Technion-Israel Institute of Technology in Haifa.114 And, according to prostate cancer research out of the University of Newcastle in New South Wales, Australia, I3C and sulforaphane (another constituent of cruciferous vegetables) each exhibit antiproliferative actions on prostate cancer cells.115 I3C also happens to have an antiproliferative effect on colon cancer cells, according to the Newcastle researchers.116

A carbohydrate derived from the peel of citrus fruit, modified citrus pectin, is also known to be of use against prostate cancer. A study presented at the Whole Person Healing conference indicated of 13 men with prostate cancer and low levels of PSA, those taking modified citrus pectin (as Pecta-Sol from EcoNugenics Inc. in Santa Rosa, Calif.) for 12 months inhibited PSA.117 Prior animal research conducted with modified citrus pectin showed oral intake of the compound significantly reduced tumor growth, spontaneous metastasis and angiogenesis.118

Another natural product that has been found to inhibit angiogenesis is a standardized multiple berry extract (as OptiBerry, developed by InterHealth Nutraceuticals, Benicia, Calif.)119. Researchers at the Ohio State University Medical Center investigated the berry extracts effects in an experimental in vivo model of angiogenesis and found both OptiBerry and a blueberry powder possessed anti-angiogenic properties.

Researchers at Hallym University in Chunchon, Korea, also investigated CLAs mechanism of action, having shown the fatty acid inhibited colon cancer in rats and induced apoptosis in a human colon cancer cell line.121 They discovered CLA decreased insulin-like growth factor (IGF)-II synthesis and down-regulated IGF-I receptor signaling, which explained CLAs inhibition of cell proliferation and its induction of apoptosis.

Dietary CLA may also be protective against colon and breast cancers, according to an animal study out of Nagoya City University in Japan.122 Rats fed a 1-percent dose of conjugated fatty acids derived from safflower oil, which is known to be high in CLA content, exhibited resistance to induced breast and colon cancer.

While cancer remains a threat to Americans and people worldwide, the increasing amounts of research may help with understanding the means of preventing and treating cancer. From in vitro research that holds promise of causing cell death in cancer lines to human research that seems to indicate increased survival rates, the scientific community and natural products industry continue to work hand in hand to reduce the threat of malignancy.

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