Cancer

Cancer

by Kim Schoenhals

Cancer is one of the leading causes of death in America, second only to heart disease. There were approximately 553,400 cancer deaths in 2001--more than 1,500 people per day--according to the American Cancer Society (ACS) (www.cancer.org). ACS also estimated the total number of newly diagnosed U.S. cancer cases in 2001 was 1,268,000, excluding basal and squamous cell skin cancers--of which more than 1 million cases were diagnosed on 2001--and in situ (noninvasive cancer) carcinomas, except urinary bladder. Lung cancer is the leading cause of cancer death in the United States (there were 157,400 lung cancer deaths in 2001), followed by colorectal cancer (56,700), breast cancer (40,600) and prostate cancer (31,500).

The single most important risk factor for cancer is age, according to the National Institutes of Health (NIH). Aside from age, smoking status and alcohol intake are telling signs of cancer risk. Approximately 172,000 cancer deaths were caused by tobacco use in 2001, and about 19,000 cancer deaths may have been related to excessive alcohol use, according to ACS. Obesity also increases the risk of certain cancers. The relative risk of breast cancer increases by 50 percent in obese women, and the risk of colon cancer increases 40 percent in obese men.

For those Americans who do not use tobacco, dietary choices and physical activity become the most important modifiable determinants of cancer risk. More than a dozen food-derived agents are currently being studied for their application in cancer prevention, according to James Crowell, Ph.D., who--with his colleagues at the National Cancer Institute (NCI)--presented a symposium as part of the Experimental Biology meeting in Washington, D.C., April 17 to 21, 1999, on the progress of cancer chemoprevention and the development of diet-derived chemopreventive agents.¹ Some compounds for which NCI is funding academic research include green and black tea polyphenols, soy isoflavones, vitamin D, vitamin E, selenium, calcium and indole-3-carbinol. "Many pharmacologically active compounds will come out of foods," Crowell said. "Because the food industry has not typically had experience in doing this type of research, I think the government has a good part to play. ... It's important that some of these [food-derived agents] be investigated in a thorough and systematic scientific way, as you would for a drug."

Because a poor diet is a significant risk factor for cancer development, vitamin and mineral intake is also closely correlated with reducing the risk of cancer. Aside from vitamin and mineral supplements, various carotenoids, botanicals and essential fatty acids may have roles in the prevention of cancer.

Vitamins and Minerals

Vitamins and minerals are among the most often studied supplements on the market and the most popular with consumers. Cancer patients are more likely than the general population to turn to alternative remedies for adjuvant support. According to the Natural Marketing Institute's Health & Wellness Trends Database--three years of trended data including more than 2,000 consumer household respondents--71.1 percent of consumers who have cancer use multivitamin and multimineral supplements compared to 66.8 percent of the general population. In addition, cancer patients are more likely to believe in the benefits of multivitamin and mineral supplements than the general population. While 33 percent of the general population "agrees completely" that vitamins and minerals are beneficial in the prevention of certain health conditions, 38.9 percent of cancer patients say the same, according to NMI.

One of the most well known bunch of vitamins and minerals are antioxidants. With their free radical fighting skills, antioxidants protect the body from oxidative damage, which is considered a major factor in cancer development. One antioxidant all-star is vitamin E. According to NMI, 58.4 percent of consumers who have cancer supplement their diet with vitamin E as compared to 45.7 percent of the general population. Vitamin E supplements usually contain alpha-tocopherol, although there are eight potentially beneficial isomers of vitamin E: alpha-, beta-, delta- and gamma-tocopherol, as well as alpha-, beta-, delta- and gamma-tocotrienol.

Researchers from NCI evaluated data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and discovered that daily supplementation with alpha-tocopherol reduced prostate cancer risk in a large, randomized cohort.² Additional research conducted by scientists from the University of Rochester determined the mechanism of action behind alpha-tocopherol's anti-carcinogenic properties could be its suppression of prostate-specific antigen (PSA), a marker for the progression of prostate cancer, as well as its inhibition of the growth of prostate cancer cells in vitro.³

Vitamin E has also been suggested to prevent gastric cancer, according to researchers at Jagiellonian University in Cracow, Poland. In reviewing 180 colorectal cancer and 80 gastric cancer cases, researchers concluded there was an inverse correlation between vitamin E and gastric cancer.⁴

One researcher from the Wake Forest University School of Medicine in Winston-Salem, N.C., conducted a research review and concluded the modest protection from breast cancer associated with dietary vitamin E may be due to the effects of the other tocopherols and tocotrienols in the diet, not just alpha-tocopherol. The researcher cited several studies in which vitamin E supplements protected against breast cancer. Specifically, alpha-, gamma- and delta-tocotrienol, as well as delta-tocopherol, reduced the growth and enhanced the death of cancer cells, which may reduce the risk of breast cancer.⁵

The tocotrienol mixture from palm oil was also determined to inhibit several lines of breast cancer cells, according to in vitro research conducted at the Palm Oil Research Institute of Malaysia in Kuala Lumpur.⁶

Another antioxidant vitamin, vitamin C, is commonly studied for its effects in cancer prevention. NMI noted that while 45.4 percent of the general population uses vitamin C supplements, 55.7 percent of cancer patients take them. Vitamin C has been linked with reducing the risk of gastric and esophageal cancer by joint research out of Yale University's School of Medicine, NCI and other institutions. Their research was a three-region, case-controlled study involving 1,095 Americans diagnosed with cancer of the esophagus or stomach and 687 healthy controls. Vitamin C use was defined as taking a supplement at least once a week for a minimum period of six months.⁷ "Our study suggests that taking a vitamin C supplement on a regular basis may protect against certain types of stomach cancer," said Susan T. Mayne, an associate professor at Yale University School of Medicine and lead investigator of the study, in a press release from the Dietary Supplement Information Bureau and IMAGINutrition Inc. "We found vitamin C supplement users to have a 40 percent lower risk of cancer in the middle and lower parts of the stomach."

Another compound with antioxidant properties is coenzyme Q10 (CoQ10), which is essential to cellular energy production. According to research out of Purdue University in West Lafayette, Ind., CoQ10 deficiency is commonly found in cancer cases.⁸ Researchers from the Medical School of Osmangazi University in Eskisehir, Turkey, found similar results. A group of 21 breast cancer patients who had undergone radical mastectomy exhibited significantly decreased CoQ10 concentrations in tumor tissues as compared to the surrounding normal tissues. Researchers concluded that supplementation with CoQ10 might induce protective effects on breast tissue.⁹

In addition to antioxidant vitamins, the B vitamins are purportedly useful against cancer. Compared to 24 percent of the general population, 27.8 percent of those fighting cancer take a B complex, according to NMI. In addition, NMI noted that 19.1 percent of cancer patients take folic acid, compared to 14.6 percent of the general population.

Folic acid is especially protective during pregnancy, according to research out of the Cancer Foundation of Western Australia in West Perth. Women who took folate supplements during pregnancy gave birth to children with reduced risk of developing acute lymphoblastic leukemia.¹⁰

Folic acid may also have protective effects against gastric cancer, as demonstrated by animal research conducted at the Shanghai Second Medical University in China. They fed 16 male dogs a chemical carcinogen for 15 months. Half of the dogs also received 20 mg/d of folic acid. All animals in the control group and only three of eight animals in the folate group developed cancer.¹¹

Human research conducted at the Albert Einstein College of Medicine in Bronx, N.Y., indicated that folic acid intake may reduce the risk of colorectal cancer. Researchers reviewed a total of 56,837 female cases from the Canadian National Breast Screening Study, of which 389 cases of colorectal cancer were diagnosed during follow-up. A subcohort of 5,681 women was randomly selected at baseline. The final analysis, which was based on 295 cases and 5,334 controls, indicated that the women with the highest intakes of folic acid were the least likely to develop colorectal cancer.¹²

Research out of Tufts University in Boston demonstrated that in addition to folic acid, vitamins B2, B6 and B12 are involved in cancer prevention because they are the source of coenzymes that participate in one carbon metabolism, a metabolic process that affects DNA. According to researchers, cancer may be partially explained by inadequate intake of these vitamins.¹³

Vitamin B6 may also offer specific protection against cancer, as indicated by recent animal research out of Hiroshima University in Japan. Researchers fed mice one of four diets (1 mg/kg, 7 mg/kg, 14 mg/kg or 35 mg/kg of vitamin B6) for 22 weeks, and the mice were given a weekly injection of azoxymethane to induce cancer. The 7 mg/kg, 14 mg/kg and 35 mg/kg diets significantly suppressed the incidence and number of colon tumors, leading the researchers to conclude that vitamin B6 suppresses colon cancer by reducing cell proliferation.¹⁴

Vitamin D is another vitamin that may have some clout in the fight against cancer. Specifically, it is believed to protect against colon cancer, according to animal research conducted by David J. Mangelsdorf, Ph.D., and investigators from the Howard Hughes Medical Institute, based in Chevy Chase, Md., who were studying the mechanism of action behind vitamin D's protective effects. Vitamin D helps the body detoxify lithocholic acid, a secondary bile acid created in the intestine during the digestion of fat, which has been shown to cause colon cancer in lab animals. However, when the lab animals were given concurrent high doses of vitamin D, they did not develop colon cancer.¹⁵ "Vitamin D is not a therapy for colon cancer," Mangelsdorf said. "It prevents it. That's why it's important to already have in your diet an adequate supply of vitamin D. ... But you have to be careful because vitamin D is toxic at high concentrations."

In addition to vitamins, minerals are a hot topic in the realm of cancer prevention. Selenium has been on the forefront of current research, especially in regard to prostate cancer. NCI is at present conducting a 10-year trial to determine the efficacy of vitamin E and selenium for preventing cancer of the prostate. Independently, low plasma levels of selenium have been associated with a four- to five-fold increase in the risk of prostate cancer, according to researchers from the Stanford University Medical Center in Stanford, Calif.¹⁶ Selenium (as SelenoExcell, manufactured by Fresno, Calif.-based Cypress Systems) is being studied in several other NCI-funded clinical trials at Tucson's University of Arizona Cancer Center to determine the mineral's role in reducing the risk of prostate cancer.

Low serum selenium levels are also indicated in the risk of developing esophageal and gastric cancers, according NCI research. Investigators based a new study on a previous nutritional intervention trial--conducted in Linxian, China, where gastric and esophageal cancers are at epidemic rates--that determined supplementation with selenium, as well as beta-carotene and vitamin E, significantly lowered cancer mortality rates. Researchers measured serum selenium levels in 590 subjects with esophageal cancer, 402 with gastric cardia cancer and 87 with gastric non-cardia cancer, as well as 1,062 control subjects. Researchers found a highly significant inverse association between serum selenium levels with the incidence of esophageal and gastric cardia cancers, and concluded selenium levels affect the incidence of certain cancers.¹⁷

Another study conducted in Japan determined that selenium, as well as zinc, may protect against gastric carcinoma. Researchers from the Hirosaki University School of Medicine investigated the link between ingestion of trace elements and gastric carcinogenesis because mortality from gastric cancer in Japan is among the highest in the world. Their findings demonstrated a protective effect from selenium and zinc against the development of gastric cancer.¹⁸

Low serum concentrations of zinc, chromium and iron may be indicators for cancer risk, according to animal research conducted at Colorado State University in Fort Collins. Researchers compared 102 canine cancer cases with control animals and discovered the ailing animals exhibited mineral abnormalities--specifically, low concentrations of zinc, chromium and iron.¹⁹

Calcium is another mineral that has been indicated in cancer nutrition and is popular among consumers. According to NMI, 50.6 percent of the general population takes calcium supplements, while 59.6 percent of cancer patients supplement their diet with the mineral. Higher calcium intake may reduce the risk of colon cancer, according to researchers at the Harvard School of Public Health. Their study--involving 87,998 female cases from the Nurse's Health Study and 47,344 male cases from the Health Professionals Follow-up Study--demonstrated that consuming 700 mg/d to 1,250 mg/d of calcium may reduce the risk of developing distal colon cancer in both men and women.²⁰

In opposition to these findings, a different group of researchers from the Harvard School of Public Health concluded that men with diets high in dairy calcium may be at an increased risk for developing prostate cancer. Researchers investigated the association between dairy products, calcium intake and prostate cancer risk as part of the Physician's Health Study, a cohort of 20,885 male physicians. Compared with men consuming 0.5 daily servings of dairy products (150 mg/d), those consuming greater than 2.5 servings (more than 600 mg/d) had a 32-percent higher risk of prostate cancer.²¹

Mushrooms, Soy and Carotenoids

In addition to vitamin and mineral supplements, extracts taken from foods--such as medicinal mushrooms and vegetables--may also be effective in the fight to prevent cancer. Beta glucan, a polysaccharide of the Maitake mushroom, has been the topic of recent cancer trials. Researchers from New York Medical College in Valhalla explored the anti-carcinogenic potential of beta glucan using human prostate cancer cells in vitro. Researchers noted 95 percent cell death within 24 hours when treated with beta glucan (as Grifron-D, manufactured by Paramus, N.J.-based Maitake Products).²²

Aside from Maitake, Agaricus blazei (Himematsutake) is another variety of mushroom purported to have anti-carcinogenic potential. Research conducted with Agaricus blazei extract (provided by Los Angeles-based Atlas World USA) indicated that it can topically and orally prevent lesions associated with skin cancer, as well as inhibit the growth of various human tumor cell lines in vitro. Research out of the Universidade Estadual de Londrina in Brazil indicated that in addition to possessing anti-carcinogenic potential, an extract of Agaricus blazei exhibited antimutagenic effects in vitro. Researchers evaluated the effects of the extract on Chinese hamster V79 cells under three temperatures and concluded that the mushroom was not mutagenic itself, and it was an efficient antimutagen in all concentrations and preparations tested.²³

The active components of Agaricus blazei are believed to be its polysaccharides, beta 1,3-glucan and beta 1,6-glucan. These beta glucans are thought to stimulate immune activity, specifically the T-cell subsets, thereby inhibiting tumor formation.²⁴

Reishi (Ganoderma lucidum or Mannentake) is another medicinal mushroom believed to have application in the realm of cancer prevention. Researchers from Hiroshima University studied the modifying effects of a water-soluble extract from Reishi on the development of aberrations in the colons of male rats. They found that Reishi both inhibited cell proliferation in vitro, as well as inhibited anchorage-independent growth of several colon carcinoma cell lines. Scientists concluded that Reishi could act as a preventive agent for colon cancer.²⁵

A derivation of medicinal mushrooms, AHCC (Active Hexose Correlated Compound), has also been studied in anti-carcinogenic applications. (Editor's note: Amino Up Chemical Co. in Sopporo, Japan, owns the trademark for AHCC and Purchase, N.Y.-based Maypro Industries distributes the raw material.) AHCC, a hybridization of several species of medicinal mushrooms, may have synergistic effects with aglycone isoflavones, or genistein combined polysaccharide (GCP), against prostate and other cancers, according to a poster presentation given by Amino Up Chemical researchers at the American Association for Cancer Research conference in New Orleans on March 26 and 27. Researchers conducted in vitro research on six human cancer cell lines and two mouse cancer cell lines, with four derived from the prostate, and one each from the bladder, bone, lung and colon. Both GCP and GCP plus AHCC treatments inhibited the growth of all cell lines in a dose-dependent manner, while AHCC did not show obvious inhibiting effects except on the colon cancer cell line.

Cancer-Treating Consumers' Usage of Selected Vitamins & Minerals Compared to GP
Source: The Health & Wellness Trends Database
The Natural Marketing Institute, 2002

To further study these compounds and their anti-carcinogenic potential, researchers induced cancer in control mice, as well as those treated with GCP, AHCC or a combination of the two. Tumor growth was inhibited by treatment with GCP and AHCC singly, although combined treatment was more effective at inhibiting tumor growth and inducing apoptosis.²⁶

While the soy isoflavone genistein was shown to have anti-carcinogenic potential in combination with AHCC, soy and its components may also have protective effects against cancer individually. Soy supplements are popular with consumers who are treating cancer, as well. NMI noted that while 7.1 percent of the general population takes soy supplements, 10.9 percent of cancer patients take them.

Researchers from the Northern California Cancer Center in Union City conducted a population-based, case-control study of thyroid cancer in the San Francisco Bay Area. They interviewed 608 cases and 558 controls and assessed phytoestrogen consumption via a food-frequency questionnaire. Consumption of traditional and nontraditional soy-based foods and alfalfa sprouts was associated with reduced risk of thyroid cancer. Researchers noted that of the seven phytoestrogenic compounds examined, daidzein and genistein, as well as the lignan, secoisolariciresinol, were most strongly associated with risk reduction.²⁷

Researchers at the Barbara Ann Karmanos Cancer Institute in Detroit determined that the mechanism of action behind the anti-carcinogenic effects of genistein and daidzein is the isoflavones' ability to prevent oxidative damage. Researchers measured levels of oxidative damage in the blood of six women taking 50 mg/d of isoflavones and six men taking 50 mg of isoflavones twice daily. Supplementation with soy (as Novasoy, manufactured by ADM Health in Decatur, Ill.) was found to reduce the levels of oxidative DNA damage in all subjects.²⁸

Animal research conducted at the University of California, Berkeley, indicated soy may also protect against skin cancer. Investigators conducted a 19-week study on mice--those given the soy protein, lunasin, showed significantly lower rates of skin cancer than the control group. Mice in the high-dose group (125 mcg twice a week) had a 70-percent reduction of malignant tumors.²⁹

One negative aspect to soy supplementation is the ongoing concern that phytoestrogen intake may adversely affect breast cancer patients. In fact, recent NIH-funded animal research out of the University of Illinois at Urbana-Champaign indicated that genistein may negate the effect of tamoxifen, a commonly prescribed pharmaceutical for women with estrogen-dependent breast cancer. In a pre-clinical study, researchers divided 66 mice (whose ovaries had been removed) into six groups to monitor the effects of estrogen and various amounts of tamoxifen and genistein. Before genistein was added to the diet, tamoxifen had stopped tumor growth; however, the addition of genistein resulted in enhanced growth of estrogen-dependent tumors and increases in estrogen-responsive gene markers.³⁰

On a more positive note, soy is currently being studied by researchers at Ohio State University Comprehensive Cancer Center for its protective effects against prostate cancer in combination with the carotenoid lycopene. Lycopene from tomato sauce may reduce the risk of prostate cancer, according to researchers in Chicago at the University of Illinois, who advised 32 prostate cancer patients to consume one tomato sauce-based pasta dish daily for three weeks before prostatectomy. Levels of oxidative DNA damage and PSA were significantly reduced after the dietary intervention--28 percent and 17.5 percent, respectively.³¹

While its most popular application is in prostate cancer, lycopene has also been shown to reduce the risk of lung cancer. Harvard researchers, who evaluated more than 124,000 male and female cases from the Health Professionals Follow Up Study and the Nurses Health Study, linked diets rich in tomato-based products to a reduced risk of lung cancer. The researchers noted that those consuming the highest dietary amounts of lycopene, in addition to mixed carotenoids--alpha-carotene, beta-carotene, lutein and beta-cryptoxanthin--had a 20 percent to 25 percent reduced risk of lung cancer.³²

Carotenoid intake--beta-carotene, lutein, alpha-carotene and beta-cryptoxanthin--has been linked with a reduced risk of breast cancer, as well. Researchers from New York University School of Medicine compared 270 cases and 270 controls for serum levels of carotenoids. The risk of breast cancer almost doubled among subjects with blood levels of beta-carotene, lutein and beta-cryptoxanthin at the lowest quartile, as compared with those at the highest quartile.³³

Of the carotenoids, lutein is especially popular among cancer patients. According to NMI, 14.7 percent of those taking supplements for cancer take a lutein supplement compared to 8.6 percent of the general population. Lutein is linked to a reduced risk of colon cancer, according to researchers at the University of Utah Medical School. They collected dietary data from 1,993 case subjects with colon cancer and 2,410 population-based control subjects. Lutein intake from dietary sources was inversely associated with colon cancer in both men and women.³⁴

Astaxanthin, a carotenoid extract taken from algae, has been studied in conjunction with other carotenoids--beta-carotene and canthaxanthin--for its protective effects against breast cancer. Researchers at Washington State University in Pullman fed mice either a control diet with no carotenoids or one of six treatment diets containing 0.1 percent or 0.4 percent of beta-carotene, astaxanthin or canthaxanthin. Researchers induced cancer in the mice after three weeks. Plasma concentrations of astaxanthin were greater than beta-carotene or canthaxanthin, and all three carotenoids generally decreased mammary tumor volume. However, astaxanthin was found to dose-dependently reduce mammary tumor growth at a higher rate than the others.³⁵

Astaxanthin exerts anti-tumor activity through enhancing immune responses, according to researchers at the University of Minnesota in Minneapolis. Investigators fed mice an astaxanthin diet starting at zero, one and three weeks before inducing tumor growth. The astaxanthin-fed mice had significantly reduced tumor size and weight than control mice when supplementation was started one and three weeks before tumor inducement.³⁶

Botanicals

An extract derived from the aloe plant is also thought to have application in chemopreventive medicine. Researchers from the National Institute of Health Sciences in Tokyo induced pancreatic cancer in hamsters through four weekly subcutaneous injections, and then the animals were given zero, 1 percent or 5 percent freeze-dried aloe (Aloe arborescens) whole-leaf powder for five weeks. At week 54, the incidences of pancreatic cancers were significantly decreased in both the 1 percent and 5 percent aloe groups as compared to the control group. In addition, total lesions were significantly lower in the 5 percent aloe group than the control group. Researchers concluded that pretreatment with aloe prevented pancreatic cancer.³⁷

Similar results were garnered by researchers at Fujita Health University in Hisai, Japan. They examined the effect of whole-leaf Aloe arborescens (Miller var. natalensis Berger) on induced colorectal cancer in rats. Rats who were fed 1 percent and 5 percent diets of aloe for nine weeks exhibited fewer colorectal aberrations compared to the control animals. Researchers concluded that aloe may be effective for chemoprevention in colon cancer, at least in the initiation stage.³⁸

Another plant-based compound, the extract from French maritime pine bark, has shown anticarcinogenic potential in recent research. Investigators at Loma Linda University School of Medicine in California conducted in vitro research comparing the response of human breast cancer cells and normal human mammary cells to apoptosis in the presence of French maritime pine bark extract (as Pycnogenol, distributed by Hillside, N.J.-based Natural Health Sciences). Researchers discovered that cell death was significantly higher in the cancer cells treated with the extract than the untreated cells, and the extract did not increase the number of normal cell deaths. Researchers concluded that the extract selectively induced cell death in human mammary cancer cells and not in healthy mammary cells.³⁹

An extract from the berries of the saw palmetto plant has been studied for its potential role in cancer--specifically, prostate cancer. Saw palmetto, which is best known for its efficacy at reducing the symptoms of benign prostatic hyperplasia (BPH), may also be a potential anti-carcinogen. While research is conflicting, NMI data indicates that 9.4 percent of consumers who have cancer use saw palmetto as compared to 6.7 percent of the general population.

Cancer-Treating Consumers' Usage of Selected Botanical/Other Supplements Versus GP
Source: The Health & Wellness Trends Database
The Natural Marketing Institute, 2002

Researchers from Boston BioProducts Inc. in Ashland, Mass., conducted in vitro research on prostatic cell lines, which were treated with a saw palmetto berry extract. Proliferation of these prostatic cell lines was inhibited to different degrees when dosed for three days with saw palmetto. Researchers found that the saw palmetto treatment reduced Cox-2 expression, which is associated with an increased incidence of prostate cancer.⁴⁰

While in vitro research is promising, human research has not thus far indicated that saw palmetto would be helpful against prostate cancer. A clinical trial conducted at the University of California, Los Angeles, involving 44 men demonstrated that the supplement did not affect PSA or prostate volume, although it was seen to be a safe, highly desirable option for men with moderately symptomatic BPH.⁴¹

Grape seed extract, which contains antioxidant compounds called proanthocyanidins, may also inhibit cancer cell growth. Researchers from Creighton University School of Pharmacy & Allied Health Professionals in Omaha, Neb., compared the antioxidant capabilities of a novel IH636 grape seed proanthocyanidin extract both in vitro and in vivo to vitamins C, E and beta-carotene. Researchers said the grape seed proanthocyanidin extract was highly bioavailable and provided superior free radical protection. In addition, the extract demonstrated cytotoxicity toward human breast, lung and gastric cancer cells while enhancing the growth and viability of normal human gastric mucosal cells.⁴²

Researchers from the University of Nebraska Medical Center in Omaha conducted in vitro research, comparing the destructive effects of chemotherapy on Chang liver cells treated with grape seed proanthocyanidins with untreated cells. The extract decreased the number of cell deaths induced by chemotherapy, leading researchers to conclude proanthocyanidin is a potential candidate for lessening the toxic effects associated with chemotherapeutic agents used to treat cancer.⁴³

Similar to proanthocyanidins from grape seeds, dietary indoles--including indole-3-carbinol (I3C), diindolylmethane, ascorbigen and gramine--can be extracted from cruciferous vegetables and some forms of grain. Of the dietary indoles present in nature, I3C and diindolylmethane are purportedly useful in inhibiting cancer growth, according to David Parish, chief executive officer of Orem, Utah-based Designed Nutritional Products, who gave a VendorWorks presentation on this topic at SupplySide East 2002 in Secaucus, N.J.

I3C has been shown to inhibit uterine and breast cancers, as well as chemical carcinogens, according to Parish. I3C reduces the damage of many chemical carcinogens by inhibiting damage to DNA and enhancing the breakdown and excretion of the chemicals, as well as slowing enzyme activation. I3C has also been shown to inhibit tumor formation in animals, according to Parish, although it may promote tumor growth if the tumor is present at the onset of supplementation. Additional animal research has shown that I3C may improve the body's response to chemotherapy.

Diindolylmethane is another dietary indole that is thought to be anti-carcinogenic. Specifically, it has been shown to promote in vitro apoptosis of breast cancer cells, according to Parish.

Essential fatty acids (EFAs), a group of naturally occurring unsaturated fats, may also have application in cancer prevention. Conjugated linoleic acid (CLA) has potential for reducing the risk of colorectal and prostate cancer, according to researchers from Harvard Medical School. They conducted in vitro research to study the antiproliferative effects of CLA (as CLA One, manufactured by PharmaNutrients in Lake Bluff, Ill.) against the growth of human colorectal and prostate carcinoma cells. Researchers concluded that novel CLA may prove effective as a chemopreventive supplement for individuals at risk or diagnosed with colorectal or prostate cancer.⁴⁴

Research involving additional EFAs--docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA)--indicated that DHA and EPA effectively reduced the risk of skin cancer while AA may not. Researchers from the University of Minnesota in Austin found that ingesting omega-3 fatty acids (EPA and DHA) had a protective effect, while ingesting the omega-6 fatty acid (AA) did not reduce risk of skin cancer. Authors concluded that the ratio of omega-3s to omega-6s in the diet is an important factor for health.⁴⁵ A healthy intake is suggested at an approximate ratio of 3-to-1 omega-3s to omega-6s.

There are dozens of diet-derived compounds and botanical options that have been studied in regard to cancer prevention, although many of them await human clinical trials. However, the in vitro and animal research is promising. The future will tell if there are diet-derived or botanical ingredients that are indisputable cancer prevention tools. Until then, manufacturers and consumers alike will continue to read the latest research and buy supplements backed by sound science. A healthy diet accompanied by a consistent exercise regimen is the surest way to protect against cancer. But because today's world is fast-paced, replete with fast-food alternatives to healthy eating and rife with environmental toxins, supplements have become popular for fortifying the immune system and fighting the free radical damage that may cause cancer.

Editor's notes: For a full list of references to this story, click here.

For additional research on vitamin K, glucaric acid (calcium D-glucarate and potassium hydrogen D-glucarate), chlorophyllin, spirulina, resveratrol, garlic, IP-6, tea polyphenols (epigallocatechin-3 gallate), melatonin, turmeric and more, click here.