Cancer Adjuvant Therapy Protocol

Essential Fatty Acids (EFAs)--
block arachidonic acid, inhibit COX-2 enzyme, regulate cell division and inhibit adhesion, prevent cachexia, potentiate traditional cancer therapies, and suppress the activity of proinflammatory cytokines
As a result of the current fat phobia, over 80% of Americans consume inadequate amounts of essential fatty acids (especially omega-3 fatty acids). Physicians report that this scarcity is contributing to epidemic proportions of degenerative diseases, including cancer (Murray et al. 1996). Illustrative of the dietary risks many Americans are taking, the omega-6 to omega-3 fatty acid ratio is typically about 20:1, whereas the optimal ratio may be nearer 1:1 (Mercola 2002a). EFAs, although not manufactured by the body, perform vital functions that prevent and control cancer.

As enzymes metabolize AA, the byproducts of the metabolism fuel the cancer process (Comprehensive Cancer Care 2001). Oxidized AA is, in fact, considered a primary initiator of cancer (Newmark et al. 2000). Joseph Pizzorno of Bastyr University explains that 1 gram of omega-3 fatty acids blocks 10 grams of AA (Pizzorno 2001).
The COX-2 enzyme (interacting with AA) can cause excess production of PGE2, promoting cancer cell growth. EPA and DHA (derived from alpha-linolenic acid or fish oil) are effective COX-2 inhibitors (Ringbom et al. 2001).
Fish oil is the most documented supplement to suppress (up to 90%) a cascade of damaging cytokines, including TNF-alpha and IL-1 (James et al. 2000). It should be noted that psychologic stress induces the production of proinflammatory cytokines, such as TNF-alpha, IL-6, and IL-10. Dutch researchers showed that increasing omega-3 fatty acids lessened the proinflammatory response to psychologic stress (Maes et al. 2000). For information regarding a blood test to obtain a cytokine profile, call (800)208-3334.
Women with high levels of alpha-linolenic acid in breast tissue have a 60% lower risk of breast cancer compared to women with low levels (Klein et al. 2000; Maillard et al. 2002). Jeffrey Bland, esteemed scientist and teacher, reported a supportive study involving 500 C3H mice (prone to breast cancer). The mice were divided into 10 groups of 50 animals and evaluated regarding the impact of various dietary oils on the occurrence of cancer. One-tenth of the animals received standard chow and served as a control group; another group received standard chow plus benzanthracene, a carcinogen. The other eight groups received isocaloric diets along with the cancer inducer; the variable was the type of fat (not the amount) fed in conjunction with the chow. Eight various oils were evaluated: tallow, fish, corn, primrose, safflower, linseed oils, and two others. At the conclusion of the study, eight of the 10 groups (400 animals) were dead with mammary cancer. The 100 survivors were animals fed omega-3 rich oils. The study was repeated using different types of oils and varying amounts of the cancer inducer. The end results were, nonetheless, the same. Researchers postulated that the omega-3 fatty edge was the oil's ability to reduce inflammatory mediators, those signaling tumor progression and metastasis (Cameron et al. 1989).
Epidemiologic and experimental studies suggest that oils rich in omega-3 fatty acids lessen the risk of colon cancer. Japanese researchers confirmed that a relatively small fraction of alpha-linolenic-rich perilla oil (25% of total dietary fat) provided an appreciable beneficial effect in reducing risk (Narisawa et al. 1994).
Low EFA status results in a lack of oncogene control with a shift toward cell proliferation (Pizzorno 2001). EFAs also regulate the adhesiveness of cancer cells, including cell-cell and cell-matrix adhesions (Jiang 1998).
Fatty acids, particularly EPA, inhibited the growth of three human pancreatic cancer cell lines (MIA PaCA-2, PANC-1, and CFPAC), suggesting therapeutic benefit to pancreatic cancer patients (Falconer et al. 1994).
Omega-3 fatty acids prevent cachexia (the muscle wasting and weight loss that occurs in some cancer patients irrespective of proper nutritional intake). Controlling the symptoms common to cachexia (anorexia, abnormal macronutrient metabolism, and fatigue) improves quality of life and extends periods of remission.
Researchers found DHA and EPA cytotoxic to myeloma cells in vitro (Sravan et al. 1997). Individuals who regularly consume fish and cruciferous vegetables appear to lessen their risk of developing multiple myeloma (Brown et al. 2001).
Studies that evaluate the response of a drug or a nutrient when administered to sick animals yield valuable information. For example, researchers at Colorado State University evaluated 32 dogs with Stage III lymphoma and their response to a dietary and chemotherapeutic regime. All of the animals were fed identical diets, but they received varying types of oils. For example, one group received menhaden fish oil (rich in omega-3 fatty acid) and arginine, while the control group received soybean oil (Ogilvie et al. 2000). The animals also received doxorubicin every 3 weeks.

As DHA and EPA levels increased in the test group, the animals experienced longer disease-free intervals and subsequently increased survival time. Dogs receiving the supplemented diet lived about 700 days; animals receiving the soybean oil lived only about 400 days. The time until relapse was also significant: 425 days in the treatment group versus 275 days in the control group. Note: Since fish oil increases the effectiveness of chemotherapeutic agents, the animals receiving the menhaden oil realized an additional advantage over the soybean-treated animals (Hardman et al. 2001).

Suggested dosages for various EFAs: Take six 1000-mg capsules a day of perilla oil, which provide 550-620 mg of alpha-linolenic. Flaxseed oil, 1000-mg softgels, is a rich source of omega-3 fatty acids. Take 7 softgels a day. A preventive dose of a fish oil concentrate called Mega EPA is 4 capsules a day (2800 mg of EPA/DHA). Cancer patients often use 8-12 Mega EPA softgels daily along with 4 Mega GLA softgels to balance the high amount of omega-3 being consumed in the fish oil. Another option for cancer patients is 8 capsules a day of Super GLA/DHA, providing a highly concentrated amount of DHA, GLA, and a moderate amount of EPA. Higher dosages should be physician supervised.

Garlic (Allium Sativum)--is inhibitory to a number of malignancies, minimizes damage imposed by known carcinogens, and boosts the immune system
No plant has the medicinal history, spanning as many cultures, of garlic. Garlic, in fact, appears to be the quintessential medicine/food, having influence on simplistic diseases from common colds to degenerative diseases. For centuries the Chinese have used garlic-containing, herbal formulas to treat tumors, but scientists were challenged to find the mechanism that rendered it efficacious.

Among those dedicated to validating garlic is Dr. Benjamin Lau, M.D., Ph.D. Dr. Lau, focusing upon cancer biology and immunology, was motivated by an epidemiological study reported by the People's Republic of China. The study compared two large populations in the Shandong Province: Cangshan Country and Qixia Country (Mei et al. 1982). Residents of Cangshan County experienced the lowest death rate due to stomach cancer (three per 100,000), regularly consuming about 20 grams of garlic a day; the people of Qixia had a 13-fold higher stomach cancer death rate, eating garlic only rarely. It appears that lowering nitrite concentrations may be the protective mechanism resulting in fewer numbers of gastric cancers. Jhinzou Liu, Ph.D., a Chinese biochemist, found garlic "much more effective than vitamin C" in keeping nitrosamines, a potentially carcinogenic compound, from forming.

Garlic's anticarcinogenic effects are not restricted to gastric malignances.

Garlic (administered intralesionally to mice) was significantly more effective than BCG (bacille Calmette-Guerin), a weakened form of the tuberculosis bacilli, in treating bladder cancer (Lau et al. 1986).
According to data released at the First World Congress on the Health Significance of Garlic and Garlic Constituents, garlic extract reduced the incidence of breast cancer (in mice) by 70-90% (Langer 1991).
Diallyl disulfide, a sulfur compound, induced apoptosis in noncell lung cancer cells (Hong et al.2000); Diallyl sulfide, a component of garlic oil, inhibited hepatocarcinogenicity following carcinogenic exposure (Hayes et al. 1987); S-allyl cysteine (a derivative of aged garlic extract) inhibited human neuroblastoma cell growth in vitro (Welch et al. 1992); allixin, one of the compounds of aged garlic extract, inhibited the development of skin cancer (Nishino et al. 1990). Diallyl sulfide was highly inhibitory during the initiation phase of esophageal cancer (Wargovich et al. 1992; Leigh, http://www.herb.org/greenpapers/garlic.htm).
S-allyl cysteine (SAC) inhibited proliferation and cell growth of nine human and murine melanoma cell lines, producing positive end results without side effects (Takeyama et al. 1993). Of equal importance, garlic modulated major cell differentiation markers of melanoma. As the cell shows distinguishable characteristics (differentiation), it eventually loses its uncontrollable propensity to divide and replicate.
Researchers from the University of Texas M.D. Anderson Cancer Center (Houston) found that S-allyl cysteine and diallyl sulfide reduced colonic damage and the incidence and frequency of colon tumors if administered 3 hours prior to each carcinogenic injection. S-allyl cysteine inhibited colonic damage by 36% and diallyl sulfide by 47% (Sumiyoshi et al. 1990). Michael Wargovish, M.D. (Houston), claims that diallyl sulfide is one of the most active chemopreventive agents known.
S-allyl cysteine (SAC) appears to be able to overcome the adverse side effects (heart and liver damage) associated with the chemotherapeutic agent doxorubicin. Doxorubicin resulted in a 58% mortality rate among laboratory mice; SAC reduced doxorubicin-induced mortality to 30% (Mostafa et al. 2000). Weight loss, typical with doxorubicin, was reduced from 13% to 9% with SAC.

Dr. Robert Lin commented that certain garlic constituents possess antioxidant properties, while other constituents act as oxidants. The latter case is strikingly demonstrated when human hemoglobin is mixed with extracts from fresh garlic and from dried raw garlic powder products. The hemoglobin-garlic extract mixtures turn dark, and their spectra reveal the oxidation of hemoglobin to methemoglobin. Contrarily, extracts from aged garlic do not cause oxidative changes.

When t-butylhydroperoxide, a free-radical generator and oxidant, is used to oxidize red blood cells, it results in rupturing of the cells and darkening of the hemoglobin. An extract of aged garlic, added to the red blood cell suspension prior to the addition of the oxidant, minimized oxidation and cell rupture (Lin 1989). Since many cancer therapies produce free radicals in an attempt to kill cancer cells, researchers concluded that garlic could offer significant protection against treatment-induced tissue damage. Comment: Please consult the protocol Cancer: Should Patients Take Dietary Supplements? to read about the appropriateness of antioxidant therapy during conventional cancer treatment.

Another benefit of garlic to the cancer patients is its effect on enhancing immune function. Here are a few of the numerous studies relating to garlic's effect on immune cells:

Garlic stimulates proliferation of lymphocytes, those cells comprising 25% of total white blood cells that carry out the principal responsibilities of the immune system (Colic et al. 2000).
Garlic quickens macrophage phagocytosis, a process by which microorganisms and cellular debris are engulfed and destroyed (Lau et al. 1991a,b).
Fraction 4 (F4), a protein isolated from aged garlic extract, enhanced the cytotoxicity of human lymphocytes. Although F4 alone increased cytotoxicity, the effect was amplified when F4 was combined with suboptimal doses of interleukin-2. Data collected from UCLA School of Medicine indicate that F4 is an efficient immune potentiator and may be used for immune therapy (Morioka et al. 1993).
Dr. Tariq Abdullah, a Florida pathologist, reported T-helper/T-suppressor ratios converted to normal among a small group of AIDs patients supplementing with garlic. Thrombocytopenia (a reduction in platelet count) is often therapy-resistant in individuals with AIDS. Yet, platelet numbers have been reported to increase, sometimes greater than 100,000, during 4 months of garlic supplementation. Although AIDS is not cancer, this feared disease has forced researchers and clinicians to look closely at the immune system. As clinical trials establish efficacy over various parameters of AIDS, it is highly possible gains will transfer to other diseases like cancer (Abdullah et al. 1989).

Research suggests that garlic preparations are not equal in pharmacologic value. While raw garlic juice, heated garlic juice, dehydrated garlic powder, and aged garlic extract all significantly enhanced natural killer cells' numbers and their activity, only aged garlic extract and heated garlic juice inhibited the growth of inoculated tumor cells (Kasuga et al. 2001).

Dr. Abdullah evaluated the percentage of tumor kill using raw and aged (Kyolic brand) garlic. To determine results, blood was drawn from test subjects and the blood was used on tumor cells in culture. Raw garlic killed 139% of tumor cells compared to an untreated group, while Kyolic killed 159% (Abdullah et al. 1988). Note: Defining the most efficacious type of garlic is confounding. Some physicians and clinicians report greater gains from odorous garlic supplementation. If garlic is part of your nutritional program, experiment with different varieties, assessing both subjective and objective improvements. It is highly possible that different metabolic types respond differently to various forms of garlic.

A good source of supplemental garlic is PureGar Caps. PureGar Caps contain the highest available potency (9 mg) of the active allicin compound, deemed by some the yardstick for measuring the worth of garlic. Use 4 capsules, 2-4 times daily, with meals. If Kyolic aged garlic is the selection, use three 1000-mg caplets daily with meals. PureGar can cause a temporary gastric burning and pungent odor, whereas Kyolic aged garlic extract is free of these effects. No serious side effects have been reported among garlic users, evaluating hundreds of subjects. However, it should be noted that garlic thins the blood, and for some individuals (particularly those using anticoagulants) it is essential to abstain from or to watchfully monitor supplementation.

Therapeutic factors contained in garlic include magnesium, selenium, 17 amino acids, 33 sulfur compounds, and vitamins B1, A, and C, as well as germanium. Germanium has been shown to induce production of interferon, enhance natural killer cell activity, and activate macrophage activity in experimental animals (Aso 1985; Goodman no date).

Glutamine--increases NK cell activity, decreases PGE2 synthesis, inhibits tumor growth, stabilizes weight loss, and reduces incidence of stomatitis and infection
Dr. Ralph Moss declared that tumors are "glutamine traps." Because tumors typically have high concentrations of glutamine, physicians have been reluctant to add supplemental glutamine to a cancer protocol. When Dr. V.S. Klimberg (University of Arkansas) challenged the glutamine-cancer hypothesis, she found that oral glutamine (1 gram per kg of body weight a day administered to rats) upregulated tissue glutathione (a powerful antioxidant) by 25% and increased natural killer cell activity 2.5-fold. PGE2 synthesis (a proinflammatory prostaglandin that fuels tumor growth) decreased and tumors were inhibited by 40% (Klimberg et al. 1996a).

When glutamine accompanied either chemotherapy or radiotherapy, it protected the host and actually increased the selectivity of therapy for the tumor. This was evidenced among a group of rats (receiving either methotrexate, cyclophosphamide, or cisplatin) whose tumor loss nearly doubled with glutamine supplementation (Klimberg et al. 1992, 1996b).

Researchers also observed that glutamine decreased progression of tumor formation in rats implanted with mammary tumors, suggesting oral glutamine may be useful as a chemopreventive in breast cancer (Feng et al. 1997). A group of Japanese scientists later found that oral glutamine maintained lymphocyte numbers and protected the gut of esophageal cancer patients during radio/chemotherapies (Yoshida et al. 1998).

Glutamine typically stabilizes weight loss by preserving intestinal function and allowing better absorption. Subsequently, glutamine prolongs survival by slowing down catabolic illness, a disorder characterized by weight loss, diminished muscle mass, and loss of body fat. Fewer incidences of stomatitis (a generalized inflammation of the oral mucosa) and bouts of infection help reduce the number of days spent in a hospital (Anderson et al. 1998a). Harvard University research showed that glutamine decreased medical expenses of leukemia patients undergoing bone marrow transplants by $21,095 per patient (MacBurney et al. 1994). (The retail cost of glutamine is $17.95 per day.)

A suggested glutamine dosage is 2 or more grams a day taken on an empty stomach. Glutamine is regarded as nontoxic, but cancer patients contemplating higher dosages should do so only after consulting with a health care provider.

Inositol hexaphosphate (IP-6)--activates natural killer cells, promotes differentiation, supports p53 activity, and normalizes the cell cycle by modifying signal transduction pathways
IP-6, a promising anticancer compound sold as a nutritional supplement, is a combination of inositol (a B vitamin) and phytic acid, also known as inositol hexaphosphate. According to Dr. A. Shamsuddin, M.D., Ph.D., who introduced IP-6 after more than 15 years of research, it works by enhancing the body's ability to defend itself against cancer, making it of equal importance as either a cancer preventive or therapeutic agent.

Inositol hexaphosphate is a sugar, very much like glucose, except it has six phosphates attached to its molecules. Every animal and plant species tested had varying levels of IP-6, but the highest amounts were found in rice, about 2% by weight: 100 grams of rice provide approximately 2 grams of IP-6, but even that amount is not readily available. Since the body is dependent upon digestive enzymes to break it down, only a meager amount is actually absorbed from foodstuffs. Thus, IP-6 in encapsulated or bulk forms should be of special interest to cancer patients and those desiring protection against cancer.

The following chemotherapeutic properties are assigned to the immune modulator:

IP-6 activates natural killer cells, amazing cells that work without antibody participation (Baten et al. 1989).
IP-6 decreases cellular proliferation (Sakamoto et al. 1993; Shamsuddin et al. 1989a). Normally, cells divide in a well-ordered fashion, with worn-out cells replaced with new, healthy cells. When regulatory control is lost, excess growth occurs and cancer can develop. Illustrative of its potential, IP-6 reduced large intestinal cancer (by regulating cell proliferation) in F344 rats even when the treatment was begun 5 months after carcinogenic induction (Shamsuddin et al. 1989b).
IP-6 promotes differentiation of cancer cells, that is, an unspecialized, atypical cell structure assumes the likeness of the tissue of origin, indicating the virulence of the malignancy is waning (Yang et al. 1995). IP-6 was shown to inhibit growth and induce differentiation in HT-29 human colon cancer cells, making it valuable as an adjunctive treatment in colon cancer. IP-6 also strongly inhibited growth and induced differentiation in human prostate cancer cells (PC-3) in both in vitro and in vivo studies (Shamsuddin et al. 1995).
Dr. A. Shamsuddin, research scientist and professor of pathology at the University of Maryland School of Medicine in Baltimore, explains that one of IP-6's cousins (IP-3, i.e., inositol with three phosphates) is a signal transduction molecule, meaning it relays messages to the cell. If the cell is exposed to a cancer-causing agent, a signal is transported from outside the cell into the cell (most probably to the nucleus) so the cell knows how to react to that particular stimulant. Since IP-3 is a "send" molecule and IP-6 is related to IP-3, but in a higher phosphorylated form, it is very possible that IP-6 could work against all varieties of cancer cells. To date, IP-6 has been effective against every cancer cell tested (Shamsuddin et al. 1997; Grases et al. 2002).
After inducing cancer in laboratory animals, IP-6 (administered orally, by injection at the site of the tumor, or intraperitoneally) resulted in tumors two-thirds smaller than the controls. As tumors reduced in size, survival rate increased (Shamsuddin et al. 1989b).
IP-6 increases expression of the tumor suppressor gene p53 by up to 17-fold. p53 acts on cells under stress, such as those with DNA damage, reducing proliferation and encouraging apoptosis. When cancer arises, a mutation in p53 is commonly involved. Lastly, since loss of p53 function increases cancer cells' resistance to chemotherapeutic agents, the stimulating action of IP-6 on p53 makes it an attractive adjuvant chemotherapeutic agent as well (Shamsuddin et al. 1997; Saied et al. 1998).
Toxicity studies (dating back to 1958) showed that a daily dose of 9 grams of IP-6 for 3 years resulted in only beneficial side effects, including lesser incidences of kidney stones and fatty liver, as well as lower cholesterol levels. It is important to note that IP-6 does not kill the cell, as most anticancer agents do; thus, hair loss and immune suppression does not occur. A suggested dosage of 1-3 grams a day is adequate for most individuals. For those requiring larger doses, a powder is available (1 scoop twice daily equals 16 capsules, supplying about 6.4 grams of Ip-6).

Lactoferrin--is immunoregulatory, inhibits angiogenesis, and binds iron
Perhaps one of the most promising therapeutic uses of lactoferrin, a milk protein with bacteriostatic properties, may be as a nontoxic, anticancer agent. Various studies show that lactoferrin (a minor fraction of whey) results in a significant reduction in the incidence of esophageal, lung, bladder, and colon cancer in laboratory rats (Ushida et al. 1999; Masuda et al. 2000; Tsuda et al. 2002).

Since evidence indicates milk products protect against colon cancer, researchers speculate that bovine lactoferrin, a natural ingredient in milk, may be the chemoprotective agent (Tsuda et al. 2000b). Rats treated with a carcinogen and supplemented with 2% bovine lactoferrin for 36 weeks reduced the incidence of colon cancer to 27% of that observed in a control group; rats receiving 0.2% reduced the incidence to 46%. Japanese researchers termed the protection "remarkable," noting a 43% reduction in spontaneous lung metastasis (compared to controls) after implanting colon carcinoma 26 (Co 26 Lu) in lactoferrin-treated laboratory animals (Tsuda et al. 2000a).

In addition to inhibiting angiogenesis (the vascular network that sustains the tumor), lactoferrin maintains the integrity of the immune system (Yoo et al. 1997; Tsuda et al. 2002). Typically, bovine lactoferrin prompts an increase in the number of natural killer cells, as well as the cytotoxicity of white blood cells (Tsuda et al. 2000a). Researchers at the University of Texas Health Science Center added that the antibiotic, anti-inflammatory, and immune-modulating properties of lactoferrin appear active against the gastritis-, ulcer-, and cancer-inducing bacterium Helicobacter pylori (Dial et al. 2002).

Lactoferrin, a natural iron-binding protein, scavenges free radicals in fluids and inflamed areas, suppressing free-radical mediated damage. Lastly, it decreases the availability of iron to invade microbial and neoplastic cells, depriving pathogens and aberrant cells of an iron supply (Khan et al. 2001; Weinberg 2001).

The suggested dosage is 300-900 mg a day of the superior apolactoferrin (iron-depleted) form of lacto-ferrin. Lactoferrin is a natural component of cows' and human mothers' milk, but is also found in the milk of sheep, goats, and pigs.

Melatonin--is an immune modulator that increases the survival time of most cancer patients
Some cancer patients are now taking melatonin, an immune-modulating neurohormone, as part of a comprehensive, nontoxic cancer treatment. The cone-shaped pineal body, a small but crucial gland located in the brain, produces melatonin, a hormone that influences sexual maturation but also appears to play an important role in cancer.

Melatonin supplementation appears to restore circadian rhythms, which diminish or disappear with age. When melatonin's circadian rhythm is abolished, the aging process is accelerated, life span is shortened, and an increase in spontaneous tumors occurs (Maestroni et al. 1999). Investigators showed that when the defense system is compromised (due to disrupted rhythms), tumors grow two to three times faster (Filipski et al. 2002).

Melatonin also protects and restores normal blood-cell production caused by the toxicity of conventional treatments, a profile shared with FDA-approved drugs Neupogen, a granulocyte colony-stimulating factor (G-CSF), and Leukine, a granulocyte-macrophage colony-stimulating factor (GM-CSF). A combination of melatonin and low-dose interleukin 2 (IL-2) neutralizes treatment-induced lymphocytopenia, a decrease in the numbers of lymphocytes in the peripheral circulation of cancer patients (Lissoni et al. 1993).

Researchers found the best way to amplify the antitumoral activity of low dose IL-2 is by not coadministering another cytokine but rather cosupplementing with the immune-modulating neurohormone melatonin (Lissoni et al., 1994a). This is hopeful news for a subset of cancer patients, because melatonin has been shown to cause tumor regression in neoplasms nonresponsive to IL-2 (Maestroni, 1999).

The Division of Radiation Oncology of the San Gerardo Hospital (Milan) developed the following protocol for 80 patients with advanced metastatic tumors (Lissoni et al. 1994a). The patients were randomized to receive 3 million IU of IL-2, 6 days a week, for 4 weeks or IL-2 plus 40 mg a day of melatonin. A complete response was achieved in 3 of 41 patients treated with IL-2 plus melatonin and in none of the patients receiving only IL-2. A partial response occurred in 8 of 41 patients treated with IL-2 plus melatonin and in 1 of 39 patients treated with IL-2. Tumor regression rate was significantly higher in patients using IL-2 and melatonin compared to those receiving IL-2 (11/41 versus 1/39). The survival rate at 1 year was higher in patients treated with IL-2 and melatonin than in the IL-2 group (19/41 versus 6/39). Lymphocytic populations were consistently higher when melatonin accompanied the treatment and thrombocytopenia (a decrease in the number of circulating platelets) occurred less frequently.

For patients with bloodborne cancers, an IL-2/melatonin combination is also promising. Twelve patients (nonresponsive to previous standard therapies) evaluated the efficacy and tolerability of a combination of low-dose IL-2 plus melatonin in advanced malignancies of the blood, including non-Hodgkin's lymphoma, Hodgkin's disease, acute myelogenous leukemia, multiple myeloma, and chronic myelomonocytic leukemia. IL-2 was given 6 days a week for 4 weeks, along with oral melatonin (20 mg a day). Cancer was stabilized and did not progress in 8 of 12 (67%) participants for an average duration of 21 months. An additional benefit accrued as the melatonin/IL-2 therapy was well tolerated (Lissoni et al. 2000).

Nonresectable brain metastasis remains an untreatable disease. Because of melatonin's cytostatic action (the ability to suppress the growth and multiplication of cells) and its anticonvulsant activity, the pineal hormone may prove effective in the treatment of brain metastasis. In a study to test the theory, 50 patients with inoperable brain metastasis were given supportive care or supportive care and 20 mg of melatonin nightly. Freedom from brain tumor progression and survival rates at 1 year were higher in patients who were treated with melatonin compared to those who received only supportive care (Lissoni et al. 1994b, 1996). Even when melatonin was unable to stop the progression of advanced, metastatic disease, it improved the performance status of patients (see Table 2).

Low melatonin levels play a role in escalating rates of breast cancer. As melatonin levels decrease, the secretion of estrogen increases. Nighttime production of melatonin inhibits the body's secretion of estrogen and decreases the proliferation of human breast cancer cells. Conversely, light during nighttime sleep decreases melatonin production and increases cumulative lifetime estrogen levels, a sequence that may increase the risk of breast cancer.

In fact, two current studies show that women who work night shifts may increase their risk of breast cancer up to 60%. Blind women have a significantly lower risk (36% less) of breast cancer than normally sighted women because of consistently higher levels of melatonin in their dark world (Kliukiene et al. 2001). Women, who are classed as only visually impaired, realize no protective effects in regard to breast cancer.

Summary of Studies Using Melatonin Lissoni's Phase II Randomized Clinical Trial Results
1-Year Survival

Tumor Type
Patient Number
Basic Therapy
Melatonin Dose
Melatonin
Placebo
Level of
Significance

Metastatic nonsmall
cell lung
63 Supportive care only
10 mg 26%
under 1% <0.05
Glioblastoma
30 Conventional radiotherapy
10 mg 43% under 1% <0.05
Metastatic breast
40 Tamoxifen
20 mg 63% 24% <0.01
Brain metastases 50 Conventional radiotherapy
20 mg 38% 12% <0.05
Metastatic colorectal
50 IL-2
40 mg 36% 12% <0.05
Metastatic nonsmall
cell lung
60 IL-2
40 mg 45% 19% <0.05
Compiled by Cancer Treatment Centers of America and published in the March 2002 issue of Life Extension Magazine.

It appears that melatonin may also reduce the number of estrogen receptors on breast cancer cells. Since estrogen effectively feeds the growth of hormone-responsive breast tumors, reducing the receptors might slow tumor growth. Science News reported that the amount of melatonin required to inhibit breast cell proliferation appears no greater than the amount commonly present in human blood at night (Science News 93; Moss 1995).

Electromagnetic fields (EMFs) are another inhibitor of melatonin production. These results provide the first evidence that ELF (extremely low frequency) magnetic fields can act at the cellular levels to enhance breast cancer cell proliferation by blocking melatonin's natural oncostatic action. The mechanism(s) of action is unknown and may involve modulation of signal transduction events associated with melatonin's regulation of cell growth (Liburdy et al. 1993). Researchers at the Wayne Hughes Institute (Minnesota) added that test-tube studies indicate that EMFs can cause a chain of enzyme reactions which cells use to relay operational directions to DNA. The EMF-activated enzymes (L-Tyrosine kinases) encourage cell proliferation, fueling the cancer process (Science News 1998).

Subscribing to the EMF/cancer link raises concern about close and prolonged contact with electrical appliances and equipment, such as electric stoves, hair dryers, televisions, electric typewriters, razors, power tools, various brands of computer monitors, power lines (e.g., high voltage lines carrying power from power plants to substations or between substations), and radio towers. Note: A gauss meter may be helpful in assessing the levels of EMFs emanating from regularly used appliances and tools in a home environment. A gauss meter may be purchased from Electric Field Measurements, West Stockbridge, MA 01266, Telephone: (413) 637-1929.

Melatonin delivers another anticancer perk through its antioxidant values. Physicians who once credited glutathione and vitamin E as being antioxidants of choice have now given special honor to melatonin. The neurohormone appears to protect against tumors by shielding molecules (especially DNA) from oxidative stress. Melatonin exerts its antioxidant properties by detoxifying the highly reactive hydroxyl radical, as well as singlet oxygen, hydrogen peroxide, and peroxynitrite anions (Kim et al. 2000).

A typical dose for a healthy individual is 300 mcg-6 mg each night. Cancer patients often take between 3-50 mg each night. Researchers at Cancer Treatment Centers of America are focusing on examining circadian activity and rest rhythms in cancer patients. It is hoped that by establishing optimal dosage and the hours to best administer, melatonin's full potential will be realized by more patients. Some currently subscribe to nocturnal dosing, while others prescribe melatonin every 4 hours (a nonchronobiological dosing pattern).

MGN--is a biological response modifier
Dr. Mamdooh Ghoneum, a research immunologist who has spent the last several years researching the immunoregulatory nature of MGN-3, earned a Ph.D. at the University of Tokyo in radioimmunology and did postdoctoral work at the UCLA School of Medicine in cellular and molecular immunology. Dr. Ghoneum is internationally recognized as an expert in the emerging field of cancer immune therapy, that is, using biological response modifiers (BRMs) to activate NK cells and optimize immune function. The results of his research are discussed in this section.

Stimulating the immune system is neither novel nor extraordinary, but maintaining long-term immune vigilance is a different story. MGN-3 (an arabinoxylan compound) appears to be specific for the job. MGN-3 is a polysaccharide composed of the hemicellulose-B extract of rice bran modified by enzymes from Shiitake mushrooms.

MGN-3's ability to sustain immune alertness without causing other endangerments makes it a unique compound. Many immunomodulators are effective for the short-term, but lose their advantage (becoming less responsive) with prolonged usage. A 5-year evaluation of patients using MGN-3 showed a keen natural kill response continued indefinitely with ongoing supplementation.

Looking at the biological nature of NK cells is fascinating. NK cells are one of the most common of white blood cells, representing up to 15% of the total population. They are extremely important because, unlike other white blood cells, they work more or less independently, not requiring antibody assistance to muster an attack. The self-governing nature of NK cells appears to grant indiscriminate action upon various types of cancer cells (Ghoneum et al. 2000).

Cancer Adjuvant Therapy Pg (1) (2) (3) (4) (5) (6) (7)

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