COMPLEMENTARY THERAPIES, continuedVitamin A
--offers protection against radiation induced tissue damage, down-regulates telomerase activity, and is involved at almost every juncture of cancer control
Retinoids induce cell differentiation, control cancer growth and angiogenesis, repair precancerous lesions, prevent secondary carcinogenesis and metastasis, and act as an immunostimulant. After FAR therapy (5-fluorouracil-retinol palmitate with radiation and surgery), the disease-specific, 5-year survival was nearly 50% in various head and neck cancers (Yamamoto 2001). Retinoids, at pharmacological levels, assist in preventing the appearance of secondary tumors following curative therapy for epithelial malignancies.
It is well-established that a vitamin A deficiency (in laboratory animals) correlates with a higher incidence of cancer and an increased susceptibility to chemical carcinogens. This is in agreement with epidemiological studies, which indicate that individuals with a lower dietary vitamin A intake are at a higher risk of developing cancer (Sun et al. 2002). The chemotherapeutic possibilities surrounding vitamin A areplentiful.
Two vitamin A analogs currently in large chemoprevention, intervention trials, or epidemiological studies are all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid (13-cis-RA).
Note: Retinoic acid is biologically active in two forms: all- trans- retinoic acid and 9-cis-retinoic acid. Vitamin A and 13-cis-RA are converted to these biologically active forms.
Thirty-two women with previously untreated cervical carcinoma (ages 14-60) were treated for at least 2 months using oral 13-cis-RA (1 mg per kg body weight a day) and alpha-interferon subcutaneously (6 million units daily): 16 of the women (50%) had major reactions, including four complete clinical responses. Remission occurred in 15 of the patients within 2 months and in one patient within 1 month; toxicity to treatment was described as manageable (Espinoza et al. 1994). The positive results were replicated in other studies using a similar model (Hansgen et al. 1998, 1999).
The role of 13-cis-RA on a human prostate cancer cell line (LNCaP) was studied. It was found that 13-cis-RA significantly inhibited PSA secretion and the ability to form new tumors. It was also noted that tumors that appeared (having escaped 13-cis-RA inhibition) were smaller compared to tumors in nontreated animals (Dahiya et al. 1994). During the course of 13-cis-RA therapy, prostate cancer cells became more differentiated, that is, they resembled (microscopically) normal prostate cells.
A combination of phenylbutyrate and 13-cis-RA as a differentiation and anti-angiogenesis strategy against prostate cancer was evaluated. Phenylbutyrate, considered nontoxic, is used to arrest tumor growth and induce differentiation of premalignant and malignant cells. Tissue examination of tumors showed decreased cell proliferation and increased apoptosis, as well as reduced microvessel density in animals treated with 13-cis-RA and phenylbutyrate; tumor growth was inhibited by 82-92%. In contrast, researchers reported 13-cis-RA and phenylbutyrate, when used singularly, were suboptimal in terms of clinical benefit (Pili et al. 2001).
A pilot study conducted at M.D. Anderson Cancer Center found ATRA alone ineffective as a long-term treatment for chronic myelogenous leukemia (CML). Only four of 13 subjects showed a transient, nonsustaining indication of an anti-leukemic effect (Cortes et al. 1997). However, combinations of therapeutic agents that included ATRA were promising in the treatment of CML. The combination included alpha-interferon plus ATRA, which reduced proliferation 50-60% (Marley et al. 2002).
Cisplatin (a popular chemotherapeutic agent) shares a similar chemotherapeutic profile with ATRA (the ability to induce cytotoxicity through apoptosis). A combination of ATRA and cisplatin induced apoptosis in significantly more cancer cells, particularly in ovarian and head and neck carcinomas, than either drug alone (Aebi et al. 1997). A combination of ATRA and IL-2 showed therapeutic value in treating resistant metastatic osteosarcoma, a malignant tumor of the bone (Todesco et al. 2000).
For decades, researchers have searched for ways to minimize the damage to the heart during Adriamycin therapy. Adriamycin, though relatively effective, damages the heart muscle. Several animal studies indicated that supplemental vitamin A reduced Adriamycin-induced inflammation and preserved heart tissue. Vitamin A appears not only to counter Adriamycin damage, but also to increase survival in animals (Tesoriere et al. 1994). Vitamin A extends similar protection to patients using cisplatin, a drug often used for bladder and ovarian cancer, as well as small cell carcinoma.
Radiation-induced lung injury frequently limits the total dose of thoracic radiotherapy that can be delivered to a patient undergoing treatment, restricting its effectiveness. Animal studies suggest that supplemental vitamin A may reduce lung inflammation after thoracic radiation and modify radiotherapy damage to the lungs (Redlich et al. 1998).
Vitamin A (in dosages of 25,000 IU a day) offers significant protection against radiation-induced tissue damage. Various cancer patients use more than 100,000 IU of a water-soluble vitamin A liquid a day, a dosage that must be supervised by a physician. Do not supplement with vitamin A if the cancer involves the thyroid gland or if the liver is damaged. Both professionals and patients should consult Appendix A to read about avoiding vitamin A toxicity. Good food sources of vitamin A include liver and fish liver oils, green and yellow fruits and vegetables such as apricots, asparagus, broccoli, cantaloupe, carrots, collards, papayas, peaches, pumpkins, spinach, and sweet potatoes. High-potency water-soluble vitamin A is available as a dietary supplement.Vitamin C
(ascorbic acid)--has a chemotherapeutic effect on many cancers, promotes collagen production, sequestering the tumor, and reduces the toxicity of conventional therapies
Linus Pauling, winner of the Nobel Prize for chemistry in 1954 and the Nobel Prize for Peace in 1963, believed strongly that vitamin C could play an important role in cancer treatment. Dr. Pauling suggested 10 grams of vitamin C a day for patients with advanced cancer for whom conventional treatments had ceased to be of benefit (Cameron et al. 1993). Over an 8-year period, 500 patients with varying stages and types of cancer were treated with vitamin C therapy. Those receiving 10 grams of vitamin C a day improved their state of well-being, as measured by increased appetite and mental alertness, as well as a decreased need for pain-killing drugs. A retrospective analysis showed that those using vitamin C lived considerably longer than those not supplemented.
Various clinics are using intravenous vitamin C and with positive results. Dr. Hugh Riordan, recognized as a world authority on this procedure, practices from Wichita, KS, at the Center for the Improvement of Human Functioning International. Dr. Riordan's vitamin C story began in 1984 when he treated his first cancer patient; a 70-year-old renal cell carcinoma patient with metastasis to the lung and liver, using injectable vitamin C. Renal cell carcinoma has only a 5% response rate.
The initial treatment began with 15 grams of vitamin C administered intravenously 2 times a week; showing excellent tolerance, the vitamin C dosage was increased to 30 grams twice weekly. Within 6 weeks, the patient showed a favorable response to treatment and at the 12-week interval was pronounced tumor-free. The patient lived 14 additional years and died of congestive heart failure with no evidence of tumors.
In light of the favorable initial response to intravenous (IV) vitamin C, ascorbic acid was investigated. Vitamin C is preferentially toxic to tumor cells, that is, it kills tumor cells but not normal cells.
In low doses, vitamin C assumes the nature of an antioxidant; in high dosages, vitamin C changes roles and becomes a prooxidant, inducing peroxide production. Tumor cells have a relative catalase deficiency, an enzyme necessary to detoxify hydrogen peroxide to water and oxygen. A 10- to 100-fold difference in catalase concentrations exists between tumor cells and normal cells. Without the protection of catalase, peroxide accumulates in cancerous cells, along with aldehydes (toxic byproducts of the reaction), causing death to malignant cells. On the other hand, normal, healthy tissues have the protection of the detoxification enzyme and are spared destruction by peroxide and aldehyde. Vitamin C, a virtually nontoxic nutrient (Bowie et al. 2000), could cause a transient diarrhea if not absorbed properly.
Vitamin C is safe compared to standard chemotherapeutics and has an ability to preserve immune function. Many patients succumb, not because of cancer, but rather from a post-chemotherapeutic toxicity, resulting from a damaged immune system. Vitamin C protects the immune system. Vitamin C is preferentially toxic to many types of cancer cells, including 20 different melanoma cell lines. Ovarian cell lines are more susceptible to vitamin C-induced toxicity than pancreatic cells. Breast cancer appears to be one of the most responsive cancers to IV vitamin C.
Much higher concentrations of vitamin C are required to kill cancer cells than originally thought, about 600 mg/dL. Also, as the density of the cells increases, the efficacy of vitamin C decreases. It is extremely difficult to reach vitamin C concentrations greater than 200 mg/dL even when administered intravenously (Riordan et al. 2000). To increase the sensitivity of tumor cells to vitamin C, other approaches need to be employed.
Alpha-lipoic acid, a water- and lipid-soluble antioxidant that recycles vitamin, enhances the toxic effect of ascorbic acid. Lipoic acid decreases the dose of vitamin C required to kill tumor cells from 700 to 120 mg/dL (Riordan et al. 2000). Vitamin C toxicity is further enhanced by 1000 mcg of vitamin B12, which forms cobalt ascorbate, a benign but cancer-cell-toxic agent. Vitamin K, selenium, quercetin, niacinamide, biotin, and grape seed extract are also regarded as potentiation factors.
The goal is to achieve and maintain 400 mg/dL of vitamin C in the plasma. At this concentration, every cancer cell line so far tested has been found to be sensitive to vitamin C. After reaching an ascorbic acid peak, as occurs during infusion, the level returns to near baseline levels 24 hours after the IV infusion.
Vitamin C has an ability to increase collagen production. Vitamin C is required for the hydroxylation of proline, which in turn is required for collagen production. Vitamin C has the ability to inhibit enzymes that degrade or break down the extracellular matrix. Vitamin C dramatically increased the collagen within tumor cells, an act that tended to immobilize the cells
Vitamin C (supported by lipoic acid) has been used as a cancer therapy. It is strongly advised that patients contact a physician trained in administering infusions and monitoring progress. By giving vitamin C intravenously, doctors can achieve a blood saturation that far exceeds that attained by administering vitamin C orally (200% versus 2%). A high dose of vitamin C is critical to achieve tumor cell kill.
A Hickman line allows large doses of vitamin C to be self-administered at home on a daily to weekly basis over a period of months, modulating down or up in frequency according to response. Otherwise the treatment can be administered as an outpatient. Contraindications to vitamin C therapy are few but include individuals with kidney failure and on dialysis, as well as those with hemochromatosis. Also, physicians should screen patients for a red blood cell glucose-6 phosphate dehydrogenase deficiency, a rare condition whose presence can lead to a hemolytic crisis involving red blood cell breakdown.
Large doses of vitamin C should be reached gradually to establish tolerance. For example, 15 grams for one or two sessions and then 50 grams to 100 grams if necessary. The exact dose is determined by the individual's plasma saturation immediately after an infusion. The therapy should not be stopped abruptly because a rebound effect could result in scurvy. Patients should allow weeks or even months to wean off the treatment, with oral vitamin C therapy used on the days between infusions.
A 10-year research project using high dose IV vitamin C has been completed. While a number of orthomolecular physicians are using IV vitamin C therapy, it is recommended that Dr. Riordan's protocol become the backbone of the therapy. Instructions are available to physicians upon request from the center (Riordan et al. 2003).
Center for the Improvement of Human Functioning
3100 North Hillside Avenue
Wichita, KS 67219
Other chemotherapeutic credits awarded to vitamin C:
- Vitamin C prolongs the lives of animals undergoing conventional cancer treatment by protecting normal cells against chemotherapy-induced toxicity; in tandem, vitamin C increases the cytotoxicity targeted at the cancer (Antunes et al. 1998; Giri et al. 1998). When 5-FU was administered together with vitamin C, the tumor cell kill rate was boosted from 38 to 95.5%. X-ray therapy decreased cancer growth 72%, but adding vitamin C to the regime decreased cancer growth by 98.2%. Full spectrum antioxidants rather than isolated nutrients are suggested (Prasad et al. 1999; Moss 2000).
- Infection: Heliobacter pylori increases the risk of developing stomach cancer (Uemura et al. 2001), as well as pancreatic cancer (Stolzenberg-Solomon et al. 2001). High doses of vitamin C inhibit the growth of H. pylori, both in vitro and in vivo (Zhang et al. 1997). A study showed vitamin C levels to be consistently low in individuals with the H. pylori infection (The Analyst 2002).
- Frequent intake of vitamin C from food and supplement sources was associated with a protective effect against multiple myeloma, particularly among Caucasians. African Americans benefited less from ascorbic acid intake (Brown et al. 2001).
- NF-kB is a central mediator of altered gene expression during inflammation and is implicated in cancer. Vitamin C inhibited the activation of NF-kB by multiple stimuli, including IL-1 and TNF-alpha (Bowie et al. 2000).
It should be re-emphasized that oral vitamin C does not bestow equal benefits compared to intravenous vitamin C. If a patient with a solid tumor elects to use oral vitamin C, ascorbic acid buffered with sodium may produce better results. If the cancer is blood-borne (leukemia, lymphoma, or myeloma), ascorbic acid crystals buffered with calcium appears to offer greater efficacy. The majority of the patients use 6-12 grams a day. Food sources of vitamin C are berries, citrus fruits, papayas, and pineapple, as well as tomatoes, broccoli, Brussels sprouts, dandelion and mustard greens, peas, red peppers, and spinach.Vitamin D
--promotes differentiation, inhibits angiogenesis, regulates cell division
Current recommendations to avoid natural sunrays to thwart the possibility of deadly melanoma may be allowing other endangerments. For more than 50 years, medical literature has affirmed that regular sun exposure is associated with a substantial decrease in death rates from certain types of cancers. It is estimated that moderate sun exposure without sunscreen - enough to stimulate vitamin D production but not enough to damage the skin - could prevent 30,000 cancer deaths in the United States each year (Ainsleigh 1993). The most damaging of the sun's rays occur between the hours of 10 a.m. and 3 p.m. and are thus the hours demanding the greatest watchfulness.
Evidence points to a prostate, breast, and colon cancer belt in the United States, which lies in northern latitudes under more cloud cover than other regions (Studzinski et al. 1995). Certain regions in the United States, such as the San Joaquin Valley cities and Tucson, AZ; Phoenix, AZ; Albuquerque, NM; El Paso, TX; Miami, FL; Jacksonville, FL; Tampa, FL; and Orlando, FL; have a lower incidence of breast and bowel cancers. Conversely, New York; Chicago; Boston; Philadelphia; New Haven, CT; Pittsburgh; and Cleveland, OH; have the highest rates of breast and intestinal cancer of the 29 major cites in the United States. The greater hours of year-round sunlight correlate to a lower rate of breast and intestinal cancer in the U.S.A.
Vitamin D is formed in the skin of animals and humans by the action of shortwave UV light, the so-called fast-tanning sunrays. Precursors of vitamin D in the skin are converted into cholecalciferol, a weak form of vitamin D3, which is then transported to the liver and kidneys where enzymes convert it to 1,25-dihydroxycholecalciferol, the more potent form of vitamin D3 (Sardi 2000). Although vitamin D exists in two molecular forms, vitamin D3 (cholecalciferol) found in animal skin and vitamin D2 (ergocalciferol) found in yeast, vitamin D3 is believed to exhibit more potent cancer-inhibiting properties and is therefore the preferred form.
Dark-skinned people require more sun exposure to produce vitamin D because the thickness of the skin layer (the stratum corneum) affects the absorption of UV radiation. Black human skin is thicker than white skin and thus transmits only about 40% of the UV rays needed for vitamin D production. Darkly pigmented individuals who live in sunny equatorial climates experience a higher mortality rate from breast and prostate cancer when they move to geographic areas that are deprived of sunlight exposure in winter months (Angwafo 1998; Sardi 2000).
Women with polymorphisms (genetic variations) of the vitamin D receptor gene may be less able to benefit from the nutrient. There is some evidence that vitamin D receptor gene polymorphisms play a role in the breast cancer (Bretherton-Watt et al. 2001); however, recent studies do not support this evidence (Buyru et al. 2003).
Identifying the at-risk groups, through the assessment of genetic variations in the vitamin D receptor, appears to be a forthcoming tool for planning intervention strategies.
Human leukemia cells cultured in the presence of vitamin D exhibited a reduced rate of tumor growth when injected into mice. Cells grown in vitamin D3 failed to form detectable tumors in 11 of 12 inoculated mice (Wang et al. 1997). The anticarcinogenic properties of vitamin D, confronts multiple stages of cancer development, including apoptosis, differentiation, angiogenesis, and metastasis, as well as regulating the cell growth cycle (van den Bemd et al. 2002).
Since vitamin D can cause calcium to be released from bones (a condition referred to as hypercalcemia), large doses of vitamin D cannot be used in patients whose medical history or genetics puts them at increased risk. Using a combination of Vitamin D3 and vanadium (a metallic element) enables vitamin D to retain its anticancer activity and vanadium addresses the problem of hypercalcemia (Basak et al. 2000).
Rats were supplemented with vanadium or vitamin D3 or both vanadium and D3 four weeks prior to induced liver cancer and continued thereafter until the 20th week. After 20 weeks of supplementation, the vitamin D3-vanadium combination had significantly reduced the number and size of abnormal hepatic nodules. The combination also showed an additive effect, reducing the number and size of hyperplastic nodes from 83.3% to 37.5%. In addition, vanadium effectively blocked the entry of calcium into cells.
A modified form of vitamin D (referred to as a deltanoid) delays the onset and reduces the number of skin cancers in laboratory mice. The microscopically altered structure of vitamin D produced a potentially effective cancer therapeutic. The vitamin D analog retains its anticancer profile but diminishes the threat of hypercalcemia. The most effective of four analogs tested was a doubly modified hybrid compound containing fluorine (Posner 2000).
During one study, mice painted with a chemical substance, inducing cancerous tumors were concurrently the animals were given the deltanoid. After 20 weeks, the fluorine-containing analog had reduced the incidence of tumors more than 28%, while the actual number fell 63% (Kensler et al. 2000). Deltanoids are in the early stages of development and, unfortunately, it may take 10 years before they become available (Guyton et al 2003). It is possible that deltanoids could lessen the need for hormone treatments or aggressive chemotherapy. Patients could theoretically stay on the treatment for the remainder of their life to keep the cancer from advancing.
Studies indicate that moderate or severe hypovitaminosis D was present in 66% of patients taking daily vitamin D in amounts less than the recommended dosage for their age. Adults may need a minimum of 5 times the 200-IU RDA, (or 1000 IU daily), to protect against cancer (Vieth 1999). Therapeutic dosages of vitamin D typically range from 800-4000 IU a day. Monthly kidney function blood tests (creatine, BUN, etc.) should be performed if daily vitamin D intake exceeds 1400 IU. These tests are included in most standard blood chemistry tests that cancer patients regularly perform to guard against anemia and overt immunosuppression.
Food sources of vitamin D include egg yolks, organ meats, fortified dairy products, butter, cod liver oil, and cold-water fish, such as salmon, herring, and mackerel. Vitamin D enhancers are vitamins A and C, calcium, magnesium, phosphorus, and choline. Antagonists are mineral oil, phenobarbital, and laxatives.Continued
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