~Cancer: Should Patients Take Dietary Supplements? Part 2

Do Antioxidants (Concurrent with Conventional Therapy) Bolster or Diminish Survival Odds?

Abram Hoffer, M.D., Ph.D., contends that the concept of antioxidants decreasing the efficacy of chemotherapy is conveyed more and more by orthodox oncologists. It is, in fact, speculated that the number of oncologists opposed to patients taking antioxidants while receiving chemotherapy may be as high as 75%.

Although antioxidant therapy is a hotly debated issue, the benefits derived from chemotherapy are equally so. Even within the field of standard oncology, there is debate as to the merit of chemotherapy except for in a small number of cancers (Moss 1995).

Before one can claim that antioxidants should be withheld, credible evidence should be presented showing that chemotherapy has merit. At the Comprehensive Cancer Care 2001 Conference, it was reported that 31% of cancer patients abandon chemotherapy before completion due to intolerable psychological and physical stresses.

Amifostine, a synthetic variant of the amino acid cysteine, is prescribed to reduce radiation toxicity. Amifostine reduces toxicity of treatment without depreciating the anti-cancer effects (Mehta 1998). There is no evidence of defusing the effects of radiotherapy with Amifostine (Perez et al. 1998). Cardiozane (ICRF187), an antioxidant with 500 papers showing its relative safety, is prescribed to counter Adriamycin toxicity (Alderton et al. 1992). Mesna, another synthetic antioxidant, makes possible the use of the anticancer drug Ifosfamide, which (otherwise) damages the urinary system (Brock et al. 1979). Synthetic antioxidants, though somewhat toxic in nature, do not generate controversy because they are physician-prescribed and not patient-managed. It appears only orthomolecular or natural antioxidants are potentially dangerous, according to mainstream oncologists.

Most natural antioxidants, including vitamin C, are under ongoing scrutiny and often attack. The charges that vitamin C impairs the effects of chemotherapy appear to have kindled from an interview conducted with Larry Norton, a chemotherapist with a focus on breast disease at Memorial Sloan Kettering. An account of the interview that ran on the front page of newspapers (in 1997) charged that Sloan Kettering researchers had found that vitamin C blunted the effects of chemotherapy in breast cancer cells.

Dr. Charles Simone, a respected voice in natural medicine, clarified the media hype by saying that researchers had simply determined that tumor cells (injected with vitamin C) take up larger amounts of the nutrient than noncancerous cells (Agus et al. 1999). The story that was ultimately reported had a different slant, that is, because tumor cells are vitamin C responsive, ascorbic acid stymies the effects of chemotherapy by neutralizing free radicals, molecules produced by various chemotherapeutic drugs to kill the cancer. Dr. Simone cautions that jumping from a fact (cancerous cells take up more vitamin C) to a factoid (vitamin C interferes with chemotherapy/radiation therapy) is an unfortunate leap that may have impeded progress for many cancer patients.

Dr. Simone cited more than 350 studies, involving 2000 cancer patients that showed that antioxidants extended the life span of cancer patients and improved quality of life. One such study involved 50 early stage breast cancer patients, some of whom were relegated to radiation therapy and others to a combination of radiation and chemotherapy. All participants (in union with conventional therapies) took large doses of nutrients. More than 90% of both groups noted improvement in their physical symptoms, cognitive ability, sexual function, general well-being, and life satisfaction. Not one subject in either group reported a worsening of symptoms (Simone et al. 2000).

Dr. Simone explains the pathways through which antioxidants work to restrain cancer:
  • Antioxidants inhibit protein kinase C, restraining tumor cell division and proliferation.
  • Antioxidants inhibit oncogene expression, genes that give rise to tumors.
  • Antioxidants promote differentiation by altering growth factors. Undifferentiated cells depart (in appearance) from the highly recognizable (differentiated) cells of the tissue of origin. For example, healthy cells have a typical appearance microscopically: A healthy liver cell cannot be mistaken for a colon cell; or a colon cell cannot be mistaken for a kidney cell. The greater the departure from the unique character of the cell (a lack of differentiation) the greater the level of malignancy.
  • Antioxidants block destruction imposed by free radicals, protecting vital tissue from damage.
Dr. Hoffer adds that he has treated more than 1100 cancer patients with high doses of vitamin C (most of whom were concurrently receiving chemotherapy) (Hoffer et al. 1993a; Hoffer et al. 1993b; Hoffer 1994; Hoffer 1996). Upon examining health histories, Hoffer found that the mean difference in prolongation of life was heavily in favor of the use of vitamins. In the first Hoffer/Pauling series published, patients on the Hoffer program lived 10-20 times longer than patients not receiving vitamin C.

Various vital functions dependent on healthy antioxidant systems are challenged during cancer. Collapse of internal defenses (either partial or total) occurs through nutrient depletion as observed among cachexic patients, that is, those individuals evidencing a profound state of general ill health and malnutrition, marked by weakness and emaciation. (About 40% of cancer patients die due to malnutrition.) Also, naturally occurring antioxidants and enzymes are often severely exhausted among cancer patients undergoing aggressive therapies, leaving the patient defenseless in regard to free-radical attack. Adjunctive antioxidant therapy is not adding something foreign to the body but rather replacing natural substances withdrawn as a result of treatment.

A valuable contribution to the quandary of whether to use antioxidants with chemotherapy or radiation is available to physicians and patients at http://www.thorne.com/altmedrev/.fulltext/5/2/152.html.

Drs. Davis Lamson and Matthew Brignall have abridged a lengthy dissertation into accessible reference guides, showing antioxidant interactions (both positive and negative) when coupled with traditional therapies, for example, popular antioxidants (vitamins A, C, E, beta-carotene, and melatonin) interlaced positively with radiotherapy, enhanc ing e therapeutic intent (Lamson et al. 2000).

Exceptions to the reference guides routinely surface, but Lamson et al. (1999) declare that (to date) only three agents, classified as antioxidants, have been shown to decrease the effectiveness of radiation or chemotherapy in vivo:
  • N-acetyl-cysteine (NAC) reduced the therapeutic effect of anthracycline-type chemotherapy agents (doxorubicin and bleomycin), which kill cells by generating oxygen radicals. Alkylating agents (such as cisplatin) and hormonal therapies were not affected.
  • Beta-carotene decreased the effectiveness of antimetabolites (5-FU and methotrexate). Conversely, beta-carotene increased the efficacy of radiotherapy, as well as alkylating, anthracycline, and platinum chemotherapy agents.
  • Tangeretin (a flavonoid found in citrus fruit) reduced the chemotherapeutic effect of platinum compounds such as cisplatin and carboplatin. Tangeretin interfered with tamoxifen, a nonsteroidal antiestrogen used to treat estrogen-dependent cancers (Bracke et al. 1999).
Dietary curcumin inhibited chemotherapy-induced apoptosis through inhibition of reactive oxygen species. A 70% reduction in chemotherapy-induced apoptosis in MCF-7, MDA-MB-231, and BT-474 human breast cancer cells was noted. Supplemental curcumin as well as curcumin-containing foods were proposed as being possible antagonists to conventional treatment. However, additional studies are needed to determine whether breast cancer patients, undergoing chemotherapy, should avoid curcumin supplementation (Somasundaram et al. 2002).

Dan Labriola, M.D., and Robert Livingston, M.D., suggest a plan for adjunctive antioxidant therapy aimed at avoiding possible undesirable interactions with conventional treatments. They acknowledge that a number of chemotherapeutic agents are dependent upon reactive oxygen species for performance. Drs. Labriola and Livingston refer to the period when conventional treatments do their work as the protected zone. They contend that the protected zone can last for varying amounts of time, depending on the drug, the procedure and dosage, other drugs or treatments in the regime, and the patient's overall health.

Pinpointing the protected zone and protecting this interval (a process that requires the expertise and clinical judgment of a physician and an oncology pharmacist) allows time for the cytotoxic agent to enact its kill. The clinical objective is to avoid high antioxidant levels while the drugs are still active and vulnerable to interference (Labriola et al. 1999). Labriola, although criticized by some for astringency, advises looking at the long-term prognosis, not the short-term "feel good" response, obtained from antioxidants while undergoing aggressive therapies.

Jeff Bland, Ph.D., scientist and educator, reported at the Comprehensive Cancer Care 2001 Conference that leaders in the field endorse pulse therapy as the appropriate means of administering nutritional support concurrent with toxic treatment. Reentering with supplementation 2-3 days after the large chemotherapeutic bolus allows time for a massive cancer kill followed by a period of rebuilding (Bland 1999; 2001). If conventional treatment is the patient's election, this dosing pattern appears to allow the body the full effects of conventional treatment, plus the benefit of an antioxidant program a few days later. Juices, rich in antioxidants, may (according to Dr. Bland) also merit caution during the few days of the protected zone.

Dr. Keith Block, director of the Block Medical Center and the Institute for Integrated Cancer Care, although in favor of antioxidant therapy, admits the ultimate answer is not available. The downside to the equation is that individuals with cancer are not able to wait for proof. The general theme of Comprehensive Cancer Care 2001 (presenting the best of worldwide research) was that it appears unreasonable and heartless to totally withhold materials that (to date) show survival enhancement. Dr. Block concluded: "I would not (personally) take chemotherapy if antioxidants were not also on board" (Block 2001). Dr. Block believes that factoring in circadian rhythms regarding chemotherapeutic administration influences toxicity and anticancer activity and best serves the patient's welfare. Dr. Block has a highly esteemed practice in Evanston, Illinois, (847) 492-3040.

An opposing view (regarding antioxidant therapy) comes from Dr. Rudolph Salganik, a Russian scientist currently at the University of North Carolina. Dr. Salganik states that free radicals, generated through chemicals and radiation, should be allowed to work unencumbered, that is, without interference from antioxidants. According to Dr. Salganik, apoptosis or regulated cell death eliminates unwanted and damaged cells, including those precancerous and cancerous. He continued, "Since reactive oxygen species (ROS) act as essential apoptotic mediators, we [our team] reasoned that increasing ROS levels might enhance apoptosis and thereby slow tumor growth." A brain tumor was used as the model to test the impact of an antioxidant-depleted diet, that is, a diet capable of increasing ROS levels compared to an antioxidant-enriched diet on tumor growth.

The antioxidant-depleted diet dramatically increased apoptosis in mouse tumor cells but did not affect normal tissue. Salganik says that the presence of increased oxidant stress within tumors indicates that the likely mechanism of apoptosis is via ROS and DNA oxidative impairment. As reactive oxygen species promoted apoptosis, tumor growth was inhibited; in contrast, the antioxidant-rich diet had no impact on the growth of the tumor. The Salganik team concluded that when the multitudes of oxidants are not suppressed by antioxidants, they mediate apoptosis, or cell death, the exact intent of cytotoxic therapies (Salganik et al. 2000).

Dr. Salganik later reported that intake of exogenous antioxidants (vitamins E, C, and beta-carotene) could protect against cancer and other degenerative processes in individuals with innate or acquired high levels of reactive oxygen species (ROS). Screening populations (for high or low levels of ROS) could provide a scientifically grounded application for antioxidant supplementation, a program that could vastly contribute to the nation's overall health (Salganik 2001).

Positive Results of High Dose Antioxidant Therapy During Chemotherapy and Radiation

Studies have demonstrated that antioxidant vitamins can enhance the efficacy of certain chemotherapeutic agents on tumor cells in culture (Prasad et al. 1994; Prasad 2003). Antioxidant vitamins could be an important adjuvant to standard treatment of human cancers (Prasad et al. 1999).

An in vitro study was undertaken to ascertain if antioxidant vitamins could enhance the cytotoxic and apoptotic effects of paclitaxel and carboplatin on non-small cell lung cancer ( Pathak et al. 2002).

The human non-small cell lung cancer cell line H-520 was treated with a mixture of the antioxidant vitamins C, E, and beta-carotene and paclitaxel and carboplatin, both individually and in combination of various doses in different sequences. The mixture of antioxidant vitamins by itself led to 15% apoptosis. Simultaneous treatment of paclitaxel and carboplatin produced 40% apoptosis, while paclitaxel treatment 24 hours prior to carboplatin treatment caused 54% apoptosis. However, the most significant improvements in the degree of apoptosis were observed when cells were pretreated with an antioxidant vitamin mixture immediately before treatment with paclitaxel and carboplatin (70% apoptosis) or pretreated with the antioxidant vitamin mixture 24 hours prior to treatment with paclitaxel, which was then followed 24 hours later by treatment with carboplatin (89% apoptosis).

The apoptotic effects of paclitaxel and carboplatin are enhanced by antioxidant vitamin pretreatment. Further, the most promising sequence of agents that emerged in this study was the pretreatment with the antioxidant vitamin mixture 24 hours prior to treatment with paclitaxel, which was then followed 24 hours later by treatment with carboplatin.

Another clinical trial was conducted to examine the outcome of treatment with paclitaxel and carboplatin alone and in combination with an antioxidant vitamin mixture of 60 mg a day of beta-carotene, 1025 mg a day of alpha- tocopherol, and 6100 mg a day of ascorbic acid on 65 cancer patients with squamous cell carcinomas (n = 37), adenocarcinomas (n = 16), large cell carcinomas (n = 6), and poorly differentiated carcinoma (n = 6). The outcome was very encouraging with overall survival at 33% after 1 year with the treatment of paclitaxel and carboplatin alone, and 54% when patients were treated with paclitaxel and carboplatin combined with the antioxidant vitamin mixture. Although the study was limited due to the small number of patients, the research confirms a need for further clinical trials to examine the role of vitamins in the treatment and management of cancer (Unpublished 2002).

For a comprehensive report on the use of antioxidants during cancer therapy, refer to the Cancer Chemotherapy and Cancer Radiation Therapy protocols.

Continued . . .


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