| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | COVER ARCHIVE | SEARCH |
|
|
|
||||||||
|
||||||||||
Electronic Letters to:
|
|
Electronic letters published:
![[Read eLetter]](/icons/misc/sectionDOWN.gif){kind=icon}
Vitamin C may have value as adjunctive cancer therapy
Should Patients Undergoing Chemotherapy and Radiotherapy Be Prescribed Antioxidants?
Antioxidants may be beneficial
Belief and Opinion Do Not Constitute Science
Cancer patients may very well tolerate the use of certain dietary supplements
|
|
|||
|
Stephen Lawson Linus Pauling Institute, Oregon State University
Send letter to journal:
stephen.lawson{at}oregonstate.edu Stephen Lawson
|
[Note from CA staff: Due to a technical oversight, this letter was not published when it was originally accepted on December 15, 2005. We apologize to the author for the error.]
The data on the use of antioxidant vitamins as cancer therapy are conflicting and do not yet permit a definitive conclusion about efficacy. However, there are a number of clinical studies showing some benefit. For instance, Jaakkola et al (1) found that the provision of micronutrients, including high-dose vitamin C, concomitantly with chemotherapy and radiation prolonged survival in patients with small-cell lung cancer compared to similar patients treated without micronutrients. Recently, Drisko et al (2) reported the very favorable response of two patients with stage III epithelial ovarian carcinoma to high-dose intravenous vitamin C and chemotherapy. Dr. D’Andrea noted that the Mayo Clinic controlled trials of vitamin C and cancer failed to find any benefit for vitamin C. However, those studies also failed to replicate the clinical work of Cameron, who initiated his terminal cancer patients with high-dose intravenous vitamin C. The Mayo Clinic used only oral vitamin C, which produces plasma concentrations of only about 200 uM instead of as high as 15,000 uM achieved with IV vitamin C. High concentrations of vitamin C have been found to selectively kill cancer cells in vitro, probably through the generation of hydrogen peroxide (3). Dr. D'Andrea mentioned that even small harmful effects of antioxidants may be important. Likewise, potentially large beneficial effects should merit consideration. Not all anecdotal clinical evidence should be dismissed, and not every benefit should be presumed. Carefully controlled clinical trials of intravenous vitamin C are urgently needed to add more evidence to the risk-benefit analysis. 1. Jaakkola K, Lahteenmaki P, Laakso J, et al. Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res 1992;12(3): 599-606. 2. Drisko JA, Chapman J, Hunter VJ. The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. J Am Coll Nutr 2003;22(2):118-123. 3. Chen Q, Espey MG, Krishna MC, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA 2005;102(38):13604-13649. |
|||
|
|
|||
|
Hadi Meeran Hussain, Final Year Medical Student Army Medical College, Rawalpindi, Abida Sultana, Associate Professor Community Medicine, Army Medical College, Rawalpindi, Pakistan
Send letter to journal:
hadimeeran{at}yahoo.com Hadi Meeran Hussain, et al.
|
In September 2005, CA: A Cancer Journal for Clinicians published a warning by Gabriella D’Andrea, MD, against the concurrent use of antioxidants with radiotherapy and chemotherapy. However, several deficiencies of the CA article have become apparent, not least the selective omission of prominent studies that contradicted the author’s conclusions. While acknowledging that only large-scale, randomized trials could provide a valid basis for therapeutic recommendations, the author sometimes relied on laboratory rather than clinical data to support her claim that harm resulted from the concurrent use of antioxidants and chemotherapy. She also sometimes extrapolated from chemoprevention studies rather than those on the concurrent use of antioxidants per se. The article overstated the degree to which the laboratory data diverged in regard to the safety and efficacy of antioxidant therapy: in fact, the preponderance of data suggests a synergistic or at least harmless effect with most high-dose dietary antioxidants and chemotherapy. The practical recommendations made in the article to avoid the general class of antioxidants during chemotherapy are inconsistent, in that if antioxidants were truly a threat to the efficacy of standard therapy, antioxidant-rich foods, especially fruits and vegetables, ought also be proscribed during treatment. Yet no such recommendation is made. Furthermore, the wide-scale use by both medical and radiation oncologists of synthetic antioxidants (eg, amifostine) to control the adverse effects of cytotoxic treatments is similarly overlooked. In sum, this CA article is incomplete: there is far more information available regarding antioxidant supplements as an appropriate adjunctive cancer therapy than is acknowledged. Patients would be well advised to seek the opinion of physicians who are adequately trained and experienced in the intersection of 2 complex fields, that is, chemotherapeutics and nutritional oncology. Physicians whose goal is comprehensive cancer therapy should refer their patients to qualified integrative practitioners who have such training and expertise to guide patients. A blanket rejection of the concurrent use of antioxidants with chemotherapy is not justified by the preponderance of evidence at this time and serves neither the scientific community nor cancer patients. |
|||
|
|
|||
|
Kenneth A. Conklin, MD, PhD, Integrative Oncologist Clinical Professor, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA
Send letter to journal:
kconklin{at}mednet.ucla.edu Kenneth A. Conklin, MD, PhD
|
The use of antioxidants during chemotherapy and radiotherapy of cancer has long been a controversial topic in the oncology community, and D'Andrea (1) has argued that use of such dietary supplements should be avoided during cytotoxic therapy. Although many oncologists hold this viewpoint, I would like to comment on a few points made in the article. D'Andrea states that “radiotherapy and many chemotherapy agents act by producing free radicals”. Radiotherapy (low linear energy transfer radiation: beta- and gamma-radiation) certainly acts via the production of very high levels of free radicals. However, despite the fact that many antineoplastic agents generate high levels of free radicals in biological systems (anthracyclines, platinum coordination complexes, alkylating agents, epipodophyllotoxins, camptothecins) (2,3), the drugs of most major classes (antifolates, nucleoside and nucleotide analogues, vinca alkaloids, taxanes, epipodophyllotoxins, camptothecins) have well established mechanisms of action that do not depend upon free radical generation (2). Even the anthracyclines, which generate a much higher level of oxidative stress than the other agents, appear to act primarily via topoisomerase II inhibition (4). Of the commonly used antineoplastic agents, the ones that clearly act via free radical intermediates are bleomycin, which cleaves DNA by hydrogen abstraction by its iron-binding arm that functions as a ferrous oxidase, and mitomycin-C, which creates DNA inter-strand crosslinks following reduction of its aziridine ring (which requires a reducing agent, an action that is carried out by antioxidants). Although D'Andrea does not make a distinction between the different types of antioxidants, it is important to recognize that all antioxidants cannot be viewed as equal. Small molecular weight antioxidants act as reducing agents, but some (e.g., glutathione, N- acetyl cysteine, and alpha-lipoic acid) also possess strong nucleophilic properties because they possess a sulfhydryl group. Whereas reduction of oxidative stress by any antioxidant should not impact the antineoplastic activity of most agents, antioxidants that are strong nucleophiles can bind and inactivate the electrophilic intermediates of antineoplastic agents that act via nucleophilic substitution reactions (platinum coordination complexes and alkylating agents). Competition between nucleophilic antioxidants and the nucleophilic cellular targets of the drugs may reduce the efficacy of therapy. D'Andrea further states that “proponents of antioxidant therapy” “claim that the protective effect of antioxidants is selective for normal cells”. Although correct, this requires clarification since using an antioxidant to prevent a drug-induced side effect will be selective only if that side effect is due to an activity that is independent of the drug's antineoplastic mechanism of action. Certainly, if a drug creates a side effect by the same mechanism that it kills cancer cells, preventing that side effect would be expected to reduce oncologic activity. An example of this would be myelosuppression, i.e., the drug destroying rapidly proliferating bone marrow cells as well as rapidly growing cancer cells (antioxidants do not interfere with myelosuppression (2)). However, if a drug causes a side effect by a mechanism other than that which accounts for its antineoplastic activity, selective protection is possible. For example, the cardiotoxicity of anthracyclines most likely results from oxidative damage to mitochondria and displacement of coenzyme Q10 from the electron transport system of the inner mitochondrial membrane (not inhibition of topoisomerase II), an effect that is selective for mitochondria of cardiac cells (4). Supplemental coenzyme Q10, in both preclinical and (limited) clinical studies, appears to prevent this toxicity without interfering with antineoplastic activity. A further example of selective protection is the use of glutathione to reduce the toxicities (nephrotoxicity, neurotoxicity, and ototoxicity) of platinum coordination complexes, effects that are attributable to protein sulfhydryl binding and inactivation of thiol-containing enzymes (not formation of inter-and intra-strand DNA crosslinks that accounts for the drugs' antineoplastic activity). Although simultaneous administration of one of these drugs and glutathione might result in inactivation of the drug, appropriate timing of glutathione administration appears to reduce toxicity without diminishing antineoplastic activity (2). D'Andrea also states that some proponents of antioxidant use claim that antioxidants “increase the effectiveness of cytotoxic therapies”. This may be true if one considers the impact of drug- induced free radical generation on antineoplastic activity (3,5). Oxidative stress slows or halts cell cycle progression, effects that can reduce the antineoplastic activity of those drugs that exhibit cell cycle phase-specific activities. Even platinum coordination complexes and alkylating agents, which are not considered to be phase-specific agents, require cells to progress through the S and G2 phase of the cell cycle in order for apoptosis to occur. Oxidative stress during chemotherapy results in lipid peroxidation that generates numerous aldehydes. Because of their strong electrophilic character the aldehydes can bind to nucleophilic cellular targets, such as the active sites of caspases. Such binding inactivates these enzymes that carry out the apoptotic process (3). The aldehydes can also bind to the nucleophilic extracellular domain of the CD95 death receptor and interfere with this pathway of drug-induced apoptosis. Thus, the antineoplastic agents that generate free radicals may reduce their own oncologic efficacy, an effect that may be prevented by the administration of antioxidants. Although the aldehydes may, in part, mediate the cytotoxicity of the exceptionally high levels of free radicals generated by radiotherapy, lower aldehyde levels likely account for interference of drug-induced antineooplastic activity that is seen with more modest levels of oxidative stress (3). D'Andrea cites several clinical studies, although except for the study by Lesperance et al. (6), none are relevant to the topic of antioxidant use during cytotoxic therapy. Even the study by Lesperance et al. fails to provide convincing evidence against the use of antioxidants because of methodological flaws (variability of supplement doses between patients, a retrospective study making it difficult to determine patient compliance with taking supplements, inadequate power to discern small differences in survival time between the two groups). However, despite a large body of preclinical evidence for the benefits of antioxidants during chemotherapy (2,4), I certainly agree with D'Andrea that further clinical study is necessary. D'Andrea concludes by stating that patients should be advised against taking antioxidants during cytotoxic therapies. In part, I agree with D'Andrea. Since some nutritional supplements may interfere with chemotherapy (sulfhydryl antioxidants, and possibly herbal supplements with high phytochemical levels that may induce hepatic microsomal enzymes or MDR-1 and MRP drug export pumps), it is important that patients should not self- medicate. However, I feel that existing data support the use of appropriately selected antioxidants during conventional cancer treatments, although for patients that wish to take supplements during therapy, this should only be done under the guidance of a knowledgeable professional. 1. D'Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin 2005; 55:319-321. 2. Conklin KA. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer 2000; 37:1-18. 3. Conklin KA. Chemotherapy-associated oxidative stress: impact of chemotherapeutic effectiveness. Intgr Cancer Ther 2004; 3:294-300. 4. Conklin KA. Coenzyme Q10 for prevention of anthracycline- induced cardiotoxicity. Intgr Cancer Ther 2005; 4:110-130. 5. Conklin, KA. Cancer chemotherapy and antioxidants. J Nutr 2004; 134:3201S-3204S. 6. Lesperance ML, Olivotto IA, Forde N, et al. Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study. Breast Cancer Res Treat 2002; 76:137-143. |
|||
|
|
|||
|
Hal David Gunn, physician Centre for Integrated Healing
Send letter to journal:
hgunn{at}healing.bc.ca Hal David Gunn
|
Dr. Gabriella D'Andrea's recent article entitled, "Use of Anioxidants During Chemotherapy and Radiotherapy Should be Avoided" was characterized as a "review of the scientific evidence" in a recent Wall Street Journal article. It is anything but. Dr. D'Andrea mentions some of the evidence which raises the possiblity of concern regarding the use of antioxidants during chemotherapy/radiation but fails to even mention any of the important studies in the growing substantial body of supportive evidence, including numerous randomized controlled clinical trials, which have demonstrated signficant benefit for the use of antioxidants during chemotherapy and radiation. To my knowledge, no RCT clinical trials of naturally occuring antioxidants taken in conjunction with chemotherapy or radiation have demonstated statistically significant concern, whereas numerous such RCT's have demonstrated benefit in terms of reducing side effects of chemotherapy, enhanced benefit from chemotherapy and/or increased patient survival. Belief and opinion do not constitute science. If the editors of the journal are interested in an evidenced-based review of this important issue rather than simply an opinion piece as provided by Dr. D'Andrea, I would be very happy to contribute the references of which I am aware. It would help elevate the level of discourse on this important topic - something I'm sure our patients would appreciate. Yours sincerely, Hal Gunn, M.D. Director, Centre for Integrated Healing Vancouver, B.C. Canada |
|||
|
|
|||
|
Neil E Levin, Nutrition Educator, Clinical Nutritionist NOW Health Group, Inc.
Send letter to journal:
neil.levin{at}nowfoods.com Neil E Levin
|
Cancer patients may very well tolerate the use of certain dietary supplements Neil E. Levin, CCN, DANLA Cancer patients may very well tolerate the use of certain dietary supplements, with some specific benefits noted in the literature. A recent article published in CA: A Cancer Journal for Physicians (D'Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin. 2005 Sep-Oct;55(5):319-21. PMID: 16166076) stated that the use of “antioxidants might reduce the effects of conventional cytotoxic therapies”. However, my own review of the literature shows that, in many cases, the use of antioxidants - and other nutritional supplements - have been determined to be compatible with conventional cancer therapies based on the published literature and that clinicians might better serve their patients if they adopt a more inquisitive approach as to whether or not specific supplements may play a role in aiding their conventional therapies. In some cases the supplements are deemed useful, but just not on the same day as the therapy. In others the supplements are highly recommended during and/or after the conventional therapies. The article’s overgeneralization has resulted in news headlines warning doctors and patients to avoid the use of all dietary supplements during cancer therapy. If true, a warning should also be issued for nutrient-rich foods like fruits, vegetables and nuts; especially if concentrated into juices. Since there is conflicting data and these nutrients are so essential, I do not support either warning. Physicians should research the documented use of nutrients that are compatible with the specific therapies that they are contemplating, which may result in better outcomes for their patients than the simple avoidance of nutrient- rich foods and dietary supplements that have already been shown to discourage cancer growth. The large percentage of cancer patients that die of malnutrition has also been ignored in this article.9 Improving the nutritional status of patients thus becomes almost as important as fighting the cancer, and in most cases the two are not contradictory. Here is a breakdown of dietary supplements that are useful during therapy, broken down by classes of supplements. I have bolded some text for emphasis, with all direct quotes indicated by quotation marks: FISH OIL: “The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include 1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor; 2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion; 3) inducing differentiation of cancer cells; 4) suppressing nuclear factor-kappaB activation and bcl-2 expression, thus allowing apoptosis of cancer cells; and 5) reducing cancer-induced cachexia. It seems reasonable to assume that after appropriate cancer therapy, consumption of omega-3 fatty acids might slow or stop the growth of metastatic cancer cells, increase longevity of cancer patients and improve their quality of life.”1 Fish oil improved outcome in patients with solid tumors and increases tumor necrosis factor production in malnourished cancer patients, prolonging survival.2 Fish oil also improved outcomes in cancer treatments: wasting syndrome3, apoptosis of cancer cells (“in combination with standard treatments, supplementing the diet with (n-3) fatty acids may be a nontoxic means to improve cancer treatment outcomes and may slow or prevent recurrence of cancer.”)4 (“We conclude that EPA inhibits the growth of HepG2 cells and mediates its effect, at least in part, via the Fas-mediated apoptosis. It appears that the effects of EPA on hepatoma cells are determined by the status of p53 and that wild-type p53 is a prerequisite for the anticancer effect of EPA.”) 5,6, impairing tumor angiogenesis (“Review of the experimental data suggests that selective inhibitors of eicosanoid-synthesizing enzymes and dietary intervention with n-3 fatty acids merit clinical evaluation as adjuvant therapy and chemopreventive agents.”) while improving blood glucose7. GLA: Gamma linolenic acid with tamoxifen as primary therapy in breast cancer: “T+GLA cases achieved a significantly faster clinical response (objective response vs. static disease) than tamoxifen controls, evident by 6 weeks on treatment (p = 0.010).”8 VITAMINS/MALNUTRITION: Malnutrition actually kills about 40% of cancer patients!9 Post- surgical lung cancer patients who take vitamin supplements are more likely to be long term survivors: “Vitamin users had a longer median censored survival compared with nonusers (41 months versus 11 months; P = 0.002).”10 A double blind clinical trial of biopsy-confirmed bladder cancer patients added either RDA-potency vitamins or megadose potency vitamins, plus zinc in RDA or megadose potency. “Overall recurrence was 24 of 30 patients (80%) in the RDA arm and 14 of 35 (40%) in the high dose arm (p = 0.0011, 2-tailed Fisher's exact test). Megadose vitamins A, B6, C and E plus zinc decrease bladder tumor recurrence in patients receiving BCG immunotherapy.”11 A trial of patients with malignant high-risk uveal (iris of the eye) melanoma (T3) were treated secondarily with biological dietary supplements after primary standard therapy, enucleation or brachytherapy. Secondary treatment consisted of natural amino-acids, trace minerals, folic acid and a diet containing neurogenic lipid fatty acid components. It presented no side effects, no toxicity and was inexpensive. None of these patients has suffered recurrent disease.12 Metastatic breast cancer treatment is enhanced with folic acid supplementation: “Treatment of anthracycline-resistant metastatic breast cancer with new antineoplastic agents remains a challenge. The 5-year survival for this disease is only 15%, and hormonal and chemotherapeutic options remain essentially palliative...The long time known 5-fluorouracil comes to the third place of the effective drugs. Continuous infusion or addition of folic acid increases the intracellular efficacy and results in 5-53% objective remissions.”13 Folic acid doubled survival rates for colon cancer patients: “In a prospective randomized multicentre trial 139 patients with metastatic colorectal carcinoma (70 men, 69 women; age 35-81 years) were given palliative treatment with fluorouracil (400 mg/m2 daily for 5 days) alone or combined with folic acid (100 mg/m2 before each dose of fluorouracil). Both groups were comparable in respect of age, sex, Karnofsky index and number of localisations of metastases. The criterion for starting the treatment was progression of the malignancy or clinical symptoms caused by the tumour. Resulting remission rates (fluorouracil monotherapy vs combination with folic acid) were: complete or partial remission, 9 vs 16%; arrest of tumour growth, 20 vs 60%; progression 71 vs 24%. Peripheral side effects, such as stomatitis and diarrhoea, were similarly frequent with the two treatment regimens and reasonably tolerable. Median survival time for the fluorouracil monotherapy was 7.24 months from onset of treatment, and 9.1 months from the time that any metastases were diagnosed. The combination treatment with folic acid achieved a significantly longer median survival time (P less than 0.0001), 14.98 months from treatment onset and 16.3 months from metastasis diagnosis. The higher rate of response and the significantly prolonged survival time signify an improvement of the therapeutic profile of fluorouracil by addition of folic acid in the palliative therapy of colorectal carcinomas.”14 ANTIOXIDANTS: Vitamin E has been used to enhance radiation and chemotherapy treatments: “This hypothesis was here tested in twelve patients with colorectal cancer (Dukes' C and D) who, prior to intervention with chemo- or radiotherapy, received a daily dose of 750 mg of vitamin E during a period of 2 weeks. RESULTS: Short-term supplementation with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to enhanced capacity by their T cells to produce the T helper 1 cytokines interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more (average, 22%) in the number of T cells producing interleukin 2 was seen after 2 weeks of vitamin E supplementation, as compared with peripheral blood monocyte samples taken before treatment (P = 0.02). Interestingly, there seemed to be a more pronounced stimulatory effect by vitamin E on naive (CD45RA(+)) T helper cells as compared with T cells with a memory/activated phenotype. CONCLUSIONS: Dietary vitamin E may be used to improve the immune functions in patients with advanced cancer, as a supplement to more specific immune interventions.”15 “Selenium (Se) is an essential nutrient, and Se deficiency is associated with disease conditions and general impairment of the immune system. Supplementation of Se to humans already consuming the RDA may help to prevent certain cancers. A convincing argument can be made for augmenting the food supply with Se...”16 “Selenium is an essential trace element involved in several key metabolic activities via selenoproteins, enzymes that are essential to protect against oxidative damage and to regulate immune function. Selenium also may have other health benefits unrelated to its enzymatic functions. It may provide important health benefits to people whose oxidative stress loads are high, such as those with inflammatory or infectious diseases like rheumatoid arthritis or human immunodeficiency virus/acquired immunodeficiency syndrome, or who are at high risk for cancers, particularly prostate cancer. Some studies have generated compelling evidence that selenium is beneficial...” 17 Regarding the use of the antioxidant red pigment Lycopene: “Quite surprising was the decrease in blood prostate-specific antigen, which was explained by the increase in apoptotic death of prostate cells, especially in carcinoma regions. Prostate cancer cell cultures (LNCaP) were also sensitive to lycopene in growth medium, which caused an increased apoptosis and arrested the cell cycle.”18 Regarding radiation and antioxidants: “It is very prudent to continue to support the well-established radiobiological concept that no radiation dose can be considered completely safe, and that all efforts must be made to reduce both the radiation dose and biological damage, no matter how small that damage might be, without sacrificing the benefits of radiation. Based on the results of many scientific experiments, formulations containing multiple antioxidants for biological protection against radiation damage in humans can be developed, and this strategy together with the existing physical concept of radiation protection, should further reduce potential risks of low doses of ionizing radiation in humans.”19 Vitamin E and breast cancer therapies: “Recent studies with alpha-TEA show it to be a potent inducer of apoptosis in a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture, and to be effective in significantly reducing tumor burden and metastasis in a syngeneic mouse mammary tumor model, as well as xenografts of human breast cancer cells. Studies also show that alpha-TEA, in combination with the cyclooxygenase-2 inhibitor celecoxib and the chemotherapeutic drug 9-nitro-camptothecin decreases breast cancer animal model tumor burden and inhibits metastasis significantly better than do single-agent treatments.”20 “A number of clinical studies have already demonstrated beneficial effects of antioxidants in ameliorating side effects of chemotherapy. More theoretical work on the chemistry of antioxidants and chemotherapy drugs suggests that antioxidants might improve therapeutic efficacy of antineoplastics by counteracting aldehydes that impede the passage of cells through the cell cycle.”21 According to a report by the Agency for Healthcare Research and Quality (AHRQ): “Subgroup analysis did identify a statistically significant 9% reduction in all cause mortality and a borderline significant 13% reduction in all-cancer mortality associated with supplemental vitamin E in combination with other micro-nutrients.”22 A Tufts University review of antioxidants and human cancer stated: “...selenium and vitamin E reduced the risk of some forms of cancer, including prostate and colon cancer, and carotenoids have been shown to help reduce breast cancer risk. Cancer treatment by radiation and anticancer drugs reduces inherent antioxidants and induces oxidative stress, which increases with disease progression. Vitamins E and C have been shown to ameliorate adverse side effects associated with free radical damage to normal cells in cancer therapy, such as mucositis and fibrosis, and to reduce the recurrence of breast cancer.”23 “Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity... At present, there is no strategy to reduce the risk of recurrence of the primary tumors or of a second cancer among survivors. Patients unresponsive to standard or experimental therapies have little option except for poor quality of life for the remainder of life. Therefore, additional approaches should be developed to improve the efficacy of current management of cancer. In this review, the author proposes that an active nutritional protocol that includes high doses of multiple dietary antioxidants and their derivatives (vitamin C, alpha-tocopheryl succinate, and natural beta-carotene), but not endogenously made antioxidants (glutathione- and antioxidant enzyme-elevating agents), when administered as an adjunct to radiation therapy, chemotherapy, or experimental therapy, may improve its efficacy by increasing tumor response and decreasing toxicity. This nutritional protocol can also be used when patients become unresponsive to standard therapy or experimental therapy to improve quality of life and possibly increase the survival time. The authors also propose that after completion of standard therapy and/or experimental therapy, a maintenance nutritional protocol that contains lower doses of antioxidants and their derivatives, together with modification in diet and lifestyle, may reduce the risk of recurrence of the original tumor and development of a second cancer among survivors. Experimental data and limited human studies suggest that use of these nutritional approaches may improve oncologic outcomes and decrease toxicity.”24 “Proanthocyanidin from grape seeds enhances anti-tumor effect of doxorubicin both in vitro and in vivo.”25 In a recent study, the conclusion was that: “Supplementation with high doses of alpha-tocopherol and beta-carotene during radiation therapy could reduce the severity of treatment adverse effects.”26 CoEnzymeQ10 (CoQ10) enhanced the efficacy of tamoxifen: “Administration of TAM along with CoQ10 restored the (antioxidant enzyme) activities to a significant level thereby preventing cancer cell proliferation. This study highlights the increased antioxidant enzyme activities in relation to the susceptibility of cells to carcinogenic agents and the response of tumour cells to the chemotherapeutic agents.”27 Selenium and Vitamin E enhanced the effects of cytostatic drugs: “Our observations regarding the role of antioxidant treatment suggest: 1) a benefic effect on DNA alkylant-induced lesions, expressed by a decrease in the level of 3H-Thymidine uptake in liver and, 2) an increase of the inhibitory activity of cytostatic on DNA replication biosynthesis in tumor cells, suggested by lower 3H-Thymidine incorporation in tumor cells. The most significant results were showed in both analyzed tissues, when the Orgasel 50 + Vitamin E administration begins at the same time with the tumor cell inoculation. These findings clearly show the organic Se salts and Vitamin E constitute a valuable adjuvant in anticancer medication, increasing the interest for the application of these antioxidants in cancer therapy and prevention.”28 “Studies involving pentoxifylline plus vitamin E demonstrated regression in RIF. The combination was more effective than placebo and may be superior to monotherapy with either agent.”29 “alpha-TS also enhances the growth-inhibitory effect of ionizing radiation, hyperthermia, some chemotherapeutic agents and biological response modifiers on tumor cells, while protecting normal cells against some of their adverse effects. Thus, alpha-TS alone or in combination with dietary micronutrients can be useful as an adjunct to standard cancer therapy by increasing tumor response and possibly decreasing some of the toxicities to normal cells.”30 In cancer patients a placebo-controlled, cross-over clinical trial using Lipid Replacement Therapy plus antioxidants demonstrated that the adverse effects of chemotherapy can be reduced in 57-70% of patients. Dietary use of unoxidized membrane lipids plus antioxidants is recommended for patients undergoing cancer therapy to improve quality of life but should not be taken at the same time of day as the therapy.31 REFERENCES: 1. Hardman WE. Omega-3 fatty acids to augment cancer therapy. J Nutr. 2002 Nov;132(11 Suppl):3508S-3512S. Review. PMID: 12421878 2. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Cancer. 1998 Jan 15;82(2):395-402. PMID: 9445198 3. Ross JA, Fearon KC. Eicosanoid-dependent cancer cachexia and wasting. Curr Opin Clin Nutr Metab Care. 2002 May;5(3):241-8. Review. PMID: 11953648 4. Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr. 2004 Dec;134(12 Suppl):3427S-3430S. Review. PMID: 15570049 5. Chi TY, Chen GG, Lai PB. Eicosapentaenoic acid induces Fas- mediated apoptosis through a p53-dependent pathway in hepatoma cells. Cancer J. 2004 May-Jun;10(3):190-200. PMID: 15285929 6. Lai PB, Ross JA, Fearon KC, Anderson JD, Carter DC. Cell cycle arrest and induction of apoptosis in pancreatic cancer cells exposed to eicosapentaenoic acid in vitro. Br J Cancer. 1996 Nov;74(9):1375-83. PMID: 8912532 7. Rose DP, Connolly JM. Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutr Cancer. 2000;37(2):119-27. Review. PMID: 11142082 8. Kenny FS, Pinder SE, Ellis IO, Gee JM, Nicholson RI, Bryce RP, Robertson JF. Gamma linolenic acid with tamoxifen as primary therapy in breast cancer. Int J Cancer. 2000 Mar 1;85(5):643-8. PMID: 10699943 9. Patrick Quillin, PhD, RD, CNS, Director of Nutrition, Cancer Treatment Centers of America. IAACN Symposium, Orlando, FL September 2005 “Endocrine Physiology of Healthy Glands & Hormones” - How Nutrients Affect the Endocrinology of Cancer (presentation) 10. Jatoi A, Daly BD, Kramer G, Mason JB. A cross-sectional study of vitamin intake in postoperative non-small cell lung cancer patients. J Surg Oncol. 1998 Aug;68(4):231-6. PMID: 9721708 11. Lamm DL, Riggs DR, Shriver JS, vanGilder PF, Rach JF, DeHaven JI. Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol. 1994 Jan;151(1):21-6. PMID: 8254816 12. Tallberg T, Uusitalo R, Sarna S, Seregard S, Werschnik C. Improvement of the recurrence-free interval using biological adjuvant therapy in uveal melanoma. Anticancer Res. 2000 May-Jun;20(3B):1969-75. PMID: 10928136 13. Kreienberg R. [Therapy of anthracycline-resistant metastatic breast carcinoma]. Schweiz Rundsch Med Prax. 1998 Apr 22;87(17):573-7. Review. German. PMID: 9623323 14. Loffler TM, Korsten FW, Reis HE, Planker M, Burghardt F, Aulbert E, Lindemann W, Schroder M, Hausamen TU, Strohmeyer G. [Fluorouracil as monotherapy or combined with folinic acid in the treatment of metastasizing colorectal carcinoma]. Dtsch Med Wochenschr. 1992 Jun 26;117(26):1007-13. German. PMID: 1618109 15. Malmberg KJ, Lenkei R, Petersson M, Ohlum T, Ichihara F, Glimelius B, Frodin JE, Masucci G, Kiessling R. A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin Cancer Res. 2002 Jun;8(6):1772-8. PMID: 12060616 16. Finley JW. United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center. Selenium accumulation in plant foods. Nutr Rev. 2005 Jun;63(6 Pt 1):196-202. Review. PMID: 16028563 17. Ryan-Harshman M, Aldoori W. The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Pract Res. 2005 Summer;66(2):98-102. Review. PMID: 15975198 18. Stacewicz-Sapuntzakis M, Bowen PE. Role of lycopene and tomato products in prostate health. Biochim Biophys Acta. 2005 May 30;1740(2):202 -5. Epub 2005 Mar 13. Review. PMID: 15949687 19. Prasad KN. Rationale for using multiple antioxidants in protecting humans against low doses of ionizing radiation. Br J Radiol. 2005 Jun;78(930):485-92. Review. PMID: 15900053 20. Kline K, Yu W, Sanders BG. Vitamin E and breast cancer. J Nutr. 2004 Dec;134(12 Suppl):3458S-3462S. Review. PMID: 15570054 21. Block KI. Antioxidants and cancer therapy: furthering the debate. Integr Cancer Ther. 2004 Dec;3(4):342-8. Review. PMID: 15523105 22. Shekelle P, Hardy ML, Coulter I, Udani J, Spar M, Oda K, Jungvig LK, Tu W, Suttorp MJ, Valentine D, Ramirez L, Shanman R, Newberry SJ. Effect of the supplemental use of antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cancer. Evid Rep Technol Assess (Summ). 2003 Oct;(75):1-3. Review. PMID: 15523748 23. Borek C. Dietary antioxidants and human cancer. Integr Cancer Ther. 2004 Dec;3(4):333-41. Review. PMID: 15523104 24. Prasad KN. Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. Integr Cancer Ther. 2004 Dec;3(4):310-22. Review. PMID: 15523102 25. Zhang XY, Bai DC, Wu YJ, Li WG, Liu NF. Proanthocyanidin from grape seeds enhances anti-tumor effect of doxorubicin both in vitro and in vivo. Pharmazie. 2005 Jul;60(7):533-8. PMID: 16076082 26. Bairati I, Meyer F, Gelinas M, Fortin A, Nabid A, Brochet F, Mercier JP, Tetu B, Harel F, Abdous B, Vigneault E, Vass S, Del Vecchio P, Roy J. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol. 2005 Aug 0;23(24):5805-13. Epub 2005 Jul 18. PMID: 16027437 27. Perumal SS, Shanthi P, Sachdanandam P. Combined efficacy of tamoxifen and coenzyme Q10 on the status of lipid peroxidation and antioxidants in DMBA induced breast cancer. Mol Cell Biochem. 2005 May;273(1-2):151-60. PMID: 16013450 28. Mihalache D, Preoteasa V, Barca V. Effects of combined selenium and vitamin E administration on DNA in Walker tumor bearing Wistar rat exposed to cytostatic acute treatment. Roum Arch Microbiol Immunol. 2003 Jul-Dec;62(3-4):239-50. PMID: 16008147 29. Chiao TB, Lee AJ. Role of pentoxifylline and vitamin E in attenuation of radiation-induced fibrosis. Ann Pharmacother. 2005 Mar;39(3):516-22. Epub 2005 Feb 8. Review. PMID: 15701781 30. Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC. Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: a review. J Am Coll Nutr. 2003 Apr;22(2):108-17. Review. PMID: 12672706 31. Nicolson GL. Lipid replacement/antioxidant therapy as an adjunct supplement to reduce the adverse effects of cancer therapy and restore mitochondrial function. Pathol Oncol Res. 2005;11(3):139-44. Epub 2005 Sep 29. PMID: 16195767 |
|||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | COVER ARCHIVE | SEARCH |
eLetters: